ConnectorSpring08 (1)

12
Timothy Lu Lemelson-MIT Program Spring 2008 newsletter for graduates, students, faculty and friends of the Harvard-MIT Division of Health Sciences and Technology The Connector Peter Farrell, an MIT alumnus and member of the HST advisory council, has donated $1 million to HST to help HST launch its Idea 2 independent research program. One of the most challenging aspects of graduate education, and of innovation in gen- eral, is choosing a problem to tackle. Finding the sweet spot — a problem that is small enough to be solvable but big enough to be relevant — can be difficult. It is par- ticularly difficult for students to find such problems on their own when they are simultane- ously grappling with developing so many other skills and support networks. More often than not, graduate students latch on to an existing problem already defined and funded by their research supervisor. While this approach is effective, it frequently does not expose students to the process of finding and refining a new problem. This is a crucial gap. To become successful scientists and innovators, students must develop these skills and build an intuition for problem definition, according to HST director Martha Gray. HST wants to close this gap by actively mentoring students through the process of problem identification through the Idea 2 program. The program invites students to engage in the process of identifying, defining, enabling and accelerating a new research effort. The program is adapted from a model de- veloped at the Deshpande Center for Innovation at MIT and is designed to fit seamlessly into the existing graduate education program. A student involved in Idea 2 proposes a problem and submits it for evaluation. If accepted, students will receive an Idea 2 research assistantship. A mentoring team of faculty, alumni and advisors will help the student refine the idea, establish a plan and, if appropriate, secure financial and other resources MIT alumnus donates $1 million for Idea 2 research program Stephen Oxenbury Peter Ferrell Timothy Kuan-Ta Lu, who received his PhD in MEMP in February 2008, is this year’s winner of the $30,000 Lemelson-MIT Student Prize, which recognizes burgeoning inventors and innovators. Lu, a third-year MD student at HMS, has invented processes that promise to enhance the effectiveness of antibiotics and help eradicate layers of bacteria, known as biofilms, in order to combat bacterial infections such as those caused by E. coli and MRSA (methicillin-resistant Staphylococcus aureus). Working with his advisor, James J. Collins, Professor of Biomedical Engineering at Boston University, Lu attacked the problem of resistance to antimicrobial treatment caused by biofilms, which are surface-associated communities of bac- teria encased in an extracellular matrix protective of bacteria. To address this issue, Lu engineered bacteriophages to express a biofilm-degrading enzyme to simultaneously attack the bacterial Lemelson-MIT Program recognizes two inventive MEMP students (continues on page 4) Keynote Speaker: Dennis W. Choi, MD, PhD Professor of Neurology and Director of the Comprehensive Neuroscience Center Emory University School of Medicine HST FORUM Thursday • April 10, 2008 2 – 7 pm New Research Building Elements Cafe, HMS 77 Avenue Louis Pasteur hst.mit.edu/forum cells in the biofilm as well as the biofilm matrix. Significant reductions in bacterial biofilm cell counts were obtained, almost reaching complete destruction of the bacterial biofilm. This work was hailed as a success of syn- thetic biology. The investigators concluded that “engineered bacteriophage treatment could be considered as an addition to the therapies against bacterial biofilm in medical, industrial and bio- technological settings” (TK Lu and JJ Collins, PNAS 2007; 104: 11197-202.) MEMP student Erez Lieberman was a final- ist for the same prize. He was the lead developer of an artificial intelligence system to enable early diagnosis of poor balance in aging adults, a tech- nology that is being commercialized. One of the early adopters was NASA. Today, Lieberman’s diagnostic system is in use by NASA astronauts. Previous HST awardees of this prize are Da- vid Berry (2005), and Daniel DiLorenzo (1999).

description

Thursday • April 10, 2008 2–7pm New Research Building Elements Cafe, HMS 77 Avenue Louis Pasteur Spring 2008 newsletter for graduates, students, faculty and friends of the Harvard-MIT Division of Health Sciences and Technology Professor of Neurology and Director of the Comprehensive Neuroscience Center Emory University School of Medicine hst.mit.edu/forum Keynote Speaker: Timothy Lu (continues on page 4) Peter Ferrell Lemelson-MIT Program Stephen Oxenbury

Transcript of ConnectorSpring08 (1)

Page 1: ConnectorSpring08 (1)

Timothy Lu

Lemelson-M

IT Program

Spring 2008

newsletter for graduates, students, faculty and friends of the Harvard-MIT Division of Health Sciences and Technology

The Connector

Peter Farrell, an MIT alumnus and member of the HST advisory council, has donated $1 million to HST to help HST launch its Idea2 independent research program.

One of the most challenging aspects of graduate education, and of innovation in gen-

eral, is choosing a problem to tackle. Finding the sweet spot — a problem that is small enough to be solvable but big enough to be relevant — can be difficult. It is par-ticularly difficult for students to find such problems on their own when they are simultane-

ously grappling with developing so many other skills and support networks. More often than not, graduate students latch on to an existing problem already defined and funded by their

research supervisor. While this approach is effective, it frequently

does not expose students to the process of finding and refining a new problem. This is a crucial gap. To become successful scientists and innovators, students must develop these skills and build an intuition for problem definition, according to HST director Martha Gray. HST wants to close this gap by actively mentoring students through the process of problem identification through the Idea2 program. The program invites students to engage in the process of identifying, defining, enabling and accelerating a new research effort.

The program is adapted from a model de-veloped at the Deshpande Center for Innovation at MIT and is designed to fit seamlessly into the existing graduate education program. A student involved in Idea2 proposes a problem and submits it for evaluation. If accepted, students will receive an Idea2 research assistantship. A mentoring team of faculty, alumni and advisors will help the student refine the idea, establish a plan and, if appropriate, secure financial and other resources

MIT alumnus donates $1 million for Idea2 research program

Step

hen

Oxe

nbur

y

Peter Ferrell

Timothy Kuan-Ta Lu, who received his PhD in MEMP in February 2008, is this year’s winner of the $30,000 Lemelson-MIT Student Prize, which recognizes burgeoning inventors and innovators. Lu, a third-year MD student at HMS, has invented processes that promise to enhance the effectiveness of antibiotics and help eradicate layers of bacteria, known as biofilms, in order to combat bacterial infections such as those caused by E. coli and MRSA (methicillin-resistant Staphylococcus aureus).

Working with his advisor, James J. Collins, Professor of Biomedical Engineering at Boston University, Lu attacked the problem of resistance to antimicrobial treatment caused by biofilms, which are surface-associated communities of bac-teria encased in an extracellular matrix protective of bacteria. To address this issue, Lu engineered bacteriophages to express a biofilm-degrading enzyme to simultaneously attack the bacterial

Lemelson-MIT Program recognizes two inventive MEMP students

(continues on page 4)

Keynote Speaker:

Dennis W. Choi, MD, PhDProfessor of Neurology and Director of the Comprehensive Neuroscience CenterEmory University School of Medicine

HS

T F

OR

UM

Thursday • April 10, 20082 – 7 pmNew Research BuildingElements Cafe, HMS77 Avenue Louis Pasteur

hst.mit.edu/forum

cells in the biofilm as well as the biofilm matrix. Significant reductions in bacterial biofilm cell counts were obtained, almost reaching complete destruction of the bacterial biofilm.

This work was hailed as a success of syn-thetic biology. The investigators concluded that “engineered bacteriophage treatment could be considered as an addition to the therapies against bacterial biofilm in medical, industrial and bio-technological settings” (TK Lu and JJ Collins, PNAS 2007; 104: 11197-202.)

MEMP student Erez Lieberman was a final-ist for the same prize. He was the lead developer of an artificial intelligence system to enable early diagnosis of poor balance in aging adults, a tech-nology that is being commercialized. One of the early adopters was NASA. Today, Lieberman’s diagnostic system is in use by NASA astronauts.

Previous HST awardees of this prize are Da-vid Berry (2005), and Daniel DiLorenzo (1999).

Page 2: ConnectorSpring08 (1)

2 Spring 2008

The ConnectorEditor Walter H. Abelmann, MD

Managing Editor/Designer Becky Sun

Editorial Assistant Fran Betlyon

Contact InformationHarvard-MIT Division of Health Sciences and Technology77 Massachusetts Ave., E25-519 Cambridge, MA 02139-4307P: (617) 253-4418 F: (617) 253-7498 E: [email protected] http://hst.mit.eduThe Connector is a quarterly publication of the

Editorial BoardPavan Cheruvu (MD ’09)Patricia A. CunninghamLisa E. Freed, MD, PhD ’88Robert S. Lees, MDLora MaurerCatherine ModicaArvind Ravi (MD ’10)Steven M. Stufflebeam, MD ’94Peter I-Kung Wu (MEMP)

Ex officioDavid E. Cohen, MD ’87, PhDMartha L. Gray, PhD ’86

Harvard-MIT Division of Health Sciences and Technology. The staff and board of The Connector would like to thank the HST alumni, faculty, staff, and students who contributed to this issue. Please send reports of your recent activities and personal news to the above address or email. Previous issues of The Connector can be found at http://hst.mit.edu.

Volume 22 • Number 2

hst news

With the sudden death of M. Judah Folkman, MD, on January 14, HST lost a good friend and long-time supporter. The Julia Dyckman Andrus Professor of Pediatric Surgery and Professor of Cell Biology at HMS, and Director of Vascular Biology and Chief of Surgery, Emeritus, at Children’s Hos-pital, was also a valued member of the HST affiliated faculty. We remember his inspiring address at the 2007 HST Commencement.

As the founder of the field of angiogenesis research, which has led to the development of angiogenesis inhibitors as therapy for neoplastic as well as ocular disease, Folkman has long served as an exemplary role model for physician-scientists in training.

An exceptional teacher and inven-tor, Folkman was a strong supporter of HST ever since he co-chaired the Research Subcommittee of the Joint Harvard-MIT Committee on Engi-neering and Living Systems in 1962, and then the Research and Develop-ment Subcommittee of the HST Plan-ning Committee in 1969.

Folkman suffered a fatal heart attack at the Denver International Airport. He was 74.

IN MEMORIAM

M. Judah Folkman

Just

in K

nigh

t

A fter many years of planning and 14 months of subsequent construction, the first phase of renovation for HST’s

headquarters building at MIT has finally been completed! Though Building E25 has been the “home” of HST since 1982, these renovations represent the next significant step toward a more centralized Division.

Beginning in November 2005, representa-tives from HST, MIT facilities and Imai Keller Moore Architects met to re-imagine the E25 space. While a second phase of renovations will focus on the first floor’s educational and social facilities, the recently completed first phase was primarily motivated by a desire to consolidate more HST faculty and labs into a single loca-tion. Planners also aimed to use the renovations as a tool for expanding and reorganizing the HST staff distribution and for updating infra-structure, space and equipment to better meet scientific research needs. Construction on the project — funded by HST, with a substantial financial investment from MIT — finally began in September 2006. The construction manage-ment firm of Barr & Barr finally finished the first phase in November 2007.

The renovations and subsequent moves have resulted in the addition of seven HST faculty labs in E25 that were previously located in other buildings. Six faculty members moved to new office spaces within the building or had their current spaces significantly renovated. For staff, the renovations have facilitated several

D i r e c t o r s ’notes

changes, including a dedicated location for IT personnel and the creation of a new suite for the office of Development, External Relations and Alumni Affairs. Faculty, students and staff are all benefiting from two new kitchen spaces, two renovated conference rooms, and the new floors, walls and artwork that has been placed throughout the building.

On February 19, HST celebrated the completion of these renovations with a festive party in E25. Members of the HST community, including faculty, students and staff, gathered for two hours to enjoy staff-led tours of select facilities, open houses of 12 labs, and a recep-tion with food and drink. Speaking at the recep-tion was Associate Provost Claude Canizares, who spoke of the challenges associated with the move and the admirable patience the Division demonstrated throughout the entire renovation process. The reception also featured remarks by HST’s own Professor Lee Gehrke, who praised the renovations for bringing more HST faculty under one roof to encourage exciting scientific conversations and collaborations.

As we said in our remarks at the reception, we would like to thank MIT Facilities, members of the administration, Imai Keller Moore Architects, Barr & Barr employees, and all the faculty and staff who made sure this phase of the renovation was a success.

—Martha L. Gray andDavid E. Cohen

Folkman was good friend

and supporter of HST

Page 3: ConnectorSpring08 (1)

The Connector 3

hst newsSukhatme Named CAO and Faculty Dean

Vikas P. Sukhatme, MD ’79, PhD, the Victor J. Aresty Professor of Medicine at HMS and BIDMC, has been appointed Chief Academic Officer and Harvard Faculty Dean of the Beth Is-rael Deaconess Medical Center. His appointment went into effect as of January 1.

Sukhatme has served as Chief of BIDMC’s Renal Division since 1992. He also was the Vice Chair for Interdepartmental and Translational

Programs and Chief of the Division of Inte rd i sc ip l inar y Medicine and Bio-technology. His re-search focuses on vas-cular biology, cancer and renal disease. He is a member of the faculty of HST 240: Translational Medi-cine Preceptorship, a course for HST GEMS (Graduate

Education in Medical Sciences) students.

Nature’s Favorites Include Lieberman’s Irregular Verbs

MEMP student Erez Lieberman’s study of the evolution and regularization of the conjuga-tion of English irregular verbs, summarized in the Winter 2007-08 issue of The Connector (page 7), was one of 18 research papers that Nature chose as its favorites for 2007.

Demirci wins Turkish AwardUtkan Demirci, PhD, Instructor in HST

and Instructor in Medicine, HMS, BWH, received the Honorary Biotechnology Award, presented jointly by the Turkish Technology Development Foundation, the Scientific and Technical Research Council of Turkey, and the Turkish Industrialists’ and Businessmen’s Association. He was honored for the development of a new lens-free cell moni-toring platform that uses an opto-electronic sen-sor array to record images of cells. This approach could provide a rapid cell counting diagnostic tool for CD4 HIV monitoring in resource limited settings.

PromotionsSteven M. Zeitels, MD, a member of the

HST affiliated faculty, has been appointed the Eugene B. Casey Professor of Laryngeal Surgery at HMS and MGH. His research team is developing new surgical procedures for treating benign and malignant lesions of the larynx, and novel recon-structive techniques for voice loss using a variety of therapies, including chemical, biomechanical and tissue engineering; acoustic and aerodynamic assessments, and high-speed imaging of vocal function.

Elfar Adalsteinsson, PhD, has been pro-moted to Associate Professor of HST and of Electrical Engineering and Computer Science, MIT. He specializes in medical imaging with magnetic resonance, focusing on optimal methods for acquisition, reconstruction and processing of in vivo imaging data.

Sangeeta N. Bhatia, PhD ’97, MD ’99, was promoted to Professor of HST and of Electrical Engineering and Computer Science, MIT. She applies micro- and nanotechnology to tissue repair and regeneration.

Collin M. Stultz, MD, PhD, was promoted to Associate Professor of HST and of Electrical En-gineering and Computer Science, MIT. He applies computational chemistry, signal processing, and basic biochemistry to the understanding of how changes in the structure of large molecules, such as proteins and lipids, influence disease.

HST Welcomes New Staff MembersHST welcomes several new members to its

administrative staff. Sherene M. Aram started as the Division’s administra-tive officer on January 7. She comes to HST from the Center for Biomedi-cal Innovation (CBI) at MIT, where she was the Assistant Director for Finance and Administra-tion. Through her experi-ence with CBI, Aram has seen first-hand the oppor-

tunities and challenges intrinsic to a community similar to HST; she brings a multidisciplinary background that matches the HST phenotype well. A graduate of Wellesley College, she has bachelor’s degrees in astronomy and physics. Her MBA is from Simmons College School of Management. In addition to CBI, her professional experience includes more than a decade at the Polaroid Corporation.

Laurie Ward, formerly the financial ad-ministrator of MIT’s Student Activities Office

(SAO) since 2000, has been appointed Graduate Administrator at HST. At SAO, Ward had managed the financial accounts of several hundred student groups. At HST, she will be responsible for the financing of graduate students by disbursing fellowships as well as re-

search and teaching assistantships. Lynn Hinds started as HST’s new Fiscal

Officer on March 3. Previously she was a budget officer in the MIT Budget Office, and in that role she had first-hand experience with the complexi-ties of HST’s cross-institutional finances. Before joining MIT, Hinds has worked in financial

Sherene Aram

administration for more than a decade at Yale Uni-versity. She holds a BS in accounting from Southern Connecticut State Uni-versity and is currently pursuing her MBA at Southern New Hampshire University.

New Core Curriculum in Biophysics and Clinical Applications of Imaging

As part of a new imaging core curriculum, the Division introduced a new course this spring. Steven Stufflebeam, MD, Instructor in Radiol-ogy at HMS and MGH, and member of the HST affiliated faculty, directs HST 563: Imaging Biophysics and Clinical Applications. This course provides a multidisciplinary look at imaging and an introduction to different modalities of imaging, including MRI, MEG/EEI, PET, CT, molecular imaging, and ultrasound. Laboratory sessions are taught at different imaging centers in the Boston area so that students are exposed to a variety of imaging procedures.

“It truly is a multidisciplinary curriculum,” Stufflebeam said. “To be successful, we need to pull in specialists from clinical sites as well as from academia. This really couldn’t be done without HST.”

Project on Origins of Autism and Dyslexia Funded

John Gabrieli, PhD, the Grover Hermann Professor of HST and Professor of Brain and Cognitive Sciences at MIT, as well as Associate Di-rector of the Martinos Center, is the co-principal investigator of a new project to study the origins of autism and dyslexia. This research will apply recent neuroimaging methods to children. Gabri-eli will lead the dyslexia components.

Suresh Wins Engineering PrizeHST affiliated faculty Subra Suresh, ScD,

Dean of the School of Engineering and the Ford Professor of Engineering at MIT, is the recipient of the 2008 A.C. Eringen Medal. This award from the Society of Engineering Science is in recognition of “sustained outstanding achieve-ments in engineering science.” Suresh has made many contributions to the fields of advanced material, cell and molecular biomechanics and nanotechnology.

HST at AAASThree HST faculty members presented at

February’s annual meeting of the American As-sociation for the Advancement of Science (AAAS) in Boston.

Two participated in the symposium “High-Tech, Low-Cost Medicine: A New Paradigm for Global Health.” Shiladitya Sengupta, PhD, As-

staff photos by Matt Merkes

Vikas Sukhatme

S. G

ilber

t

(continues on page 4)

Laurie Ward

Lynn Hinds

Page 4: ConnectorSpring08 (1)

4 Spring 2008

hst news

required to pursue the idea. That team of mentors will support the research project for its duration by providing advice, con-nections and collaboration.

“The idea of asking HST students to think through this process should result in a better learning experience,” said Farrell in an email interview. His own work focuses on the very real problem of sleep-disordered breathing, an under-recognized but treat-able condition that can lead to hypertension and, in turn, cardiac disease and stroke. Farrell considers it a prime candidate for new research questions.

“If this donation can add just a little further light on this important field, I would be delighted,” he said.

“We are extremely grateful to Peter Farrell for his support of this new initia-tive,” Gray said. “HST students will benefit considerably from a process that explicitly supports and develops their abilities to find and develop new research questions.”

Farrell is founder and CEO of ResMed, a company that develops products for the diagnosis and treatment of sleep-disordered breathing. In 2005 he was named Ernst & Young Entrepreneur of the Year in the Health Sciences category.

— Elizabeth Dougherty

sistant Professor of HST and of Medicine, HMS, BWH, suggested how drugs might be combined so that more than one drug may be delivered in a single dose. Such combinations might include large particles with nanoparticles inside. For example, a chemotherapy drug could include a smaller steroid drug, providing an anti-angiogenesis agent for anti-cancer therapy.Utkan Demirci, PhD, Instructor in HST and in Medicine, HMS, BWH, urged that research be done toward developing simple, robust systems based on technologies such as micro-fluidics, fluorescence and optical devices, inexpensive and easy to use. Examples are drugs that can be delivered in small amounts and blood cell counting systems to measure HIV infections.

A symposium on “Universities Without Walls: Endeavors in Global Education” featured HST Co-Director Martha L. Gray, PhD, on “Inter-institutional Training in the Life Sciences and Engineering.” She characterized HST as a unique collaboration, providing an interdisciplin-ary inter-professional and inter-institutional edu-cation. Gray also described some of the resulting innovations and drew attention to the replication of the HST model around the globe, specifically in India and China.

Happy 50th, EPL!The Eaton-Peabody Laboratory of Auditory

Physiology will celebrate 50 years of research with a symposium and poster session on June 13. Speakers include:

Christopher A. Shera, PhD• , Associate Professor of HST and of Otology and Laryn-gology at HMS and MEEI, on “Cochlear Mechanics and Emissions”Jennifer R. Melcher, PhD• , Assistant Profes-sor of HST and of Otology and Laryngology at HMS and MEEI, on “Imaging Auditory Function and Tinnitus”

For more information, go to research.meei.har-vard.edu/EPL/EPL50.html

Institute Honors Feld with MLK AwardMIT’s Martin Luther King, Jr. Committee

presented one of five Leadership Awards to Mi-chael S. Feld, PhD, Professor of Physics at MIT and member of the HST affiliated faculty.

The MLK Committee cited Feld and fellow recipient Leo Osgood, Jr. for their co-leadership of the MLK Committee over the past decade and their instrumental roles in establishing the MLK Visiting Professor program. Feld is also former chair of MIT’s Equal Opportunity Committee.

Two HST MD Students Win Soros Fellowships

Robert Koffie and Vijay Yanamadala, both in the HST MD class of 2011, have been awarded the 2008 Paul & Daisy Soros Fellowship for New Americans.

Koffie is a MD-PhD student who will soon begin his graduate studies in biophysics. A na-

tive of Ghana who moved to the U.S. in 2002, he graduated from Indiana University with BS degrees in physics and biochemistry.

Yanamadala received his BS degree in bio-chemical sciences and his MA in chemistry, both from Harvard University. He was born in Texas to parents who had immigrated from India.

The fellowships, which includes a $20,000 maintenance grant and tuition grant equal to half of the cost of graduate school, are awarded to indi-viduals who “will make a success of their lives and who will contribute something to this country, in whatever area of endeavor they choose.”

Finkelstein Writes the Book on America’s Prescription Drug Crisis

Stan N. Finkelstein, MD ’95, is co-author of Reasonable Rx: Solving the Drug Price Crisis (FT Press 2008).

According to the publisher, “this book dif-fers from the many other books and articles on this topic to take a longer and deeper look at

the problem of high drug prices. It reviews the history of drug deve lopment , to explain how this window of opportunity was created, describes the industry that transferred new discoveries into drugs that could be swallowed, including how

the government has been involved in this process from its inception. Finally, and most importantly, it presents a plan that could keep this window open for all our fellow citizens.

“By examining recent changes in the phar-maceutical industry in more depth, the authors explain how more radical changes can both reduce prices and improve the flow of new drugs.”

Finkelstein is Senior Research Scientist in the Engineering Systems Division at MIT; Co-Director of the MIT Program on the Pharmaceuti-cal Industry (POPI); Senior Lecturer on Health Care Policy at HMS; and member of the HST affiliated faculty.

Research on Resistant TBLucila Ohno-Machado, MD, PhD, Associ-

ate Professor of Health Sciences and Technology and Associate Professor of Radiology at HMS and BWH, is co-investigator of a study of multi drug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, which has just received a $14 million grant from the National Institutes of Health. This study is very timely: In a survey of over 90,000 TB patients in 81 countries, WHO has just found that levels of MDR TB were far

higher than expected. The survey also found cases of XDR TB, which is virtually untreatable, in 45 countries.

Seeking Nominations for the Next HST Co-Director

A search committee to find a successor for Martha Gray, who is stepping down from the HST Director position at the end of this academic year, is seeking nominations.

The committee, which is headed by HST professor Emery Brown, is looking for a “distin-guished researcher in a field of science, engineer-ing or medicine with demonstrated accomplish-ments in a major leadership role. The Director is responsible for overall Division leadership and administration, and works closely with the HST Director counterpart at HMS. The MIT and HMS Directors of HST jointly oversee a longstanding, multi-institutional program that includes MIT, HMS, Harvard University, several Boston area teaching hospitals, and a number of research centers that, collectively, form a unique collaboration that integrates science, medicine and engineering to solve problems in human health.”

To submit a nomination, please contact Professor Brown, at [email protected].

(continued from page 1)

Peter Farrell

Am

azon

.com

imag

e

Page 5: ConnectorSpring08 (1)

The Connector 5

HST news

The MIT General Clinical Research Center (GCRC) was established in 1964, with grant support from the National Institutes of Health, to provide a facility in which MIT investigators and their collaborators could apply the Institute’s expertise in basic biochemical and biophysical mechanisms to the analysis of normal and patho-logic processes in humans.

MIT’s GCRC was the first federally sup-ported clinical research center located in a uni-versity and not within a hospital, and it remains one of only two or three such centers. It is now formally linked to the Mallinckrodt CRC at MGH and also to HST.

The GCRC especially promotes translational research between leading scientists at MIT and other institutions, and advances patient care by fostering the development of innovative, high-impact ideas or technologies into biomedical treat-ments. As an ambulatory clinical research center, the GCRC provides a wide array of services to investigators including: out-patient beds, routine and specialized nursing care, routine and special-ized nutrition services, assistance with specimen collections and measurements, out-patient subject testing rooms and a core laboratory.

The MIT GCRC also serves as an educa-tional mission for the MIT community by training investigators at every stage of their career. The MIT center currently includes seven subject beds (two infusion rooms), subject lounge, investigator offices and research space, and a research kitchen and dining area. These facilities allow for proce-dures like IV insertion and maintenance, drug administration, bioelectric impedance analysis, high-performance liquid chromatography, mass spectrometry, and measuring bone density, body composition and resting energy expenditure.

Furthermore, because this CRC is not located in a hospital, it aims to enhance community outreach.

Ravi Thadhani and John Gabrieli serve as co-directors of the MIT GCRC. Thadhani directs HST S12, a seminar course conducted at the MIT GCRC aimed at introducing the principles of human clinical investigation to MIT undergradu-ates. This spring semester course, in its fifth year, involves faculty from MGH, MIT and industry. Annual feedback from students and faculty has remained extremely positive. Indeed, graduates from this course have already begun to return to the GCRC and other clinical investigative arenas around Boston to actively participate in clinical research. Thadhani will continue in his role as the course director of HST S12.

Gabrieli is developing research protocols

HST-affiliated GCRC vital for training and research

More than 80 HST graduates and faculty attended the second annual Alumni Association Networking Reception, held on January 28 at Genzyme Cooporation’s headquarters in Cam-bridge.

Joseph Mad-sen, MD ’81, Presi-dent of the Alumni Association, wel-comed the group a n d e x p r e s s e d thanks for the gen-erosity of the Gen-zyme Corporation and the Fleming Foundation. After introducing the members of the

Board of the Association, Madsen presented the new Chair of the HST Advisory Board, Anthony Williams, Esq, Partner at the law firm of Baker and McKenzie, New York.

Martha L. Gray, PhD ’86, who is stepping down as HST Co-Director at the end of this academic year, expressed her appreciation to the alumni for their continuing support. Following Gray was Claude Canizares, Associate Provost of MIT, who stated that MIT rests on the shoulders of its alumni and thanked Gray for her great contributions to the growth and accomplishments of HST. He also invited suggestions to the search committee for a successor.

Next, Irving London, MD, expressed plea-sure at seeing so many alumni present, and gave homage to the effective collaboration of Drs. Gray and Joseph V. Bonventre over the years. London,

Alum networking event looks toward future

Joseph Madsen and Irving London at the alumni networking reception.

photos by John Rich

Anthony Williams

in turn, introduced HST Co-Director David Cohen MD ’87, PhD, attesting to his sterling leadership qualities and long association with HST. Cohen concluded the meeting by expressing his complete confidence in HST’s bright future.

that integrate the use of the MIT GCRC and the Martinos Imaging Center at the McGovern Institute for Brain Research, which is two blocks away from the GCRC.

Approximately 10 to 12 new studies per year are initiated at the MIT GCRC. The following MIT professors have ongoing studies or have directed a study within the last year, utilizing GCRC staff and resources:

Monty Krieger, Biology; Leona Samson, Center for Environmental Health Sciences; Lau-rence Young, HST and Aeronautics & Astronau-tics; Emery Brown, HST and Brain & Cognitive Science; Ed Boyden, Program in Media Arts and Sciences; and Emilio Bizzi, Brain & Cognitive Science.

—Ravi Thadhani and John Gabrieli, with Suzanne Miller, CRC Administrative Officer

Mozelle Soule, GCRC research physician assistant, checks Joann Goggin-Vining’s blood pressure.

Fran Betlyon

Page 6: ConnectorSpring08 (1)

6 Spring 2008

research newsReprogramming Human Cells to Pluripotency

George Q. Daley, PhD, MD ’91, Associate Professor of Biological Chemistry and Molecular Pharmacology at HMS, Associate Professor of Pediatrics at HMS and CHB, and member of the HST affiliated faculty, is senior author of “Reprogramming of human somatic cells to pluripotency with defined factors.”

Embryonic stem cells are pluripotent, i.e., are able to generate all tissues in the organism. Recent work has shown that murine fibroblasts can be reprogrammed by ectopic expression of four transcription factors to yield pluripotent stem cells (iPS). Using these transcription factors (Oct 4, Sox 2, KIf4 and Myc), these authors were able to derive iPS cells from fetal, neonatal and adult primary cells, including dermal fibroblasts isolated from a biopsy of healthy human skin. Only the first two genes were found to be es-sential. However, it must be kept in mind that a significant percent of mice carrying iPS cells have been shown to develop tumors. Thus, this approach is not yet ready for clinical interventions (IH Park et al., Nature 2008; 451:135-6).

Improved Cryopreservation of Single Cells

Utkan Demirci, PhD, Instructor in Medicine and Health Sciences and Technology at HMS, and BWH, is first author of “Cell encapsulating droplet vitrification.” Rapid, reli-able encapsulation of one or a few cells without significant reduction in viability is desirable for tissue engineering, high-throughput screening, clinical diagnostics and therapeutics. Here, a new method is presented which allows vitrifica-tion at low concentration of cryoprotectant. The method was applied successfully to mammalian hepatocytes, fibroblasts and cardiomyocytes, as well as to mouse embryonic and RAJI cells. (Lab Chip 2007; 7: 1428-33.)

Prerequisites for Clinical Use of Nanoparticles

John V. Frangioni, MD, PhD ’94, Associ-ate Professor of Radiology and Medicine at HMS and BIDMC, is senior author of “Renal clearance of quantum dots.” Nanoparticles hold promise for the diagnosis and treatment of disease. However, they also are potentially toxic if they accumulate in the liver, spleen and bone marrow. Furthermore, residual particles might interfere with medical imaging. The authors used quantum dots, metallic semiconducting particles that fluo-resce in blue light, as models for metal-containing nanoparticles. By monitoring these quantum dots in mice and rats, they were able to determine the size requirements and change characteristics for renal filtration and urinary excretion of in-organic, metal-containing nanoparticles. They used organic coatings to prevent absorption of some proteins which could increase the diameter

and prevent renal excretion. Three requirements were proposed for potentially clinically useful nanoparticles: a hydrodynamic diameter <5.5 nm, and/or a formulation with completely non-toxic components, and/or biodegradability to renal clearable components (CH Choi et al., Nat Biotechnol 2007; 25: 1165-70).

Bending of Intervertebral Discs May Induce Cell Injury

Jeffrey C. Lotz, PhD ’88, is senior author of “Biological and mechanical consequences of transient intervertebral disc bending.” To inves-tigate how mechanical loading at levels below those known to cause acute trauma may lead to cellular injury, mouse-tail discs were subjected to static bending for one week and then allowed to recover for 3 weeks and 3 months. The bent discs demonstrated loss of annular cellularity on the concave (compressed) side. Chrondrocyte-like cells were seen within the concave annulus on the recovered discs, with evidence of proliferation at the annulus/endplate interface. In the recovered discs, the annular architecture and biomechani-cal properties did not differ from controls. Thus it was demonstrated that transient compressive stress can induce cellular injury and that recellu-larization is slow in this avascular tissue (C Court et al., Eur Spine J 2007; 16: 1899-906).

Lotz is Professor of Orthopaedic Surgery and Director, Orthopaedic Bioengineering Labora-tory, University of California, San Francisco.

Phagocyte-derived Catecholamines Enhance Acute Inflammatory Injury

Richard R. Neubig, MD, PhD ’81, is co-author of a report with this title, based on an in-vestigation on whether phagocytes are capable of de novo production of catecholamines. Exposure of phagocytes to lipopolysaccharide was found to release catecholamines and induce catecholamine-generating and degrading enzymes, indicating the presence of an intracellular mechanism for the generation, release and inactivation of catecholamines. In two rodent models of acute lung injury, blockade of alpha 2-adrenoreceptors or catecholamine-generating enzymes suppressed lung inflammation, whereas the opposite was observed either for an alpha 2-adrenoreceptor agonist or for the inhibition of catecholamine-degrading enzymes. These studies identify phago-cytes as a new source of catecholamines, which enhance the inflammatory response. (MA Flier et al., Nature 2007; 449: 721-5).

Neubig is Professor of Pharmacology at the University of Michigan and Associate Director of the Center for Chemical Genomics.

Capture of Specific Cells by Cell RollingJeffrey M. Karp, PhD, is senior author and

Ali Khademhosseini, PhD, and Robert Langer,

ScD, are co-authors of “Covalent immobilization of P-Selectin enhances cell rolling.”

Cell rolling along vascular endothelium in viscous shear flow plays an important role in the recruitment of white blood cells to inflammatory sites and in tumor cell metastasis, as well as in homing of hematopoietic progenitor cells after intravenous injection. Cell rolling is regulated by proteins such as P-selectin. In the presence of P-selectin on a vessel wall, sensitive cells will adhere to the wall and roll across it. This report describes chemical methods to immobilize P-selectin co-valently on glass substrates modified by amine, aldehyde, and epoxy. The prepared surfaces were tested in a flow chamber by flowing microspheres functionalized with a cell surface carbohydrate that binds to P-selectin. Effective cell rolling was observed and also confirmed in vitro with isolated human neutrophiles. These results are applicable to the design of therapeutic as well as diagnostic devices for capturing specific cells (S Hong et al., Langmuir 2007; 23: 12261-12268).

Karp is instructor in Health Sciences and Technology and in Medicine at HMS and BWH. Khademhosseini is Assistant Professor of Health Sciences and Technology and of Medicine at HMS and BWH. Langer is Professor of Health Sciences and Technology and Institute Professor at MIT.

Predictors of Bronchopulmonary Dysplasia in Prematurely Born Infants

Isaac S. Kohane, MD, PhD is senior author of “Perturbation of gene expression of the chroma-tin remodeling pathway in premature newborns at risk for bronchopulmonary dysplasia.” One-third to one-half of all infants born before the 28th week of gestation develop bronchopulmonary dysplasia (BPD). This is a cross-sectional study of infants born at less than 28 weeks of gestation (n = 54). Sections of umbilical cord were obtained at birth from 20 infants who later developed BPD and from 34 who did not develop BPD. Infants who subsequently developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways. These findings are consistent with previous investigations implicat-ing inflammatory and bioenergetic processes in prematurity (J Cohen et al., Genome Biol 2007; 8: R210[E pub ahead of print]).

Kohane is the Lawrence J. Henderson As-sociate Professor of Health Sciences and Technol-ogy; Associate Professor of Pediatrics at HMS and CHB; and Director of the Bioinformatics and Integrative Genomics Training Program at HST.

Key to Avian Flu in HumansRam Sasisekharan, PhD, is senior author

and Viswanathan Sasisekharan, PhD, is co-author of “Glycan topology determines human adaptation of avian HSN1 virus hemagglutinin.” This research addresses the question of what de-

Page 7: ConnectorSpring08 (1)

The Connector 7

research newstermines the virulence and transmission of avian flu to humans. Previously, it had been believed that a switch in specificity of avian influenza A vi-ruses’ hemagglutinin (HA) from avian-like (alpha 2-3 sialylated glycans) to human-like (alpha 2-6 sialylated glycans) receptors is associated with ad-aptation to infect humans. This study’s integrated biochemical, analytical and data-mining approach demonstrated that the hemagglutinins from the human-adapted H1N1 and H3N2 viruses, but not H5N1 bird flu viruses specifically bind to long alpha 2-6 sialylated glycans with this topol-ogy. This is thought to explain why H5N1 viruses will not infect humans. The authors express their hope that this new understanding may lead to improved strategies of surveillance and potential vaccines. (A Chandrasekaran et al., Nat Biotechnol 2008; 26: 207-13).

Ram Sasisekharan is the MIT Underwood Prescott Professor of Biological Engineering and Professor of Health Sciences and Technology. Viswanathan Sasisekharan is a visiting scientist at HST.

Abusive Partners’ Health Care ImpairedRobert Sege, MD, PhD ’88, is senior

author of “Abused women disclose partner inter-ference with health care: an unrecognized form of battering.” Over 2,000 female outpatients attending clinics in five different medical depart-ments were surveyed in writing. One in 20 (4.6%) reported interference in health care by a partner. Of the 276 women who had suffered abuse in the past year, 17% reported interference with health care, compared to 2% of women without abuse. About 60% of women with interfering partners reported incomes of less than $20,000, compared with 30.3% of women without interference. Part-ner interference raised the odds of women having poor health (odds ratio = 1.8) (LA McCloskey et al., J Gen Med 2007; 22: 1062-72).

Sege is Associate Professor of Pediatrics at Tufts University School of Medicine, and Chief of General Pediatrics, Floating Hospital For Children, New England Medical Center.

Discovery of MicroRNAs That Suppress Metastasis

Sohail F. Tavazoie, PhD, MD ’03, a post- doctoral fellow at Memorial Sloan-Kettering Cancer Center, New York, is first author of “Endogenous human micro RNAs that suppress breast cancer metastasis.” Authors’ Abstract:

“A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumour growth and proliferation, whereas miR-335 regulates a set of genes whose

collective expression in a large cohort of human tumours is associated with risk of distal metasta-sis. miR-335 suppresses metastasis and migration through targeting of the progenitor cell transcrip-tion factor SOX4 and extracellular matrix com-ponent tenascin C. Expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either microRNA is associated with poor distal metastasis-free survival. miR-335 and miR-126 are thus identified as metastasis suppressor microRNAs in human breast cancer” (Nature 2008; 451: 147-52).

Culture Influences Brain FunctionJohn D. Gabrieli, PhD, the Grover Her-

mann Professor of Health Sciences and Technol-ogy, Associate Director, Athinoula A. Martinos Center for Biomedical Imaging, HST, and Pro-

fessor of Brain and Cognitive Sciences, MIT, is senior author of “Cultural influences on neural substrates of attentional control.”

It has been known that people from East Asian cultural contexts perform better on tasks with interdependent (relative or contextual) demands than on those with independent (abso-lute or contest-independent) demands, whereas people from Western cultural contexts perform better on tasks with independent demands than on tasks with interdependent demands.

This study used functional magnetic reso-nance imaging (fMRI) to examine where in the brain cultural experience alters processing of simple perception (making judgments regarding line length) in conditions involving independent (relative) judgments. The subjects were ten East Asians recently arrived in the USA and ten Ameri-

(continues on page 10)

Using Light for Minimally Invasive Screening of CancerVadim Backman, PhD ’01, Professor of Biomedical Engineering at Northwestern Uni-

versity in Evanston, Illinois, is senior author of “Optical markers in duodenal mucosa predict the presence of pancreatic cancer.”

The authors report the application of their newly developed optical techniques, four-dimensional elastic light-scattering fingerprinting (4D-ELF) and low-coherence enhanced backscattering (LEBS) spectroscopy to the minimally invasive diagnosis of carcinoma of the pancreas. Endoscopically and histologically normal-appearing periampullary duodenal biopsies were obtained from 19 patients with cancer of the pancreas and compared with those obtained from 32 control subjects. The 4D-ELF and LEBS-derived optical markers from normal-appearing periampullary duodenal mucosa discriminated between cancer patients and controls with a sensitivity of 95% and a specificity of 91%. Thus, optical analysis of histologically normal duodenal mucosa promises to provide an accurate, minimally invasive means of risk assessment, which allows determination of which patients require intensive radiologic assessment (Y Liu et al., Clin Cancer Res 2007; 13: 4315-6).

Nicolle R

ager Fuller / National Science Foundation

Light is showing promise as a tool for cancer detection.

Page 8: ConnectorSpring08 (1)

8 Spring 2008

faculty profile

Cryobiologist, tissue engineer, bioMEMS researcher. Cancer detection, reproduc-tive medicine, HIV T-cell tracking.

Professor of Surgery, co-founder of the Center for Engineering in Medicine, founder of the MGH BioMEMS Resource Center. If he put his protean mind to it, Mehmet Toner could probably leap tall buildings in a single bound — or at least untangle the biology of how Superman does it.

Toner is Professor of Surgery (Biomedical Engineering) and Health Sciences and Technol-ogy at HMS and MGH. Born and raised in Istanbul, he studied mechanical engineering at the Istanbul Technical University before coming to MIT. As a master’s student in MIT’s Depart-ment of Mechanical Engineering, he recalls that he had no background and “no interest” in biology. He didn’t even know biomedical engi-neering existed until a professor at Yale, where he also applied for graduate school, told him he should go into this new field which was starting up at MIT.

“I started learning about it and I loved it. I learned how one can be effective at the interface of medicine, and I just knew this was what I

wanted to do,” he says.Toner’s undergraduate and master’s work

gave him a strong background in thermal sci-ences, and his PhD thesis was related to low temperature biology — how to take living systems and put them in suspended animation at cryogenic temperatures. He graduated from MEMP in 1989.

“It was a great combination of engineering, physical science and biology, as well as applica-tions. I was very interested in the applications of a number of different fields: tissue engineering, stem cell biology, reproductive biology, long-term storage of living cells and living tissues.”

A common thread in all his research, he says, captures the essence and nature of the HST program.

“All the problems I work on are really both multidisciplinary — which means you need colleagues who can help you — and quan-titative, for which you have to apply quantita-tive tools to get to the solution of a problem — sometimes through theoretical work, sometimes through modeling, sometimes experimentally.”

He talks about how the MEMP program today is different from the one that he went

through two decades ago. “I would never make it into an HST class

today,” he says. “I had a hardcore engineering background, and that was the phenotype at the time I applied. HST took students with mini-mal exposure to bio and exposed them through the program. In the ’80s, most students were like me — with little exposure to biology and chemistry.”

He still remembers his first HST lecture. “I had no knowledge of cells at the time.

I walked into the first day of pathology a little late, the instructor was lecturing, and there was a beautiful, colorful slide. I thought it was a painting, but it was actually a cell! That’s when I knew it wasn’t going to be easy.

“There’s been a big change between students then and the students who come to the program now. They are more mature in their exposure to life sciences, and they make a com-mitment to the field when they are younger. That’s a change that’s been happening over the past fifteen years.”

More recently, he has seen another wave of change with the growth of departments of biomedical engineering. The first stage of HST

Toner Talks

aboutMEMP then and today, his two families, and the lab on a chip

by Catherine Modica

Page 9: ConnectorSpring08 (1)

The Connector 9

PhD students were hardcore engineers; those in a second stage had more life science back-ground; and in this third stage, they are more interdisciplinary.

Toner’s observations of the current “third wave” of HST students come not only from training students in his lab and from serving as an academic advisor, but from serving, for the past four years, as chair of HST’s PhD admis-sions committee. Possessing a combination of kindheartedness and tough-mindedness, he was a perfect choice to take on the chairmanship when Roger Mark stepped down from the posi-tion in 2004. Each year, visiting candidates hear Toner declare that he has “the best job at HST.”

“I really mean that about admissions,” he says. “It’s crucial because you’re building the family. Of course we have an army of people helping us make the decisions, which is espe-cially important during times, like the present, when there are major changes in one of the programs. [This year, for the first time, most MEMP students will be admitted directly to HST, without a traditional collaborating depart-ment, and will eventually be qualified for their PhD work by HST].

“It’s been very exciting, both because the quality of the students is so great, and because we are bringing good people into the family — people who will be good contributors.”

In addition to his tending of the HST family, Toner invests a great deal of time and energy into his own family. He and his wife, who is also from Turkey and whom he met in Washington, D.C., have two sons who will soon turn 14 and nine, respectively.

“Our family life is very important to me,” he notes. “Our ties to Turkey remain very strong: our parents visit back and forth, our family spends each summer in Turkey, and our kids are fully bilingual. We love to travel togeth-er but also just to spend time at home together. I need to travel a great deal for my work, both to present my own work and to meet people to talk about the HST program, but I try to do my traveling only on weekdays, and to keep my weekends free so that I can be at home.”

Toner notes that there are three different projects or periods in his work of which he is particularly proud. First, his PhD thesis on cryobiology: “I took a difficult problem and tried to understand it at a fundamental level: when you freeze a cell, how does ice form inside it? I was able to take this challenging problem and do a good enough job with it that it’s been helpful to other people who’ve worked on the problem after I did — some trying to demon-strate that I was right, but others trying to prove that I was wrong!” This problem sparked quite a bit of fire in the field, he says, and attracted a number of good minds to work on it.

Known for being an active and engaged mentor, it is no surprise that the students he has nurtured are another one of his sources of pride.

“When I first got into tissue engineering projects, Sangeeta [Bhatia, MD, PhD, now a

Professor in HST and MIT’s Department of Electrical Engineering and Computer Science] joined the lab and did her PhD in liver tissue engineering. She’s just a superstar, and I’m proud that I was part of her experience. I tend to take credit for her work,” he jokes, “but in truth, I learned more from her than the other way around.”

Most recently, his work in cancer research has been a source of great excitement.

“I think it’s a true breakthrough, and in a way it feels similar to how I felt about my PhD work, in that previously there was consensus in the general field. In this case, the consensus was that cancer kills you through the spreading of tumors powered by circulating tumor cells, but that the number of those cells, which were not removed by the immune system before they could be found, was too small to be useful in diagnostic work. My idea was that the tools we had weren’t sensitive enough to find those extremely rare circulating tumor cells.”

In response, Toner and his colleagues recently designed the CTC-chip, a microfluidic platform — or “lab on a chip” — that, using thousands of microscopic posts coated with epithelial cell adhesion molecule antibodies, can sort out circulating tumor cells from peripheral blood. As a result, many more of these circulat-ing tumor cells, which comprise as little as only one to 10 cells per milliliter of blood, can be isolated than had ever been possible before.

“With this new technology, we can locate them in an order of magnitude that’s totally dif-

HST GRADUATIONJune4,2008•9a.m.to2p.m.

HarvardClub•374CommonwealthAve.,Boston

Keynote Speaker

Irving M. London, MDFounding DirectorHST

Professor of Biology, EmeritusMIT and HST

Professor of Medicine, EmeritusHMS

Jim H

arrison

ferent from what we could previously do. We’re turning the field upside down by showing that these cells are much more common than we had thought. I can’t wait for the developments over the next five years, because I believe the role of circulating tumor cells is going to become enor-mously important both in cancer management and in cancer diagnosis.”

He expects that the CTC-chip will be able to be used to monitor the tumor loads of individual patients during treatment.

“I use an analogy that clinical medicine is like a jail: everybody is wearing the same uniform, and depending on what you did you fall into a particular stratification in which everyone is treated in the same way. We do the same thing in medicine, treating people based on a population average. But this technology will provide us the ability to monitor the tumor load of individual patients during treatment. The idea of being able to see whether they’re responding to treatment and to make clinical decisions based on the patient’s individual response — that’s extremely powerful. If a patient is in remission, you’ll be able to screen early for possible relapses.

“Of course early detection is very impor-tant, but applications for use after diagnosis, if they can be individualized to the patient, can be equally important.

“We now know much more about the molecular aspects of cancers and how they respond to treatments. Basically,” he says with clear excitement, “we’re gaining a window into the biology of a tumor.”

Page 10: ConnectorSpring08 (1)

10 Spring 2008

HST students, alumni,

faculty and staff are invited

to submit articles on

educational, research or travel

experiences for consideration

for publication in

The Connector.

Please submit to the Editor:

walter_abelmann@

hms.harvard.edu

WRITERSWANTED

cans of Western European ancestry. In each group, activation in frontal and parietal brain regions, known to be associated with attentional control, was greater during culturally non-preferred judgments than during culturally preferred judg-ments. The authors conclude that “these findings show how experience in and identification with a cultural context may shape brain responses as-sociated with attentional control even during a relatively simple and abstract task” (T Hedden et al., Psychol Sci 2008; 19: 12-17).

Therapeutic Angiogenesis for Myocardial Ischemia

Joanna J. Wykrzykowska, MD ’02 , Clinical Fellow in Medicine, HMS, BIDMC, is co-author of “Skin derived micro organ autotrans-plantation as a novel approach for therapeutic angiogenesis.”

Many patients with coronary heart disease have regions of ischemic myocardium unre-sponsive to conventional therapy and thus are potential candidates for therapeutic angiogenesis. Clinical trials with single growth factors have not been promising. Here, a novel approach to improve myocardial perfusion was effective in a porcine model of ischemia. This involved small skin fragments, termed skin microorgans (SMOs) to promote the development of collateral blood vessels. These SMOs transcribe tissue-specific genes, including an array of angiogenic fac-tors. Eighteen pigs underwent placement of an aneroid constrictor on the proximal circumflex coronary artery. After three weeks, split-thickness skin biopsies were obtained and the pigs were randomized to lateral wall implantation of either SMOs or controls. Three weeks after treatment, SMO implants were associated with significant improvement of perfusion of the lateral wall during pacing, neovascularization was increased, and increases in VEGF and CD31 expression were documented in the ischemic areas of treated animals (P Voisine et al., Am J Physiol Heart Circ Physiol 2008; 294: H213-9).

Progress toward an HIV vaccineEllis L. Reinherz, MD ’75, Professor of

Medicine, HMS, BWH, DFCI, is senior author of “HIV-1 broadly neutralizing antibody extracts its Epitope from a Kinked gp41 ectodomain region on the viral membrane.”

Vaccines against the human immune de-ficiency virus-1 (HIV-1), to be effective, must provide broadly neutralizing antibodies (BNAbs) to prevent entry of the HIV retro virus into T cells to block viral replication, as well as proviral integration into the host genome. The most broadly BNAbs against HIV-1 strains target the membrane-proximal ectodomain region (MPER) of viral gp-41. The authors studied the structure of MPER in the lipid environment by a combination of magnetic resonance, electron paramagnetic resonance and surface plasmon

resonance techniques. The findings “provided a structural rationale both for how BNAbs func-tion to block HIV-1 infection and for improving HIV vaccine design to elicit them (ZY Sun et al., Immunity 2008; 28: 52-63).

Repair of Ischemic Injury of the KidneyJoseph V. Bonventre, PhD, MD ’76, the

Robert H. Ebert Professor of Health Sciences and Technology and of Medicine at HMS and BWH, and Director of the Renal Division at BWH, is senior author of “Intrinsis Epithelial Cells Repair of the Kidney after Injury.”

The kidney has the capacity to repair acute renal injury by means of a rapid proliferative cellular response. This research investigated the origin of the cells that replace injured tubular epi-thelia. Transgenic mice were generated in which 94% of tubular epithelial cells, but no interstitial cells, were labeled with either βgalactosidase or red fluorescent protein (RFP).

Two days after ischemia-reperfusion injury, 50.5% of epithelial cells co-express Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. These re-sults indicate that regeneration by surviving tubu-lar epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney. This information may lead to new therapeutic strategies (BD Humphreys et al., Stem Cell 2008; 2: 1-8).

Pathophysiology of Vaso-occlusion in Sickle Cell Disease

Sangeeta N. Bhatia, PhD ’97, MD ’99, and David T. Eddington, PhD, are co-authors of “Sickle cell vaso-occlusion and rescue in a micro fluid device.” This study of the pathophysiology of vaso-occlusion by sickle cells, using an artificial microfluidic environment, demonstrates that it is possible to evolve, control and inhibit the col-lective vaso-occlusive or jamming event in sickle cell disease. Using a combination of geometric, physical, chemical and biological means permit-ted quantification of the onset of a jamming event as well as its dissolution. Polymerization and melting of the oxygen-dependent sickle hemoglobin sufficed to recreate jamming as well as rescue. The authors conclude that their results provide “a potential tool for optimizing and indi-vidualizing treatment and identifying therapies” (JM Higgins et al., Proc Natl Acad Sci USA 2007; 104: 20496-500).

Bhatia is Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT. Eddington was a postdoctoral fellow at HST.

Statin-Induced Myopathy ElucidatedVikas P. Sukhatme, MD ’79, PhD, is

research newsco-author of “The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity,” a collaborative study of BIDMC, the National Research Institute of Fisheries Sci-ence in Yokohama, Tokyo University Japan, the Schepens Eye Institute, HMS, the Department of Cell Biology at HMS, and Scripps Mercy Hospital in San Diego.

Statins, prescribed widely for hypercholes-terolemia, are known to be associated with muscle pain. In one in 10,000 patients this may be as-sociated with rhabdomyolysis, which is occasion-ally fatal. This is a report of studies in zebrafish embryos, in vitro murine skeletal muscle cells, in humans with statin myopathy, and in cultured mouse myotubes. Lovastatin induced the expres-sion of atrogin-1, a key gene involved in atrophy of skeletal muscle. Induction of atrogin-1, was associated with morphological changes in muscle fibers. Knockdown of atrogin-1 in zebrafish em-bryos prevented lovastatin-induced muscle injury. Over-expression of PGC-1 alpha, a transcrip-tional coactivator, was demonstrated to prevent lovastatin-induced muscle damage (J Hanai et al., J Clin Invest 2007; 117: 3940–3951).

Sukhatme is the Victor J. Aresty Professor of Medicine at HMS and BIDMC, and Chief of the Renal Division at BIDMC.

Page 11: ConnectorSpring08 (1)

The Connector 11

alumni news1970s

The Reverend Ray Hammond, MD ’75, was the keynote speaker at MIT’s 34th annual celebration of the life and legacy of Martin Lu-ther King, Jr. on February 21. Hammond is the founding pastor of the Bethel African Methodist Episcopal Church in Boston, as well as the chair and co-founder of the Ten Point Coalition, an ecumenical group of clergy and lay leaders work-ing to prevent violence.

1980s

Robert A. Star, MD ’80, has been named director of the Division of Kidney, Urologic and Hematologic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH. He had been acting director of the extramural research division since September 2006. As division director, Star will oversee a $400 million program of grants and contracts. His own innovative, translational research on early identification, prevention and pre-emption of sepsis and acute renal injury will continue.

Patricia A. Wallike, MD, PhD ’80, has been appointed Chief Medical Officer of Oxi-gene, a biopharmaceutical company in Waltham, Mass., that’s developing treatments for cancer and eye diseases.

T. Jake Liang, MD ’84, has been elected to membership in the Council of the American Society for Clinical Investigation for 2007-08. He is Chief of the Liver Disease Branch, NIDDK, NIH. Liang’s research involves hepatitis B and C viruses, which are the leading causes of chronic liver diseases in the world. Other research efforts are directed at molecular strategies for vaccine and antiviral development, and animal models of viral hepatitis.

Peter Diamandis PhD, MD ’89, Founder, Chairman and CEO of the X-Prize Foundation, delivered the 2007 Lovett C. Peters Lecture in Public Policy at the Boston Harbor Hotel on November 13, 2007, under the title “Eyes on the X Prize; Can a Competition Change the World?” He offered his thoughts on how mega-prizes can help solve seemingly intractable problems.

This lecture was sponsored by the Pioneer Institute for Public Policy Research and its Shamie Center for Better Government.

1990s

George Q. Daley, MD ’91, is the new president of the International Society for Stem Cell Research, an independent, nonprofit group formed in 2002. Daley, a hematologist, is also

He is also a Clinical Instructor in Neurol-ogy, at HMS and MGH, HST. He has previously authored another book: The Memory Cure: New Discoveries on How to Protect Your Brain Against Memory Loss and Alzheimer’s Disease (McGraw-Hill 2004).

Jack Tsao, MD ’97, PhD, was promoted to Associate Professor of Neurology at the Uni-formed Services University. He continues to do research on phantom limb pain and nerve degen-eration. His wife, Joan, an HMS alumna, finished her pediatric NIH fellowship and is staying on at NIH to continue her research on obesity.

Matthai Mammen, MD ’98, PhD, co-founder of Theravance Inc., in South San Fran-cisco, has been appointed Senior Vice President for Research, effective in January 2008. He will be responsible fore the company’s research strategy and drug discovery activities.

2000s

Joseph W. Carlson, MD ’03, is now a Spe-cialist Physician in the Department of Pathology at Karolinska University Hospital in Stockholm, Sweden.

Karen Taraska Hastings, MD ’00, PhD, writes, “I completed my dermatology residency and immunology post-doctoral research at Yale University. A year and half ago, I accepted a tenure-track assistant professor position as a founding faculty member of the new medical school track at the University of Arizona, in partnership with Arizona State University in Phoenix. My research combines my clinical and basic science interests as I explore the immune recognition of melanoma antigens. I co-direct and teach the immunology, hematology and cancer curriculum for the first and second year medical students.

“On a personal note, Keith Hastings, who was attending Harvard Business School while I was completing my MD-PhD, and I were married almost five years ago, and we have a one-year-old son, Colin.”

Chris K. Varma, PhD ’05, joined Flagship Ventures, a venture capital firm in Cambridge, Mass., as Partner in 2007. He focuses primarily on Life Science investments. Previously, he was with Novartis, where he was a director in phar-maceutical sales.

associate director of the Stem Cell Program at Children’s Hospital Boston.

Pedro E. Huertas, MD, PhD ’93, has been named Chief Development Officer at Advanced Cell Technology in Worcester, Mass., in charge of programs to create novel therapeutics using stem cells. He holds appointments at McLean Hospital, MGH, and Harvard University Health Services.

Alice W. Flaherty, MD, PhD ’94, is the author of The Luck of the Loch Ness Monster: A Tale of Picky Eating (Houghton Mifflin 2007). The book, about a girl who tosses her dreaded morn-ing oatmeal overboard (which is then gobbled up by a hungry sea worm that grows to enormous proportions), is aimed at children age 4-8.

She has also written books on neurology, the most recent one being The Midnight Disease: The Drive to Write, Writer’s Block, and the Creative Brain (Houghton Mifflin 2004). Flaherty is As-sistant Professor of Neurology at MGH.

Majid Fotuhi, PhD, MD ’97, is the author, along with The New York Times, of Crosswords to Keep Your Brain Young: The 6-Step Age-Defying Program (St. Martin’s Griffin 2008). Fotuhi is Director of the Center for Memory and Brain Health, Life Bridge Health and Spine Institute at Sinai Hospital of Baltimore.

Amazon.com images

Page 12: ConnectorSpring08 (1)

12 Spring 2008

The Harvard-MIT Division ofHealth Sciences and Technology77 Massachusetts Ave., E25-519Cambridge, MA 02139 USA

Non-ProfitOrganizationUS Postage

PAIDCambridge, MA

Permit No. 54016The Harvard-MIT Division ofHealth Sciences and Technology77 Massachusetts Ave., E25-519Cambridge, MA 02139 USA

Non-ProfitOrganizationUS Postage

PAIDCambridge, MA

Permit No. 54016

MEMP students give Introduction to Clinical Medicine and Medical Engineering course (HST 201) a hearty thumbs up. The course, directed by Valerie Pronio-Stelluto, MD (far right, front row), takes place every year at Mount Auburn Hospital in Cambridge.

Thumbs up for Intro to Clinical Medicine

Phot

o co

urts

y Va

leri

e Pr

onio

-Ste

lluto

, MD