July 18th- 21st, 2018 Hotel Maksoud Plaza – São Paulo - SP

Preliminary Program

Organization

Sociedade Brasileira de Biologia Celular S.B.B.C.

XIX Meeting of the Brazilian Society for Cell Biology

Dear Colleagues:

The Brazilian Society for Cell Biology (SBBC) chose São Paulo to be the city host for our biennial

meeting, during which we will celebrate the 40th anniversary of SBBC. The Scientific Program

will cover different areas in Cell Biology, with emphasis on multidisciplinary approaches.

The SBBC biennial meetings are internationally recognized as a productive environment to

present and discuss the many aspects of research and education in Cell Biology presented in

keynote talks, plenary conferences, and concurrent symposia. As part of the meeting tradition,

XIX SBBC Congress will include pre-meeting courses around the country, sessions dedicated to

young investigators, a large exhibition, and enthusiastic poster sessions. Additionally, in 2018,

new activities were introduced to the Program: Art & Science/ Science & Art, Bio Cel no Boteco

and a fantastic giant cell that will be exhibited at Catavento Cultural.

The Scientific and Organizing Committees received excellent suggestions from SBBC members

and selected a broad spectrum of themes and concepts that shall make this year’s Congress

inspiring and motivating for scientists at all ages, experience levels, and interests.

The winner of the Young Researcher Award, 2nd edition, will be announced at the closing

ceremony. SBBC received seventeen applications from candidates who published their papers

recently, and the five finalists selected by the Award Committee will present their studies to

the board audience. The congress will also continue with the series of conferences entitled

"Classics in Cell Biology" that honor eminent senior scientists in Brazil, a conference in which

they can share insights of their life, carrier, and contribution to Science for the education of

the new generation of Cell Biologists.

The Thematic Modules activities, inspired by the ASCB Special Interest Subgroups, were a great

success in XVIII SBBC, and will be reissued this year, in the themes Education in Cell Biology,

Data Reproducibility, and Microscopy. These modules allow the integration of research groups

with similar subject interests.

We are thrilled to welcome more than 1,000 cell biologists and to create a favorable

environment for new ideas, collaborative work, and innovation.

Thank you for joining us in São Paulo!

Estela Bevilacqua, Marimélia Porcionatto and Patricia Gama

Co-chairs

• Profa. Dra. Marimélia Porcionatto Departamento de Bioquímica Universidade Federal de São Paulo

• Profa. Dra. Estela Maris Andrade Forell Bevilacqua

Departamento de Biologia Celular e do Desenvolvimento Instituto de Ciências Biomédicas Universidade de São Paulo

Committees

Executive committee Chao Yun Irene Yan (USP) Cláudia Mermelstein (UFRJ) Enilza Espreafico (USP) Giselle Zencker (UNIFESP) Hernandes F Carvalho (UNICAMP) Marinilce Fagundes dos Santos (USP) Patrícia Gama (USP)

Program Committee Chao Yun Irene Yan (USP) Cláudia Mermelstein (UFRJ) Cleida A Oliveira (UFMG) Enilza Maria Espreafico (USP) Estela Bevilacqua (USP) Giselle Zenker Justo (UNIFESP) Hernandes F Carvalho (UNICAMP) Jacqueline C Rinaldi (UEM) José Garcia Abreu (UFRJ) Luiz Eurico Nasciutti (UFRJ)

Marcelo L Lamers (UFRGS) Moacyr Jesus Barreto (UFPE) Patrícia Gama (USP) Rodrigo Nunes da Fonseca (UFRJ) Roger Chammas (USP) Silvia R Batistuzzo de Medeiros (UFRN) Vanessa Morais Freitas (USP) Vilma R Martins (CIPE Hospital A.C. Camargo) Vivaldo Moura Neto (UFRJ) Wilson Savino (FIOCRUZ)

Executive Organization

Av. das Américas 3500 – Bl. Hong Kong 3000 - Sl. 405 Le Monde Office - Barra da Tijuca - RJ - 22640-102

Tel.: 55 21 3326-3320 Fax: 55 21 2437-1483 www.interevent.com.br

GENERAL INFORMATION

ATTENDEE AND EXHIBITOR REGISTRATION (LEVEL A - FOYER)

Wednesday, July 18th 7h00-17h00

Thursday, July 19th 7h00-16h00

Friday, July 20th 7h30-16h00

Saturday, July 21st 8h00-12h30

SBBC MEETING MANAGEMENT/BUSINESS OFFICE

8h00-17h00- LEVEL A ROOM TAPAJÓS

MEDIA DESK & VIP ROOM 8h00-17h00 (LEVEL A - ROOM TAPAJÓS)

BADGES/REPLACEMENT POLICY

Meeting badges must be worn at all times while in Maksoud Plaza Hotel. Children over the age of 12 must wear a badge (registration desk for information). In case you lose or damage your badge there will be a R$ 50,00 fee to issue a new one. Photo identification will be required for replacement. To avoid these charges, please remember to bring your meeting badge and materials with you.

CAMERAS

Any kind of camera and recording devices are prohibited in Poster Sessions.

CERTIFICATES

SBBC adopts paper-free policy and, thus, certificates will be available ONLY online, after July 28th.

DRINKING AND SMOKING POLICIES

The SBBC encourages responsible drinking for those drinking alcohol. Coffee and water will be offered at coffee breaks. Alcoholic beverages are allowed only in specific areas.

It is prohibited to smoke in any area at any public area, including the Convention Center.

EXHIBIT HALL HOURS (LEVEL A)

Wednesday 14h00 - 17h30 Thursday and Friday 08h00 - 17h00 Saturday 08h30 - 12h30

LOST AND FOUND - MESSAGE CENTER

Please contact Registration Counter for lost and found.

Messages for invited speakers and/or attendees should be left at Registration Counter.

POSTER SESSIONS

Poster Sessions will be held at LEVEL B and will be organized according to the different areas (informed below).

Poster Session I: Thursday, July 19th - 13h30 to 15h15 Poster Session II: Friday, July 20th - 13h30 to 15h15

13h30 - 14h20 - even number 14h20 - 15h15 - odd numbers

Poster Session III: Saturday, July 21st - 10h00 to 10h45

10h00 - 10h45 - even and odd numbers

Poster Session I Poster Session II Poster Session III Developmental Biology Cancer and Cell Biology Cancer and Cell Biology Extracellular Matrix Cell Biology of Inflammation Education in Cell Biology Morphology and Cell Biology Cell Death General Cell Biology Reproductive Biology Cell Proliferation and Differentiation Stem Cell Biology Cell Signaling Tissue Engineering Host-Pathogen Interaction Neurobiology Plant Cell Biology

Poster numbers will identify the boards. Tapes and hangers should be brought to the poster area by presenters. The Organizing Committee will not provide these items.

Poster tear down: 17h00 – 18h00 on Poster Session day (I and II) and at 11h00 (session III). The Organizing Committee will not collect and keep Posters that are left on the Boards, which will be discarded immediately after the indicated hours.

Posters will be evaluated by speakers, that will be invited to visit the Sessions and indicate the best studies according to their criteria. Awards will be announced during Closing Ceremony.

SAFETY AND SECURITY

We are committed to make the necessary efforts to ensure a safe, productive and nice event for everyone. Please remember to take off your badge when exiting the Convention Center. Please be aware of your surroundings at all times. For emergencies while in Maksoud Plaza Hotel, contact a uniformed security officer, and follow the specific instructions provided by the hotel. If you plan to move around and go sight-seeing, please consult a travel/tour agency for specific instructions. There are always places to avoid in large cities!

WEATHER

The winter in São Paulo is mild and sub-dry; temperatures range between 11 and 23°C (52 and 73 °F). The Tropic of Capricorn, at about 23°27' S, passes through north of São Paulo and roughly marks the boundary between the tropical and temperate areas of South America. Because of its elevation, however, São Paulo has a temperate climate.

MORE ON TRAVELLING INFORMATION

PASSPORT & VISAS

Passports are required for all foreigners. Brazil’s visa requirements are based upon reciprocity. If your home country requires a visa for Brazilian travelers, you will need one for your trip. Additional information can be obtained from the nearest Brazilian Embassy or Consulate. Your passport expiration date should be at least six months from the date of your arrival.

For more information, visit www.passportsandvisas.com/visas/brazil-visa-faq.asp

AIRPORTS

São Paulo three main airports are Guarulhos International Airport (GRU), Viracopos International Airport (VCP, in Campinas), and Congonhas Airport (CGH). GRU and VCP operate for international, domestic and regional flights, and CGH mainly for domestic flights. Guarulhos International Airport (GRU), also known as "Cumbica" is 25 km (16 mi) north-east of the city center, VCP is at 100 km (64 mi) in Campinas, and CGH is at 6 km (3.7 mi) from city center.

GROUND TRANSPORTATION

Cars are the main means to get into the city, and heavy traffic is common on the city's main avenues. If you prefer to use cars in São Paulo rather than public transport, you can rent a car or you can use taxis and apps. It is very common and simple to ask for taxis and Uber (and other apps) through mobiles. You only need to upload the apps and follow their instructions (the most common apps are “99taxi” or “Easy Taxi” for taxis and “Uber”for ubers, and Cabify).

The taxis in São Paulo are usually white colored and have an indication board on their top. Cars from apps (ubers and cabify) are not identified, but you might check the model of the car you have contacted through the app.

Bikes- biking lanes are identified in red in the streets, avenues and pathways. They can be rented through bank apps (Itau- orange and Bradesco- red). To use them combined with public transport, please check the links below.

PUBLIC TRANSPORT

São Paulo has three rapid transport systems: the underground rail system (called "metrô"); the suburban rail system (called “CPTM”); and the fast-lane bus system: there are many bus lines in the city, which are street-level, placed on large avenues and connected with the underground or suburban train stations.

For itinerary information:

Bus: www.sptrans.com.br/itinerarios

Subway: www.metro.sp.gov.br use the links “trajeto” and “mapa da rede”

For the subway and CPTM system, you can buy tickets at the station (R$ 4,00/ticket). Cards are available for multiple rides for subway and bus. The system is called “bilhete único” (there is a flat rate independent of distance travelled):

www.metro.sp.gov.br/sua-viagem/bilhetes-cartoes/bilhete-unico.aspx

If you take a bus, you can also pay inside (R$3,80).

A new train line (13- Jade) connects GRU to city center, for more information, please check: http://www.cptm.sp.gov.br/sua-viagem/Pages/Linhas.aspx

AIRPORT BUS SERVICE

It is a bus service that connects Guarulho´s airport to different spots in São Paulo, and one of them is right in front of Maksoud Plaza Hotel. If you want to go from the airport to Maksoud Plaza, you should buy an Airport Bus Service ticket at the airport to “Avenida Paulista (via República)”. It costs about R$ 50,00.

If you want to go from the hotel to the airport, you can buy the ticket inside the bus (from the bus driver), for the same price (R$ 50,00).

For more information about the Airport Bus Service: www.airportbusservice.com.br/en/home

Another option from GRU to city center is the combination of bus and metro as: bus to Tatuape subway station and the metro from there to your stop (check the links above).

HEALTH

There is no compulsory health requirement for entry into Brazil, but some areas are endemic for yellow fever. We suggest that you contact your local Consulate for current advice. Please note that if you are entering Brazil via Colombia, Equador or Peru, you will be required to provide a current yellow fever vaccination certificate for immigration purposes.

MEDICAL AND INSURANCE SERVICES

São Paulo has many hospitals, clinics and doctors, but treatment is costly, so visitors are strongly advised to purchase medical trip insurance.

The Congress Organization is not liable for any health problems, personal accidents, lost baggage or cancellation of travel arrangements, flights etc. We recommend that participants provide their own insurance policies.

FOOD & DRINKS

The most common dishes feature various meats, rice and the ubiquitous Brazilian black beans (feijão), while restaurants many times offer all-you-can-eat barbecues and buffets.

Many kinds of alcoholic drinks are available, including excellent lager style beers such as Antarctica, Brahma, Cerpa and Skol. The most popular local beverage is Cachaça, most commonly served as 'Caipirinha' with slices of lime or lemon. There are no restrictions on licensing hours. Soft drinks include Guarana (a carbonated cola-like drink, made from the Amazon fruit, guarana) and many varieties of fruit juices (sucos). Brazilian coffee tends to be served less strong than Italian coffee, so if stronger coffee is desired, request express coffee (café expresso). If you would like to avoid sugar in juices or coffee, you should specifically request that it not be added.

FOREIGN EXCHANGE

The Brazilian monetary unit is the Real (R$). Exchange rates are published daily in the newspaper. Cash and traveler checks, especially US Dollars (USD), can be exchanged at most banks, exchange houses and major hotels.

• Bank notes (paper money) are in denominations of R$ 100, R$ 50, R$20, R$ 10, R$ 5, R$ 2. • Coins are 1.00 real, 50 centavos (cents), 25 centavos, 10 centavos and 5 centavos. • Banking Hours - 10:00-16:00 Monday to Friday.

TIPPING

In most restaurants and bars, a 10% service fee is added to the bill. More sophisticated places may add 15%. If service is not included, it will be stated at the bottom of the bill: “Serviço não incluído.” Airport and hotel porters: the R$ is equivalent to the USD of $1.00 per suitcase. Hotels: Hotels generally include any service charge on the bill. Restaurants: Tips are discretionary, but often found on the final bills as a "suggestion." In Brazil, a typical tip remains 10%. Taxis: Tips are not expected by taxi drivers although most passengers will round the fare up if satisfied with the service

SOME LAST ADVICES TO ENJOY SÃO PAULO

Below, you will find a few general recommendations to help you enjoy a safe and relaxing trip to São Paulo:

Never leave your luggage unattended or with a stranger and please be aware that some may attempt to create a distraction to divert your attention from your belongings.

The sunlight in Brazil can be more direct and stronger - extra precautions are necessary to avoid excessive tanning and/or skin burns, specially for clear less-pigmented skin.

Avoid wearing eye-catching jewellery or watches. Carry limited amounts of cash and keep your passport and other important travel documents in your hotel. When not in use, it is advised that you carry your cell phone and camera in your pocket and as a precaution, be sure to carry your bag in front of you.

IMPORTANT PHONE NUMBERS Brazil code: 55 São Paulo code 11 Police: 190 Emergency and Fireman 193 Guarulhos International Airport (11) 2445-2945 Maksoud Plaza Hotel (11) 3145-8000

MAP OF MAKSOUD PLAZA AREA

Congress activities are planned at different rooms inside Maksoud Plaza Hotel.

jul/18 jul/19 jul/20 jul/21

Walking at Trianon Park @ 6h45

Room Room Room Room Room Room Room Room Room Room Room Room

Mato Grosso DF São Paulo Brasil Mato Grosso DF São Paulo Brasil Mato Grosso DF São Paulo Brasil

8h00 Registration desk opens

Poster setup Poster setup Poster setup

Symp 1 - Cellular micro

environments (Roger

Chammas)

Symp 2 - Regenerative

medicine (Silvya Maria-

Engler)

Symp 3 - Advanced

microscopy (Hernandes Carvalho)

Symp 4 - Cell biology of neuroimmune

interactions (Wilson Savino)

Symp 11 - Cannabionoids

and neuro degererative

diseases (Lucianne Madeira)

Symp 12 - Cellular and molecular

mechanisms of tumor

progression (Luiz E

Nasciutti)

Symp 13 - DNA damage,

Epigenetics and LncRNA in

cancer (Enilza

Espreafico)

Symp 14 - YOUNG

INVESTIGATORS (Christina

Barja-Fidalgo)

these sessions start @ 8h30

Conf 12 Emer Ferro

Conf 13 João Viola

Conf 14 Anselmo Moriscot

Conf 15 Sebastião

Taboga

Conf 16 André Pupo

Conf 17 Glaucia Santelli

Conf 18 Tiago

Rodrigues

Conf 19 Hernandes Carvalho

09h30

Pre-meeting courses Conf 1

Dennis Discher

Conf 2 Martin Lowe

Conf 3 Shankar Srinivas

Conf 4 Indira

Mysorekar

Conf 5 Jaime

Grutzendler

Conf 6 Kirill

Afonin

Conf 7 David

Kashatus

Conf 8 Douglas Green 9h00 Conf 20 -

Regina Markus

Conf 21 Luisa Iruela-

Arispe

Conf 22 Sara Saad

Conf 23 Cleida

Oliveira

10h30 Coffee break Coffee break @ Terrace Coffee break @ Terrace Poster Session 3 & Coffee break 10h00- 10h45 Rooms Minas Gerais + Rio de Janeiro

11h00

Symp 5 - Extracellular

matrix (Marcelo Lamers)

Symp 6 - RNA and cell

biology (Patrícia Coltri)

Symp 7 – New genetic

tools (Rodrigo Nunes

da Fonseca)

Symp 8 – Glia and diseases

(Vivaldo M Neto)

Symp 15 - Neural stem

cells (Marilene H Lopes)

Symp 16 - Cells &

Organelles (Luis

Lamberti)

Simp 17 - Developmental

biology (José Garcia

Abreu)

Symp 18 - YOUNG

RESEARCHER AWARD GE

Closing conference @ 11h00

Jason Mills

12h30 Nikon Greiner EMBRAPII SENAI BioMinas BD SBBC Young Researcher Award @ 12h15

13h00- 15h30 Thematic sessions Ensino

Reprodutibilidade Microscopia Exhibition

Silvia Batistuzzo de Medeiros

13h30 Poster Session 1 Poster Session 2

Level B - Rooms Minas Gerais + Rio de Janeiro Level B - Rooms Minas Gerais + Rio de Janeiro

15h00 Coffee break @ Terrace Coffee break @ Terrace

15h30

Symp 9 - Cell Migration (Claudia Mermelstein)

Conference 1 Dennis Discher

Symp 10 - Cell proliferation & death

(Gustavo P Amarante- Mendes)

Symp 19 - Parkinson's

Disease (Silvana Allodi)

Symp 20 - Chromatin remodeling

and DNA repair (Silvia

Batistuzzo)

Symp 21 - Cell migration

and differentiation

(Manoel da Costa)

Symp 22 - YOUNG

INVESTIGATORS (Giselle Zenker)

17h00 Opening Ceremony

SBPC 70 anos Lucile Winter

Classics in Cell Biology Helena Nader

Conf 9 Vilma

Martins

Conf 10 Ana

Marisa Chudzinski

Tavassi

Conf 11 Leonid Peshkin

ELEVATOR TALKS

(Irene Yan)

17h30

Conference 18h00 Peter Friedl 18h15 BioCel no Boteco SBBC General Assembly SBBC 40 years Estela Bevilacqua

CURSOS PRÉ- CONGRESSO

ID Nome do curso Data Horário Vagas Instituição e local Cidade Ministrantes email

M1 Análise e processamento de imagens usando ImageJ 18/07/2018 9h00-

12h00 40 Hotel Maksoud Room Pernambuco São Paulo

Marcelo Lamers Lisiane Bernardi

marcelo.lamers@ufrgs.br bernardi.lisiane@gmail.com

M2 Aplicações da Microscopia de Força Atômica e Espectroscopia Raman na Biologia Celular 18/07/2018 9h00-

12h00 30 Hotel Maksoud Room Paraná São Paulo Alexandre Borbely

alexandre.borbely@icbs.ufal.br

M3 Inovação Terapêutica em Oncologia: A experiência de um banco de moléculas

brasileiro 18/07/2018 9h00-

12h00 30 Hotel Maksoud Room Santa Catarina São Paulo

Moacyr Rego moacyr.rego@gmail.com

M4 Bases da migração celular e regulação por microRNAs 18/07/2018 9h00-

12h00 30 Hotel Maksoud Room Xingu São Paulo Cilene Rebouças

cilima77@gmail.com

U1 Reparo e bioengenharia do Tecido ósseo: das ciências básicas à clínica. 08/06/2018 9h00-

17h00 40 UNFESP, São José dos Campos - SP. CEP 12231-280.

São José dos Campos, SP

Luciane Portas Capelo Ana Lia Anbinder

lcapelo@unifesp.br ana.anbinder@ict.unesp.br

U2 Mecanismos celulares e moleculares da inflamação 06/07/2018 9h00-

17h00 15 UNIFESP, campus São Paulo São Paulo, SP Cristiane Damas Gil; Alexandre Dantas Gimenes; Frans Eberth Costa Andrade

cristiane.gil@unifesp.br

U3 Terapias Celulares em doenças cardiovasculares 10/07/2018 9h00-

17h00 40 UFABC Santo André, SP Marcela Sorelli Carneiro Ramos Daniele Ribeiro de Araújo

msorelli@gmail.com

U4 Programação fetal: Do ambiente uterino ao envelhecimento da prole. 12/07/2018 9h00-

17h00 60 UNESP/Botucatu. Instituto de Biociências, Espaço IB Eventos. Botucatu, SP

Luis Antonio Justulin Junior Débora Cristina Damasceno Maeli Dal-Pai-Silva Luis Fernando Barbisan

justulin@ibb.unesp.br damascenofmb@gmail.com maeli@ibb.unesp.br barbisan@ibb.unesp.br

U5 Cultura celular: Diferentes técnicas associadas 13/07/2018 9h00-

17h00 40 UFRN Natal, RN

Hugo Alexandre de Oliveira Roca Susana Margarida Gomes Moreira

hugo-alexandre@uol.com.br ssmargarida@gmail.com

U6 Câncer, regeneração e envelhecimento: da cromatina ao metabolismo celular 13/07/2018 9h00-

17h00 40 USP FMRP Ribeirão Preto, SP Enilza Espreafico emesprea@gmail.com

U7 Cultura celular: sistemas 2D e 3D, co-cultura e modelo de chimeras 14/07/2018 9h00-

17h00 15 UEM, Universidade Estadual de Maringá, bloco H79 Maringá, PR Jaqueline Rinaldi jak.rinaldi@gmail.com

U8 Instabilidade genômica em câncer: métodos de detecção 16/07/2018 9h00-

17h00 20

UNIFAL, Departamento de Biologia Celular e do

Desenvolvimento, Instituto de Ciências Biomédicas.

Alfenas, MG Angel Mauricio Castro Gamero Marisa Ionta

amcgen@gmail.com marisaionta@gmail.com

U9 Obtenção, tratamento e análise de imagens em microscopia 12/07/2018 9h00-

17h00 15

UFG, Departamento de Histologia, Embriologia e

Biologia Celular, Instituto de Ciências Biológicas

Goiania, GO

Manoel Francisco Biancardi Mara Rubia Marques Fernanda Cristina Alcântara dos Santos Hernandes F Carvalho

mrubia.01@hotmail.com mfbbio@yahoo.com.br

U10 Microscopia confocal aplicada ao imageamento in vivo e ex vivo 17/07/2018 9h00-

17h00 40 UFMG, ICB, Center for Gastroinestinal Biology

Belo Horizonte, MG Gustavo B Menezes

menezesgb@gmail.com

U11 Estudos em Biologia do Desenvolvimento:de regeneração a ecotoxicologia 17/07/2018 9h00-

17h00 20 UFRJ, NUPEM Macaé, RJ Natália M Feitosa Rodrigo Nunes da Fonseca

nataliafeitosa@gmail.com rodrigo.nunes.da.fonseca@gmail.com

U12 Célula artificial: microfabricação e microfluidica 17/07/2018 9h00-

17h00 40 IB, UNICAMP Campinas, SP Monica Cotta Marisa Beppu Hernandes F Carvalho

hern@unicamp.br

Thematic Session

July 18th 13h00- 15h30

The Thematic Sessions were organized to allow the discussion of specific topics in Science and Cell Biology in Brazil.

Possibilidades de Inovação em Ensino

Room MT Cleida Oliveira, ICB UFMG Fernanda Ortis, ICB USP Lucianne Fragel Madeira, UFF Eduardo Galembeck, IQ UNICAMP Claudia Mermelstein, ICB UFRJ

Reprodutibilidade em pesquisa Room DF

Tiago Goss dos Santos, CIPE A.C. Camargo Olavo Amaral, UFRJ Márcia Mayer, ICB, USP

Microscopia avançada: facilidades e dificuldades

Room Pernambuco Ruy G Jaeger, USP Rita Sinigaglia, UNIFESP Marinilce F Santos, USP Hernandes F Carvalho, UNICAMP Gustavo Menezes, UFMG Kildare Miranda, UFRJ

Macrocélula- Catavento Cultura, São Paulo

July 3rd to September 2nd

A permanent cell built in one of the most important exhibition spots in Sao Paulo. Macrocelula was designed by Andrea Amarante Paffaro from Universidade Federal de Alfenas, that houses the structure at the Museum. In a dark room, this cell allows children, teens and adults to learn about organelles and cell functions in a totally different way.

Bio Cel & Arts/ Arts & Bio Cel

July 18th to 21st- Level B- room Espírito Santo

This exhibition was planned and organized by Irene Yan and Wilson Savino. The idea is to bring together Sciences and Arts through the work of investigators and artists in the world, combining painting, music, drawing and the many kinds of expression.

BioCel & Technology

July 19th at 12h30

Nikon Gustavo Menezes. Expanding horizons: visualizing cell biology in a native environment using confocal intravital microscopy. Greiner Angélia Silveira. Magnetic 3D cell culture and bioprinting for drug screening and disease modeling.

EMBRAPII Jorge Guimarães. O papel da EMBRAPII no fomento à inovação industrial. Oportunidades para empresas e grupos de pesquisas das universidades.

July 20th at 12h30

BD Renan Antonialli, MsC. Citometria para não citometristas da purificação à imagem. A citometria e a microscopia para análise celular multiparamétrica. SBPC: 70 years & Classics in Cell Biology

July 19th at 17h00- Room São Paulo

The Brazilian Society for Science Progress (SBPC) is celebrating 70 years in 2018 and Dr Lucille Winter (IB USP) will talk about the history of SBPC and introduce Dr Helena Nader that will present her studies in the series “Classics in Cell Biology”.

BioCel no Boteco

July 19th at 18h15

A special committee (Ivarne Tersariol, Emer Ferro and Fábio Nascimento) organized a different meeting to gather our speakers and participants in bars at Maksoud lively neighborhood. Come and join us! The schedule and addresses will be posted soon and will be available at Registration Counter area.

Elevator Talk

July 20th at 9h30

The Elevator Talk competition is a video competition where the contestants explain briefly (the equivalent of a short Elevator trip) their research focus. The short period duration of the videos make this a dynamic presentation where the researcher is challenged to be effective, efficient and exciting.

BioCel, Technology and Enterpreneurship

July 20th at 12h30

SENAI- Room Mato Grosso

Apresentaremos a rede nacional de Institutos SENAI de Inovação. Em São Paulo já são operantes dois institutos: o ISI em Materiais Avançados e Nanocompósitos, o qual atua no desenvolvimento e na otimização do uso de materiais não metálicos, como polímeros (plásticos e borracha), cerâmicas e compósitos; e o ISI em Manufatura Avançada e Microfabricação, que possui uma equipe multidisciplinar, a qual atua no desenvolvimento de produtos, elaborando projetos e soluções tecnológicas de design e engenharia integrados. Além destes, está em fase de planejamento o ISI em Biotecnologia. São Paulo é o estado onde se concentram 48% das empresas de biotecnologia. Este Instituto será voltado para Pesquisa, Desenvolvimento e Inovação na área da saúde.

ISI em Manufatura Avançada e Microfabricação.

Luis Umbelino dos Santos (Coordenador de Tecnologia do ISI-MAMF),

luis.santos@sp.senai.br

ISI em Materiais Avançados e Nanocompósitos.

Gustavo Spina Gaudêncio de Almeida (Coordenador de Tecnologia do ISI-MAN)

Biominas - Room Distrito Federal

Empreendedorismo e inovação com pesquisas de impacto: O cenário mundial na área de saúde tem mudado muito nos últimos anos e este ciclo de mudança está cada vez menor. Isso se deve, principalmente ao surgimento de novas tecnologias que estão revolucionando a forma de trabalhar nesta área e possibilitando coisas que pareciam impossíveis até poucos anos atrás. Para acompanhar esta revolução, é necessário criar novas tecnologias e conseguir dar uma aplicação prática para elas no mercado. Pensando nisso, a Biominas Brasil, por meio de uma série de programas de empreendedorismo, visa dar oportunidade para aqueles pesquisadores que possuem algum projeto ou tecnologia que tem um potencial de impactar a sociedade e o mercado de alguma forma, mas não sabe exatamente como fazê-lo. Contamos com apoio e proximidade de grandes empresas e especialistas do setor para direcionar os esforços de pesquisa e desenvolvimento do negócio, afim de encurtar a distância que exite hoje entre a academia e o mercado, gerando novos negócios que impactam positivamente a sociedade e geram riqueza para o país. Gustavo Furegato Pedreira de Freitas gustavof@biominas.org.br

SBBC 40 years

SBBC is celebrating 40 years and a special session will remember the history and advances of Cell Biology in Brazil. We will also show Cell Biology Mini-Docs- videos prepared with those of our main investigators when SBBC started its activities.

Program- July 18th

8h00 Registration desk opens

9h00 - 12h00

Pre-meeting courses Level B Rooms TBC 10h30- Coffee break- foyer Level B

13h00 -15h30

Thematic sessions 1-3 Level B Rooms Mato Grosso, DF, Pernambuco Exhibition starts @ 14h00- Terrace 15h30- Coffee break-foyer Level B

17h00 Opening Ceremony Level A Rooms São Paulo+Brasil

18h00 Opening conference Chair: Marinilce F Santos Peter Friedl

OPENING CEREMONY

July 18th, 17h00- Level A Rooms São Paulo+Brasil Patrícia Gama Estelva Bevilacqua Marimélia Porcionatto Sociedade Brasileira de Biologia Celular

OPENING CONFERENCE

July 18th, 18h00 Chair: Marinilce F Santos

Plasticity of cancer cell invasion and metastasis Peter Friedl Radboudumc, Nijmegen, The Netherlands & Division of Cancer Medicine MD Anderson Cancer Center, The University of Texas

Program- July 19th

Room Room Room Room Mato Grosso DF São Paulo Brasil

8h00 Poster setup

Symp 1 Cellular micro environments

Roger Chammas

Symp 2 Regenerative

medicine

Silvya Maria-Engler

Symp 3 Advanced

microscopy

Hernandes Carvalho

Symp 4 Cell biology of neuroimmune

interactions Wilson Savino

09h30 Conference 2 Martin Lowe

Conf 3 Shankar Srinivas

Conf 4 Indira Mysorekar

10h30 Coffee break @ Terrace

11h00

Symp 5 Extracellular matrix

Marcelo Lamers

Symp 6 RNA and cell

biology

Patrícia Coltri

Symp 7 New genetic tools in developmental

biology Rodrigo Nunes da

Fonseca

Symp 8 Glia and diseases

Vilvado Moura

Neto

12h30 Nikon Greiner EMBRAPII

13h30 Poster Session 1

Level B - Rooms Minas Gerais + Rio de Janeiro

15h00 Coffee break @ Terrace

15h30

Symp 9 Cell Migration

Claudia Mermelstein

Conference 1 Dennis Discher

Symp 10 Cell proliferation & death

Gustavo P Amarante- Mendes

17h00

SBPC 70 anos Lucile Winter

Classics in Cell Biology

Helena Nader Poster tear down

18h15

BioCel no Boteco

Ivarne Tersariol, Fábio Nascimento e Emer Ferro Information at Registration Desk

SBBC General Assembly

Program- July 19th

Room Mato Grosso (level B) 8h00- 9h30 Symposium #1 Cellular microenvironments Chair: Roger Chammas, FM USP ICESP (S1, 19) Integration of Mechanical and Molecular Microenvironmental Signals in the Endothelium Luisa Iruela Arispe, UCLA (S1, 19) Pericytes at the crossroads between tissue regeneration and pathology Alexander Birbrair, UFMG (S1, 19) Galectin-3 integrates tumor cell adaptive responses in stressed tissue microenvironments Ana Carolina Ferreira Cardoso, Silvina Odete Bustos, Luciana Nogueira de Souza Andrade and Roger Chammas. Instituto Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo. 10h30- 11h00- Coffee break @ Terrace 11h00- 12h30 Symposium #5 Extracellular Matrix Chair: Marcelo Lazaron Lamers, UFRGS (S5, 19) Extracellular matrix gene expression signature of prostate cancer Sérgio L Felisbino, IBB, UNESP (S5, 19) ADAMTS-1 disrupts HGF/c-MET signaling and HGF-stimulated cellular processes in fibrosarcoma cells Vanessa M Freitas, ICB, USP (S5, 19) Extracellular matrix as a modulator of tumor metastasis Marcelo L Lamers, UFRGS 12h30- 13h30 Tech Conference: Nikon Expanding horizons: visualizing cell biology in a native environment using confocal intravital microscopy Gustavo Menezes, Center for Gastrointestinal Biology, UFMG 15h00- 15h30- Coffee break 15h30- 17h00 Symposium #9 Cell Migration Chair: Cláudia Mermelstein Conference #1 Chair: Ruy Jaeger, USP, Brazil

From matrix rigidity to nuclear mechanobiology in development and disease Dennis Discher, University of Pennsylvania, USA

(S9, 19) Neural stem cell response to brain injury: unraveling a new function for the chemoattractant protein prokineticin 2 Marimelia Porcionatto, UNIFESP (S9, 19) MicroRNAs and the Impairment of Fibroblast Migration Under High Glucose Concentrations Marinilce F Santos, ICB, USP (S9, 19) Crosstalk between Wnt, cholesterol and Rho/ROCK during tumor cell migration Cláudia Mermelstein, ICB, UFRJ

Program- July 19th

Room Distrito Federal (level B) 8h00- 9h30 Symposium #2 Regenerative Medicine Chair: Silvya Stuchi Maria Engler, FCF, USP (S2, 19) Neuroprotection by gene therapy: from bench to cageside Rafael Linden & Hilda Petrs-Silva, Instituto de Biofísica, UFRJ (S2, 19) Marimelia Porcionatto, UNIFESP (S2, 19) Silvya Stuchi Maria Engler, FCF USP 9h30- 10h30 Conference #2 Chair: Ana Cláudia Torrecilhas

Mechanisms of vesicle transport at the Golgi apparatus Martin Lowe Division of Molecular and Cellular Function. The University of Manchester, London, UK

10h30- 11h00- Coffee break 11h00- 12h30- Symposium #6 RNA & Cell Biology Chair: Patricia P Coltri, ICB, USP (S6, 19) Understanding Immunomodulatory Properties of Nucleic Acid Nanoparticles Kirill Afonin and Marina A. Dobrovolskaia, University of North Carolina (S6, 19) The regulatory protein Ki-1/57 (or HABP4): from an RNA binding protein to a possible novel tumor suppressor protein Jorg Kobarg, FCF, IB, UNICAMP (S6, 19) Investigating microRNA splicing regulators in mammalian cells Patricia P. Coltri, Marcelo M. Paiva, Romina S. Horianski, Maria Gabriela P. dos Santos, Guilherme H. Gatti da Silva, ICB, USP 12h30- 13h30 Tech Conference: Greiner Magnetic 3D cell culture and bioprinting for drug screening and disease modeling Angélica Silveira, Ph.D 15h00- 15h30- Coffee break 15h30- 17h00 Symposium #9 Cell Migration Chair: Cláudia Mermelstein (S9, 19) Neural stem cell response to brain injury: unraveling a new function for the chemoattractant protein prokineticin 2 Marimelia Porcionatto, UNIFESP (S9, 19) MicroRNAs and the Impairment of Fibroblast Migration Under High Glucose Concentrations Marinilce F Santos, ICB, USP (S9, 19) Crosstalk between Wnt, cholesterol and Rho/ROCK during tumor cell migration Cláudia Mermelstein, ICB, UFRJ

Program- July 19th

Room São Paulo (level A) 8h00- 9h30- Symposium #3 Advanced Microscopy Chair: Hernandes F Carvalho, IB, UNICAMP (S3, 19) An immune and metabolic shift during neonatal development reprogram liver identity and function Gustavo Menezes, Center for Gastrointestinal Biology, UFMG (S3, 19) Carlos Lenz Cesar (S3,19) Fluorescence life-time imaging microscopy - monitoring single cell metabolism Hernandes F Carvalho, IB UNICAMP 9h30- 10h30- Conference #3 Chair: Irene Yan

Deciphering epithelial cell movements during anterior pattering in the mouse embryo Shankar Srinivas, PhD, MPhil, MA, BSc Department of Physiology, Anatomy and Genetics, University of Oxford, Medical Sciences Division

10h30- 11h00- Coffee break 11h00- 12h30- Symposium #7 New genetic tools in developmental biology Chair: Rodrigo Nunes da Fonseca, UFRJ, Macaé, RJ (S7, 19) Self-propagating gene drives as a molecular tool for functional analysis in non-model insects Helena Araujo and Mateus Berni, ICB, UFRJ (S7, 19) Stem cell features in blood progenitors of ascidians, our closest invertebrate relatives Federico Brown, IB USP (S7, 19) Functional genomic tools in the identification of new genes and regulatory elements in non-model arthropods Lupis Ribeiro, Diego Guerra, Alessandra Alvarenga, Vitória Tobias-Santos, Natalia Martins Feitosa, Rodrigo Nunes da Fonseca, NUPEM-UFRJ-Macaé 15h00- 15h30- Coffee break 15h30- 17h00- Symposium #10 Cell Proliferation & Death Chair: Gustavo P Amarante- Mendes, ICB USP (S10, 19) CDK6 – the new kid on the block Veronika Sexl, Institute of Pharmacology and Toxicology, VetmedUni Vienna (S10, 19) Oncogene-Induced Replication Stress and Chromosome Instability in Human Cancer Leonardo Karam Teixeira, Brazilian National Cancer Institute, INCA, RJ (S10, 19) New insights on cd8-mediated immune responses Gustavo P. Amarante- Mendes, ICB USP 17h00- 18h00- SBPC 70 years & Classics in Cell Biology SBPC 70 anos- Lucille Winter, IB USP Classics in Cell Biology: Helena B Nader, UNIFESP 18h15 SBBC General Assembly

Program- July 19th

Room Brasil (level A) 8h00- 9h30- Symposium #4 Cell biology of neuroimmune interactions Chair: Wilson Savino, IOC FIOCRUZ (S4, 19) Multiple Sclerosis: How Inflammation, Degeneration and the Gut Microbiota interact to trigger Brain Autoimmune Disease. Hartmut Wekerle, Max Planck Institute, Germany (S4, 19) Carmem Gottfried, UFRGS, Brazil (S4, 19) Wilson Savino, IOC FIOCRUZ 9h30-10h30- Conference #4 Chair: Estela Bevilacqua, ICB USP

The placenta as the frontline defense against maternal-fetal transmission: Lessons from the Zika virus Professor Indira U Mysorekar, Washington University School of Medicine, St. Louis, USA

10h30- 11h00- Coffee break 11h00- 12h30- Symposium 8 Glia and diseases Chair: Vivaldo Moura Neto, UFRJ, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro (S8, 19) Deciphering neuron-glia interactions and therapeutic opportunities in neurodegenerative diseases Dora Brites, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal (S8, 19) Microglia-glioblastoma interaction: the role of microglial factors in tumor progression Flavia Lima, Anna Fonseca, Rackele Amaral, Celina Garcia, Diana Matias, Luiz Henrique Geraldo, ICB UFRJ (S8, 19) Astrocytes: Are they all the same? Implications for synapse function and neurodegenerative diseases Flávia A C Gomes, ICB, UFRJ 12h30- 13h30 Tech Conference: EMBRAPII O papel da EMBRAPII no fomento à inovação industrial. Oportunidades para empresas e grupos de pesquisas das universidades. Jorge Guimarães, EMBRAPII 15h00- 15h30- Coffee break 15h30- 17h00- Symposium #10 Cell Proliferation & Death Chair: Gustavo P Amarante- Mendes, ICB USP (S10, 19) CDK6 – the new kid on the block Veronika Sexl, Institute of Pharmacology and Toxicology, VetmedUni Vienna

(S10, 19) Oncogene-Induced Replication Stress and Chromosome Instability in Human Cancer Leonardo Karam Teixeira, Brazilian National Cancer Institute, INCA, RJ (S10, 19) New insights on cd8-mediated immune responses Gustavo P. Amarante- Mendes, ICB USP 17h00- 18h00- SBPC 70 years & Classics in Cell Biology SBPC 70 anos- Lucille Winter, IB USP

Classics in Cell Biology: Helena B Nader, UNIFESP

18h15 SBBC General Assembly

Program- July 20th

Room Room Room Room Mato Grosso DF São Paulo Brasil

8h00 Poster setup

Symp 11 Cannabionoids and neurodegererative

diseases Lucianne Madeira

Symp 12 Cellular and molecular

mechanisms of tumor progression

Luiz E Nasciutti

Symp 13 DNA damage,

Epigenetics and LncRNA in cancer Enilza Espreafico

Symp 14 YOUNG

INVESTIGATORS Christina Barja-

Fidalgo

09h30 Conference 5 Jaime Grutzendler

Conference 6 Kirill Affonin

Conference 7 David Kashatus

Conference 8 Douglas Green

10h30 Coffee break @ Terrace

11h00 Symp 15

Neural stem cells Marilene H Lopes

Symp 16 Cells & Organelles

Luis Lamberti

Simp 17 Developmental

biology José Garcia Abreu

Symp 18 YOUNG

RESEARCHER AWARD GE

12h30 SENAI BioMinas BD

13h30 Poster Session 2

Level B - Rooms Minas Gerais + Rio de Janeiro

15h00 Coffee break @ Terrace

15h30 Symp 19

Parkinson's Disease Silvana Allodi

Symp 20 Chromatin

remodeling and DNA repair

Silvia Batistuzzo

Symp 21 Cell migration and

differentiation Manoel da Costa

Symp 22 YOUNG

INVESTIGATORS Giselle Zenker

17h00 Conference 9 Vilma Martins

Conference 10 Ana Marisa C Tavassi

Conference 11 Leonid Peshkim

ELEVATOR TALKS Irene Yan

Poster tear down

18h15 SBBC 40 years

Estela Bevilacqua

Program- July 20th

Room Mato Grosso (level B) 8h00- 9h30 Symposium #11 Cannabinoids and neurodegenerative diseases Chair: Lucianne Fragel Madeira, UFF, RJ (S11, 20) Role of cannabinoid receptors and TRPA1 in cell death induced by ischemia Karin Calaza, UFF, RJ (S11, 20) Cannabidiol in neurodegenerative disorders Francisco Silveira Guimarães, Department of Pharmacology, School of Medicine of Ribeirão Preto, USP (S11, 20) Cannabinoids and epilepsy Fabrício Moreira, ICB UFMG (S11, 20) Modulation of endocannabinoid system induced neuroprotection in a murine model of retinitis pigmentosa Camila F. Magalhães, Daniella S. Lopes, Rafael F. Azevedo, Lucianne Fragel-Madeira, UFF, RJ 9h30- 10h30- Conference #5 Chair: Silvana Allodi

Uncovering the role of glia in neurodegeneration: one image at a time Jaime Grutzendler, MD, Center for Experimental Neuroimaging, Yale School of Medicine, New Haven,USA

10h30- 11h00- Coffee break 11h00- 12h30 Symposium #15 Neural stem cells Chair: Marilene H Lopes, ICB USP (S15, 20) Human pluripotent stem cell-based nervous system disease modeling William T Hendriks, Massachusetts General Hospital/Harvard Medical School, USA (S15, 20) Henrique Souza, IB UNICAMP (S15, 20) Prion protein: a pivotal driver and target in glioblastoma stem cells Marilene H. Lopes; Rebeca Iglesia, Mariana B. Prado, Tiago Góss dos Santos, ICB USP 12h30- 13h30 BioCel, Technology and Enterpreneurship: SENAI ISI em Manufatura Avançada e Microfabricação. Luis Umbelino dos Santos

ISI em Materiais Avançados e Nanocompósitos. Gustavo Spina Gaudêncio de Almeida

15h00- 15h30- Coffee break

15h30- 17h00 Symposium #19 Parkinson´s disease Chair: Silvana Allodi, UFRJ (S19, 20) Zooming in on alpha-synuclein aggregation: imaging super-powers Tiago Outeiro, University Medical Center Goettingen, (S19, 20) New approaches in L-dopa induced dyskinesia: the prominence of glial cells Elaine A del Bel Belluz Guimarães, USP (S19, 20) Is the spinal cord affected by physical exercise in bilateral model of Parkinson’s disease? Silvana Allodi, UFRJ 17h00- 18h00- Conference #9 Chair: Marilene H Lopes

The role of exosome secretion regulation in tumor recurrence and patient survival Vilma R Martins, A.C.Camargo Cancer Center, Brazil

Program- July 20th

Room Distrito Federal (level B)

8h00- 9h30 Symposium #12 Cellular and molecular mechanisms in tumor progression Chair: Luiz Eurico Nasciutti, ICB UFRJ (S12, 20) HMGA1 tackles NUMB in the match against glioblastoma stem cell asymmetric division. Francesca Puca, Nadia Tosti, Sonia Morlando, Alfredo Fusco and Sabrina Battista, Istituto di Endocrinologia ed Oncologia Sperimentale - CNR, Naples, Italy (S12, 20) Tumor-derived Extracellular Matrix Mediating Epithelial-Mesenchymal Transition in Breast Cancer Cells Thereza Christina Barja- Fidalgo, UERJ (S12, 20) Characterizing and promoting immune responses to tumors

Martin H Bonamino, INCA, RJ 9h30- 10h30 Conference #6 Chair: Roger Chammas, FM USP, ICESP

Dynamic RNA and DNA nanoassemblies with controlled immunological properties Kirill Afonin, University of North Carolina at Charlotte, USA

10h30- 11h00- Coffee break 11h00- 12h30- Symposium #16 Cells & Organelles Chair: Luis Lamberti P. da Silva, FMRP, USP (S16, 20) Extracellular vesicles modulate innate immune response in protozoa infection Ana Claudia Trocoli Torrecilhas, UNIFESP (S16, 20) Phosphoinositide control of cytokinesis Martin Lowe, The University of Manchester, UK (S16, 20) Hijacking the Golgi: insights into the mechanism of Orthobunyavirus assembly in mammalian cells Natalia S. Barbosa, Marcos V. S. Dias; Leila R Mendonca; Marjorie Pontelli; Michael Schindler; Eurico Arruda and Luis Lamberti P. da Silva, Center for Virus Research, FMRP, USP 12h30- 13h30 BioCel, Technology and Enterpreneurship BioMinas Empreendedorismo e inovação com pesquisas de impacto. Gustavo Furegato Pedreira de Freitas 15h00- 15h30- Coffee break 15h30- 17h00 Symposium #20 Chromatin remodeling and DNA repair Chair: Silvia Batistuzzo de Medeiros, UFRN (S20, 20) DUSP3-NPM-p53: a new signaling axis in the control of genomic stability Lilian C. Russo, Pault Y.F. Minaya, Jessica O. Farias & Fabio L. Forti, IQ USP

(S20, 20) Single-strand break repair and human genetic disorders Nicolas Hoch, Hana Hanzlikova, Emilia Komulainen, Stuart Rulten, Grace Yoon, Keith Caldecott, University of Sussex, UK, IQ USP (S20, 20) Mesenchymal stem cells: instability, senescence and DNA repair DA Cornélio, JT Fonseca, JCMT Marques, KK Silva, EV Silva, and Silvia R Batistuzzo de Medeiros, UFRN 17h00- 18h00 Conference #10 Chair: Leonardo Teixeira, INCA, RJ

Ana Marisa Chudzinski-Tavassi Butantan Institute

Program- July 20th

Room São Paulo (level A)

8h00- 9h30- Symposium #13 DNA damage, Epigenetics & LncRNA in cancer Chair: Enilza M Espreafico, FMRP, USP (S13, 20) Molecular profiling of murine melanoma progression identifies independent prognostic factors for melanoma patients Flávia Eichemberger Rius, Ana Carolina Monteiro, Ana Luisa Pedroso Ayub, Diogo Pessoa, Fernando Andrade, Regine Schneider-Stock, Christopher Mason, André Fujita, Eduardo Rego Reis, Miriam Galvonas Jasiulionis, Universidade Federal de São Paulo (S13, 20) Characterization of DNA repair mechanisms associated with astrocytoma progression and resistance to therapies Rodolfo B. Serafim, Cibele Cardoso, Luis F. M. Di Cristofaro, Enilza M. Espreafico, Maria L. Paçó-Larson, Brendan D. Price and Valeria Valente, UNESP (S13, 20) Exploring the roles of long non-coding RNAs associated with major oncogenic pathways in melanoma Enilza M Espreafico, FMRP USP 9h30- 10h30- Conference #7 Chair: Enilza M Espreafico

Mitochondrial fission promotes KRas-driven metabolic changes and pancreatic tumor growth Sarbajeet Nagdas, Jennifer A. Kashatus, Aldo Nascimento, Riley E. Trainor, Sarah R. Pollock, Sara J. Adair, Alex D. Michaels, Hiromi Sesaki, Edward B. Stelow, Todd W. Bauer, David F. Kashatus University of Virginia, School of Medicine Charlottesville, Virginia USA

10h30- 11h00- Coffee break 11h00- 12h30- Symposium #17 Developmental Biology Chair: José Garcia Abreu, ICB UFRJ (S17, 20) Cardiac chamber selectivity arising in the Galliform Bird radiation: from viral repeats to a complex nuclear receptor element José Xavier Neto (S17, 20) Neural crest stem cells: from the developmental biology to the regenerative medicine Andrea Trentin, UFSC (S17, 20) How Xenopus can help cancer research: Lessons from Wnt signaling José Garcia Abreu, ICB UFRJ 15h00- 15h30- Coffee break 15h30- 17h00- Symposium #21 Cell migration and differentiation Chair: Manoel Luis Costa, ICB UFRJ (S21, 20) Multiple signals to establish neuronal positioning and orientation in the developing zebrafish retina

Flávio Zolessi, Facultad de Ciencias, Universidad de la República / Institut Pasteur de Montevideo. Uruguay (S21, 20) Clonal analysis in skeletal muscle growth and repair Roberta Escaleira and Simon M. Hughes, Instituto de Pesquisas Biomédicas do Hospital Naval Marcílio Dias – Marinha do Brasil, Rio de Janeiro, Brazil.

(S21, 20) Blastema is an evolutionary conserved structure for tissue regeneration: Epithelial-mesenchymal interaction and transition are necessary for de-differentiation, general cell migration and eventually the formation of sponge blastema. Cristiano C. Coutinho, Ivone de Andrade Rosa, Leonardo R. Andrade, Manoel Luis Costa, Claudia Mermelstein, ICB – UFRJ 17h00- 18h00- Conference #11 Chair: José Garcia Abreu

Evo-Devo in the age of single-cell transcriptomics. Leonid Peshkin, Department of Systems Biology, Harvard Medical School, USA

18h15- SBBC 40 years Chair: Estela Bevilacqua, ICB USP

Program- July 20th

Room Brasil (level A)

8h00- 9h30- Symposium #14 Young Investigator Session Chairs: Christina Barja-Fidalgo, UERJ, Irene Yan, USP e Luciana Harumi (S14, 20) Cellular and immunological outcomes from trophoblast cell silencing of versican Camilla Mendes Gonçalves, UFAL (S14, 20) Purification and evaluation of antifungal properties of dectin-fc proteins against aspergillus fumigatus Claudia Rodríguez-de la Noval, UFRJ (S14, 20) Effect of bone marrow mesenchymal stem cell transplantation on the epithelial-mesenchymal transition in the kidney of rats with renovascular hypertension Aline de Almeida Azevedo, UERJ (S14, 20) Extracellular vesicles derived from the intestinal protozoa giardia intestinalis contain a wide repertoire of micrornas Bruno Gavinho, UFPR (S14, 20) Secretion of gaussia luciferase as an indicator of caspase 3/7 activity in response to ADCDKN2AIRESP53 treatment of human glioblastoma (GBM) cell lines. Daniel Vieira Conde Oliveira, USP (S14, 20) Effect of a collagen I derived matricryptin in thrombosis and vascular remodeling on mice abdominal aorta Caroline Fernanda Sanches Dal Pozzo, UNICAMP 9h30-10h30- Conference #8 Chair: Wilson Savino, IOC FIOCRUZ

Targeting LAP: LC3-associated phagocytosis in anti-cancer immunity and inflammatory disease Douglas Green St. Jude Children's Research Hospital, Memphis, TN, USA

10h30- 11h00- Coffee break 11h00- 12h30- Symposium 18 2nd SBBC Young Researcher Award- GE The five finalists will present their studies in this session and the awardee will be announced during the closing ceremony. Chairs Silvia R Batistuzzo de Medeiros, UFRN, Luiz Eurico Nasciutti, UFRJ and Hernandes F Carvalho, IB UNICAMP Bruno Silvestre Lira, USP João Agostinho Machado Neto, USP Luana de Almeida Pereira, UFF Stellee Marcela Petris Biscaia, UFPR Tábata Bergonci, UNIFESP 12h30- 13h30 Tech Conference: BD Citometria para não citometristas da purificação à imagem. A citometria e a microscopia para análise celular multiparamétrica. Renan Antonialli, MsC

15h00- 15h30- Coffee break

15h30- 17h00- Symposium #22 Young Investigator Session Chair: Giselle Zenker UNIFESP, Claudio Simon, UFTM e Marisa Ionta UFAL (S22, 20) Endogenous TCF21/POD-1 expression through CRISPR/DCAS9 system decreases cell migration and invasion of human adrenocortical carcinoma cells Jean Lucas Kremer, USP (S22, 20) Interaction between laminin-derived peptide C16 and B1 integrin and C16 location in breast cancer cells Maria Raquel Unterkircher Galheigo, USP (S22, 20) The role of TLR4 interactor with leucine-rich repeats (TRIL) in hypothalamic inflammation Alexandre Moura Assis, UNICAMP (S22, 20) Effects of lipoxins on the metabolic profile of tumor-associated macrophages Natália Mesquita de Brito, UERJ (S22, 20) Functional analysis of PKCΛ mutations in cancer Damian Emilio Berardi, USP (S22, 20) Leukocyte receptor tyrosine kinase interacts with secreted midkine to promote survival of migrating neural crest cells Felipe Monteleone Vieceli, California Institute of Technology 17h00- 18h00 Elevator Talks Chairs: Chao Yun Irene Yan, Cláudio Simon, Shankar Srinivas

Program- July 21st

Walking at Trianon Park @ 6h45 Room Room Room Room Mato Grosso DF São Paulo Brasil Poster setup Sessions start @ 8h30

8h30 Conference 12 Emer S Ferro SBBC- SBFTE

Conference 13 João P Viola

Conference 14 Anselmo Moriscot

Conference 15 Sebastião Taboga

9h00 Conference 16

André Pupo SBBC- SBFTE

Conference 17 Glaucia MM

Santelli

Conference 18 Tiago Rodrigues

Conference 19 Hernandes F

Carvalho

9h30 Conference 20 Regina P Markus

SBBC- SBFTE

Conference 21 Luisa Iruela-Arispe

Conference 22 Sara Saad

Conference 23 Cleida A Oliveira

10h00 Poster Session 3 & Coffee break 10h00- 10h45

Rooms Minas Gerais + Rio de Janeiro 11h00 Closing conference @ 11h00

Jason Mills

12h00 Closing Remarks SBBC Awards

SBBC Young Researcher Award @ 12h15 Silvia R Batistuzzo de Medeiros

Room Mato Grosso (level B) SBBC- SBFTE Session

8h30- 9h00 Conference #12 Chair: Regina Markus, IB USP

Intracellular peptides from biology to pharmacology Emer S Ferro, ICB USP

9h00- 9h30- Conference #16 Chair: Emer S Ferro, ICB USP

Exploring agonism bias at alpha-1 adrenoceptors in the male urogenital system André Pupo, UNESP, Botucatu

9h30- 10h00- Conference #20 Chair: André Pupo, UNESP, Botucatu

Extra-Pineal Melatonin: how this new player in defense response distinguish between infective and sterile inflammation Regina P Markus, IB USP

10h00- 10h45- Coffee break & Posters

Room Distrito Federal (level B)

8h30- 9h00 Conference #13 Chair: Glaucia Maria Machado- Santelli, ICB USP

Gene regulation during lymphocyte activation João P Viola, INCA, RJ

9h00- 9h30- Conference #17 Chair: João P Viola, INCA, RJ

Targeting key cancer proteins in monolayer and 3D cell cultures: canonic versus non-canonic effects Glaucia Maria Machado- Santelli, ICB USP

9h30- 10h00- Conference #21 Chair: João P Viola, INCA, RJ Mechanisms that regulate regenerative responses M. Luisa Iruela- Arispe, UCLA, USA 10h00- 10h45- Coffee break & Posters

Room São Paulo (level A) 8h30- 9h00 Conference #14 Chair: Tiago Rodrigues, UFABC

Cellular and molecular mechanisms in skeletal muscle plasticity Anselmo S Moriscot, ICB USP

9h00- 9h30- Conference #18 Chair: Sara T O Saad, UNICAMP

The complexity of phenothiazine-induced cell death: drug repurposing for cancer therapy Tiago Rodrigues, UFABC

9h30- 10h00- Conference #22 Chair: Anselmo S Moriscot, ICB USP

New targets of acute myeloid leukemias Sara T O Saad, UNICAMP

10h00- 10h45- Coffee break & Posters

Room Brasil (level A) 8h30- 9h00 Conference #15 Chair: Cleida A Oliveira, ICB, UFMG

A new type of stromal cell in the male reproductive system: Essays on the role of telocytes in prostatic stroma. Sebastião R Taboga, IBILCE, UNESP, São José do Rio Preto

9h00- 9h30- Conference #19 Chair: Sebastião R Taboga, IBILCE, UNESP, São José do Rio Preto

Prostate immunology - attributing functions to macrophages and lymphocytes Hernandes F Carvalho, IB, UNICAMP

9h30- 10h00- Conference #23 Chair: Hernandes F Carvalho, IB, UNICAMP Cleida A Oliveira, ICB, UFMG 10h00- 10h45- Coffee break & Posters

Room São Paulo (level A) 11h00 Closing Conference Chair: Estela Bevliacqua

Paligenosis: a Conserved Cellular Plasticity Program in Regeneration and Cancer Jason C. Mills, MD, PhD Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO USA

12h00 Closing Remarks Estela Bevilacqua Yong Investigators Awards - Announcement Chao Yun Irene Yan and Giselle Zencker Justo 2nd SBBC Researcher Award - Announcement Silvia R Batistuzzo de Medeiros

CONFERENCES AND SYMPOSIA ABSTRACTS

OPENING CONFERENCE July 18th, 18h00- Rooms São Paulo and Brazil Plasticity of cancer cell invasion and metastasis Peter Friedl Radboudumc, Nijmegen, The Netherlands & UT MD Anderson Cancer Center, Houston, TX, USA Cancer cell migration is a plastic and adaptive process generating molecular and physical heterogeneity of migration mechanisms and metastatic routes, including single-cell and collective metastasis. When monitored in vivo using intravital multiphoton microscopy, tissue microniches provide invasion-promoting tracks that enable collective migration along tracks of least resistance. In regions of tissue confinement, invading cancer cells undergo a jamming transition towards collective migration and circulate as both individual cells and multicellular clusters for collective organ colonization. Using multi-targeted interference with integrin adhesion systems, conversion from collective invasion to amoeboid single-cell dissemination followed by increased rates of lung colonization was detected. Similar amoeboid dissemination was induced by hypoxia or stabilization of hypoxia-inducible factor (HIF). The data suggest that metastatic cancer cells can undergo physicochemical reprogramming in response to encountered tissue environments, and thereby balance cell-intrinsic adhesion and mechanocoupling with encountered cues. Dissecting the microenvironmental determinants underlying individual-to-collective plasticity, and vice versa, will enhance to derive combined “antimigration” and cytotoxic therapies and combat metastatic transitions

CLOSING CONFERENCE July 21st, 11h00- Rooms São Paulo and Brazil Paligenosis: a Conserved Cellular Plasticity Program in Regeneration and Cancer Jason C Mills Washington University School of Medicine In 1900, George Adami detailed how mature cells in adult tissues had the capacity to become proliferative again; he predicted that they would have to scale down their existing cell architecture to retool it for energy and building blocks for proliferation. Furthermore, he, and others of the time, reckoned that it might be dangerous for mature cells to become proliferative again, which is why this aspect of cellular plasticity might be how precancerous lesions like metaplasia and even cancer develop. We and others have shown that Adami, and other scientists of his era, were right: mature cells can re-enter the cell cycle to repair large-scale damage. We have shown that, across multiple tissues and species, there is a conserved program that cells have evolved that does indeed involve retooling cellular energy. Mature, mitotically quiescent cells tend to have elaborate, specialized subcellular architecture (eg rER and abundant secretory granules in a secretory epithelial cell) and have relatively high levels of mTORC1 to maintain the translation of proteins to be secreted. Upon damage to the tissue that requires these mature cells to be recruited back into the cell cycle for repair, the cells downscale all of this apparatus as they shut off mTORC1. In this first stage, autodegradative of the program, autophagy and lysosomes accumulate as rER and granules are recycled. In the next stage, progenitor (often embryonic or developmental) and metaplastic genes are increased (eg SOX9). In the third stage, mTORC1 levels rise again, and cells re-enter the cell cycle. These stages are conserved across multiple cells and tissues and constitute a program we call paligenosis, which seems to haev evolved as the regenerative alternative to apoptosis when a mature cell confronts massive tissue damage. Progression through each stage is inhibitable: if autophagy/lysosome activity are blocked, the cells cannot downscale and do not turn on progenitor genes; if mTORC1 activation is blocked, cells can undergo autodegradation and then re-express progenitor genes but cannot enter S-phase of the cell cycle. We are currently studying the cohort of conserved genes that are specific to paligenosis in a way that, say, caspases are specific to apoptosis

CLASSICS IN CELL BIOLOGY July 19th, 17h00 Rooms São Paulo and Brazil Helena B Nader

CONFERENCES (C for conference number; xx for date of presentation)

July 19th

(C1, 19) From matrix rigidity to nuclear mechanobiology in development and disease Dennis Discher, University of Pennsylvania, USA Differentiation of soft and featureless embryos to organs with form and function requires expression of extracellular matrix proteins that become the most abundant proteins in animals and dictate whether a tissue has low matrix and is soft (like brain) or has abundant matrix and becomes stiff (like heart, or rigid bone). Cell adhesion to matrix leads to cells exerting contractile tensions on matrix in relation to stiffness but also on the nucleus within. Based on mechanisms of tension-stabilization against degradation, levels of matrix collagen and nuclear lamins scale together across many normal cell and developmental systems, feeding back into transcription and differentiation, and sculpting basic architectures and properties of tissues and nuclei. However, if a nucleus is highly stressed, its rupture causes mis-localization of DNA repair factors and increases DNA damage. Such processes might explain the high genomic heterogeneity of solid tumors relative to liquid tumors. A coordinated interplay of adhesion and the contractile cytoskeleton with the stiffness of matrix thus regulates the nuclear lamina and chromatin in key cell fate decisions.

(C2, 19) Mechanisms of vesicle transport at the Golgi apparatus Martin Lowe, Division of Molecular and Cellular Function. The University of Manchester, London, UK The Golgi apparatus lies at the heart of the secretory pathway, acting as a hub for intracellular protein trafficking. Within the Golgi apparatus, COPI coated transport vesicles mediate the traffic of numerous resident proteins, most notably abundant glycan processing enzymes, between Golgi cisternae. The role of COPI in vesicular transport is well established, but the extent to which other proteins may contribute to COPI function is much less clear. In this presentation I will discuss our recent work on GORAB, the protein mutated in the rare skin and bone disorder gerodermia osteodyslastica (GO). Our results identify GORAB as a new player in COPI traffic. GORAB acts as a scaffold to recruit COPI to discrete membrane domains that are required for efficient recycling of Golgi-resident glycan processing enzymes. Loss of GORAB results in impaired glycosylation of secretory cargo proteins, including major constituents of the extracellular matrix, helping to explain the skin and bone defects seen in GO patients. Moreover, we identify an unexpected role for the cytoskeleton in maintaining GORAB domains, and therefore in supporting COPI function at the Golgi apparatus. GORAB is therefore identified as a new COPI accessory protein whose loss leads to disease in humans, likely via the dysregulation of glycosylation of secreted extracellular matrix proteins.

(C3, 19) Deciphering epithelial cell movements during anterior pattering in the mouse embryo Matthew Stower, Holly Hathrell, Felix Zhou, Korsuk Sirinukunwattana, Jens Rittscher, Xin Lu and Shankar Srinivas, PhD, MPhil, MA, BSc. Department of Physiology, Anatomy and Genetics, University of Oxford, Medical Sciences Division The early post-implantation mammalian embryo is composed of two simple epithelial sheets, the pluripotent epiblast and the visceral endoderm (VE). The epiblast contributes the majority of the cells of the fetus while the VE contributes predominantly to the yolk sac. However, the VE also has an important patterning role. The correct orientation of the embryonic anterior-posterior axis within the epiblast is specified by inductive signals from a specialised population of VE cells, the anterior visceral endoderm (AVE). These cells show stereotypic migration within the VE from their point of formation to the prospective anterior, essential for correct orientation of the A-P axis. During this migration, AVE cells negotiate their way through surrounding VE cells, which remains a monolayer and retains epithelial integrity. We do not understand how cells within intact epithelia such as the VE show directed migration and the extent to which it is coordinated with cell movements in adjacent tissues. To address these questions, we have used lightsheet microscopy in combination with several fluorescent reporter lines to visualise cell movements, shape changes and division

within the VE. We have also used a conditional reporter strategy to visualise for the first time not just the apical surface of the VE, but also its basal surface, as well as the abutting basal surface of the epiblast. To analyse these multi-dimensional image volumes, we have developed several approaches based on cartographic projections and machine learning based convolutional neural networks. These reveal new cellular behaviour during AVE migration such as the presence of ‘vortexes’ of cell movement and non-random patterns of cell division within the VE. In this presentation, I will briefly describe the development of these enabling technologies and the insights they provide into AVE migration and epithelial cell migration in general.

(C4, 19) The placenta as the frontline defense against maternal-fetal transmission: Lessons from the Zika virus Professor Indira U Mysorekar, Washington University School of Medicine, St. Louis, USA Zika Virus (ZIKV) is a global public health threat that causes microcephaly, intrauterine growth restriction, and spontaneous abortion in women infected during pregnancy. ZIKV is the first flavivirus known to breach the placental barrier to infect the developing fetus. We must obtain a deeper understanding of ZIKV pathogenesis and develop therapies to prevent ZIKV-induced fetal defects. We established a model of in utero ZIKV transmission and showed that ZIKV colonizes placental trophoblasts, crosses the placental barrier to infect fetal endothelial cells, enters fetal circulation, and ultimately effects brain damage and fetal demise. We also identified the autophagy pathway as a key player in placental host defense and demonstrated that the autophagy inhibitor hydroxychloroquine (HCQ), an antimalarial and anti-rheumatic drug FDA-approved for use during pregnancy, attenuated ZIKV infection and reversed adverse placental and fetal outcomes. A series of molecular docking analyses were performed, which revealed that HCQ binds with considerable affinity to the ZIKV NS2B-NS3 protease complex. HCQ was administered to ZIKV-infected placental trophoblasts, and it successfully dampened ZIKV titers by qRT-PCR and immunofluorescence. Trophoblasts deficient in key autophagy genes and mouse models of autophagy deficiency were infected with ZIKV and investigated using imaging and biochemical approaches, which showed that ZIKV infection increased lipophagy, the degradation of cellular lipids through the action of autophagy proteins. Our work demonstrates that ZIKV co-opts lipophagy and that HCQ inhibits ZIKV infection of trophoblasts by inhibiting the ZIKV NS2B-NS3 protease. This study provides a greater insight into the mechanisms underlying HCQ inhibition of ZIKV and ZIKV infection of the placenta. Given that HCQ is relatively inexpensive and already used by women throughout pregnancy, HCQ may prove to be an ideal therapeutic to treat pregnant women who test positive for ZIKV.

July 20th

(C5, 20) Uncovering the role of glia in neurodegeneration: one image at a time Jaime Grutzendler, MD, Center for Experimental Neuroimaging, Yale School of Medicine, New Haven, USA Recent genetic studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathophysiology of Alzheimer's disease (AD). However, the precise mechanisms by which microglia alter the course of AD neuropathology remain poorly understood. Here we discuss current evidence of the neuroprotective functions of microglia with a focus on optical imaging studies that have revealed a role of these cells in the encapsulation of amyloid deposits ("microglia barrier"). This barrier modulates the degree of plaque compaction, amyloid fibril surface area, and insulation from adjacent axons thereby reducing neurotoxicity. We discuss findings implicating genetic variants of the microglia receptor, triggering receptor expressed on myeloid cells 2, in the increased risk of late onset AD. We provide evidence that increased AD risk may be at least partly mediated by deficient microglia polarization toward amyloid deposits, resulting in ineffective plaque encapsulation and reduced plaque compaction, which is associated with worsened axonal pathology. Finally, we propose possible avenues for therapeutic targeting of plaque-associated microglia with the goal of enhancing the microglia barrier and potentially reducing disease progression.

(C6, 20) Dynamic RNA and DNA nanoassemblies with controlled immunological properties Kirill A. Afonin, University of North Carolina at Charlotte, USA The use of nucleic acids to engineer well-defined, fully programmable, self-assembling nanoparticles has established the emerging fields of RNA and DNA nanotechnology. By constructing nanoscaffolds out of nucleic acids, scientists can precisely incorporate various functional moieties such as short interfering RNAs, aptamers, small molecules, and proteins for various applications. The programmable multitasking together with the ability to dynamically respond to the environment further makes nucleic acids an attractive material for tailor-made applications in biotechnology. This talk will focus on our latest achievements in the field of dynamic RNA nanotechnology.

(C7, 20) Mitochondrial fission promotes KRas-driven metabolic changes and pancreatic tumor growth Sarbajeet Nagdas, Jennifer A. Kashatus, Aldo Nascimento, Riley E. Trainor, Sarah R. Pollock, Sara J. Adair, Alex D. Michaels, Hiromi Sesaki, Edward B. Stelow, Todd W. Bauer, David F. Kashatus, University of Virginia, School of Medicine Charlottesville, Virginia USA Many tumors exhibit dysregulation of mitochondrial dynamics, yet the role of altered mitochondrial morphology in tumorigenesis has remained elusive. Here we show that the mitochondrial fission GTPase Drp1 is required for KRas-driven cellular transformation in part through the regulation hexokinase-2 and glycolytic flux. Furthermore, deletion of Drp1 imparts a significant survival advantage in a genetically engineered model of KRas-driven pancreatic cancer, and KRas-driven tumors exhibit a strong selective pressure against complete deletion of Drp1. Drp1 null cell lines generated from established tumors exhibit global metabolic reprogramming, including the restoration of hexokinase-2 and glycolytic flux. Furthermore, Drp1 null tumor cells increase the catabolism of cellular lipids in order to overcome a loss of mitochondrial function. Collectively, this work demonstrates that Drp1 contributes to KRas-driven tumorigenesis both by promoting a shift to a glycolytic metabolism but also by maintaining mitochondrial metabolic function, and suggests that Drp1 may represent a viable therapeutic target. (C8, 20) Targeting LAP: LC3-associated phagocytosis in anti-cancer immunity and inflammatory disease Douglas Green, Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA Two ancient processes, phagocytosis and macroautophagy, arose as mechanisms of meeting the energy demands of the cell. Both also evolved into mechanisms of host defense. We have described a process we term “LC3-Associated Phagocytosis” (LAP), in which signals that are generated upon engulfment of particles by phagocytic cells induce components of the autophagy machinery to associate with the phagosome, promoting its fusion to lysosomes (phagosome maturation). While engulfment of latex beads (for example) does not induce LAP, particles that engage TLR1/2, TLR2/6, TLR4, FcR, or receptors for engulfment of dying cells, cause recruitment of LC3 (ATG8) to the phagosome membrane. Like macroautophagy, this LC3 association depends on Beclin1, PI3P generation, ATG5, and ATG7, but unlike autophagy, LC3 associates with the single phagosome membrane (rather then the double membrane of autophagosomes). Further, unlike macroautophagy, LAP proceeds in the absence of elements of the autophagic pre-initiation complex, ULK1, ATG13, and FIP200, and involves a novel PI3K complex. This raises an intriguing possibility: It is now well established that defects in some components of the autophagy machinery, promote inflammatory disease and compromise host defense to intracellular infections. While such effects are generally interpreted as consequences of defective macroautophagy, the existence of LAP as a discrete phenomenon suggests that at least some such effects may specifically relate to LAP. I will discuss LAP and its relationship to phagosome maturation, and its roles in tumor associated macrophages and anti-cancer immunity, and in neurodegenerative disease (C9, 20) The role of exosome secretion regulation in tumor recurrence and patient survival Fernanda Giudice, Michele Landemberger, Clóvis Pinto, Marcos Salles Dias, Luiz Paulo Kowalski and Vilma R. Martins*, A.C. Camargo Cancer Center; National Institute for Science and Technology in Oncogenomics and Therapeutic innovation Extracellular vesicles (EVs), in particular exosomes, are secreted from different cells and their cargo can modulate physiological and pathological conditions besides providing a comprehensive set of biomarkers for treatment response and disease prognosis. Recent evidences have shown that the tumor development and the metastatic progression are supported by exosomes, which are released from the tumor cells to the blood or lymphatic system. Indeed, it is essential to understand the molecular mechanisms involved in the control of

exosome biogenesis and secretion. In order to evaluate the role of exosome secretion in tumor progression we studied Head and Neck Squamous Cell Carcinoma (HNSCC) that is considered to be one of the six most common malignancies worldwide related to a high rate of morbidity and mortality. The poor prognosis of HNSCC shows remarkable association with local invasion and subsequent metastasis. Three HNSCC cell lines were characterized to secrete different amounts of exosomes and a correlation between greater secretion levels; higher expression of prion protein (PrPC) and lower RAB7 expression was determined. Further experiments were conducted in tissue samples from 223 patients with HNSCC. Immunohistochemistry analyses revealed that patients presenting poor prognosis (cancer recurrence or cancer-related death during the 5 years of follow-up) had significantly lower Rab7 and higher PrPC expression than those patients presenting good outcome (disease-free survival or non–cancer-related death during the 5 years of follow-up). Thus, a significant overexpression of Rab7 and lower PrPC levels were predictive of better survival (log-rank test, p = 0.003). In addition, the combination of poor prognosis factors (high PrPC and low RAB7 expression) with alcohol and tobacco consumption increased cancer recurrence significantly. Thus, the regulation of exosome secretion is a key element in HNSCC progression and directly affects tumor recurrence and patient survival. Supported by, FAPESP, CNPq and CAPES. (C10, 20) Ana Marisa Chudzinski-Tavassi, Butantan Institute (C11, 20) Evo-Devo in the age of single-cell transcriptomics. Leon Peshkin, Harvard Medical School. In this talk I will review some technical aspects and current limitations of single cell transcriptional profiling, present anecdotes from a comparative study of the early embryos in three distinct species over hundreds of thousands of cells, and speculate about the challenges and opportunities in the field of evo-devo in light of new technologies. Specifically, we produced and recently published time series of single cell transcriptomes from whole Xenopus embryos, spanning zygotic genome activation through early organogenesis. From the data we derive a detailed catalog of cell states in vertebrate development, and show that these states can be assembled into temporal maps tracking cells as they differentiate over time. The inferred developmental transitions recapitulate known lineage relationships, and associate new regulators and marker genes with each lineage. We find that many embryonic cell states appear far earlier than previously appreciated, and assess conflicting models of vertebrate neural crest development. By further incorporating a matched time series of zebrafish, we perform global analyses across lineages, time, and species, revealing similarities and differences in developmental gene expression programs between frog and fish.

July 21st

(C12, 21) Intracellular peptides from biology to pharmacology Emer S Ferro, ICB USP Oligopeptidases were first described as kininases from rabbit brain in the early 70’s by Prof. Antonio C.M. Camargo at USP Ribeirão Preto Medical School. Studies from our research group suggested that more than 90% of thimet oligopeptidase (EC3.4.24.15; THOP1) and neurolysin (EC3.4.24.16; Nln) are concentrated inside the cells; these data suggested some doubts about the major function of oligopeptidases in generating and degrading neuropeptides such as bradykinin. The first intracellular function described for THOP1 was in processing and degradation of antigens associated with major histocompatibility class I complex. The development and use of a novel substrate-capture assay using catalytically inactive THOP1 or Nln led to intracellular peptides first description. Here, we intend to present recent advances on the biological significance of intracellular peptides and potential pharmacological applications.

(C13, 21) Gene regulation during lymphocyte activation João P Viola, INCA, RJ

(C14, 21) Cellular and molecular mechanisms in skeletal muscle plasticity Anselmo S Moriscot, ICB USP In this talk the basics on skeletal muscle plasticity will be approached and subsequently recent findings on the main pathways involved and particularly the role of microRNAs will be discussed. (C15, 21) A new type of stromal cell in the male reproductive system: Essays on the role of telocytes in prostatic stroma. Sebastião R Taboga, IBILCE, UNESP, São José do Rio Preto Telocytes (TCs) are CD34-positive cells localized in the stroma of numerous organs, known to exert several functions in several organs. TCs are characterized by a distinctive morphology - small cell body with very long, slender prolongations, termed telopodes. Thus, our group objected to verify the TCs in prostate stroma in rodents, as the stroma of this gland is a dynamic microenvironment. Morphological and immunohistochemical assays demonstrate that TCs have small cellular bodies with very thin and extremely long cellular processes. They were found primarily in the subepithelial region and also at the periphery of smooth muscle cells (SMC). TCs also exhibited moniliform processes, caveolae and nuclei surrounded by small amounts of cytoplasm. Close contacts between TCs podomers were evident, particularly in the adjacent epithelium. In mature gland, they exist in close association with the acini and their telopodes form networks whose functions remain unclear. Thus, our group explores the history that led to such a concept and then discusses hypotheses and presents new evidences about the roles exerted by TCs in the prostate. First is given emphasis on the role that these cells possibly play in paracrine signaling employed in the differentiation of SMC periacinar are then discussed other roles potentially performed by TCs in the prostate, such as the organizational, where these cells would act in order to delimit stromal microenvironments, thereby assisting the differentiation of the prostatic compartments. In addition, the pacemaker function of SMC contraction, as evidenced by the presence of caveolae and gap-type junction and, finally, the role of TCs in prostate remodeling and the possible action as adult progenitor cells. Thus, we have invested efforts to affirm that TCs are distinct cells of other stromal cells and the importance of this new cell type for normal prostatic metabolism and during the prostate development.

(C16, 21) Exploring agonism bias at alpha-1 adrenoceptors in the male urogenital system André Pupo, UNESP, Botucatu Alpha-1 adrenoceptor (alpha1-AR) activation plays a paramount role in reproduction by producing forceful contractions of the smooth muscles of the male reproductive tract leading to sperm transport and seminal emission. We investigated the ability of commonly used alpha1-AR agonists to produce intracellular Ca2+ increases ([Ca2+]i) and receptor internalization in HEK293 expressing human alpha1A- or alpha1B-ARs, and to contract and desensitize tissues from the male reproductive tract of the rat (seminal vesicles, vas deferens and cauda epididymis) in vitro. In HEK293 cells expressing human alpha1A-ARs, some ligands including phenylephrine, A61603 and naphazoline presented biased agonism towards [Ca2+]i, whereas others such as dopamine and oxymetazoline were biased towards receptor internalization. Interestingly, an opposite bias pattern was observed in HEK293 cells expressing human alpha1B-ARs, that is, phenylephrine, A61603 and naphazoline were biased towards internalization and dopamine was biased towards [Ca2+]i. As expected, the normalized transduction coefficient (delta)log(tau/KA) for the agonists in the contractions of seminal vesicles, vas deferens and cauda epididymis were similar to those determined for the [Ca2+]i signalling in HEK293 cells expressing the human alpha1A-AR, but not in cells expressing the alpha1B-AR. Furthermore, some of the agonists that were biased for the internalization of alpha1A-ARs in HEK293 cells were more capable than norepinephrine to produce tachyphylaxis in the contractions of organs from the male reproductive tract, showing that the biased agonism observed in recombinant receptors can also be observed in native alpha1A-ARs. In addition to increase our knowledge on the pharmacological properties of some of the most commonly used alpha1-AR agonists, these data indicates that some of these agonists might be further explored in the search of ligands that selectively desensitize the alpha1-ARs of the male reproductive tract.

(C17, 21) Targeting key cancer proteins in monolayer and 3D cell cultures: canonic versus non-canonic effects Glaucia Maria Machado- Santelli, ICB USP Considering the relevance of lung cancer as one of the leading cause of cancer death worldwide, and that non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer deaths, in the present study we used two NSCLC derived cell lines: A549 and LC-HK2.A549 and HK2 cells presented, respectively, 3 and 6 ErbB1 gene copies per nucleus, both lines express vimentin and cytokeratin, and chromosomal instability. Additionally, to monolayer we establish three-dimensional spheroids cultures, since they have proven to be useful to create closer in vivo conditions. EGFR activation or inhibition did not promote changes in cell proliferation compared to control groups in spheroids, but promoted cell migration. ERK and Akt pathways mediated cell migration induced by EGF stimulation. Searching for interfering in cell proliferation we treated LC-HK2 cells and a non transformed cell line RPE1 with vincristine (VCR) during 24h (~50% delayed mitosis) followed by periods of recovery in drug-free medium. Microtubule-targeting agents can contribute to cancer progression or suppression. The results showed that VCR treatment led to similar defects in both cell lines, but only cancer cells were able to proliferate in the presence of aneuploidy. During recovery periods, multipolar mitosis and aneuploidy were observed only in cancer cells, concomitant with overexpression of Aurora A. In contrast, normal cells treated with VCR showed the opposite behavior. In this context, it was important to analyze the cell senescence after centrosome amplification. First, they were treated with telomerase inhibitors, resulting in different responses: TMPyP4 increased the percentage of cells with membrane damage, induced change in cell morphology, and decreased mRNA expression of vimentin and vinculin; Thymoquinone increased the frequency of senescent cells, cells with membrane damage and induced cell death.(FAPESP, CNPq).

(C18, 21) The complexity of phenothiazine-induced cell death: drug repurposing for cancer therapy Tiago Rodrigues, UFABC (Federal University of ABC) Cancer is a malignant proliferative disease and it is among the major cause of death worldwide. Despite the recent advances in cancer treatment, including targeted and immunotherapy, resistance is still a current problem. Also, not all patients have access to these modern and expensive therapies, mainly in underdeveloped countries. Therefore, the search for new antitumor drugs and targets is one of the major challenges encountered by cancer researchers, and drug repurposing has emerging as an important therapeutic alternative in this scenario. In this regard, the antipsychotic phenothiazines (PTZ) were discovered in 50’s to treat schizophrenia and other neuroleptic disorders, but they exhibit several other interesting biological effects. Earlier studies described PTZ as calmodulin antagonists and also as classical inhibitors of the mitochondrial permeability transition (MPT). However, at higher concentrations, these drugs are able to induce MPT and cell death. The PTZ-induced cell death was already demonstrated from prokaryotes to eukaryotes, including resistant cancer cells, and with a high cytotoxic potency. Mechanistic studies have revealed the multiplicity of targets and the complexity of PTZ-induced cell death in different types of tumor cells, resulting in an antitumor activity in vivo.

(C19, 21) Prostate immunology - attributing functions to macrophages and lymphocytes Hernandes F Carvalho, IB, UNICAMP Prostate immunology is largely unknown. Different cell types are found in the gland and, additionally, the gland stromal and epithelial cells express a number of immune-system related molecules, and a large part of them are secreted. In spite of the existing knowledge, an integrated view of prostate immunology is still missing. In this talk, I will present recent results from our lab regarding the functions of macrophage subpopulations within the gland and evidences connecting the gland to the common mucosal immune system. Macrophages are involved with the clearance of apoptotic cells as well as the maintenance of the non-inflammatory state of the gland during castration-induced regression. Mucosal immunization results in increased number of dendritic cells and plasma cells, producing IgA and IgG. IgA reaches the lumen via

transcytosis. Additionally, I will present a series of questions regarding prostate immunology that remains to be answered.

(C20, 21) Extra-Pineal Melatonin: how this new player in defense response distinguish between infective and sterile inflammation Regina P Markus, IB USP The immune-pineal axis is activated by different forms of injuries, resulting in a transient reduction, or even suppression of nocturnal pineal melatonin synthesis, and sequential induced synthesis of melatonin by immune-competent cells. The reduction of nocturnal melatonin concentration in the plasma favors the migration of leukocytes to the injured site. Activated dendritic cells, macrophages, microglia, and lymphocytes synthesize melatonin. The synthesis of melatonin is highly conserved from unicellular to mammals. The first step is the conversion of serotonin to N-acetylserotonin (NAS) by the phosphorylated form of AANAT (arylalkyl-N-acetyltransferase) followed by the conversion of NAS in melatonin by acetyl O-methyltransferase (ASMT). We studied how bacteria, fungi, parasites, necrosis and proliferative diseases control the expression of the genes for AANAT and ASMT. Nuclear factor kappa B (NFkB) is the central modulator, as it could lead to both induction or repression of Aanat transcription. The output depends on the dimers of NFkB available in each cell. In addition, the high amounts of ATP released by necrosis or necroptosis lead to activation of P2X7 receptors and reduction of ASMT in pinealocytes, suggesting that NAS could be signaling darkness. In summary, here we will we will revisit the mechanisms triggered by the various molecular patterns that signal pathogens, danger or tissue death on the control of melatonin production to disclose selective pharmacological tools.

(C21, 21) Mechanisms that regulate regenerative responses Austin I McDonald, Aditya S. Shirali, Raquel Aragón, Feiyang Ma, Gloria Hernandez, Don A. Vaughn, Julia J. Mack, Tiffany Y. Lim, Hannah Sunshine, Peng Zhao, Vladimir Kalinichenko, Tsonwin Hai, Matteo Pelegrini, Reza Ardehali, M. Luisa Iruela-Arispe, University of California – Los Angeles. To identify the cellular and molecular events associated with endothelial cell regeneration in large arteries, we used a reproducible in vivo injury model of cellular denudation and applied a variety of genetic strategies. These allowed us to define the origin of the regenerated cells, pinpoint the mechanisms used for cellular renewal, and identify the molecular mechanisms that triggered and sustained endothelial regeneration. Our findings revealed a collective behavior of endothelial cells in response to injury that included rapid changes in the transcriptome of fully differentiated cells and a nearly synchronic entry into cell cycle of a subpopulation of cells. Furthermore, using multi-fluorescent labeling for clonal tracing, we identified discrete populations that significantly contributed to regenerating the denuded area. Importantly, the process of endothelial regeneration requires the activation of stress cell response genes, and in particular Atf3. Inactivation of Atf3 significantly impairs the repair response, converting young into old endothelium.

(C22 ,21) New targets of acute myeloid leukemias Sara T O Saad, UNICAMP Acute myeloid leukemias are aggressive disorders with low healing potential. Complete remission in adults is below 50%, and those who are not cured during the first year, rapidly succumb to the disease. Cross-talk between hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) is essential for HSCs regulation and leukemogenesis. We will focus in new proteins involved in these crosstalk as VEGFA, SEMA3A, HCK, SPINT and NR4A1. The competition of SEMA3A, secreted by MSCs, and VEGFA, secreted by the leukemic cells by the neuropilin 1 receptor ( NRP1) will be demonstrated. Moreover, VEGFA overexpression confer AML cell advantages and SEMA3A seems to reverse this effect. Indeed , the orphan nuclear receptor NR4A1, will be presented as a potential tumor-suppressive molecule, related to glycolytic flux in leukemia cells. Finally, we will show the ability of the serine protease inhibitor kunitz-type 2 (SPINT2/HAI-2), an inhibitor of hepatocyte growth factor (HGF) activation, to contribute to functional and morphological abnormalities of the microenvironment

niche and cancer cell progression as well as the role of hematopoietic cell kinase (HCK) in normal hematopoiesis and in leukemia pathogenesis. (C23, 21) Microenvironmental changes in the epithelium of aging prostate lesions Cleida A Oliveira, ICB, UFMG Male aging is characterized by changes in the endocrine system, which frequently lead to proliferative disorders of the prostate gland, such as hyperplastic and cancerous growth. Hormonal changes appear to include imbalance in androgen:estrogen levels as well as decrease in vitamin D. Estrogen roles on prostate tissue are complex as both pro- and anti-neoplastic effects have been described depending upon the receptor involved, whether ERα or ERβ. Vitamin D is also an important modulator of cellular proliferation and death, thus being implicated in anticancer activities. We have mapped the expression pattern of components of the estrogen, androgen and vitamin D responsive systems throughout prostate aging, which was possible after the establishment of a reliable animal model (Wistar rats) with the advantage of naturally developing aging-related prostate lesions similar to some of those affecting the human prostate. Lesions induced by androgen+estrogen supplementation, as well as castration followed by hormonal supplementation have also been investigated. We found punctual reduction of ERβ, AR, VDR and its partner RXR, as well as key calcium transporters (TRPV6, Calbindin and PMCA), but increase in ERα in areas of proliferative lesions and inflammation in the natural aging prostates. Alterations closely resembling the aforementioned has also been found in prostates with altered hormonal milieu. Noteworthy many proliferating cells were negative for ERβ and VDR. Furthermore, cells intensely positive for aromatase were found in the basal compartment of the epithelium at aging or castration. These cells aromatase positive have been characterized as basal cell as well as macrophages, thus revealing a complex local source of estrogen, which may be contributing to the microenvironmental changes in the epithelium of prostatic lesions. Financial Support: CAPES, CNPq, FAPEMIG.

SYMPOSIA

(S for conference number; xx for date of presentation)

July 19th

(S1, 19) Pericytes at the crossroads between tissue regeneration and pathology Alexander Birbrair, UFMG Perivascular multipotent cells, pericytes, contribute to the generation and repair of various tissues in response to injury. They are heterogeneous in their morphology, distribution, origin and markers, and elucidating their molecular and cellular differences may inform novel treatments for disorders in which tissue regeneration is either impaired or excessive. Moreover, these discoveries offer novel cellular targets for therapeutic approaches to many diseases. In this talk, we will discuss our recent findings that support the concept that pericyte subtypes play distinctive roles in myogenesis, neurogenesis, adipogenesis, fibrogenesis and angiogenesis.

(S1, 19) Galectin-3 integrates tumor cell adaptive responses in stressed tissue microenvironments Ana Carolina Ferreira Cardoso, Silvina Odete Bustos, Luciana Nogueira de Souza Andrade and Roger Chammas. Instituto Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo. Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular galectin-3. Supported by FAPESP and NIH/NIGMS Consortium for Functional Glycomics.

(S1, 19) Integration of Mechanical and Molecular Microenvironmental Signals in the Endothelium Luisa Iruela Arispe, UCLA (S2, 19) Neuroprotection by gene therapy: from bench to cageside Rafael Linden & Hilda Petrs-Silva, Instituto de Biofísica, UFRJ Management of neurodegenerative diseases is notoriously difficult due to the multiplicity of factors that control the sensitivity of neurons to programmed cell death. Glaucoma is a neurodegenerative disease of the retina, associated with structural damage to the optic nerve, progressive loss of retinal ganglion cells, visual dysfunction, and eventual blindness. Here we describe the journey from early studies of mechanisms of programmed cell death in the developing retina in vitro, to the discovery of the neuroprotective role of the transcription factor Myc-associated protein X (Max), followed by the ongoing development of a gene-based therapeutic procedure that prevents retinal degeneration and visual dysfunction in a rodent model of glaucoma. Max was originally shown by our group to undergo nuclear exclusion early in the process of RGC degeneration due to optic nerve damage, preceding the execution phase of apoptosis. A viral vector derived from adeno-associated virus was then constructed to overexpress Max (rAAV-Max), and injected into the eye

of Lister-hooded rats subject to two distinct experimental models of glaucoma, either by optic nerve crush, or following subacute increase in intraocular pressure. Robust neuroprotective effects of the rAAV-Max vector were found in both cases. In addition, rAAV-Max prevented cell death in an in vitro model of cerebral hypoxia-ischemia. The results suggest that gene therapy by overexpression of Max may be further developed as a novel therapeutic procedure for glaucoma and, possibly, for other neurodegenerative conditions as well. Supported by grants from CNPq and FAPERJ.

(S2, 19) Marimelia Porcionatto, UNIFESP (S2, 19) Silvya Stuchi Maria Engler, FCF USP (S3, 19) An immune and metabolic shift during neonatal development reprogram liver identity and function Gustavo Menezes, Center for Gastrointestinal Biology, UFMG Liver is the main hematopoietic site in embryos, becoming a crucial organ in both immunity and metabolism in adults. However, it is unclear how different hepatic cell populations reprogram their phenotype to face major dietary and infectious challenges after birth. We collected, imaged and analyzed liver samples from mice at day 0 after birth up to adults. Human biopsies from newborns and adults were also examined. Liver immune cells were high-dimensionally phenotyped using mass cytometry and hepatic expression of genes belonging to metabolic and immune pathways was measured. Mice were challenged with intravenous injection of fluorescently labeled bacteria. Blood and liver samples were collected and analyzed, and intravascular bacterial arresting was visualized by liver intravital microscopy. In a set of experiments, mice were prematurely weaned and fluctuations in gene expression of metabolic pathways were evaluated. Human and mouse newborns have a sharp different hepatic cellular composition and arrangement compared to adults. We identified several myeloid populations in mouse neonatal livers along with a relative lack of metabolic functions. However, neonatal mice were more susceptible to infections, but rapidly evolved to an efficient immune response in later timepoints. In contrast, livers from older mice had large populations of lymphoid cells and the expression of enzymes belonging to lipid and carbohydrate metabolism peaked around the weaning period. Interestingly, early weaning profoundly disturbed the expression of several hepatic metabolic pathways. In conclusion, liver immunity and metabolic profile in newborns are dramatically different from adults, and dietary and antigen cues can shape liver enzymatic and cellular composition during postnatal development. (S3, 19) Carlos Lenz Cesar (S3,19) Fluorescence life-time imaging microscopy - monitoring single cell metabolism Hernandes F Carvalho, IB, UNICAMP Fluorescence provides enhanced contrast and sensibility. However, in most cases, it relies on exogenous fluorophores. Increased capacity of detectors and pulsed lasers led to the development of systems capable to detect single photons at the nanosecond time scale, which allows precise measurement of fluorescence lifetime in discrete parts of a microscopical sample. Fluorescence life time imaging microscopy (FLIM) is important to monitor environmental changes around one given fluorophore. Furthermore, it is capable to image endogenous fluorescent molecules such as NAD(P)H and FAD, providing details on the metabolic state of individual cells within a cell population, as well as sub-cellular resolution on the distribution of the same molecules. In addition to provide technical information about FLIM and details of the multiuser system installed in INCT-INFABIC (Unicamp), some examples of the application of FLIM will also presented in this talk. (S4, 19) Multiple Sclerosis: How Inflammation, Degeneration and the Gut Microbiota interact to trigger Brain Autoimmune Disease. Hartmut Wekerle*, Max Planck Institute, Germany As noted already by Charcot and Babinski, degeneration of myelin and neuronal axons coincide with round cell infiltrations to form the hallmarks of the active MS lesion. 140 years later, we assume that these changes are initiated by autoimmune T cells, which are activated in the peripheral immune system, break through the cerebrovascular blood-brain barrier and, together with ancillary phagocytes, mount an attack against cerebral resident target cells. However, only recently, it has become evident that this autoimmune attack is under the

tight control of the intestinal immune system and its microbial content, the gut flora. This control is dual. Firstly, the gut microbiota controls the brain’s innate immune reactivity, which decides on survival and function of immigrant immune cells. Intestinal signals derived from microbial components and metabolites act on brain cells via diverse ways, including neuronal pathways, hormones and via the blood circulation. By this, the microbiota create a fertile soil for subsequent adaptive autoimmune responses. Secondly, experimental studies showed that brain-reactive T cells, which are regular components of the healthy immune repertoire, undergo activation within the gut-associated lymphatic system (GALT). Activation enables these originally innocuous T cells to enter the central nervous system and attack its tissues. They create inflammation and degeneration of resident brain components. Thus, the gut and its microbiota has become a pivotal component in the pathogenesis of MS, and implicitly, presents as a potentially rewarding target of therapeutic intervention. *HW has been incumbent of a Hertie Senior Professorship

(S4, 19) Carmem Gottfried, UFRGS, Brazil (S4, 19) Wilson Savino, IOC FIOCRUZ (S5, 19) Extracellular matrix gene expression signature of prostate cancer Sérgio L Felisbino, IBB, UNESP Prostate cancer is a very complex disease, with a high heterogeneity of genetic and epigenetic alterations, including somatic mutations, deletions and gene amplification, chromosomal rearrangements, and changes in DNA methylation. Omics studies on ECM related components, receptors and enzymes has been used as a new approach for classifying tumors, patient’s outcome and response to therapies. In order to identify candidate biomarkers, we sought to define ECM signature of metastatic prostate cancer with poor prognosis. We have used enrichment of extracellular matrix (ECM) genes up and down regulated in the transcriptome of two mouse models for prostate cancer: the first one representing indolent tumors with Pten deletion; and another model representing aggressive castration-resistant tumors with Trp53 and Rb1 double knockout. The list of de-regulated genes were compared with human prostate cancer samples available in the SurvExpress plataform. We have found a robust signature of ECM protein characteristic of each tissue, indolent and aggressive, using mouse model and human dataset. Comparisons with gene expression data from TCGA and MSKCC cohorts of patients confirm the association of subsets of the genes identified by these analysis with tumor progression and metastasis, such as ACAN, MMP11, BGN, AGRN, ANXA1, COL10A1, COMP, SPP1 and others. The ECM protein signatures of indolent and aggressive prostate cancer defined in this study, offer promise for development of diagnostic and prognostic signatures of metastatic potential of prostate tumors. Financial Support: FAPESP, CNPq, CAPES, UNESP. (S5, 19) ADAMTS-1 disrupts HGF/c-MET signaling and HGF-stimulated cellular processes in fibrosarcoma cells Vanessa M Freitas, ICB, USP Extracellular matrix (ECM) serves as a reservoir for biologically active factors, such as growth factors and proteases that influence the tumor cell behavior. ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a secreted protease that has the ability to modify the ECM during physiological and pathological processes. We analyzed the role played by ADAMTS-1 regulating HGF in the high-grade fibrosarcoma cell line (HT1080). We generated HT1080 and HEK293T cells overexpressing ADAMTS-1. HT1080 cells overexpressing ADAMTS-1 (HT1080-MPA) exhibited a significant decrease in cell proliferation and migration velocity, both in presence of HGF. We obtained similar results with ADAMTS-1-enriched conditioned medium from other cell type. Immunoblotting showed that ADAMTS-1 overexpression disturbs c-Met activation upon HGF stimulation. Downstream ERK1/2 and FAK signaling pathways are also influenced by this protease. Additionally, ADAMTS-1 decreased the size of the fibrosarcospheres, both under normal conditions and in the presence of HGF. Likewise, in presence of HGF, ADAMTS-1 overexpression in HT1080 disrupted microtumors formation in vivo. These microtumors, including individual cells, presented characteristics of non-invasive lesions (rounded morphology). Our results suggest that ADAMTS-1 is involved in regulating HGF-related functions on fibrosarcoma cells. This protease may then represent an endogenous mechanism in controlling the bioavailability of different growth factors that have a direct influence on tumor cell behavior.

(S5, 19) Extracellular matrix as a modulator of tumor metastasis Marcelo L Lamers, UFRGS Metastasis is one of the main causes of failure in cancer treatment. It is characterized by the migration of tumor cells into the tissue and blood vessels until they reach a new favorable place to survive and proliferate. In order to migrate, cells need to interact with a complex extracellular matrix (ECM) composition, which varies according to localization. In Oral Squamous Cell Carcinoma (OSCC), we already demonstrated that ECM composition is able to modulate migration properties towards a more aggressive single-cell migration mode through changes on adhesion dynamics and RhoGTPase signaling. In order to find a common ECM marker for OSCC, we analyzed the transcriptome of 500 OSCC samples and it was observed that the gene expression varies wildly according to the localization of the tumor in the oral cavity, but there is a consistent change on the expression of genes related to ECM, Rho-GTPase and cell-cell adhesion. Also, since clinical data indicate that more aggressive OSCC tumors show hard borders, we hypothesized that ECM stiffness might contribute to modulate the behavior of tumor cells. In fact, we observed that cells plated in stiff environments shows an increase on epithelial to mesenchyme transition (EMT) markers, which correlates with a more aggressive migration. In conclusion, OSCC tumors show changes on the expression of ECM-related genes, which might contribute to the metastatic behavior by modulating migration properties and EMT markers. Financial Support: CAPES, CNPq, FAPERGS, PROPESQ-UFRGS. (S6, 19) Understanding Immunomodulatory Properties of Nucleic Acid Nanoparticles Kirill Afonin and Marina A. Dobrovolskaia, University of North Carolina Therapeutic nucleic acids have evolved as a promising platform for the detection and treatment of a wide range of diseases. In the past years, however, there have been several announcements that U.S. biotech companies have discontinued clinical development of therapeutic nucleic acids formulated using lipid-based carriers citing severe “cytokine storm” inflammatory reactions and limited efficacy among reasons for the discontinuation of such formulations. To address these barriers, more sophisticated formulations that employ rationally designed RNA molecules have been designed. The ability of RNA to assemble into discrete and uniform shapes make them a viable option for a number of biomedical applications and to become one of the next milestones in personalized medicines along with small molecule and protein-based pharmaceuticals. It is becoming apparent that interactions between RNA nanoassemblies and the immune system must be defined to permit the successful translation of this technology to the clinic. Therefore, to address fundamental questions regarding the immune recognition of these novel materials, we have designed the following study in which features such as size, shape, composition, and physicochemical properties of RNA and DNA nanoparticles were related to their therapeutic activity in human cancer cells and activation of immune responses in human immune cells. We designed, assembled and characterized a series of RNA, DNA, and RNA/DNA hybrid nanoparticles and further surveyed the link between their size, composition, physical and chemical properties to the pro-inflammatory responses. The biomarkers of pro-inflammatory response were cytokines and type I interferons. This work is instrumental in bridging the rapidly narrowing gap between basic research on nucleic acid nanoparticles and advanced pharmaceuticals containing these novel materials. (S6, 19) The regulatory protein Ki-1/57 (or HABP4): from an RNA binding protein to a possible novel tumor suppressor protein Jorg Kobarg, FCF, IB, UNICAMP Ki-1/57 (also named HABP4) has been discovered as an intracellular cross-reactant of the monoclonal antibody Ki-1 (against CD30), the first to specifically detect malignant cells in Hodgkin's lymphoma. The protein CGI-55, also named SERBP1 (or PAIRBP1), has been first described as an RNA binding protein involved in the regulation of PAI-1 mRNA stability, by binding to its mRNA 3′- UTR. Ki-1/57 and CGI-55 share 40.7% identity and 67.4% similarity, which suggest that they might be paralogs, with similar or redundant functions in human cells. Yeast two-hybrid system based protein–protein interaction maps were generated and revealed that both are involved in multiple steps of the gene expression regulation, although their exact roles and the majority of their possible target genes in human cells remain to be identified. Their protein interactomes suggest predominantly roles at the transcriptional regulatory (CHD-3, DAXX, MEF2c and p53) and mRNA metabolism levels (HnRNP-Q, SFRS9). Furthermore, several links hint to an involvement with tumorigenesis, since both paralogs show altered expression levels in several tumor cells and the Ki-1/57 gene is found in a region of chromosome 9q that represents a haplotype for familiar colon cancer. In biochemical in vitro studies we found that Ki-1/57 binds to RNA oligonucleotides in gel shift assays, localizes to splicing spleckles in the nucleus of human cells and regulates mRNA splicing in a E1A pre-mRNA mini-gene reporter assay, in humans cells. In order to gain further in

vivo insights on the function of Ki-1/57 we generated gene knock out mice through CRISPR/Cas 9 technology. We submitted these mice to an AOM/DSS experimental colitis protocol and found that the knock out mice develop significantly more numerous and larger tumors than the identically treated wild type control mice. More interestingly, we found in Western Blot analyses with antibodies against proteins from the cell cycle and cell activation and survival pathways, that the untreated knock out mice show the same expression or phosphorylation levels as the treated control mice (colon tissues). In summary, together with other data, this may suggest that Ki-1/57 acts as a novel type of tumor suppressor, since removing its gene resulted in mice pre-disposed and hyper-sensitized to the develop colon cancer. This provides new insights that may help to explain these proteins putative involvement in tumorigenic events. Acknowledgements: Financial support by Fapesp and CNPq. Dra. Angela Saito (LNBio) generated the knock out mice, with support from Dr. José Xavier Neto (LNBio) and Richard Behringer (Anderson Cancer Center). Dra. Talita D.M. Hanchuk performed the experiments with the knock out mice with help from Dra. Maria Carolina S. Mendes and Prof. Jose B. Carvalheira (UNICAMP) and Dra. Flavia Regina M. da Silva and Carolina Colleti. (S6, 19) Investigating microRNA splicing regulators in mammalian cells Patricia P. Coltri, Marcelo M. Paiva, Romina S. Horianski, Maria Gabriela P. dos Santos, Guilherme H. Gatti da Silva, ICB, USP RNA processing events are critical for cellular maintenance. Pre-mRNA splicing is one of the most fundamental processes to modulate eukaryotic gene expression. Despite the increasing information on spliceosome structure, specific regulation of splicing in different pre-mRNA transcripts is largely unexplored. MicroRNAs are important modulators of gene expression and are frequently transcribed from introns. We asked whether composition of spliceosomes assembled upon microRNA-containing introns was similar to that of transcripts without microRNAs. To investigate proteins involved in splicing regulation of microRNA-containing introns, we created a reporter system and isolated spliceosomes from cultured mammalian transfected cells. Immunoprecipitated spliceosomes were analyzed by mass spectrometry, revealing 50 proteins. Among these, twenty-four were involved with RNA splicing, regulation and spliceosome assembly. ELAVL1 (HuR) protein and hnRNP-A1 were among the identified proteins. Interestingly, hnRNP proteins have previously been associated with microRNA splicing in mammalian systems. Although ELAVL1 is not a core spliceosome component, it has been previously observed associated to the complex. We investigated the association of these proteins to the intronic cluster miR17-92. We over-expressed FLAG-tagged proteins in cultured cells and immunoprecipitated bound RNAs. Both ELAVL-1 and hnRNP-A1 showed association to miR-17-92 components in different cell lines. hnRNP-A1 has previously been associated to miR-18a in HeLa cells, and we now observed it is specifically associated to miR-18a and miR-19a in HEK-293T cells. ELAVL-1 is associated to miR-19a in HEK-293T and BCPAP cells. We also observed cells over-expressing ELAVL1 showed a higher migration rate, indicating cell proliferation is positively regulated by this protein. Our results indicate specific spliceosome proteins might be regulating microRNA-intron splicing and therefore contributing to gene expression modulation. (S7, 19) Self-propagating gene drives as a molecular tool for functional analysis in non-model insects Helena Araujo and Mateus Berni, ICB, UFRJ Analysis of gene function, particularly during development, has mainly relied on the use of model organisms. However, the discovery of RNA interference has allowed the widespread use of gene knockdown in a number of species, with great impact on the Evo-Devo field. More recently, CRISPR technologies are being directed to non-model organisms, aimed at editing the genome to generate locus deletions, directed mutations, to tag endogenous genes and for insertion of exogenous sequences. Despite the current success of CRISPR/Cas9 gene edition, a few limitations must be overcome to definitely establish the use of this technology for Evo-Devo studies. One of these caveats is the need to maintain edited sequences in the modified lineage, which tend to be lost with time among a heterozygous population. Here we show how a recently developed method enables the rapid generation of a homozygous population of edited animals. The Mutagenic Chain Reaction (MCR) is a self-propagating gene-drive technology based on the CRISPR/Cas9 system. By using MCR, guide RNA + Cas9 endonuclease-containing constructs spread through a population in a non-mendelian fashion, replicating during meiosis via homologous recombination. In only three generations, more than 90% of Drosophila melanogaster or Anopheles stephensis insects have been shown to carry the MCR construct as homozygotes. Here we discuss the use of this technology for the study of non-model insects and how we are tackling this problem for genome edition in the hemiptera Rhodnius prolixus, vector of Chagas disease.

(S7, 19) Stem cell features in blood progenitors of ascidians, our closest invertebrate relatives Federico Brown, IB USP Mesenchymal progenitor cells are present in all metazoans. In various ascidian species, putative circulatory stem cells (CSCs), have been suggested to be involved on asexual reproduction and whole body regeneration. However, studies of these cell population/s are restricted to colonial species. Here, we investigate CSCs in the blood of solitary Styela plicata, known for its ability to regenerate its adult central nervous system. We used morphology and aldehyde dehydrogenase (ALDH) activity in blood cells sorted by imaging flow cytometry to characterize putative CSCs in S. plicata. The correlation between these two parameters allowed us to determine 2 gates that showed enrichment of putative CSCs. We found cells with low granularity within a gate of cells that showed high aldehyde dehydrogenase (ALDH) activity. Next, we performed an exhaustive histological survey for cells with stem cell features, using classical histological stains and immunohistochemistry with stem cell (CD34, piwi) and proliferation (pHH3) markers. We found aggregations of stem cell-like cells, corroborated by morphological and ultrastructural analysis, as well as expression profiles that support the intestinal submucosa as a possible stem cell niche. We found higher rates of CD34+ and piwi+ cells, as well as a higher frequency of proliferation in this tissue, which we believe may serve as a source of progenitors for the CSCs in S. plicata. Because ascidians have evolved multiple times independently solitary species that reproduce only sexually, or colonial species that reproduce both asexually and sexually, we argue that the ability to reproduce clonally by budding is related to the remarkable potential of regeneration in tunicates and a high evolvability in the mechanisms that regulate adult stem cell development. (S7, 19) Functional genomic tools in the identification of new genes and regulatory elements in non-model arthropods Lupis Ribeiro, Diego Guerra, Alessandra Alvarenga, Vitória Tobias-Santos, Natalia Martins Feitosa, Rodrigo Nunes da Fonseca, NUPEM-UFRJ-Macaé While classical developmental biology studies were performed using model organisms, the availability of several non-model arthropod genomes opened new avenues for studies of disease vectors and agricultural pests. During this talk I will present two study cases where functional genomic tools helped to identify new genes and regulatory elements in non-model arthropods. Previously, we have shown that in the beetle Tribolium castaneum, zelda is a major transcription factor particularly involved in the control of maternal-zygotic transition, segment formation and post-embryonic processes such as wing, antenna and leg formation and cell differentiation. Here, I will present the analysis of transcriptomes of wild-type and zelda down-regulated eggs. Over 140 genes were down-regulated after zld RNAi when compared to the wild-type. At least one of these genes lack orthologs outside Coleoptera and is essential for embryogenesis, since it is lethal upon knock-down using RNA interference. Thus, transcriptome analysis might unveil the discovery of new and order specific genes. A second study case was obtained by the analysis of available transcriptomes from several insects. In the past years, a few genes encoding small open reading frames (smORFs) were shown to be important for developmental processes. Using several arthropod genomes from distinct orders we applied a bioinformatic approach to uncover new smORFs in non-model arthropods. Hundreds putative order-specific conserved smORFs were identified in the T. castaneum, the hemiptera Rhodnius prolixus, and the mosquito Aedes aegypti. Several smORFs are expressed during embryogenesis and at least one of them is essential for R. prolixus embryogenesis in head and segment formation, probably interacting with the Notch pathway. Altogether, these new technics help to unveil new genes and new regulatory interactions among arthropods. (S8, 19) Deciphering neuron-glia interactions and therapeutic opportunities in neurodegenerative diseases Dora Brites, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal Neurodegenerative diseases such as Alzheimer’s (AD) and Amyotrophic Lateral Sclerosis (ALS) are debilitating and untreatable conditions strongly linked with age and neuroinflammatory processes, in which astrocytes and microglia play a key role. Imbalance of anti-/pro-inflammatory mediators by microglia may result from dysregulated non-coding microRNAs (miRNAs) in exosomes from diseased neurons. Heterogeneous microglia activation states were shown after interaction with exosomes from AD and ALS neuronal cells [1,2]. Exosomes from ALS-SOD1G93A (mSOD1) NSC-34 cells were enriched in miRNA(miR)-124, and those from SH-SY5Y APPSwe cells contained an added cargo in miR-125b and miR-21. Moreover, amyloid-beta treated microglia and ALS spinal microglia were shown to switch from M1 to M1/M2 phenotypes with altered inflammatory-associated miRNAs, when aged [3]. Lately, we identified overexpressed miR-155 in both pre-symptomatic and symptomatic stages, as well as in microglia and astrocytes isolated from the spinal cord of mSOD1 mice pups, highlighting its value as an early biomarker [4]. However, a downregulation of miR-146a was observed in the

brain cortex from matched mSOD1 mice samples [5], pointing to regional and cell type-specific changes in ALS. Furthermore, inflammatory profile, but not aberrant phenotype, decreased in spinal ALS astrocytes treated with anti-miR-155. In contrast, pre-miR-146a protected cortical astrocytes from both aberrancy and inflammatory profiles, while neutralized their neurotoxic properties, supporting its potential as an innovative therapeutic target. Remarkably, pre-miR-146a modulation in astrocytes led to its exosomal enhanced content, while declined the level of miR-155 in cells and extracellular vesicles. Astrocyte phenotypic diversity was also validated in astrocytes directly converted from the fibroblasts of ALS patients, opening a window of opportunity to stratify patients and test mono- and combined therapeutic strategies. References [1] Pinto et al. Front Neurosci 2017 [2] Fernandes et al. Biochimie 2018 [3] Caldeira et al. Front Aging Neurosci 2017 [4] Cunha et al. Mol Neurobiol 2018 [5] Gomes et al. Mol Neurobiol 2018 (in revision) Funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND) project from the European Union’s Horizon 2020 (grant agreement No 643417) and Fundação para a Ciência e Tecnologia (FCT), Lisboa, Portugal (JPco-fuND/0003/2015 to DB, FCT-EXPL/NEU-NMC/1003/2013 to AF and UID/DTP/04138/2013 to iMed.ULisboa), as well as by the Research Grant on ALS from Santa Casa da Misericórdia de Lisboa (SCML), Portugal (to DB). (S8, 19) Microglia-glioblastoma interaction: the role of microglial factors in tumor progression Flavia Lima, Anna Fonseca, Rackele Amaral, Celina Garcia, Diana Matias, Luiz Henrique Geraldo, ICB UFRJ Our group has investigated factors secreted by microglia that modulate growth and invasion of brain tumors, particularly glioblastomas (GBMs). These tumors are extremely aggressive, with a high degree of invasion and proliferation, as well as insensitive to radiation and chemotherapy. In this context, little is known about the immune response, specifically, interactions of microglia with GBMs. Microglia can acquire an interesting phenotype accumulating on the border of tumor and possibly produce factors that promote tumor growth. The prion cellular protein (PrPC) and its ligand, the stress inducible protein 1 (STI1) are among tumor factors that our group has been studying. In normal brain, PrPC is highly expressed and promotes survival and differentiation of neural cells. In a pathological context, STI1 induces proliferation in GBM cell lines. In the present study, we have investigated the role of PrPC-STI1 in the microglia-GBM interaction. In vivo, our studies have shown that STI1 expression increases with tumor progression. We have demonstrated in vitro that STI1 is secreted by microglia, regulates the activity of the MMP9 and promotes proliferation and migration of GBM cells in a PrPC independent manner. Other factors and signaling pathways that we have been studying are the Wnt /β-catenin, via that is activated in gliomas, the CCL21 chemokine and its receptor CCR7 and the lysophosphatidic acid, a bioactive lipid associated with migration/invasion tumor. Understanding the pathways involved in the interaction between the cells that compose the tumor environment (microglia and infiltrating macrophages, endothelial cells, astrocytes and lymphocytes) and glioblastoma cells will contribute to the development of new prognostic markers and therapeutic targets. (S8, 19) Astrocytes: Are they all the same? Implications for synapse function and neurodegenerative diseases Flávia A C Gomes, ICB, UFRJ Astrocytes constitute a heterogeneous population of cells that considerably influence synapse formation and function, however, the mechanisms underlying the diversity of their synaptogenic profile are poorly known. In this talk, we will discuss the role of astrocyte-derived molecules and pathways in synapse formation and the impact of human and murine astrocyte heterogeneity to the synapse homeostasis. We have shown that astrocytes control formation of excitatory and inhibitory synapses by differential activation of transforming growth factor-β1 (TGF-β1) pathway in the cerebral cortex. In addition, we have shown that astrocytes from distinct brain regions (cerebral cortex, cerebellum, hippocampus and midbrain) exhibit different profiles of synaptogenic molecules, which might be responsible for the heterogeneity of astrocyte-synapse interactions. We will discuss how glial dysfunction might distinctly contribute to the cognitive deficits associated with neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. We will argue that astrocytes from distinct brain regions impact synapse function differently. We will also discuss how understanding pathways involved in this process might be relevant to provide molecular-level rationale to understand synapse pathology.

(S9, 19) Neural stem cell response to brain injury: unraveling a new function for the chemoattractant protein prokineticin 2 Marimelia Porcionatto, UNIFESP Traumatic brain injury is an important cause of mortality and morbidity all over the world. After the initial injury there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim not only to counteract these mechanisms but also to replenish the lost cell population in order to achieve a better recovery. The adult mammal brain in not as plastic as the postnatal, but it has at least two neurogenic regions that maintains physiological functions in the brain; the subgranular zone of the dentate gyrus of the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) of the lateral ventricles, that produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that SVZ cells migrate to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis by promoting the directional migration of neuroblasts, is induced in the injured cortex. Using PROK2 receptor antagonist and recombinant PROK2 we show for the first time that PROK2 can directionally attract SVZ cells in vitro and in vivo. The data we present links one more element of the inflammatory process, PROK2 secreted by microglia, to the attempt to regenerate an acutely injured mammalian cortex. (S9, 19) MicroRNAs and the Impairment of Fibroblast Migration Under High Glucose Concentrations Marinilce F Santos, ICB, USP Impaired migration of dermal fibroblasts is observed in individuals with Diabetes Mellitus, contributing to deficient wound healing. The mechanisms involved, however, are poorly understood. Our research group has shown that high glucose concentrations impair fibroblast migration at least partially through mechanisms involving the oxidative stress promoted by increased glucose metabolism. Cell velocity and directionality are impaired due to the activation of the small GTPase Rac1, decreased cellular contractility and reduced adhesion maturation to the extracellular matrix (potentially linked to reduced integrins expression and lowered cell contractility). MicroRNAs (miRNAs), whose expression may be modulated by high glucose and reactive oxygen species, are potentially involved in the regulation of cell migration. The expression of miR-31-5p is increased in NIH-3T3 fibroblasts exposed to 30 mM glucose, as well as in dermal fibroblasts derived from streptozotocin-induced diabetic rats, dependent of reactive oxygen species. Functional studies employing miR-31-5p mimics and anti-miR31-5p suggest that this miRNA might be partially responsible for the migratory phenotype of cells exposed to high glucose, having Rho kinase 1 (Rock 1), Rock 2 and Radixin as targets. Other miRNAs are also affected by high glucose, such as miR-29c, which regulates the expression of different extracellular matrix molecules. Accordingly, a three-dimensional matrix produced by fibroblasts exposed to high glucose is thinner and less organized than the matrix produced by cells exposed to physiological concentrations of glucose. In conclusion, high glucose affects fibroblast migration and extracellular matrix production, through a mechanism involving oxidative stress and miRNAs. Financial support: CAPES, FAPESP, CNPq. (S9, 19) Crosstalk between Wnt, cholesterol and Rho/ROCK during tumor cell migration Cláudia Mermelstein, ICB, UFRJ Migration and invasion are hallmarks of cancer cells that allow their dissemination to other tissues. Many membrane molecules have been described as being involved in tumor cell migration, and among them is cholesterol. We have been studying the role of membrane cholesterol during the migration of breast tumor cells. The human mammary gland/breast epithelial cell line MDA-MB 231 was used and membrane cholesterol was depleted with methyl-beta-cyclodextrin. Cell migration was measured in a cell-based scratch assay and the involvement of the Wnt signaling was tested using Lef-1/TCF reporter activation in permanently transfected MDA-MB 231 cells. Cell morphology was analyzed using fluorescent phalloidin to label F-actin structures. Our results show that membrane cholesterol depletion reduces cell migration, induces changes in cell morphology and particularly in membrane protrusions. Cholesterol depletion also induces an increase in the secretion of IL-10, a cytokine involved in the control of cell migration. These effects involve the activation of the actin-related non-canonical Wnt pathway. Fasudil, a ROCK inhibitor, inhibited cell migration, modified tumor cell morphology and disorganized actin stress fibers. The collection of our results suggests the involvement of membrane cholesterol, non-canonical Wnt signaling, IL-10 secretion and Rho/ROCK pathway during breast tumor cell migration.

(S10, 19) CDK6 – the new kid on the block Veronika Sexl, Institute of Pharmacology and Toxicology, VetmedUni Vienna Inhibitors directed against cyclin dependent kinase 4 and 6 (CDK4/6) have been declared a major breakthrough by the FDA in cancer therapy and their effectiveness was primarily assigned to their ability to block cell cycle progression. In hematopoietic malignancies high levels of CDK6, but not CDK4, are frequently found presumably to CDK6's function in cell-cycle progression. Over the last years we have assigned a novel unexpected role for CDK6 as global transcriptional regulator which occurs partially in a kinase –independent manner. The transcriptional effects are pronounced under conditions of stress and transformation, where CDK6 is required to counteract p53 induced responses. Novel insights in the dual function of CDK6 as regulator of cell proliferation, (leukemic) stem cell hemostasis and transformation will be presented (S10, 19) Oncogene-Induced Replication Stress and Chromosome Instability in Human Cancer Leonardo Karam Teixeira, Brazilian National Cancer Institute, INCA, RJ Cell cycle progression is regulated by the Cyclin-Dependent Kinase (CDK) family of proteins, so named because their activation depends on association with regulatory subunits known as Cyclins. Cyclin E normally accumulates at the G1/S boundary, where it promotes S phase entry and progression by activating CDK2. In normal cells, Cyclin E/CDK2 activity is associated with DNA replication-related functions. On the other hand, deregulation of Cyclin E leads to inefficient assembly of pre-replication complexes and insuficient levels of nucleotides, causing replication stress and eventually genomic instability. Cyclin E is frequently overexpressed in human cancers, correlating with decreased survival in breast cancer patients. However, the mechanisms by which Cyclin E deregulation causes genomic instability are not completely understood. Our group has demonstrated that high levels of Cyclin E delay S phase progression of mammary epithelial cells, allowing cells to enter into mitosis before completion of DNA replication. Incomplete DNA replication induces aberrant mitosis, including formation of anaphase bridges and micronuclei. High levels of Cyclin E leads to persistent chromosome aberrations in proliferating cells, such as endoreduplication, chromosome pulverization, and premature separation of sister chromatids, eventually causing aneuploidy. Our work aims at understanding how oncogene-induced replication stress and genomic instability contribute to human carcinogenesis. Financial support: INCA, CNPq, CAPES, FAPERJ, PEW Foundation (S10, 19) New insights on cd8-mediated immune responses Gustavo P. Amarante- Mendes, ICB USP Immune-mediated elimination of cancer cells is accomplished largely by CD8+ cytotoxic T lymphocytes (CTLs). Tumor-specific CTLs have been isolated from tumor-infiltrating lymphocytes and successful anti-cancer immunotherapies based on checkpoint inhibitors resulted in increased anti-tumor CTL responses with beneficial outcome for the patients. However, a substantial number of patients remains refractory to checkpoint-based immunotherapy, possibly because of the weak immunogenic characteristic of tumor cells. Therefore, it is important to develop new strategies to improve anti-tumor CD8 T cell responses. Our lab is currently exploring the use of genetically modified infectious agents, such as recombinant human adenovirus 5 (rhAd5) and Listeria monocytogenes, as delivery vectors for anti-cancer vaccines. In addition, since growing evidences suggest that DNA methyltransferase inhibitors (DNMTis) can upregulate immune signaling in cancer cells through viral mimicry and upregulation of tumor-associated antigens, we are also investigating the effect of clinically relevant doses of DNMTis on in vivo and in vitro CD8 T cell responses. Finally, despite significant progress, there is still limited information on the molecular mechanisms implicated in target-driven degranulation, effector cell survival and composition and structure of the CTL lytic granules. Therefore, we use a proteomic approach in combination to molecular biology and functional studies to better understand the composition and function of the CTL lytic machinery. Some of our latest results will be discussed at the meeting. Financial support: FAPESP, CNPq, CAPES

July 20th

(S11, 20) Role of cannabinoid receptors and TRPA1 in cell death induced by ischemia Karin Calaza, UFF, RJ (S11, 20) Cannabidiol in neurodegenerative disorders Francisco Silveira Guimarães, Department of Pharmacology, School of Medicine of Ribeirão Preto, USP Cannabidiol (CBD) is a phytocannabinoid derived from Cannabis sativa that lacks the psychotomimetic activity induced by the plant main component, delta-9-tetrahydrocannabinol (THC). CBD is already clinically used to treat some forms of children epilepsy and, together with THC, pain and spasticity present in patients with multiple sclerosis. In laboratory animals, CBD prevents brain damage associated with ischemic stroke and neurodegenerative disorders such as Parkinson and Alzheimer’s diseases. In addition, it favors synaptic plasticity, increasing, for example, hipocampal adult neurogenesis and preventing synaptic remodeling induced by chronic stress. CBD acts through several mechanisms that involve anti-inflammatory and ant oxidative effects, facilitation of endocannabinoid signaling, and interaction with 5HT1A, TRPV1, GPR55, and PPARγ receptors. This multi-target profile probably explains the wide-range therapeutical potential of CBD in neurodegenerative and others disorders. (S11, 20) Cannabinoids and epilepsy Fabrício Moreira, ICB UFMG Cannabinoids are a chemical class of compounds produced by the plant Cannabis sativa ("marijuna"). They include tetrahydrocannabinol (THC) and cannabidiol (CBD). THC, which is responsible for the typical effects of marijuana, exerts its pharmacological effects by binding to a specific target, the cannabinoid CB1 receptor. This receptor is also activated by endogenous compounds, termed endocannabinoids, which are synthesized and hydrolyzed by specific enzymes in the brain. Altogether, the CB1 receptor, the endocannabinoids and their metabolizing enzymes are part of a neurotransmission system called endocannabinoid system. Several functions have been ascribed to the endocannabinoid system, such as neuroprotection and modulation of excitatory activity. This talk aims to present experimental evidence suggesting that this system is a promising target for developing new treatments for epilepsies and related disorders. Potential strategies include natural cannabinoids, such as CBD, synthetic compounds that facilitate endocannabinoid activity in the brain, and TRPV1 blockers. CBD efficacy against convulsive seizures has been demonstrated in animal model and in clinical studies. This cannabinoid has already reached the marked as a treatment for refractory epileptic syndromes, particularly Dravet and Lennox-Gastaut Syndromes. Regarding compounds that facilitate endocananbinoid activity, the most promising strategy is the development of inhibitor of endocannabinoid hydrolysis, particularly by inhibiting FAAH, the enzyme responsible for terminating the action of the endocannabinoid anandamide. Another possibility is the blockage of the TRPV1 (vanilloid) channel. This ion channel is activated by anandamide, facilitating excitatory neural activity. Accordingly, TRPV1 blockers exert antiseizure activity in animal models. Thus, CBD, endocannabinoid hydrolysis inhibitors and TRPV1 blockers might represent future new classes of antiepileptic drugs. (S11, 20) Modulation of endocannabinoid system induced neuroprotection in a murine model of retinitis pigmentosa Camila F. Magalhães, Daniella S. Lopes, Rafael F. Azevedo, Lucianne Fragel-Madeira, UFF, RJ Retinitis pigmentosa is an inherited disease manifested by progressive degeneration of photoreceptors cells and does not have cure yet. Cannabinoids became known for its beneficial effects in the central nervous system diseases, more specifically in retinal injuries. Two principal endocannabinoid ligands present in mammalian retina are anandamide and 2-arachidonoylglycerol which are degraded by enzymes such as Fatty Acid Amide Hydrolase (FAAH). Our work aimed to modulate pharmacologically endocannabinoids levels in a murine model of retinitis pigmentosa, Pde6βrd10 mouse, in order to prolong survival of photoreceptors cells. At 15 postnatal days (P15), we observed cells in inner nuclear layer of retina displaying puncta of FAAH in rd10 mice which were not shown on C57/Bl6 control mice. Also, since P19 we observed cells in outer nuclear layer (ONL), where photoreceptor cells are found in the retina, presenting intense labeling for FAAH. We performed daily intraperitoneal injections of URB597 (0.3mg/kg), a FAAH inhibitor, in rd10 mice. As results, the number of cells labeled for recoverin, a photoreceptor marker, increased 43% in treated animals compared to control at P19,

whereas at P25 this increase was about 25%. There was also an increase on ONL thickness of about 25% at P19, however this effect was lost at P25. The number of TUNEL and recoverin positive cells did not change at P19 after treatment with URB597, but we observed a decrease in cell death at P25 when compared to control. We also observed FAAH inhibition decreased GFAP fluorescence intensity in 35% whereas microglial number in ONL remained the same. Taken together these results suggest endocannabinoids may provide a neuroprotector effect rescuing photoreceptors from cell death, and become a promising target of research in the context of retinitis pigmentosa. Financial support: Capes, FAPERJ, CNPq. (S12, 20) HMGA1 tackles NUMB in the match against glioblastoma stem cell asymmetric division. Francesca Puca, Nadia Tosti, Sonia Morlando, Alfredo Fusco and Sabrina Battista, Istituto di Endocrinologia ed Oncologia Sperimentale - CNR, Naples, Italy Glioblastoma multiforme (GBM) is one of the most aggressive types of cancer, affecting two- three per 100,000 adults per year. Its rapid course, poor prognosis and unresponsiveness to therapy make the identification of new ways to tackle it down an open challenge for cancer research. Initiation, maintenance and recurrence are due to few GBM initiating stem-like cells, arising from the transformation of adult neural stem cells (NSCs) and representing the ideal target for cutting-edge therapies. Increase in stem cell symmetric divisions, at the expenses of asymmetric divisions, plays a pivotal role in this transformation process. HMGA1 is an architectural transcription factor, overexpressed in many malignant tumors and stem cells. We demonstrate that HMGA1 is overexpressed in GBMs compared to other gliomas, especially in the proneural subtype. We report that HMGA1 is overexpressed in a subset of Brain Tumor Stem Cell (BTSC) lines from human GBMs. We also show that HMGA1 knockdown in these cells reduces tumor initiation ability in vivo, stemness and sphere forming efficiency, favors differentiation and sensitizes BTSCs to temozolomide. By performing paired-cell assays, we demonstrate that HMGA1 knockdown is able to increase the asymmetric divisions rate in BTSCs. Accordingly, we show that HMGA1 exerts a massive action on the expression of NUMB (one of the most important, conserved regulators of asymmetric division), by acting at transcriptional and post-transcriptional level. These results demonstrate a pivotal role of HMGA1 in GBM cancer stem cells and endorse HMGA1 as suitable target for cancer stem cell-specific GBM therapy. (S12, 20) Tumor-derived Extracellular Matrix Mediating Epithelial-Mesenchymal Transition in Breast Cancer Cells Thereza Christina Barja- Fidalgo, UERJ The unique composition of the extracellular matrix (ECM) produced by tumors can be a determinant factor to change the profile of surrounding cells. Fibroblasts, endothelial cells, immune cells and even other tumor cells are susceptible to change their behavior and fate on the dependence of the microenvironment settled up by the tumors. Previously, we demonstrated that ECM produced by malignant melanoma induced endothelial cells differentiation, through the engagement between integrins and Src signaling pathways, in a cross-talk with VEGFR2, up-regulating angiogenesis (Helal-Neto, 2016). We are now presenting data showing that ECM derived from an aggressive human breast cancer cell line (MDA-MB-231) triggers epithelial-mesenchymal transition (EMT) in an epithelial, non-invasive, phenotype of breast cancer cells (MCF-7). The matrix produced by MDA-MB-231cells (ECM-MDA) decreased cell-cell contacts and E-cadherin expression, and increased the expression of mesenchymal cell markers and migration of MCF-7 cells. The interaction of these cells with ECM-MDA activated intracellular signaling pathways associated to integrin and potentiated canonical TGF-β receptor signals inducing an EMT-like phenotype in MCF-7 cells, favoring invasion. The data provide novel potential target molecules for antitumor and antimetastatic therapies and also represent an important contribution to the understanding of the adhesion-related mechanisms involved in EMT. (Authors: Renata M Brandão-Costa, Edward Helal-Neto, Andreza M Vieira, Pedro Barcellos-de-Souza, José Andrés Morgado-Díaz, Christina Barja-Fidalgo). Financial Support: FAPERJ, CAPES, CNPq

(S12, 20) Characterizing and promoting immune responses to tumors Martin H Bonamino, INCA, RJ The immune responses undergoing in tumors play pivotal roles either restraining or promoting tumor growth. In order to promote antitumor responses it is mandatory to characterize such immune-tumor responses. We have recently established bioinformatics based-algorithms for gene expression large scale sequencing analysis to characterize the immune response patterns in tumor samples showing that immune responses are correlated and impacted by different cells in the tumor microenvironment and that tumor associated antigen characterization can lead to potential antitumor response promotion. These strategies can be applied to heavily mutated or immune modulated tumors. For tumors displaying poor natural immune responses, the modification of lymphocytes with strategies such as loading Chimeric Antigen Receptor (CAR) molecules in these cells can lead to antigen specific tumor recognition and elimination, representing a promising strategy for promoting antitumor responses. (S13, 20) Molecular profiling of murine melanoma progression identifies independent prognostic factors for melanoma patients Flávia Eichemberger Rius, Ana Carolina Monteiro, Ana Luisa Pedroso Ayub, Diogo Pessoa, Fernando Andrade, Regine Schneider-Stock, Christopher Mason, André Fujita, Eduardo Rego Reis, Miriam Galvonas Jasiulionis, Universidade Federal de São Paulo Cutaneous melanomas are tumors extremely aggressive, and although significant advances were obtained with targeted and immune therapies, acquired resistance is a common problem. Several molecular alterations have been described in melanomas, however there is no integrated knowledge regarding alterations involved in different stages of melanoma genesis. In this context, knowing molecular pathways altered during melanoma progression might contribute not only to a better understanding of melanoma biology, but also to the identification of both novel potential targets to therapy, and molecular signatures used as biomarkers for prognosis and response to therapies. Our group had established and explored a murine model of malignant transformation and tumor progression consisting of: a spontaneously immortalized melanocyte lineage called melan-a; pre-malignant melanocytes named 4C, obtained after subjecting melan-a cells to 4 cycles of adhesion impediment; non-metastatic melanoma cell line, 4C11-, obtained after a limiting dilution of spheroids formed by 4C adhesion impediment; metastatic cell line, 4C11+, obtained after spontaneously loss of p53 by 4C11- cells. This linear model has been explored aiming to obtain a comprehensive view of molecular alterations related to both early and late stages of melanoma genesis. In this regard, transcriptome (NanoString, and RNA-Seq), methylome (ERRBS), and miRnome (Taqman miRNAs arrays and NanoString) were analyzed, revealing molecular pathways dynamically altered throughout melanoma progression. Genes and miRNAs of interest were mapped to their human orthologues and data of human melanoma samples obtained from TCGA were separated in two groups according to the median expression or promoter methylation value among samples in the cohort. Uni- and multivariate COX regression analysis were performed to select possible prognostic markers for disease-free survival. Among others, the expression of SNAI1, VAV1, CHD1, ANGPT2 and miR-142-3p, and the promoter methylation of VEGFC and ANGPT2 were shown to correlate with melanoma patient survival, thus been promising prognostic factors for melanoma. Supported by FAPESP and CNPq (S13, 20) Characterization of DNA repair mechanisms associated with astrocytoma progression and resistance to therapies Rodolfo B. Serafim, Cibele Cardoso, Luis F. M. Di Cristofaro, Enilza M. Espreafico, Maria L. Paçó-Larson, Brendan D. Price and Valeria Valente, UNESP Astrocytomas comprise the most common type of primary brain tumors in adults. Among them, glioblastoma (GBM) is the most frequent and aggressive type, and the majority of patients survive approximately only one year after diagnosis due to invasiveness and high resistance of tumor cells to radio and chemotherapy. We have previously found that HJURP (Holliday Junction Recognizing Protein) is highly overexpressed in GBMs, strongly correlated with patient survival, and essential for survival of GBM cell lines but not for astrocytes and non-tumor fibroblasts. HJURP was primarily associated with DSBs repair by Kato et al. (2007) that described increased expression of HJURP after genotoxic stress and its interaction with proteins of the MRN complex, which is active in the recognition of DNA lesions. However, additional reports to support this function are still required. HJURP also acts as the chaperone of the centromeric variant of histone H3 (CENP-A), performing its loading in chromatin. This activity is well established and quite characterized, regarding mechanisms, protein domains involved and the regulation in cell cycle. Here we further investigated the involvement of HJURP in DNA repair function. Our results revealed the recruitment of HJURP to sites of DSBs immediately after damage induction by irradiation. We also demonstrated that recruitment is dependent on PARP and is required for

ATM activation and phosphorylation of H2AX, an important response in damage signaling. Additionally, HJURP knockdown compromised anchoring of CtIP and RAD51 at DNA lesions and compromised repair activity through the homologous recombination pathway. These defects promoted an overall reduction in DSB repair competence. Finally, we observed that increased HJURP expression conferred proliferative competence and resistance to ionizing radiation for GBM cells. Altogether, these results show that HJURP favors DNA repair and is directly correlated with the proliferative capacity and high resistance to radiation of GBM cells. (S13, 20) Exploring the roles of long non-coding RNAs associated with major oncogenic pathways in melanoma Enilza M Espreafico, FMRP USP Melanoma is a highly mutated and aggressive type of cancer derived from the malignant transformation of melanocytes. The MAPK pathway plays central role in melanoma tumorigenesis and provides key targets for therapy, but therapeutic resistance poses a major challenge today. The discovery of new genes with tissue-specific expression and associated with genetic events of BRAF activating mutations may provide new insights to the field and opportunities for novel therapeutic approaches. Long non-coding RNAs (lncRNAs), have recently emerged as numerous and diversified functional RNAs with tissue, developmental stage and disease restricted expression. RMEL genes, first described by our group in 2010, are potential lncRNAs with expression restricted to melanoma. In this lecture, we will discuss recent findings of our laboratory on the ongoing characterization of four RMEL lncRNAs highly expressed in melanoma, three of them highly associated with the presence of BRAFV600E, the major driver mutation of tumorigenesis in melanoma, and one correlated with MITF, a major transcription factor required for melanocytic differentiation/survival. Knockdown or overexpression approaches indicate that all four RMEL lncRNAs, in different ways and intensity, act by promoting survival and proliferation of melanoma cells. Transcriptomics, proteomics and bioinformatics integrative analyses show that knockdown of these lncRNAs in melanoma cells influences the expression of major component of the MAPK and PI3K pathways involved in proliferation/survival, as well as genes involved in therapeutic resistance to BRAF/MEK inhibitors and immunotherapy. Ongoing studies are focusing on the characterization of subcellular localization, structure and molecular interactions of these lncRNAs. Financial support: FAPESP, CNPq, CAPES, FAEPA.

(S14, 20) Young Investigator Session (S14, 20) Cellular and immunological outcomes from trophoblast cell silencing of versican Camilla Mendes Gonçalves, UFAL (S14, 20) Purification and evaluation of antifungal properties of dectin-fc proteins against aspergillus fumigatus Claudia Rodríguez-de la Noval, UFRJ (S14, 20) Effect of bone marrow mesenchymal stem cell transplantation on the epithelial-mesenchymal transition in the kidney of rats with renovascular hypertension Aline de Almeida Azevedo, UERJ (S14, 20) Extracellular vesicles derived from the intestinal protozoa giardia intestinalis contain a wide repertoire of micrornas Bruno Gavinho, UFPR (S14, 20) Secretion of gaussia luciferase as an indicator of caspase 3/7 activity in response to ADCDKN2AIRESP53 treatment of human glioblastoma (GBM) cell lines. Daniel Vieira Conde Oliveira, USP (S14, 20) Effect of a collagen I derived matricryptin in thrombosis and vascular remodeling on mice abdominal aorta Caroline Fernanda Sanches Dal Pozzo, UNICAMP (S15, 20) Human pluripotent stem cell-based nervous system disease modeling William T Hendriks, Massachusetts General Hospital/Harvard Medical School, USA Human pluripotent stem cell (hPSC) technology provides a powerful tool for basic biomedical research, drug discovery and regenerative medicine. With the current rapid development of genome editing tools it is now possible to create isogenic hPSC lines to avoid “masking” of very subtle disease phenotypes due to differences in genetic background. Our lab studies dystonia-parkinsonism and Parkinson’s Disease (PD) and we use hPSC-based in vitro modeling to perform functional genomics and assay development. This will enable us to unravel

disease mechanism and eventually potential therapeutics. In this presentation I will provide a brief overview of stem cell-based in vitro (neurological) disease modeling in combination with CRISPR/Cas9 gene editing tools and show how we have leveraged these technologies to find the causative gene variant in X-linked Dystonia-Parkinsonism (XDP), a neurodegenerative movement disorder. (S15, 20) Henrique Souza, IB UNICAMP (S15, 20) Prion protein: a pivotal driver and target in glioblastoma stem cells Marilene H. Lopes; Rebeca Iglesia, Mariana B. Prado, Tiago Góss dos Santos, ICB USP Glioblastoma (GBM), the most aggressive and frequent form of brain malignant tumors in adults, contains a subpopulation of tumor cells, called GBM stem cells (GSC), essential for tumor maintenance, metastasis and resistance to therapy. GSC plasma membrane markers functionally relevant present potential as a therapeutic target for the treatment of this aggressive disease. Our group has shown that the GPI-anchored membrane glycoprotein, prion protein (PrPC) is enriched in GSC and is co-expressed with conventional GSC markers, such as CD133. The loss-of-function of PrPC in GSC results in inhibition of self-renewal, proliferation, and capacity for tumor formation. Several ligands have been described for PrPC, including some extracellular matrix and transmembrane proteins functionally relevant to the biology of GSC. Majors GSC markers are able to interact and/or share with PrPC the same membrane microdomain, being preferentially located in lipid rafts. It has been proposed that PrPC acts as a scaffold protein on the cell surface, recruiting and organizing molecules on signaling platforms with different biological consequences. Thus, we propose to use the scaffold concept for PrPC as an alternative for the development of new strategies for the treatment of glioblastoma, besides to demonstrate that PrPC can act as a key regulator of GSC stemness maintenance. (S16, 20) Extracellular vesicles modulate innate immune response in protozoa infection Ana Claudia Trocoli Torrecilhas, UNIFESP Chagas’ disease or American trypanosomiasis is caused by the protozoan parasite Trypanosoma cruzi. In Latin America, it is estimated that over 6-8 million people are infected and approximately 120 million people are at risk of acquiring the infection. Infective trypomastigote forms of T. cruzi release vesicles rich in α-galactosyl epitopes. EVs were obtained from the conditioned medium of cell-derived trypomastigotes and fractionated by gel-filtration, followed by affinity chromatography using immobilized anti-αGal antibodies from patients with chronic Chagas’ disease and analyzed by ESI-MS. We have identified many proteins specific of T. cruzi, including several members of the trans-sialidase/gp85 and gp63 superfamilies, which are known to play a key role in the host cell adhesion and invasion by the parasite. EVs (parasite) induced in vitro high levels of proinflammatory cytokines and nitric oxide by murine macrophages, and considerably enhanced invasion of host cells. Using Toll-like receptor (TLR) 2- and TLR4-transfected CHO cells and macrophages derived from TLR2-knockout mice, we demonstrated that both proinflammatory response and host-cell invasion-enhancing activity were mediated by TLR2. Finally, both phenomena were abolished when EVs were pre-treated with alpha-galactosidase, suggesting that EVs virulence factors engage TLR2 and as yet unknown host alpha-Gal receptor(s). Our data clearly show that vesicles secreted by T. cruzi contain the major virulence factors responsible for promoting the parasite entry into the host cell and for its evasion from the host immune response. In conclusion, EVs contain large number of proteins related to virulence, pathogenesis, and proinflammatory activity. These findings may explain the ability of these vesicles to modulate host inflammatory response and to increase parasite infectivity. We believe EVs components could be eventually explored as molecular targets for the development of new therapeutic approaches to prevent or treat Chagas’ disease. Funding: CNPq and FAPESP (2016-01917-3) (S16, 20) Phosphoinositide control of cytokinesis Martin Lowe, The University of Manchester, UK Phosphoinositide lipids control numerous cellular processes by recruiting and/or activating downstream effector proteins. Phosphoinositide abundance is tightly controlled in both space and time to ensure the correct recruitment and subsequent action of the downstream effectors. During cytokinesis, PtdIns(4,5)P2 is enriched at the cleavage furrow to ensure recruitment of actin-associated effector proteins that drive furrow ingression, which leads ultimately to the physical separation of the newly forming daughter cells. The mechanisms responsible for restricting PtdIns(4,5)P2 to the cleavage furrow are poorly understood, but the inositol phosphatase OCRL, which is mutated in the X-linked disorder Lowe syndrome, appears to play an important role in this process. However, the mechanisms controlling OCRL activity in interphase and cytokinesis remain poorly

defined. In this presentation I will discuss our recent work on the OCRL binding protein IPIP in controlling OCRL function within cells. IPIP is required to physically couple OCRL to endocytic BAR domain proteins, which is essential for proper control of PtdIns(4,5)P2 hydrolysis. Loss of IPIP leads to mislocalization of PtdIns(4,5)P2, cortical membrane blebbing and aberrant cytokinesis. These phenotypes are seen in both Drosophila and human cells. Our results therefore identify IPIP as an evolutionary conserved modulator of cellular PtdIns(4,5)P2 homeostasis that is required for normal cytokinesis, and highlight the importance of scaffolding proteins in controlling inositol phosphatase activity within cells. (S16, 20) Hijacking the Golgi: insights into the mechanism of Orthobunyavirus assembly in mammalian cells Natalia S. Barbosa, Marcos V. S. Dias; Leila R Mendonca; Marjorie Pontelli; Michael Schindler; Eurico Arruda and Luis Lamberti P. da Silva, Center for Virus Research, FMRP, USP Peribunyaviridae is one of the largest families of RNA viruses with several members that cause mild to severe diseases in humans. In this study, we analyzed the assembly pathway of Oropouche virus (OROV), a peribunyavirus of the orthobunyavirus genus that is the etiologic agent of a frequent arthropod-transmitted viral disease in South America countries. OROV is neurotropic and causes a debilitating febrile illness, which can progress to meningitis and/or encephalitis in some patients. Our electron microscopy analyses showed that the assembly of OROV involves budding of virus particles toward the lumen of Golgi cisternae. These Golgi subcompartments become enlarged and physically separated from Golgi stacks, forming Oropouche viral factory (Vf) units. As revealed by conventional confocal and superresolution microscopy, while these Vfs lack typical early and late endosome markers, they are enriched in Golgi proteins and endosomal complex required for transport (ESCRT) elements. Further microscopy and viral replication assays showed that functional ESCRT machinery is required for efficient Vf morphogenesis and production of infectious OROV particles. Although many enveloped viruses have evolved to usurp elements of the ESCRT machinery for assembly and budding, our data provides unprecedented evidence that ESCRT proteins may be relocated to Golgi compartments during viral replication, and that this machinery is required for assembly/egress of an Orthobunyavirus. (S17, 20) Cardiac chamber selectivity arising in the Galliform Bird radiation: from viral repeats to a complex nuclear receptor element José Xavier Neto Optimal cardiac work requires appropriate contractile proteins in heart chambers. Atria require slow myosins to act as variable reservoirs, while ventricles demand fast myosins for swift pump function. How was myosin expression matched to atria and ventricles during development and evolution? We used the quail SMyHC3 paradigm to show that chamber expression is controlled in a dualistic manner according to the context: activation in atria and repression in ventricles. The switch between SMyHC3 promoter states is autonomously orchestrated by a complex nuclear receptor element (cNRE), a 32-bp sequence with overlapping hexanucleotide binding repeats. Unliganded, widely expressed, glucocorticoid (GR) receptors associate with the cNRE in ventricular repression, while the switch to active states in atria requires protein-to-protein interaction between two repressors: the sino-atrial-restricted orphan nuclear receptor COUPTF-II and the pervasive, unliganded androgen receptor (AR). We provide evidence that the cNRE is an endogenous viral element derived from an unidentified virus with limited homology to HSV-1. Comparative genomic studies suggest that the cNRE linked to the SMyHC3 gene through infection of an ancestral host germline and further recombination into the genome of a Galliform bird ancestor at the root of the Galliformes radiation in the Cretaceous, about 100 million years ago. The cNRE example suggests a pathway to selective cardiac chamber expression through nuclear receptor signalling and underscores the haphazard nature of regulatory genome innovation. (S17, 20) Neural crest stem cells: from the developmental biology to the regenerative medicine Andrea Trentin, UFSC The neural crest is a transient structure of vertebrate embryos arising at the closing borders of neural tube during neurulation. It consists of multipotent cells able to give rise to neural, melanocytic and mesodermal (in the head) derivatives. Some of these progenitors were demonstrated as endowed with the self-renewal capacity, and thus displaying stem cell characteristics. The fate and differentiation potential of the neural crest stem cells is profoundly influenced by microenviomental factors they found during migration through embryonic tissues. Moreover, neural crest-like stem cells were recently found in many adult tissues such as hair follicles, dental pulp, dorsal rooth ganglia and cornea among others. As they generate cell types of potential clinical

importance, the presence and accessibility of these multipotent stem cells open new avenues in cell base therapies and regenerative medicine. (S17, 20) How Xenopus can help cancer research: Lessons from Wnt signaling José Garcia Abreu, ICB UFRJ Wnt/β-Catenin signaling pathway is important for embryonic axis patterning and tissue maintenance. Due to the speed and clarity of embryological assays, Xenopus has become important for the study of morphological changes in development. Perturbation of Wnt/β-catenin pathway entails the most straightforward and reproducible phenotypes. Errors in the regulation of Wnt/β-catenin pathway can be catastrophic for embryonic development and in adult tissues it triggers tumorigenesis as in the case of colon cancer. The wide involvement of Wnt signaling in disease has led to extensive efforts in the investigation of small molecules, synthetic or natural, capable of modulating this pathway. Here we will present a functional chemical screening combining specific reporters for the Wnt/ß-catenin pathway as well as Xenopus embryo experiments. We found a set of compounds with inhibitory activity in Wnt/β-catenin signaling and anti-tumor growth properties in colon cancer cell lines. Our findings have been validated in mouse colon cancer model. (S18, 20) 2nd SBBC Young Researcher Award- GE The five finalists will present their studies in this session and the awardee will be announced during the closing ceremony. Chairs Silvia R Batistuzzo de Medeiros, UFRN, Roger Chammas, ICESP, FM USP and Hernandes F Carvalho, IB UNICAMP (S19, 20) Zooming in on alpha-synuclein aggregation: imaging super-powers Tiago Outeiro, University Medical Center Goettingen Parkinson’s disease (PD) is the second-most common neurodegenerative disorder, affecting 2–3% of the population over 65 years of age. Neuronal loss in the substantia nigra and intracellular protein inclusions containing misfolded α-synuclein (aSyn) are the neuropathological hallmarks of PD. Thus, the aggregation of aSyn is tightly associated with neurodegeneration, and the current hypothesis is that aSyn propagates in a prion-like manner throughout the brain, and perhaps even from peripheral tissues. Although this hypothesis is fascinating, and could eventually open new therapeutic avenues aimed at preventing such spreading, there is still no definitive proof for the trans-neuronal spread of aSyn aggregates. Until recently, available imaging techniques did not allow the visualization of the 3D-architecture of the brain at a cellular resolution. However, we now have available several techniques for tissue clearing in which whole organs are rendered macromolecule permeable and optically transparent, thereby exposing their cellular structure with intact connectivity. Other techniques allow us to overcome the diffraction limit for optical microscopes, and enable us to image stained objects with nanoscale precision and thus higher resolution. We are applying these novel imaging techniques to zoom in on aSyn aggregation and spreading, in cells and in the mouse brain. Ultimately, we expect that the use of these novel approaches may shed new light into the molecular mechanisms underlying PD and other synucleinopathies. (S19, 20) New approaches in L-dopa induced dyskinesia: the prominence of glial cells Elaine A del Bel Belluz Guimarães, USP In Parkinson's disease L-DOPA therapy leads to the emergence of motor complications including L-DOPA-induced dyskinesia (LID). LID relies on a sequence of pre- and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. A number of preclinical studies in rodent models of Parkinson's disease have reported an exacerbated inflammatory response to the chronic dyskinetic L-DOPA treatment, in the dopamine-denervated striatum, where changes related to dyskinesia occur. Among these mechanisms, considerable attention has been focused on L-DOPA-induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated. Recently, our group described a dramatic upregulation of astrocytosis in the striatum of 6-OHDA-lesioned rats displaying LID was reported supporting a role of astrocytes in LID. Also we described that LID has been associated with increased expression of induced nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). Inhibition of nitric oxide production decreases LID concurrently with reduction of nNOS and iNOS expression. We propose that in presence of severe dopaminergic degeneration, a required condition for the development of LID, the preexisting pro-inflammatory environment in the striatal nucleus fosters L-DOPA to produce an exacerbated inflammatory response. The microglia-astrocyte crosstalk is fundamental to neuronal

functions and dysfunctions. Chronically and abnormally activated microglia and astrocytes lead to an aberrant neuron-glia communication, which affect synaptic activity and neuroplasticity contributing to the development of LID. This work was supported by the Brazilian foundations: FAPESP (Tematic Project 2012/17626-7; 2014/25029-4); CNPQ: 467467/2014-5 CNPq/MS/SCTIE/DECIT-Pesquisas sobre Doenças Neurodegenerativas and CNPQ: 402658/2012-4 CNPQ –Ciências sem Fronteiras Program; CNPQ 466805/2014-4; CNPQ: 400967/2013-8. (S19, 20) Is the spinal cord affected by physical exercise in bilateral model of Parkinson’s disease? Silvana Allodi, UFRJ Physical exercise has been reported as a non-pharmacological therapeutic strategy in neurological disorders, including Parkinson’s disease (PD). In animal models of PD, physical exercise protocols are generally of two types: forced or voluntary. In the forced exercise, the animals do not choose the dosimetry to carry out the physical exercise. In the latter, the animals choose the parameters, such as time and speed. Some benefits related to physical exercise in PD are intensive activity maximizes synaptic plasticity; complex activity promotes better structural adaptation and dopaminergic neurons are highly responsive to exercise and inactivity (use and disuse). Although many studies have demonstrated positive aspects of physical exercise in PD, little attention has been given to the influence of physical exercise on the spinal cord in animal model of PD. In this presentation the following aspects of our research will be approached: a) The physical exercise protocol based on forced exercise (treadmill training) used to investigate motor behavior (pole, footprint and open field tests) and the production of some neurotrophic factors (CDNF and BDNF) and tyrosine hydroxylase (TH) in the cervical spinal cord; b) The CDNF, BDNF and TH-positive cells in animals from control (sedentary and exercise) and PD (sedentary and exercise) groups. During the talk we will discuss the possible benefits of this approach. (S20, 20) DUSP3-NPM-p53: a new signaling axis in the control of genomic stability Lilian C. Russo, Pault Y.F. Minaya, Jessica O. Farias & Fabio L. Forti, IQ USP The dual specificity phosphatase 3 (DUSP3) or VHR (vaccinia virus VH1-related phosphatase) is an atypical tyrosine phosphatase that dephosphorylates residues of p-tyrosine and p-threonine in protein substrates. DUSP3 is overexpressed in some human tumors, such as cervix and prostate, where it regulates cell cycle progression and has preferably nuclear localization. However DUSP3 contributes to cellular genomic stability though mechanisms not fully understood and our group used biochemical, bioinformatics, proteomics and interactome approaches to identify and validate nuclear proteins interacting with DUSP3 under cellular conditions of genotoxic stress promoted by UV radiation. Results from shotgun proteomics showed that DUSP3 interacts with nucleolin (NCL), nucleophosmin (NPM) and ribonucleoprotein C (hnRNPC), whereas co-immunoprecipitation experiments showed they are tyrosine-phosphorylated, and with a slight increase in the cells knocked-down for DUSP3. However, DUSP3 knockdown did not affect the total levels of NCL, NPM and hnRNPC proteins expression. Surface Plasmon Resonance (SPR) analyses allowed a real-time, label-free detection of a very strong physical bimolecular interaction between DUSP3 and NPM. To access tyrosine-phosphorylated NPM, we further designed phospho-specific antibodies against the four different tyrosine residues present in the NPM; immunoblotings revealed that DUSP3 deficiency differentially affects tyrosine phosphorylation under stress conditions. Since NPM has key roles in DNA repair, cells deficient for nucleotide excision repair (NER) pathway are still more sensitive to UV effects under DUSP3 knockdown, compared to NER proficient cells, and exhibit delay in DNA repair with accumulation of cyclobutane pyrimidine dimers (CPD) and 6,4-photoproducts. Furthermore an unexpected increase in phospho-p53-Ser15 is observed in DUSP3 deficient cells submitted to genotoxic stress, which can be correlated to nuclear NPM functions in the repair of UV-promoted DNA lesions. Altogether our data point out DUSP3 unknown roles in different signaling modules regulating biological processes involved in genomic stability through an unusual target, the NPM protein. (Fapesp, CNPq, Capes) (S20, 20) Single-strand break repair and human genetic disorders Nicolas Hoch, Hana Hanzlikova, Emilia Komulainen, Stuart Rulten, Grace Yoon, Keith Caldecott, University of Sussex, UK, IQ USP XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. This latter phenotype is recapitulated in a related syndrome caused by mutations in the XRCC1 partner protein PNKP and implicates hyperactivation of poly(ADP-ribose) polymerase/s as a cause of cerebellar

ataxia. Indeed, remarkably, genetic deletion of Parp1 rescued normal cerebellar ADP-ribose levels and reduced the loss of cerebellar neurons and ataxia in Xrcc1-defective mice, identifying a molecular mechanism by which endogenous single-strand breaks trigger neuropathology. Collectively, these data establish the importance of XRCC1 protein complexes for normal neurological function and identify PARP1 as a therapeutic target in DNA strand break repair-defective disease. (S20, 20) Mesenchymal stem cells: instability, senescence and DNA repair DA Cornélio, JT Fonseca, JCMT Marques, KK Silva, EV Silva, and Silvia R Batistuzzo de Medeiros, UFRN To use mesenchymal stem cells as potential therapeutic vehicles it is fundamental the understanding of their basic cell biology. There are controversies in the literature concerning the stability of these cells in culture and /or their contribution to cancer development. In the present study, we followed the behavior of MSC with normal and altered karyotype, in the presence of microparticles of titanium, until senescence. This analysis were done by classical and molecular cytogenetics as well as by the transcriptome. Different comparisons were done as: i) senescente and young cells with normal karyotype; ii) senescent and young cells with altered karyotype; iii) young cells with normal and altered karyotype and iv) senescent cells with normal and altered karyotype. Using a gene set enrichment analysis, the behavior of DNA repair genes, were assessed. The results have indicated that: i) titanium particles induces chromosomal alterations; ii) MSC alterations are similar to those occurred in pluripotent ones; iii) MSC have a high frequency of nucleoplasmic bridges but a low frequency of micronucleus; iv) senescent cells present alterations characteristics of giant cell tumor of the bone; v) senescent cells have a more differentially expressed genes than young cells; vi) LAMA 5 is highly expressed in cells with inverted karyotype; vii) EGF is the bottleneck of the general network; viii) LAMA5, JAG1 and TNFRSF21 were the hubs connecting with EGF; ix) DNA repair genes decrease in senescente cells ande even more in those with altered karyotype; x) the presence of HR and NHEJ repair pathway in young cells with both karyotype, explaining the low frequency of micronucleus. All together, these findings suggest new candidates molecules as possible association between senescence and tumorigenesis. (S21, 20) Multiple signals to establish neuronal positioning and orientation in the developing zebrafish retina

Flávio Zolessi, Facultad de Ciencias, Universidad de la República / Institut Pasteur de Montevideo. Uruguay Neuronal differentiation implies a series of events that begin at the last mitosis and ends with the functional, synaptically-connected mature cell. Among these events, relatively little is understood on the mechanisms involved in neuronal final positioning and orientation regarding the surrounding tissue, which are essential for the subsequent differentiation process. We have used the accessible zebrafish embryo neural retina to study neuronal differentiation in vivo, mostly concentrating on its projection neuron, the retinal ganglion cell (RGC). In our early studies, we observed a stereotyped morphological differentiation process on these cells, which after being born from progenitors, undergo a gradual transition from an epithelial to a neuronal cell type of polarity, concomitantly orienting themselves with the axon always extending towards the basal side of the retinal neuroepithelium. This orientation, but not the intrinsic ability to polarize, can be lost upon disruption of neuroepithelial apico-basal polarity. We also demonstrated that Laminin1 is an essential extracellular signal for localized axon outgrowth, although our evidence suggested that other signals might act on differentiating RGCs to help establishing their final position and orientation. Looking for localized signals, we observed that these differentiating cells have a primary cilium that is always apically localized during apical process retraction and axon outgrowth. Genetic ablation of these cilia caused defects in the specific generation of RGCs and on their translocation towards the retinal basal region, but not evident polarization or orientation defects. Hence, other cellular signals might be involved in determining the site of axon outgrowth. Being axon repulsive signals the main candidates for this function, we analyzed the possibility that Slit-Robo signaling might be involved. Our genetic manipulation studies of this pathway, combined with that of Laminin1 signaling, strongly suggest that these two pathways collaborate to finally position and orient RGCs in the living zebrafish retina. (S21, 20) Clonal analysis in skeletal muscle growth and repair Roberta Escaleira and Simon M. Hughes, Instituto de Pesquisas Biomédicas do Hospital Naval Marcílio Dias – Marinha do Brasil, Rio de Janeiro, Brazil. Gradual cell lineage restriction is a major determinant of animal development. Understanding of cell lineage origins and diversity is also important for designing regenerative stem cell therapies. Distinct myogenic precursor cell (mpc) lineages populations have been proposed to be a factor controlling vertebrate myogenesis. In contrast, much less is known in mesenchymal tissues with a complex three dimensional structure. In order to

study clonal muscle precursor cells (mpcs) behaviour in skeletal muscle growth and repair we have optioned for zebrafish as experimental model. Danio rerio is a tropical fish native to Southeast Asia with fast development, clear optically at larval stage and biologically similar to human because the zebrafish shares the majority of the same genes. Using confocal microscopy analysis of a transgenic zebrafish line we could be tracing marked clones of motile mononucleated cells in somites during long periods of time. During muscle growth, we show that clones of cells contribute stably to patches mesenchymal tissue throughout the life of an animal. At embryonic stages, these clones are generally contained within single somites and contribute to regions of muscle constituting a broad zone of fibres. The muscle precursor cell behaviour during repair was investigated by proceeding a needle injury in a 4dpf (days post-fertilisation) embryo somite and analysing the same region on subsequent days after wound. In this presentation, we show clones of mononucleated muscle precursor cells (mmpcs) participating in skeletal muscle growth as soon as clusters of cells determining new fibres formation and contributing for muscle repair. Support: Marinha do Brasil, CNPq. (S21, 20) Blastema is an evolutionary conserved structure for tissue regeneration: Epithelial-mesenchymal interaction and transition are necessary for de-differentiation, general cell migration and eventually the formation of sponge blastema. Cristiano C. Coutinho, Ivone de Andrade Rosa, Leonardo R. Andrade, Manoel Luis Costa, Claudia Mermelstein, ICB – UFRJ Sponges are modern organisms earlier diverged from the main evolutionary brunch of other animals. They have the remarkable ability to regenerate a new juvenile sponge from any piece of their body, even pieces with millimetrical size. The ability to regenerate is pivotal for animals and is probably evolutionary conserved. The common process is the formation of a proliferating stem cell mass, the blastema, at the base of the regenerating region. The evolutionary origin of this process is addressed here. The regeneration program to form a new Hymeniacidon heliophila individual from an explant is here described at the cellular and tissue level, using time lapse photo microscopy, florescent explant tracking on different host regions, classical histology and SEM. Epithelial/mesenchymal interaction and epithelial/mesenchymal conversion is observed prior to oriented migration toward a central cell mass during the developmental process for sponge blastema formation. Converted basoepithelial and migrating mesenchymal cells have similar adhesion proprieties, suggesting a dedifferentiation process. They both integrate into the mesohyl (with mesenchymal cells) and adhere over silica substrate (a natural substrate for basoepithelium). The evidence also suggests that mesenchymal cells and converted cells have stronger cell-cell or cell-collagen adhesion than to the silica. It was not possible to follow the grafted cells for more than 16hs to test the cell differentiation potential of converted and mesenchymal cells. Nevertheless, like in other animals, the data points toward a dedifferentiation process to blastema formation, suggesting a conserved evolutionary process.

(S22, 20) Young Investigator Session (S22, 20) Endogenous TCF21/POD-1 expression through CRISPR/DCAS9 system decreases cell migration and invasion of human adrenocortical carcinoma cells Jean Lucas Kremer, USP (S22, 20) Interaction between laminin-derived peptide C16 and B1 integrin and C16 location in breast cancer cells Maria Raquel Unterkircher Galheigo, USP (S22, 20) The role of TLR4 interactor with leucine-rich repeats (TRIL) in hypothalamic inflammation Alexandre Moura Assis, UNICAMP (S22, 20) Effects of lipoxins on the metabolic profile of tumor-associated macrophages Natália Mesquita de Brito, UERJ (S22, 20) Functional analysis of PKCΛ mutations in cancer Damian Emilio Berardi, USP (S22, 20) Leukocyte receptor tyrosine kinase interacts with secreted midkine to promote survival of migrating neural crest cells Felipe Monteleone Vieceli, California Institute of Technology

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