The Connector
Winter 2007-08
newsletter for graduates, students, faculty and friends of the Harvard-MIT Division of Health Sciences and Technology
HST FORUM
The National Institutes of Health have awarded HST faculty member Emery N. Brown, MD, PhD, one of 12 prestigious 2007 NIH Director’s Pioneer Awards. The award provides winners with $2.5 million over five years to support their highly innovative and potentially transformative early stage research. Winners are characterized by their extraordinary creativity and their pioneering approaches to medical research. With the award funding, Brown, Professor of HST and Computational Neuroscience at MIT and MGH, and Professor of Anaesthesia at HMS, plans to apply the tools of systems neuroscience to the question of how anesthesia works. “While the practice of anesthesia is very safe, the way the drugs work is still a mystery,” said Brown. This novel approach to studying anesthesia will combine his clinical work in anesthesiology with neurophysiological experiments, use of new signal processing algorithms for data analysis, and mathematical modeling of neural circuits under general anesthesia. Brown proposes to study the five “behaviors” that characterize patients under anesthesia — loss of consciousness, a lack of pain, amnesia, immobility, and stability — using systems neuroscience tools such as fMRI and multielectrode recordings. These tools will help him examine the brain activities behind these behaviors the same way neuroscientists do. Adding anesthesia into the mix
Thursday • 4/10/2008 2 – 7 pm New Research Building Elements Cafe, HMS 77 Avenue Louis Pasteur
hst.mit.edu/forum
will allow him to see how these activities change under the influence of anesthetic drugs. Most studies of anesthetic drugs today focus on molecular biology to determine how the drugs interact with different receptors in the brain. But this type of research doesn’t explain the whole story of how these interactions lead, for example, to a loss of consciousness. In his new line of investigation, Brown will explore this question of how these molecular changes in specific brain areas translate into behavioral changes. Brown’s findings may eventually lead to safer and more effective anesthetic drugs. “Because these drugs act in areas where we don’t need them, we end up with side effects,” said Brown. For instance, an anesthetized patient stops breathing, plus his blood pressure and heart rate drop. For patients with health problems, these side effects can be very serious. With a better understanding of how the anesthesia suspends consciousness, pain and other behaviors, it may be possible to target drugs so they affect only the desired neural systems. Brown credits HST and relationships with MIT’s Brain and Cognitive Sciences department and MGH for creating an environment where this kind of multi-disciplinary, innovative research is both possible and probable. “We are optimized to do it here,” said Brown. With the combined resources at MGH, the Athinoula A. Martinos Center for Medical Imaging,
HST file photo
Emery Brown wins NIH Pioneer Award
Emery Brown
and BCS, “I can just walk down the hall and say, ‘Let’s do an anesthesia experiment,’” said Brown. Everything he needs is already there. — Elizabeth Dougherty
Gray to step down as HST director After 12 years of leading HST, Martha L. Gray, PhD, will step down as Director at the end of this academic year. During the years of Gray’s leadership, HST has undergone several fundamental transformations. She was instrumental in turning a small, voluntary faculty into a structured and defined community of over 60 dedicated and bonafide HST faculty members. She expanded the Division’s academic programs to include novel approaches to educating biomedical innovators, such as the Biomedical Enterprise Program (BEP) and the Graduate Education in Medical Science (GEMS) program. Gray also expanded HST’s community by shepherding the creation of HST’s BioMatrix mentoring program for MIT undergraduates, its Alumni Association and its Advisory Board
and Council. One thing that all of these transformations have in common is an emphasis on building connections between people. Through her spirited and steady outreach, Gray personifies HST’s philosophy that puts all professions and disciplines on — as she is fond of saying — “equal footing.” Because of her efforts, HST is now a community that holds tremendous potential for synergetic and rewarding connections. Although she’s stepping down, she’s not stepping out. Gray will continue to work with HST as a faculty member, scientist, mentor, alumna (she graduated from MEMP in 1986), and a champion of HST’s mission and initiatives. A fuller perspective and appreciation of the Martha Gray years is planned for a later issue. — Elizabeth Dougherty
hst news HST by the numbers 37
years old
64
faculty
422
students
1,267
alumni and alumnae
70
US institutions with HST alumni/ae on the faculty
75%
proportion of HST alumni/ae who hold faculty appointments
about 20%
proportion of HST students in each HMS graduating class
about 40%
proportion of the Honors in a Special Field awards given to HST students at each HMS graduation
HST students by degree program SM (52) MD (101)
PhD (179) MD/PhD (90)
MIT Visiting Committee highlights faculty, students Chartered by the MIT Corporation, Visiting Committees assess departments and divisions across MIT every two years. The most recent HST Visiting Commitee meeting took place on November 14 and 15, just as the renovations to E25 were wrapping up and HST faculty were preparing to move into their new laboratories. The meeting consisted of a busy agenda, which highlighted multiple facets of HST and was masterfully orchestrated by Mark Dávila. Martha Gray opened with a presentation that enumerated the impressive growth and expansion of HST, particularly over the past decade. David Cohen then offered a view of the opportunities and challenges for HST during the coming years. This was followed by a session in which Lee Gehrke, Brett Bouma and Roger Mark discussed the numbers and diversity of our faculty. Next, Jeffrey Karp provided an overview of BioMatrix and its role in mentoring throughout the MIT community. Julie Greenberg discussed the new Graduate Education in Medical Sciences program; the session ended with a panel discussion highlighting students Anna Morys, Keron Lezama and Michael Goldberg. Laurence Young presented an overview of the bioastronautics training program. The first morning concluded with presentations on the Biomedical Enterprise Program by BEP faculty Ernst Berndt and Fiona Murray, student Brian L. K. Miller as well as Brian Pereira, a member of the HST Advisory Board. After a luncheon with students and meetings with faculty, the Visiting Committee was treated to presentations by faculty and students from each of six research “nuclei” in a session moder-
The Connector Editor Walter H. Abelmann, MD Managing Editor/Designer Becky Sun
21%
12% 24%
43%
Editorial Assistants Georgia Santander, Fran Betlyon Contact Information Harvard-MIT Division of Health Sciences and Technology 77 Massachusetts Ave., E25-519 Cambridge, MA 02139-4307 P: (617) 253-4418 F: (617) 253-7498 E: hst@mit.edu http://hst.mit.edu
ated by Rick Mitchell. Bruce Rosen and student Peng Yu discussed research at the HST Athinoula A. Martinos Imaging Center. Next, Bouma and student Brian Goldberg provided a sampling of their work at the Wellman Center for Photomedicine at MGH. Shiladitya Sengupta and student Stephanie Piecewicz offered a view of the HST Center for Biomedical Engineering at BWH. This was followed by Vikas Sukhatme from BIDMC. The Children’s Hospital Informatics Program was masterfully represented by Peter Park and Blanca Himes, and Charles Liberman and Jocelyn Songer concluded with a description of their research at MEEI. The afternoon concluded with a presentation from Jennifer Melcher and a keynote address by Emery Brown on his research on general anesthesia, which was recently recognized by an NIH Pioneer Award (see page 1). The second day featured a discussion of the HST in India initiative by Sengupta, who provided an overview of the vision for this exciting endeavor and highlights from student clinical rotations in India that are already underway. The program ended with a wonderful presentation from a special visitor, Raghunath Anant Mashelkar, former Director General of the Council of Scientific & Industrial Research in India, who delivered a powerful message concerning the healthcare challenges and opportunities in India. The members of the Visiting Committee expressed great enthusiasm for the achievements and promise of the diverse group of dedicated faculty, students and staff who contribute to the success of HST! — David E. Cohen, MD, PhD, Co-Director, HST
Volume 22 • Number 1 Editorial Board
Pavan Cheruvu (MD ’09) Patricia A. Cunningham Elizabeth Dougherty Lisa E. Freed, MD, PhD ’88 Robert S. Lees, MD Pamela McGill Catherine Modica Arvind Ravi (MD ’10) Konstantina Stankovic, PhD ’98, MD ’99 Steven M. Stufflebeam, MD ’94 James C. Weaver, PhD Peter I-Kung Wu (MEMP)
Ex officio
David E. Cohen, MD ’87, PhD Martha L. Gray, PhD ’86
The Connector is a quarterly publication of the 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.
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Winter 2007-08
hst news Promotions Keith Quenzel
Two members of the HST affiliated faculty have been appointed to full professorship at HMS. Jeffrey Cooper, PhD, Clinical Professor of Anesthesia at MGH, is Director of Biomedical Engineering for the Partners HealthCare System and Executive Director of the Center for Medical Simulation, which he founded in 1994 as a means for education and research in preventing and managing critical events. Jeffrey Macklis, MD ’84, Professor of Surgery and Professor of Neurology at MGH, is CoDirector of the Regeneration and Repair Program at the Harvard Center for Neurodegeneration and Repair, as well as Director of the MGH-HMS Center for Nervous System Repair, and Program Head, Neuroscience/Nervous System Diseases, at the Harvard Stem Cell Institute.
IEEE honors Roger Mark The IEEE Board of Directors named Roger G. Mark, MD, PhD, to be an IEEE Fellow, the Institute’s most prestigious honor, in recognition of his development of physiologic signal databases and automated arrhythmia analysis.
Innovation Honors
Donna Coveney/MIT
Hugh M. Herr, PhD, Associate Professor of HST, Assistant Professor in Media Arts and Sciences at MIT, and Director of the Biomechatronics Groups at MIT, has won two awards for innovative inventions. He received the 13th annual $250,000 Heinz Award for Technology, the Economy and Employment for “breakthrough innovations in prosthetics and orthotics.” Time took notice of Herr’s work too and named his robotic ankle one of the magazine’s best inventions of 2007. Time also recognized Dava Newman, PhD, HST affiliated faculty and Professor of Aeronautics and Astronautics at MIT. Her prototype BioSuit, designed to allow superior mobility when humans eventually reach Mars or return to the moon, was one of 2007’s best inventions under the Space category.
Collin Stultz, Rick Mitchell and Matthew Frosch chat during the annual HST Faculty Poster Session held September 28 at the Courtyard Café at HMS. More than 150 students, faculty and alumni attended. The session allowed faculty members to showcase their research and attract HST students to their laboratories. There were 35 posters, presented by faculty at HMS, affiliated hospitals and MIT, covering a wide spectrum of basic and clinical research.
Stultz appointed W.M. Keck Chair Collin M. Stultz, MD ’97, PhD, Assistant Professor of Health Sciences and Technology and Assistant Professor of Electrical Engineering and Computer Science at MIT, has been appointed to the W.M. Keck Career Development Professorship at MIT for a three-year term.
Biomaterials Surgical Video Library Jeffrey M. Karp, PhD, newly appointed Instructor of Medicine in HST and Director of the Laboratory for Advanced Biomaterials and Stem-Cell-Based Theraputics at BWH, has created a downloadable Biomaterials Surgical Video Library for the Society for Biomaterials. Lectures and Seminars, as well as videos of operations are presented. The latter include Total Knee Arthroplasty, Angioplasty and Mitral Valve Repair. Access via lectures.biomaterialsvideos.org. Ali Khademhosseini, Assistant Professor of Medicine at HST, won first prize in the doctoral thesis category of the 2007 BMW Science Award competition. The award was presented December 6 during a ceremony at the Deutsches Museum in Munich. His 2005 dissertation, based on research in the Langer Laboratory at MIT, focused on miniaturizing tissue cultures by means of micro and nanotechnology.
Brown is elected Fellow in two societies
Dava Newman in a Bio-Suit
Emery N. Brown, MD, PhD, Professor of Health Sciences and Technology, Professor of Anesthesia at HMS and MGH, and Professor of Computational Neuroscience at MIT, has been
elected a Fellow in the American Association for the Advancement of Science as well as the Institute of Electrical and Electronics Engineers.
Amadio is bioethics fellow Jordan Paul Amadio, a student in the HST MD program as well as at Harvard Business School, has been selected as one of nine 2007-08 student fellows at the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics. He will focus on the bioethical implications of his research in neuroscience.
HHMI appoints Daley as researcher George Q Daley, MD ’91, PhD, 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, has been appointed as patient-oriented researcher by the Harvard Hughes Medical Institute. This program, begun in 2002, is aimed at physician-scientists who divide their time between research and patient care, translating basic scientific research into treatments.
Sasisekharan wins Thai award Ram Sasisekharan, PhD, Professor of Biological Engineering and HST, is one of four recipients of the 2007 Princess Chulabhorn Gold Medal. This award honors world-renowned individuals or organizations that have provided outstanding support for the activities of the Thailand-based Chulabhorn Research Institute, as well as important support for the advancement of science in developing countries. The Connector
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hst news Health, sports and technology make for a successful fundraising event
Photo courtesy The Red Sox
Photo courtesy Fenway Park
For the more than 200 people who attended HST’s second annual fundraiser on September 24, few will soon forget it. The evening of “Health, Sports and Technology at Fenway Park” began on the Green Monster, where HST fans sat in the otherwise empty stadium with burgers and beer and took in the romance of the nation’s oldest ballpark. The event, presented by HST’s Alumni Association and Advisory Board and Council, raised over $100,000 for student support and featured a star-studded lineup of speakers. The first one, Joe Castiglione — otherwise known as “the voice of the Red Sox” — greeted HST supporters with a warm welcome. With his voice still echoing in their heads, the group filed into the State Street Pavilion for dinner, slowed by groups stopping for a last photo or glimpse of the park. HST Associate Director Rick Mitchell, the evening’s emcee, turned the crowd’s attention to what drew them all together: HST students. “They are the best and the brightest,” Mitchell said, “but what impresses me most is their drive, intellectual curiosity and their generosity of spirit.” Over the last five years, the resources required to support HST students has more than doubled. In such times, the Division is grateful for the support of donors and friends. HST alumnus and Alumni Association President Joseph Madsen followed with thanks to the event’s sponsors, particularly noting Servier and InfoSciTex, the Cy Young Sponsors. HST Advisory Board Chair Tony Wil-
Fenway Park and its famous left field wall, also known as the Green Monster
liams then introduced Stuart Hershon, MD, the Yankees’ team physician. Hershon turned boos to cheers by pointing out that the Yankees had lost earlier that day. He went on to marvel at medical progress and the promise of new technologies. Madsen then introduced Art Day, MD, the BWH neurosurgeon who shared a personal story about Baseball Hall of Famer Ted Williams. Next, HST Directors Martha Gray and David Cohen honored Joseph Ciffolillo, the first chair of the HST Advisory Board (from 2000 to 2002), with the MVP Award. During his tenure, the board grew from an informal 14-person group to a 40-member board and council. His guidance has been instrumental to HST, and he offered this advice: “Continue to support HST, continue to focus and don’t lose the excitement.” No two better speakers could have followed Ciffolillo’s advice. HST faculty member Hugh Herr and HST alumnus Mark Price spoke about exactly the kind of exciting and innovative research done at HST and by HST-trained scientists. Herr spoke first about “wearable robotics” — the present and future of prosthetics. Herr, himself a double-amputee, develops prosthetic Joe Ciffolillo (left) receives the HST MVP Award from HST Directors Martha knees and ankles. Gray and David Cohen. 4
Winter 2007-08
“Technology has the power to rehabilitate, to heal, and to transform lives,” he said. Any doubts were cast aside by Herr’s videos, including one of an Iraq war veteran who had lost two legs and an arm. Outfitted with several prostheses, he was able to walk on his own. Herr shared several new ideas from his lab, including Fancy Pants, a sort of exoskeleton designed to allow people to carry heavy loads with ease, and a new shoe design with shock absorption that promises to reduce injuries and knock minutes off a marathon. His lab’s goal is to “blur the boundary between human and synthetic structures” with the aim to both aid people with disabilities and to push human performance beyond its biological limits. Last in the lineup, Price took an internal look at human performance, exploring the reasons why he will never pitch like Curt Schilling. The fact is, he explained, that “pitchers are different.” Their bones are different, allowing a wider rotation, and their tissues are different, allowing a longer extension. Batters, too, are different. Professional batters break rule number one of batting: keep your eye on the ball. Instead they watch the ball to a point, then look away, making rapid and protective movements, then at the last microsecond refocus on the ball, which is speeding towards them at 90 miles an hour, making contact (one hopes). HST thanks those who attended for their generosity and support. Special recognition goes to the event’s steering committee members Richard Anders, Joe Bonventre, Fred Bowman, Dean Calcagni, Norm Jacobs, Joe Madsen, Scott Sarazen and Dan Shannon, and event coordinators Pam McGill, Nina Restuccia and Georgia Santander. —Elizabeth Dougherty
HST news HST international growing in India If only for a year, HST is home to Prof. Raghunath Mashelkar, FRS, who has been appointed an HST visiting professor for 2007-08. Mashelkar is the current president of the Global Research Alliance and the Indian National Science Academy. The only Indian to be a foreign associate of the US National Academies of Sciences as well as Engineering, Mashelkar has traveled a long way from his childhood days of poverty to the position of the director general of the Council for Scientific and Industrial Research (CSIR) India, a consortium of 39 research laboratories with over 20,000 PhDs; he also chairs numerous national and international commissions. His experiences, therefore, are a source of inspiration for the many students who attended his lectures and round-tables during his visit. In many ways, his life reflects the growth of India, from a state of limited resources to an economic powerhouse. It is this emerging India which fascinates people and offers the opportunity to learn from the diversity and challenges that exist. It’s been just over two years since Mashelkar first visited HST as part of a high-level delegation from India. Since then HST’s engagement with India has grown significantly, both in terms of education and research. We were part of the process of evolving a national business plan competition jointly sponsored by the department of Science and Technology, the government of India and Intel. A new HST203 India program has been
developed, where students can complete their clinical preceptorship in India after having completed HST201 and 202. Funded by the Indo-US Science & Technology Forum, an organization that facilitates Indo-US linkages, the first batch of HST students spent six weeks last year rotating through three different hospitals. They were exposed to the different structures in the Indian healthcare system: federally subsidized tertiary care at national institutes such as the All India Institute of Medical Sciences, which selects 50 students for its MBBS (equivalent to MD) program from over 75,000 applicants; primary healthcare at the village level under community medicine; and private healthcare at the Rockland Hospital, which caters to the upper economic strata. The first year of this program was a success. One student in the HST203 India program wrote, “I truly hope that this program will be an option for future HST students. I have absolutely loved my time here, especially at AIIMS; I am like a kid in a candy store. There is so much to do and see that threre is never enough time! “This country grows on you. I have come to love being a part of the Delhi pandemonium. They say that India is ‘an assault on the senses.’ It’s a place of unimaginable contrasts, and yet there is something so peaceful about being part of the chaos. It must be experienced.” This year, we are expanding the program to send four students, funded by NSF and the Indo-
HST Summer Institute accepting applications for 2 biomed tracks HST is now accepting applications for its 2008 summer experience in two exciting tracks: Bioinformatics and Integrative Genomics (BIG) and Biomedical Optics. From June 9 to August 8, Summer Institute students will learn scientific research skills in a lab affiliated with MIT, Harvard or MGH, take graduate level classes, and meet frequently with mentors such as HST affiliate George Church, Professor of Genetics at Harvard University and a founder of the Human Genome Project. The HST Summer Institute is a unique opportunity for outstanding undergraduate students considering a career in biomedical engineering and medical science. “The welcoming personalities of my mentors and the exposure to a supportive research environment have helped to solidify my decision to attend graduate school in pursuit of a PhD in bioinformatics,” said two-time Summer Institute
student Jakaiser Smith. The Summer Institute is part of an effort at MIT to help facilitate the involvement of talented students in engineering and science research, in particular underrepresented minorities, first-generation college students, and those from disadvantaged backgrounds. Please encourage undergraduates who are interested in bioinformatics, genomics or optics to apply. Students must be sophomore, junior or senior undergraduates in September 2008 to join the BIG program, while applicants to the Biomedical Optics program must be junior or senior undergraduates in September 2008. (Consideration will be given to first- or second-year graduate students in complementary fields.) All applicants must be US citizens or have permanent residence status. For more information, visit http://web.mit.edu/ hstsummer. The application deadline is January 31, 2008.
US Forum, who will rotate through Neurology, Ob/Gyn, Urology, General Medicine, Cardiology, and Community Medicine. In addition, they will also spend one to two weeks at an engineering school. The goal of this program is to expose HST students to new challenges, nurture future bridges with academia in India, and also create an environment for translational research in India. A second initiative, which was announced during MIT president Susan Hockfield’s recent visit to India, is the establishment of a Translational Health Science and Technology Institute there. In a letter of intent signed by Martha Gray and Dr. Maharaj Bhan, Secretary of the Department of Biotechnology for the Government of India, HST will assist in the development of an interdisciplinary translational research program at the new institute by helping to recruit and train the faculty. Organizers anticipate that the new campus will host a series of advanced research and training centers, including the UNESCO regional center for biotechnology, a vaccine research center, a nanoscience institute, and a clinical center — all of which will evolve dynamically in the next three to five years. For HST, it will be an exciting time to forge new pathways on the international stage, with the ultimate goal of bringing together the synergistic strengths of HST and India to revolutionize medicine at a scale not seen before. — Shiladitya Sengupta, PhD Assistant Professor of Medicine and HST
HST at AAAS HST is helping to organize two symposia for the 2008 annual meeting of the American Association for the Advancement of Science, to be held February 14-18 in Boston. The theme of the 2008 meeting is “Science and Technology from a Global Perspective.” The first symposium, “Universities Without Walls: Endeavors in Global Interinstitutional Education,” features Martha Gray on “Inter-Institutional Training in the Life Sciences and Engineering.” The symposium on “High-Tech, Low-Cost Medicine: A New Paradigm for Global Health” includes Shiladitya Sengupta and Utkan Demirci. Sengupta will speak on “Using Technology to Meet Global Healthcare Needs;” Demirci will present “A Low-Cost HIV Diagnostic Kit.” The Connector
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research news Genome-Wide Map of Chromatin State MEMP student Tarjei S. Mikkelsen is first author, and Erez Lieberman and Richard P. Koche, also MEMP students, are co-authors of “Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.” Proteins called histones bind to DNA, and different types of chemical modifications (“methylations”) to the histones correlate with how well a particular gene is expressed. A technique called chromatin immunoprecipitation was used to select DNAprotein complexes carrying specific protein modifications, and single-molecule high throughput DNA sequencing technology was used to profile over four billion bases. The analysis allowed the group to predict cell state and lineage potential by matching the histone methylation pattern with specific genes. The potential of this approach is to understand, for example, what makes a liver cell different from a muscle cell (or a normal cell from a cancerous cell) by defining their chromatin state (TS Mikkelsen et al., Nature 2007; 448: 553-60).
Key Protein in Iron Metabolism Jane-Jane Chen, PhD, is senior author and Sijin Liu, PhD, co-author of “The Function of heme-regulated elF2α kinase in murine iron homeostasis and macrophage maturation.” The hormone hepcidin, produced in the liver, is the key regulator of systemic iron homeostasis. Hepcidin in turn is regulated by inflammatory cytokines, linking it to the anemia of inflammation and of chronic disease, which is associated with decreased iron in serum and in macrophages. Heme-regulated eIF2α kinase (HRI), expressed predominantly in erythroid cells, is an important physiologic regulator of gene expression and survival of erythroid cells. This research investigated homeostasis and hepcidin expression in HRI deficient mice. It is documented that HRI protein is normally present in murine macrophages, albeit at a lower level than in erythroid cells. HRI (-/-) mice exhibited impaired macrophage maturation and a weaker anti-inflammatory response with reduced production of cytokines, as well as decreased production of hepcidin, decreased iron content in splenic macrophages, and increased serum iron. Thus, HRI deficiency attenuates expression of hepcidin and iron homeostasis in mice, indicating a potential role of HRI in the anemia of inflammation (S Liu et al., J Clin Invest 2007; 117: 296-305). Chen is Principal Research Scientist at HST, and Liu is an HST Postdoctoral Fellow.
New Potential Strategy to Combat Aging Toren Finkel, MD ’86, PhD, is senior author of “Augmented Wnt signaling in a mammalian model of accelerated aging.” Depletion or dysfunction of stem and progenitor cells is considered a mechanism of aging. This study examined stem cell dynamics in a genetic model 6
Winter 2007-08
of accelerated aging, the Klotho mouse, which is characterized by a decrease in the number of stem cells and an increase in progenitor cell all senescence. Klotho mice lack the expression of Klotho, a transmembrane secreted protein and are characterized by early onset of arteriosclerosis, decreased fertility and atrophy of the skin. Normally, Klotho was found to be bound to various Wnt proteins, known soluble mediators of stem cells; this interaction resulting in suppression of Wnt biological activity. Both in vivo and in vitro, continuous exposure to Wnt triggered accelerated cellular senescence. This unexpected connection between aging and the Wnt signaling pathway led the authors to suggest strategies targeting soluble mediators of stem cell function as an approach to combat aging and age-related diseases (H Liu et al., Science 2007; 317: 803-6). Finkel is Principal Investigator in the Cardiovascular Branch of the NHLBI at NIH.
New Strategy to Enhance the Regenerative Capacity of Adult Hearts Roger J. Hajjar, MD ’90, Professor of Medicine/Cardiology and of Gene and Cell Medicine at the Mt. Sinai Medical Center, New York, is co-author of “Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair.” The usual response to myocardial injury is fibrosis with negligeable proliferation of cardiomyocytes. This study of isolated cardiomyocytes from rats, which had undergone experimental myocardial infarction, revealed that periostin, a component of the extracellular matrix, induced re-entry of differentiated mononucleated cardiomyocytes into the cell cycle. Periostin also improved cardiac function after myocardial infarction, reducing fibrosis and infarct size (B Kuhn et al., Nat Med 2007; 8: 962-9).
Potential Anti-Fibrotic Therapy for Cardiac Fribrosis HST affiliated faculty Raghu Kalluri, PhD, Associate Professor of Medicine at HMS and BIDMC, is senior author of “Endothelialto-mesenchymal transition contributes to cardiac fibrosis.” Cardiac fibrosis is a common feature of cardiomyopathy, increasing cardiac stiffness and resulting in diastolic dysfunction. Cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells. In two independent mouse models of heart disease, this study demonstrated that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT). Transforming growth factor-beta1 (TGF-beta1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in these mouse
models of pressure overload and chronic allograft rejection. Inhibition of EndMT by rhBMP-7 is proposed as a viable therapeutic strategy against cardiac fibrosis (EM Zeisberg et al., Nat Med 2007; 13: 952-61).
Early Diagnosis of Osteoarthritis Martha L. Gray, PhD ’86, and Deborah Burstein, PhD ’86, are first and second authors of “Magnetic resonance imaging of cartilage glycosaminoglycan: Basic principles, imaging technique, and clinical applications.” This is an overview of their laboratory’s contribution to the development of non-invasive techniques to image the molecular state of cartilage in both bench and clinical studies. Both sodium MRI and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) based on proton MRI permit “visualization” of the charged glycosaminoglycan (GAG) distribution in articular cartilage in vitro and in vivo. Diseased cartilage is lacking in GAG, which thus is a biomarker for degeneration, regeneration and repair of cartilage. (J Orthop Res 2007; [E pub ahead of print]). Gray is the Edward Hood Taplin Professor of Medical Electrical Engineering and Co-Director of HST. Burstein is Associate Professor of HST and also of Radiology at HMS and BIDMC. This article is the winner of the 2007 Elizabeth Winston Lanier Award from the Kappa Delta Sorority.
Pathogenesis of Cognitive Deficits and Alterations of Memory in Depression and Anxiety Disorder Kerry J. Ressler, MD ’00, PhD, is senior author of “Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories.” Authors’ abstract: “Brain-derived neurotrophic factor (BDNF) is known to play a critical role in the synaptic plasticity underlying the acquisition and/or consolidation of certain forms of memory. Additionally, a role has been suggested for neurotrophin function within the hippocampus in protection from anxiety and depressive disorders. Understanding the function of this important gene in adult animals has been limited however, because standard knockouts are confounded by gene effects during development. There are no BDNF receptor-specific pharmacological agents, and infusions of neuropeptides or antibodies have other significant limitations. We injected a lentivirus expressing Cre recombinase bilaterally into the dorsal hippocampus in adult mice floxed at the BDNF locus to facilitate the site-specific deletion of the BDNF gene in adult animals. Significant decreases in BDNF mRNA expression are demonstrated in the hippocampi of lenti-Cre-infected animals compared with control lenti-GFP-infected animals. Behaviorally, there were no significant effects of BDNF deletion on locomotion or baseline anxiety measured with
research news startle. In contrast, hippocampal-specific BDNF deletions impair novel object recognition and spatial learning as demonstrated with the Morris water maze. Although there were no effects on the acquisition or expression of fear, animals with BDNF deletions show significantly reduced extinction of conditioned fear as measured both with fear-potentiated startle and freezing. These data suggest that the cognitive deficits and impairment in extinction of aversive memory found in depression and anxiety disorders may be directly related to decreased hippocampal BDNF” (SA Heldt et al., Mol Psychiatry 2007; 12: 656-70). Ressler is Assistant Professor of Psychiatry and Behavioral Sciences in the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine.
Normobaric Oxygen Therapy of Value after Ischemic Stroke A. Gregory Sorensen, MD, is co-author of “Magnetic: Resonance Spectroscopy Study of Oxygen Therapy in Ischemic Stroke.” The metabolic effects of normobaric oxygen therapy upon acutely ischemic brain tissue were investigated in six patients randomized to therapy vs. control. Multivoxel magnetic resonance spectroscopic imaging (MRSI) and diffusion-perfusion MRI (DWI and PWI) were performed at baseline, 4 hours (during therapy), and 24 hours. Voxel-based analysis showed excellent correlation between apparent diffusion coefficient values, lactate, and N-acetyl-aspartate levels at all time points. Lactate decreased during normobaric oxygen therapy (NBO) and increased post-NBO. Nacetyl-aspartate decreased in patients receiving room air but not in NBO-treated patients. The author concluded that NBO improves aerobic metabolism and preserves neuronal integrity in the ischemic brain (AB Sirshal et al., Stroke 2007; 38: 2979-84). Sorensen is Associate Professor of Health Sciences and Technology, Associate Professor of Radiology at HMS and MGH, and Associate Director of the Athinoula A. Martinos Center for Biomedical Imaging,
Simple and Affordable Method of CD4 Cell Counting
Reduction in Size of Experimental Cerebral Infarcts HST affiliated faculty members David A. Boas, PhD, Associate Professor of Radiology at HMS and MGH, and Michael A. Moskowitz, MD, Professor of Neurology at HMS and MGH, are co-authors of “Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits pre-infarct depolarizations in experimental focal ischaemia.” Cerebral ischaemia was induced by
New Method to Assess Infant Brain Development Angela M. Franceschini, PhD, is first author and David A. Boas, PhD, is co-author of “Assessment of Infant Brain Development With Frequency-Domain Near-Infrared Spectroscopy.” This report introduces frequency-domain nearinfrared spectroscopy (FD-NIRS) as a safe, rapid, inexpensive, portable technique for quantitative and reliable monitoring of regional brain development. NIRS provides bedside monitoring of cerebral blood volume and oxygen consumption, a measure of cerebral metabolism. Forty-seven healthy infants were studied, ranging in age from premature to 12 months (Pediate Res 2007; 61: 546-51). Franceschini is Assistant Professor of Radiology at HMS and MGH, and Boas is Associate Professor of Radiology at HMS and MGH. Both are members of the HST Affiliated Faculty.
How irregular verbs straightened up
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by ath Jon an Saragosti
MEMP student Erez Lieberman’s research on language evolution landed him and his coauthors on the cover of the October 11 issue of Nature. In “Quantifying the evolutionary dynamics of language,” his team studied of the evolution and regularization of the conjugation of English irregular verbs over the past 1,200 years. A linguistic rule emerged to signify past tense with the dental suffix “-ed.” Of 177 Old-English irregular verbs, 145 remained irregular in Middle English, and 98 are still irregular. Regularization was a function of the frequency of word usage: the half-life of an irregular verb scales as the square root of its frequency. Thus, a verb that is 100 times less frequent regularizes 10 times as fast. Verb size in this image corresponds to frequency of usage: Large (frequently used) verbs tend to stay at the top, whereas smaller verbs tend to fall through to the bottom (Nature 2007; 449: 713-6). This work is a collaboration of the Program of Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, and Department of Mathematics at Harvard University, the Harvard School of Engineering and Applied Sciences, and the Department of Systems Biology at HMS.
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Kamran Badizadegan, MD ’93, is coauthor and Michael S. Feld, PhD, is senior author of “Tomographic phase microscopy.” The refractive index is important in studies involving the interaction of light with cells and tissues, cell and tissue light scattering and flow cytometry. Here, a technique is reported for quantitative threedimensional mapping of refractive index in live cells and tissues, using a phase-shifting laser interferometric microscope with variable illumination angle. Refractive index tomography successfully examined physiological changes in living cells. Tomographic imaging of multicellular organisms is also possible, as illustrated with the nematode C. elegans, visualizing the digestive tract (W Choi et al. Nat Methods 2007; 4: 717-9). Badizadegan is Assistant Professor of Health Sciences and Technology and of Pathology at HMS and MGH. Feld is Professor of Physics at MIT and member of the HST affiliated faculty.
occlusion of the distal middle celebral artery in normoxic or byperoxic mice. Two-dimensional multispectral reflectance imaging and laser speckle flowmetry were used to non-invasively determine the impact of normobaric hyperoxia on cerebral blood flow and oxygenation. Post-ischaemic normobaric hyperoxia caused an immediate and progressive increase in oxyhaemoglobin concentration and an increase of cerebral blood flow, while infarct size was reduced by 45% (HK Shin et al., Brain 2007; 130: 1631-42).
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Mehmet Toner, PhD ’89, Professor of Surgery at HMS and MGH and HST faculty, is co-author of “A microchip approach for practical label-free CD4+ T-cell counting of HIV-infected subjects in resource-poor settings.” This development addresses the urgent need for an accurate, affordable and simple CD4 cell counting method for staging and monitoring HIV-infected patients in resource-limited settings. A microfluidic system is used for high-efficiency insulation of pure populations of CD4+ T-cells based on cell affinity chromatography. This method compared favorably with standard flow cytometry (X Cheng et al., Acquir Immune Defic Syndr 2007; 2007; 45:257-61).
Mapping of Refractive Index by Tomographic Phase Microscopy
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research news Heritable Risk Factors Identified for Multiple Sclerosis HST affiliated faculty David A. Hafler, MD, the Breakstone Professor of Neurology at HMS and BWH, is first author of “Risk alleles for multiple sclerosis identified by a genomewide study” by the International Multiple Sclerosis Consortium. DNA microarray technology was used to identify common DNA sequence variants in 931 family trios (affected child and both parents) who were then tested for association. For replication and controls, a total of 1,540 family trios, 2,322 case subjects and 5418 control subjects were studied. A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 trios revealed 49 SNPs with an association with multiple sclerosis. Alleles of IL2RA and IL7RA and those in the HLA locus were identified as heritable risk factors for multiple sclerosis (N Eng J Med 2007; 357: 927-9).
Robotic Activators and Motile Devices from Muscular Thin Film Kevin Kit Parker, PhD, HST affiliated faculty member and Assistant Professor of Biomedical Engineering at the School of Engineering and Applied Sciences, Harvard University, is senior author of “Muscular thin films for building activators and powering devices.” Using neonatal rat ventricular cardiomyocytes cultured on polydimethylsiloxane (PDMS) thin films, biohybrid materials were assembled. Shortening of cardiomyocytes during synchromons contractions caused the PDMS thin film to bend during systole and return to its original shape during diastole. This approach permitted the fabrication of simple oscillators, soft robotic activators, and motile devices that could walk and swim (AW Feinberg et al., Science 2007; 317: 1366-70).
Regulatory Functions Found for Some Noncoding Sequences of the Human Genome Shamil R. Sunyaev, PhD, Assistant Professor of Health Sciences and Technology and Assistant Professor of Medicine at HMS and BWH, is co-author of “Widely distributed noncoding purifying selection in the human genome.” Authors’ Abstract: “It is widely assumed that human noncoding sequences comprise a substantial reservoir for functional variants impacting gene regulation and other chromosomal processes. Evolutionary conserved noncoding sequences (CNSs) in the human genome have attracted considerable attention for their potential to simplify the search for functional elements and phenotypically important human alleles. A major outstanding question is whether functionally significant human noncoding variation is concentrated in CNSs or distributed more broadly across the genome. Here, we combine whole genome sequence data from four nonhuman species (chimp, dog, mouse, and rat) with recently available comprehensive 8
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human polymorphism data to analyze selection at single-nucleotide resolution. We show that a substantial fraction of active purifying selection in human noncoding sequences occurs outside of CNSs and is diffusely distributed across the genome. This finding suggests the existence of a large complement of human noncoding variants that may impact gene expression and phenotypic traits, the majority of which will escape detection with current approaches to genome analysis (S Asthana et al., Proc Natl Acad Sci USA 2007; 104: 12410-5).
A Health Information Network for Public Health, Research and Clinical Care Kenneth D. Mandl, MD; Ben Y. Reis, PhD; Henry C. Chueh, MD ’89; and Isaac S. Kohane, MD, PhD are co-authors of “A Selfscaling, Distributed Information Architecture for Public Health, Research, and Clinical Care.” Building on the Shared Pathology Information Network (SPIN), as a model to protect patient privacy, grant institutional autonomy, and exploit legacy systems and data sharing agreements, this work demonstrates SPIN as a prototype architecture for the National Health Information Network (NHIN). It adopts a distributed approach to data storage to protect privacy, permits strong institutional autonomy to engender participation, provides oversight and transparency to ensure patient trust, allows variable levels of access, and encourages voluntary regional collaborations that form a nationwide network. The model was validated by a large-scale, multi-institutional study involving seven medical centers for cancer research. It is broadly applicable for regional and national clinical information exchanges (AJ McMurray et al., J Am Med Inform Assoc 2007; 14: 527-533). Mandl is Assistant Professor of Pediatrics at HMS and CHB and a member of the HST affiliated faculty, Reis is Instructor in Pediatrics at HMS and CHB and a member of the HST affiliated faculty, Chueh is Assistant Professor of Medicine at HMS and MGH, and Kohane is the L. J. Henderson Associate Professor of HST and Director of HST’s Bioinformatics and Integrative Genomics Training Program.
New Method of Culturing Functioning Hepatocytes Sangeeta N. Bhatia, PhD ’97, MD ’99, Associate Professor of HST and of Electrical Engineering and Computer Science, MIT, is senior author, and Salman R. Khetani, PhD, HST Research Staff, is first author of “Microscale culture of human liver cells for drug development.” This report presents a miniaturized, multiwell culture system for human liver cells with optimized microscale architecture that maintains phenotypic function for several weeks. These cultures permit assessment of gene expression profiles, phase I/ II metabolism, canalicular transport, secretion
of liver-specific products and susceptibility to hepatotoxins (SR Khetani and SN Bhatia, Nat Biotechnol 2007; [E pub ahead of print]).
Obesity-Related Genes Atul J. Butte, SM ’02, PhD ’04, is senior author of “Evaluation and integration of 49 genome-wide experiments and the prediction of previously unknown obesity-related genes.” The authors evaluated 49 obesity-related genome-wide published experiments, including microarray, genetics, proteomics and gene knock-down from human, mouse, rat and worm, for their ability to rediscover a comprehensive set of genes previously found to be associated with obesity. Ability to rediscover known obesity-associated genes was poor. The authors then created an integrative model which out- performed all 49 individual genome-wide experiments. They thus created a list of genes with the highest likelihood of association for obesity (SB English and AJ Butte, Bioinformatics 2007; 23: 2910-7). Butte is Assistant Professor of Medicine (Medical Informatics) and Pediatrics at the Stanford University School of Medicine.
New Algorithms for Prosthetic Devices for Impaired Patients MD student Lakshminarayan Srinivasan, PhD, is first author, Emery N Brown, MD, PhD, Professor of HST and of Computational Neuroscience at MIT, is senior author, and Urit Eden, PhD ’06, is coauthor of “General purpose filter design for neural prosthetic devices.” This is the report of a coherent estimation framework which motivates new applications of prosthetic devices driven by action potentials, local field potentials, electrocorticography, electroencephalography or electromyography. This framework was tested in an arm/reaching task and a wheelchair navigation task. This unified framework was shown to outperform prior approaches (J Neurophysiology 2007; 98: 2456-75.)
New Approach to Treating Brain Cancer MEMP student Grace Y. Kim is first author, and Jeffrey M. Karp, PhD, and Robert S. Langer, ScD, are co-authors of “Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model.” A resorbable, multi-resevoir polymer microchip drug delivery system was loaded with 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU). A syngeneic Fischer 344 9L gliosarcoma rat model was used to study the tumoricidal efficacy of BCNU delivery from the microchip or homogenous polymer wafer. Tumors treated with BCNU microchips shrank significantly in size compared to empty controls. This work is the first demonstration of in vivo efficacy of brain cancer therapy by means of a polymer microchip (J Control Release, 2007; 123: 172-178). Karp is Instructor of Medicine and HST. Langer is Professor of HST and an Institute Professor at MIT.
faculty profile
Joysuccess of others Countesy of S. Gilbert
from the
by Catherine A. Modica
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fter a distinguished career of more than 20 years as a neuro-oncologist and a professor of neurology at Yale University and YaleNew Haven Hospital, Thomas N. Byrne, MD, moved to Cambridge — to MIT and to HST — in Fall 2004 with his wife, Susan Hockfield, as she assumed the presidency of MIT. He is gratified by the new professional turn in his life afforded by his affiliation with HST, where he is Clinical Professor of Neurology and Health Sciences and Technology, and also Senior Lecturer in MIT’s Department of Brain and Cognitive Sciences (BCS). After graduating as valedictorian of his New Jersey Medical School class, internship at Brown and neurology residency at Yale, Byrne decided in 1979 to go into neuro-oncology, which was not yet a defined field, at Memorial Sloan-Kettering. He enjoyed being part of the coming together of two previously separate disciplines and notes his continued involvement in multidisciplinary work — which he calls “a wonderful aspect” of HST. “HST provides a home for people from different fields and disciplines. I have gotten to know people with a great variety of intellectual interests as I’ve joined this community, all of whom are working towards a common good,” he says. One of the huge advantages he sees is HST’s combined, spectacular talents in sciences, engineering and clinical medicine. “I don’t know where else they have this combination,” he adds. Byrne believes that the big challenges in health need a multidisciplinary approach. He notes that the solutions of complex problems with big impact often require the integration of knowledge from multiple disciplines. As an example, he mentions the advances in medical imaging that have already taken place, thanks to the collaboration of HST faculty. Byrne knows about collaboration from personal experience. About 15 years ago, he discussed the invasiveness of gliomas (primary brain tumors) with his wife, a neurobiologist, who had just discovered a protein that is expressed during development and is critical in permitting cells to move through the immature
developing brain. The result of that discussion led to the discovery that gliomas use the same developmental protein to facilitate their invasion in the adult brain, opening up the potential for new therapies. Byrne exhorts students to stay open to the unexpected and to learn from what life brings. “I try to teach students that unexpected events occur in life that can become defining moments. We all have these, but the question is: Do we recognize them as such when they occur, and what do we make of them?” He is candid about some of his own defining experiences. While he was intellectually fascinated by neurology, he was drawn to his life’s work in large part due to personal experience. When Byrne was 21, his father became a cancer patient. When he was 22, he himself was diagnosed with cancer. “My experience inspired me to want to care for cancer patients, to make my experience meaningful.” His present plate is a very full one. He teaches two courses that are jointly offered with BCS. HST.422: A Clinical Approach to the Human Brain provides an introduction to neuroscience using clinical cases. He is course director for HST.424: Diseases of the Nervous System, which gives students a chance to see how clinician-scientists tackle diseases. (The course enrollment for the latter is limited and is already fully subscribed for Spring 2008.) Another important area of focus for him is MIT development. Recently, he was involved with the gift of $100 million from MIT alumnus David Koch to create the Koch Institute for Integrative Cancer Research. In talking with MIT supporters, as in his work with patients, he searches for what motivates them. “Everyone wants to make a difference. Some have the financial capacity to make a big difference, but want to know they’re supporting something they really believe in. As a doctor, listening to a life story helps you understand a patient. In philanthropy, one of my goals is to listen for that which inspires individuals and see if we at MIT
can help them realize their dream.” Many current students know Byrne best in his role as a mentor. Whether hosting lunches for premed undergraduates, meeting with students at the Burchard Scholars program, during office hours or staying long past the end of a BioMatrix dinner to continue a conversation, he is deeply interested in students — hearing their stories and telling them his own. He notes that one of his greatest sources of satisfaction is the occasional encounter with former students who describe an influential experience. “To have someone come up to me and say, ‘You taught me 20 years ago,’ and then go on to describe how my teaching was the impetus for them to move in a particular direction — to know that you’ve had a positive impact is an enormously gratifying experience.” Byrne says that his greatest joy now is the success of others. “It’s like seeing your child be better than you; that’s what you want your students to have. And it’s not that you made it happen, but you had some role in it. You reach a point in your career when the greatest pleasure is to see that you have helped others succeed.”
S! U Alumni N J OI Association Networking Reception Monday, Jan. 28, 2008 5 – 7:30 p.m. Genzyme Corporation 500 Kendall Street Cambridge, MA Remarks by Claude Canizares, Irving London and David Cohen The Connector
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alumna profile
f l ow in the
This Speech & Hearing alumna is happily absorbed in career and family
Courtesy of Konsantina Stankovic
by Patricia A. Cunningham
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fter years of studying and preparing and starting a family, Konstantina Stankovic feels that she has finally achieved “flow” — that state of total absorption that is accompanied by feelings of happiness, satisfaction and ability. Born and raised in former Yugoslavia, “Tina” (Trbovic) Stankovic has always been fascinated by math and science. Encouraged by her experiences as a high school exchange student and by her host family, Stankovic decided to stay in the US and apply to MIT. She matriculated to MIT as a physics major in September 1988, but a growing fascination with clinically relevant problems led to an additional major in biology. One of her early mentors in the Physics Department, Dr. Felix Villars, suggested she pursue a joint MD-PhD program to fulfill her career goals, and steered her to HST. Dr. Villars also referred her to another member of the HST faculty, Dr. Nelson Kiang; he and Dr. Don Eddington provided early mentorship in her career as a budding speech and hearing research scientist. She performed her senior research project in the Cochlear Implant Laboratory at MEEI under their guidance, studying how the auditory nerve responds to electrical stimulation using mathematical modeling. The synergy of that research — combining physical and biological sciences with clinical medicine — was such an attraction that she and her husband, Alex Stankovic, decided to stay in Boston. Tina Stankovic was drawn to HST because of 10
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its quantitative approach to medicine, outstanding faculty and students, and the whole philosophy of bringing together science, technology and medicine. She was accepted to a joint HST MD– Speech and Hearing Sciences PhD program in 1992. She deferred matriculation to HMS for one year to begin graduate school, and thus was a member of the first HST Speech and Hearing Sciences class — one marked by its enthusiasm and pioneering spirit, she said. Her PhD research focused on the olivocochlear efferent system through which the brain controls the function of the cochlea and the auditory nerve, under the guidance of Dr. John J. Guinan, Jr. She found, using techniques of electrophysiology, that the efferent effects on auditory-nerve responses to tones are more potent than previously reported, producing substantial inhibition even at high sound levels and tail frequencies. Starting her graduate studies before medical school proved fortuitous, as she already had a sense of some of the problems in the hearing research arena and was able to apply what she learned in medical school. Her MD honors thesis work on ionic channels in the ear came out of this. She learned in Anatomy and Renal Pathophysiology that the kidney and the inner ear develop at the same time embryologically. Also, the pH regulating proteins and aquaporins that were
previously described in the kidney also exist in the inner ear, and provide a basis for understanding disease processes that lead to both sensorineural hearing loss and renal malfunction. The research group she brought together — consisting of renal physiologist Dr. Dennis Brown of MGH, molecular biologist Dr. Seth Alper of BIDMC, and otohistochemist Dr. Joe Adams of MEEI — was the first to describe this. After graduating with a PhD in 1997 and an MD two years later, Stankovic embarked on a surgical internship at MGH, followed by a residency in otolaryngology — head and neck surgery — at HMS. Amazing technological advances have allowed surgery through the nose with imaging guidance, rather than making large, disfiguring cuts through the face and head. In the ear, they have used technology such as implantable cochlear devices that can restore hearing, and auditory brain stem implants that alleviate hearing loss. In conjunction with her residency program, Stankovic was a post-doctoral fellow (at HHMI and Children’s Hospital) under the mentorship of Dr. Gabriel Corfas. She furthered her understanding of the auditory nerve by exploring cellular and molecular mechanisms that promote its survival. During her current clinical fellowship in Neurotology–Skull Base Surgery at MEEI, she is (continues on page 11)
alumni news 1970s
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Dennis W. Choi, MD ’78, PhD, is Executive Director of the Comprehensive Neuroscience Initiative at Emory University in Atlanta. This university-wide neuroscience initiative comprises 250 faculty neuroscientists in 20 departments. Previously, Choi was the former Executive VicePresident of Neurosciences at Merck Research Laboratories (2001-06) and Professor of Pharmacology at Boston University (2006-07).
Mark B. McClellan, MD ’92, PhD, spoke on “Health Care Regulation for the 21st Century: Regulating Personalized Medicine” on October 23 at Harvard’s Institute of Politics, Kennedy School of Government. He is a senior fellow and director of the Engelberg Center for Health Care Reform at the Brookings Institute in Washington, D.C.
Nai-Kong Cheung, MD ’78, PhD, is featured in Science’s Newsmakers section (Oct. 19, 2007). With his encouragement, seven fathers of children with neuroblastoma completed a crosscountry bike ride dubbed “The Loneliest Road,” which netted $200,000 for his research at Memorial Sloan-Kettering Cancer Center in New York City. (Editor’s note: The Connector profiled him in the Spring 2007 issue.)
Kathleen M. Donahue Schmainda, PhD ’93, is the recipient of a five-year, $1.4 million grant for continued development of MRI contrast agent methods to study angiogenesis in brain tumors. She is Associate Professor of Radiology and Biophysics at the Medical College of Wisconsin in Milwaukee and a faculty member of the Functional Imaging Research and Biotechnology and Bioengineering Center.
1980s Ira S. Nash, MD ’84, has been appointed Vice-Chairman of the Department of Medicine at Mount Sinai Medical Center in New York and Chief of Medicine at the affiliated Bronx VA Medical Center. Yuri Imanishi, MD ’85, now practices internal medicine in New York City. Previously, she had a practice in Wailuku, Hawaii. Her e-mail is yimanishi@gmail.com. Peter Diamandis, MD ’89, founder and CEO of the X-Prize Foundation, announced a new competition to put an unmanned rover on the moon within five years. The first nongovernmental team to land a vehicle safely, drive it for 500 meters and beam back high-quality videos by 2012 will win $20 million. Diamandis is also issuing a challenge for an efficient car model that can be mass produced; a qualifying race is planned for 2009.
Daniel J. DiLorenzo, MD ’99, PhD ’99, SM ’99, MBA (MIT ’99), writes, “After getting my company BioNeuronics — now renamed NeuroVista — funded and fully staffed, I resumed neurosurgery residency in Houston at the Methodist Hospital. I’m also editor of a new textbook, Neuroengineering, which was published in November.”
2000s Anita Goel, PhD, MD ’05, is Founder, Chairman and CEO of Nanobiosym Inc. of Medford, a privately held firm founded in 2004. Nanobiosym has won a $2 million contract from the United States Defense Threat Reduction Agency, a branch of the US Department of Defense, to develop its genetic-detection technology to sense biological threats. Vikram Kumar, MD ’04, was elected an at-large HST Alumni Board Member,
effective October 1. He is He is Co-founder, Chairman and Chief Medical Officer of Dimagi, Inc., a company based out of Cambridge, Mass., that focuses on technology solutions for developing and developed countries.
Missing Alumni/ae Help the HST Alumni Office locate missing graduates. If you have contact information for any of the following alumni/ ae, contact The Connector at hst@mit.edu. Thank You! Steven Nelson Bailey, MD ’07 John Ng, MD ’07 Mark M. Pomerantz, MD (CITP SM ’07) Jennifer Kyung Son, MD ’07 Teresa Patricia G. Santos, PhD ’06 Francis Joseph Alenghat, MD ’05 Allen Jeremias, MD (CITP SM ’05) Lea Marcie Alhilali, MD ’04 Anna Berkenblit, MD (CITP SM ’04) George Stuart Mendenhall, MD ’03 Sohail Fakhr Tavazoie, MD ’03 Siobhan Hutchinson, MD (CITP SM ’02) I-Fan Theodore Mau, MD ’02 Peter G. Danias, MD, PhD (CITP SM ’01 Hafiza H. Khan, MD (CITP SM ’01) Christopher R. Wright, MD (CITP SM ’01) Christopher Brian Reid, MD ’00, PhD Grant Schaffner, PhD ’00 Orlando Rodriguez, MD (CITP SM ’98) Craig N. Shapiro, MD ’83 Matthew J. Narrett, MD ’82 Kenneth R. Bridges, MD ’76
Tina Stankovic (continued from page 10)
working with Dr. Michael McKennon exploring the molecular basis of the uniqueness of the bone surrounding the ear using tools of genomics and bioinformatics, with a special interest in understanding how this otic capsule contributes to the normal function of the auditory nerve. Given her intense schedule, Stankovic cherishes every moment together with her family. She and Alex have been married 15 years, and have two children, Michael (5) and Gabriel (3). She enjoys singing with her boys while accompanying them on the piano. In fact, she credits the instrument with fostering her interest in surgery; the manual aspects of surgery, like playing the piano, appealed
to her, and allowed her to reconnect with music. She and Alex, an electrical engineer at Northeastern University, share their love of science with their sons and enjoy carrying out scientific experiments with them, such as building volcanoes with baking soda and vinegar. Tina occasionally brings the children to work on the weekends. Seeing their mother in her clinical and lab settings has led to many questions. They are very empathetic and love to hear about their mother’s work and patients. Seeing that her children appreciate what she does, and knowing that they were part of it, is important, and helps her re-focus her efforts. She says that the highlights of her HST
education were the relationships and friendships she formed with her fellow students, teachers and mentors. By drawing on this network, she notes that she can find the answer to any question she developed within half a day. As her training comes to an end, Stankovic will stay on staff at MEEI and start her own lab. She plans to continue her research in understanding how the ear works, from every angle and as a system, mechanically, electronically and ionically. She looks forward to gathering data, sifting through them and developing good questions to develop approaches for study and treatment. Now is a time of synthesis — now she is in the flow. The Connector
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All I really need to know I learned in med school!
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Winter 2007-08
Valerie J. Pronio-Stelluto, MD
The 101st annual Second Year Show, featuring members of the 2010 HMS/HSDM Class, took place November 15-17 at Roxbury Community College. This year’s production, entitled All I Really Need to Know I Learned in Medical School, drew similarities between the earliest years of schooling (apologies to Robert Fulghum’s “All I Really Need to Know I Learned in Kindergarten”) and the first year of medical school. The plot focused on that oft-expressed fear of all incoming students: the HMS Admissions Committee made its first mistake and that they did not belong there. As the audience followed students through the first year, we discovered that HMS Admissions does not make mistakes, and everyone is where they truly belong! The performance lived up to high expectations, notably Laura Rosow, the daughter of HST Pharmacology Professor Carl Rosow, and Marc Walker, the second year class president and erstwhile “HST student who could not pipette.” HST participants included Jonathan Abraham (crew), Dan Buckland (writer/stage manager), Ann Cai (choreography/dance), Erin Chen (program/t-shirt/ poster), Steve Huffaker (dance), Neel Kantak (chorus), Charles Lei (dance), Karolina Maciag (dance, Big Bird), Arvind Ravi (dance), Yin Ren (dance), Cameron Sadegh (acting/dance), and Corinna Zygourakis (dance). Firstyear students Amy Xu and Lydia Ng provided musical accompaniment. — Patricia A. Cunningham
A gratuitous ‘bhangra’ dance, always appreciated, ushers in the end of the 101st annual Second Year Show.