Cancer Center Support Grant Site ReviewDate

Cancer Center Support Grant Site ReviewDate

Signals, Pathways and Targets

Program Leaders: John Lowengrub, Ph.D.

Marian L. Waterman, Ph.D.2011 Chao Family Cancer Center Retreat

Palm Springs

Rationale

• Cancer is a complex adaptive system with dynamic regulatory pathways (Dev Biol, Cell Biol, Biochem)

• Modeling dynamic interactions is critical for understanding progression and response to treatment (Systems Biol)

• The SPT program reflects this multi-disciplinary approach to cancer

Systems, Pathways and Target Program: 56 members

The SPT ProgramCancer Relevant SPT Publications, 1/2011 – 9/2011

Total for Program SPT(Cancer Projects)

NCI

Other NIH

ACS

NSF

Other Peer Reviewed

Industry Non-Peer Reviewed

Other Non-Peer Reviewed

$17,134,815 Total Annual Direct Costs (peer reviewed)

$2,695,977 (NCI)

Signals, Pathways and Targets: Program Metrics

Systems, Pathways and Targets Program ThemesSystems Organ Pathway Target

Baldi (Blumberg) Anderson (Bardwell)

Bardwell Calof Arora (Edinger)

(Calof) Donovan Blumberg (Fruman)

Frank (Hoang) Casali Kaiser

(Komarova) (Krowleski) Chan Komarova

Lander (Lander) Cho (Steele)

Nie (Lee, E) Dai (Thompson)

Thornton Limoli Edinger (Walsh)

Wan (Lowengrub) Fan (Waterman)

(Wodarz) (Nie) Fruman Wodarz

(Zlotnik) Schilling Hoang (Zlotnik)

Steele Huang, L

(Wan) Huang, T

(Zhou) Kaiser

Krolewski

(Lander)

Lee, E

Levin

Lilly

(Nie)

Sandmeyer

Sassone-Corsi

(Schilling)

Thompson

(Want)

Walsh

Warrior

Waterman

Yokomori

Zlotnik

Program Co-Leader: John Lowengrub

•Angiogenesis•Macrophages•Fibroblasts•Immune cells

NIH GO Grant. PIs: Lander, Lowengrub

13 National Centers for Systems Biology (NIH P50)PI: Lander (SPT)Other key personnel: SPT: Calof, Bardwell, Nie, WanOIB: Gratton

http://www.systemscenters.org/

Renewal (2011):Theme B (Calof): Control of Growth

and MorphogenesisSPT: Edwards, Lander, Lowengrub,

Nie, Waterman

Intestinal organoids

New research initiative•Cellular cross-talk in the human colon cancer microenvironmentNIH/PPG: Expected submission: May 2012PI: Hughes (ABT); Project leaders: Waterman (SPT), Hughes (ABT), George (ABT), Lowengrub (SPT); Core directors: Hughes, Edwards (SPT), Hui

Waterman Hughes

George Lowengrub

Komarova Wodarz

Systems Modeling

Bench to Bedside: Krolewski, Fruehauf, Lilly, Dash

Prostate Disease Oriented Team (DOT) Clinical Trials Open for Accrual: 11Trials developed directly from DOT activities: 3 (UCI-10-11; UCI-10-41; UCI-

11-02)

cMetNeuropilin

Dr. Bang HoangWnt Signaling in Sarcomas

Wnt Signaling and Metastasisin OsteosarcomaWIF-1, Frzb

Druggable Wnt Target Genesc-METNeuropilin

2011 Kappa Delta Ann Doher Vaughn Award

Career Development Award: 2011 - 2014

NIH K08 CA11600

Dr. Bang HoangWnt Signaling in Sarcomas

PP242INK128

Bench to Bedside: Dr. David Fruman

Dr. David Fruman

Next-Gen mTOR inhibitors

A New Target: Dr. Aimee Edinger

PI: Aimee Edinger (SPT)Collaborators: David Fruman (SPT), Michael Lilly (SPT)

Oct. 2011

Proteomic ToolsScientific Highlights

Dr. Lan Huang, PhD: Mass Spectrometry1. New protein tagging strategies: tandem tags, in vivo biotinylation

2. Novel cross-linking chemistries: click-chemistry, novel spacers

3. Rapid Protein Complex IsolationProteasome network – collaboration with Dr. Peter Kaiser

Global Ubiquitination, Neddylation Network – collaboration with Dr. Peter KaiserRNA/Protein complexes (MS2-BioTRAP) – NCI IMAT R21CA133275

Tsai BP, Wang X, Huang L, Waterman ML.

2011. Mol Cell Proteomics.

“Quantitative Profiling of In Vivo-assembled RNA-Protein Complexes Using a Novel Integrated Proteomic Approach”

planned: NCI IMAT R33 Multi-PI RO1

CSB

SPT Discoveries:Moving Targets Closer to the Bedside

p53 Rescue A Functional Census of p53 Cancer and Suppressor MutantsDr. Peter Kaiser (SPT; PI) and Dr. Rick Lathrop (CSB; contact PI)

NCI R012010

Currently: in silico screen of >2,000,000 small molecules small molecule synthesis and test in cells

Scientific Highlights:

BiologyKaiser Lab, PI (SPT)Biological Chemistry

ChemistryChamberlin Lab (CSB)Pharmaceutical Sciences

Machine LearningLathrop Group, PI (CSB)Computer Science

Molecular BiologyHatfield Lab Computational BiologyResearch Laboratory

Molecular Dynamics

Amaro Group Pharmaceutical Sciences

Mouse GeneticsLee Lab (ABT)Biological Chemistry

Structural BiologyCocco Lab (NMR) (CSB)Luecke Lab (X-ray) (CSB)Molecular Biology and Biochemistry

Cancer Center - Value AddedNIH/NCI T32 #CA113265GHTF CoreCFCCC Seed grants

The p53 TeamScientific Highlights

The SPT ProgramChallenges• Size• Diversity of Discipline• Geographic Location (UCIMC, Main Campus, SOM)

Meeting the Challenges• Communication• Monitoring• Meetings• Goal: Linking Basic and Clinical groups

Disease Oriented TeamsJohn Krolewski (SPT): Prostate CancerRob Edwards (SPT)/Jason Zell (PPS): Colon

Cancer

Systems, Pathways and Targets ProgramCo-Leaders: Dr. John Lowengrub, Dr. Marian Waterman