HST Connector Spring 2009

Spring 2009

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

The Connector

HST graduate student Geoffrey von Malt-zahn has been named winner of the Lemelson-MIT Student Prize and received an unrestricted cash gift of $30,000 for two promising innova-tions in the area of cancer therapy: a new class of cancer therapeutics and a new paradigm for enhancing drug delivery to tumors.

Von Maltzahn is working to combine nano-technology, medicine, and engineering to improve tumor detection and revolutionize chemotherapy treatment. His advisor is Sangeeta Bhatia, Profes-sor of HST and EECS at MIT, Howard Hughes Medical Investigator, and a member of the David H. Koch Institute for Integrative Cancer Research at MIT. The goal of their research is to precisely target and destroy tumor cells without affecting healthy tissue.

One of von Maltzahn’s noted innovations is the use of gold nanorods to detect and destroy tumor cells. His nanorods are very small particles on the nanometer scale that are specially designed to absorb infrared radiation. They are so efficient at absorbing infrared energy that von Maltzahn has dubbed the devices “nano-antennas.”

When these nano-antennas are injected into the blood stream, they concentrate around cancerous tumor cells. Once the tumors have been found, the nano-antennas can be remotely heated — using infrared light — to toxic temperatures,

killing all nearby tumor cells. Preclinical trials reveal that a single intravenous nanoparticle in-jection eradicated 100 percent of tumors in mice using a near-infrared light.

“The significant motivation behind my work,” von Maltzahn said, “is seeing the toxicity and limited efficacy of current cancer therapies. This is driven both by the inherent toxicity of current drug arsenal and by our limited ability to deliver them to tumors.” Indeed, frequently less than one percent of chemotherapy drugs administered to patients go to tumor cells. The remaining 99 percent of the drugs maliciously affect normal healthy cells, resulting in undesir-able side effects like hair loss, fatigue, and nausea. Von Maltzahn hopes to develop new treatments that will minimize side effects and improve tumor eradication.

At age 28, von Maltzahn has already made a significant impact in the fields of medicine and nanotechnology. He has not only submitted 19 scholarly papers and eight patent applications, but he has also founded two companies.

In addition to designing this new class of nano-antenna therapeutics, von Maltzahn’s sec-ond invention aims to fundamentally improve the intravenous delivery of drugs to tumors. This work draws on insights from natural structures,

This academic year has presented signifi-cant challenges, remarkable opportunities and inevitable changes. HST remains vital to profound medical advances in the areas of stem cell research, nanotechnology and biomedical informatics, among others. Moreover, the time is more excit-ing than ever to be immersed in research and education. The ever-evolving medical, scientific and engineering landscape is vastly different from the one that Dr. Irving London and his fellow pioneers encountered when they established HST in the 1970s. Now the impact of the cur-rent global financial crisis and the likelihood of continuing turbulent economic times necessitate the re-evaluation of our current landscape and the charting of a new path for HST into the 21st century.

This past year’s director search fostered deep reflection and debate among members of the search committee, the HST community, as well as both MIT and Harvard. These discussions illuminated new opportunities to focus HST’s impact on education, as well as basic and transla-tional research, and helped prepare us to address the economic crisis that became evident this fall.

We would particularly like to thank Prof. Lee Gehrke for acting as interim HST director during this past year. He has worked tirelessly, together with the leadership, faculty and staff. Without his passionate support in this and so many other ways, HST would not be at the forefront in the application of science and technology to educa-tion and research.

Academic institutions are facing unprec-

edented financial challenges. In HST we are anticipating a significant budget reduction for the coming fiscal year. Reductions such as this require more than trimming at the margins; all of our activities and programs will need to be examined and must become more closely aligned with the resources that support them. Appreciating that endowment funds provide much of the operating budget for HST and that payouts in the years ahead may continue to perform at lower levels, long-term structural changes will be required to put HST on a firm footing.

Although we must plan prudently for this protracted period of financial constraints, this is not all bad news. We can take this opportunity to focus on our core mission: providing exemplary

MEMP student receives Lemelson top prize for cancer research

Geoffrey von Maltzahn (continues on page 11)

Directors’ Notes: HST’s Evolving Landscape

(continues on page 2)

Photo courtesy of Lemelson-M

IT Program / C

Mark O

stow

2 Spring 2009

hst news

The ConnectorEditor Walter H. Abelmann, MD

Managing Editor/Designer Becky Sun

Editorial Assistant Lindsay Ramm

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.edu

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.

Volume 23 • Number 2

Editorial BoardSherene Aram H. Frederick Bowman, PhDPavan Cheruvu (MD ’09)Patricia A. CunninghamLisa E. Freed, MD, PhD ’88Christine L. Hsieh (SHBT)Sravisht Iyer (MD ’11) Lora MaurerCatherine ModicaLaurie PassArvind Ravi (MD ’10)Steven M. Stufflebeam, MD ’94

Ex officioDavid E. Cohen, MD ’87, PhDRam Sasisekharan, PhD

(continued from page 1)

Directors’ Notes

ThursdayApril 23, 2009

Student Poster Session2 ~ 5 p.m.

Plenary Session Talks by HST Alumni5:15~6:15 p.m.

Presentation of Prizes, Awards and Certificates6:15~6:45 p.m.

Gala Reception6:45~8 p.m.

Joseph Martin Conference Center(New Research Building)77 Avenue Louis PasteurBoston, MassachusettsH

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education and research opportunities at the inter-section of science, technology and medicine.

We have also embarked on reviews of every aspect of HST in order to clarify programmatic goals and their support. We view this as an op-portunity to redefine the model of HST, allowing us to evolve into a more strategically focused pro-gram. Discussions to date have already stimulated creative solutions based on valuable input from students, alumni, faculty, advisors and staff. Ef-forts are underway to help support activities for which support has been reduced or eliminated from our operating budget. For example, Joe Madsen, president of our Alumni Association, is taking steps whereby the Association may help the graduate student government fund time-honored student life activities. Importantly, HST’s faculty are seeking innovative means to support student research, including new government stimulus dollars. As we always have in the past, we con-tinue to look to all of you to help support our educational goals.

We welcome your thoughts and suggestions as we make our way through this defining period and to working with all of you to guarantee HST’s prominence at the intersection of science, engineering and medicine.

—David E. Cohen and Ram Sasisekharan

The poster session at this year’s HST Forum will feature 35 students and their ongoing re-search. Among the wide range on topics, neurosci-ence, molecular biology and speech/hearing were especially prominent. Here are some examples:

Shilpa Joshi (MD ’11) reports “Collagen-Platelet Composite Enhances Histologic Heal-ing of the ACL.” Twenty-seven four-month-old Yorkshire pigs underwent complete transection of the anterior cruciate ligament (ACL) and suture repair. Suture repair augmented with collagen-platelet composite hydrogel (CPC) was compared to suture repair alone, after intervals of up to 3 months. CPC therapy caused a significant increase in ligament cellularity, compared to controls.

Carrie Niziolek, a SHBT student who matriculated in 2005, submitted “The Neural Basis of Auditory Feedback Control Across and Within Phonetic Categories.” She investigated how subjects change their speaking patterns when they hear an altered version of their own speech fed back to them, with the ultimate goal to develop a framework of the neural process underlying the motor control of speech. Her fMRI data show increased activation of bilateral inferior frontal and superior gyrus and supplementary motor areas for across-category shifts compared to within-category shifts.

Oded Shaham, who entered the MEMP/BIG (Bioinformatics and Integrative Genomics) program in 2004, reports “A Plasma Biochemical Signature of Human Mitochondrial Disease.” Disorders of the mitochondrial respiratory chain (RCD) are common inborn errors of metabolism. Searching for markers of disease, he analyzed 190 metabolites in spent media from muscle cell cultures by means of mass spectrometry of

plasma from 17 patients with mitochondrial RCD, compared to 25 controls. Eight of the 32 culture-derived metabolites differed between patients and controls. These metabolic trends represent potential markers of disease.

Amy Xu (MD-PhD ’11), presents “vWF Unfolding and Cleavage in von Willebrand Dis-ease.” This disease, one of the more prevalent inherited bleeding disorders, results from a variety of mutations of the von Willebrand factor. Type2a vWF disease, the most common form, is caused by increased vWF cleavage. Here, optical tweezers were used to characterize vWF proteins unfolding with high spatial resolution, and a single flow array served to characterize vWF cleavage. Comparing wild type and mutant constructs revealed lower unfolding forces for the mutant, increased vWF cleavage with increased force, and increased cleav-age of the mutant, compared to the wild type, at low force.

Robert M. Koffie (MD ’11) submitted “Oligomeric Amyloid ß Associates with Postsyn-aptic Densities and Correlates with Excitatory Synapse Loss Near Senile Plaques.” This work addresses the question whether the synapse loss, which is associated with the cognitive decline in Alzheimer’s disease (AD), is due to fibrillar deposits known as senile plaques or to soluble oli-gomeric forms of amyloid ß (Aß). The study used array tomography, a technique which combines ultrathin sectioning with immunofluorescence. Senile plaques were found to be a potential res-ervoir of oligomeric Aß, which colocalizes with postsynaptic density and is associated with spine collapse. Thee findings reconcile the apparently competing schools of thought of “plaque” vs. “oligomeric Aß” as the synaptotoxic species in the brain of AD patients.

HST Forum Preview

The Connector 3

PromotionsJennifer Melcher, PhD, has been promoted

to Associate Professor of Otology and Laryngol-ogy and Associate Professor of Health Sciences and Technology. Her research focuses on how sound is coded in population neural activity of the human central auditory system. Her work uses functional MRI to assay brain activity and high-resolution structural MRI to examine brain architecture. Melcher’s current research falls into three broad categories: (1) determining functional and structural organizational principles of the human central auditory system, (2) identifying neural correlates of sound perception, and (3) establishing the neural mechanisms of tinnitus, a poorly understood auditory disorder with no uniformly effective treatment.

Stephen C. Blacklow, MD ’91, has been promoted to Professor of Pathology at HMS and BWH. He is a member of the HST affiliated faculty and also serves as Director of the MD-PhD Program in the Basic Sciences at HMS. His laboratory has focused on the relationship between structure and function in proteins of the LDL receptor family and in human Notch receptors. Ongoing research on the Notch signaling pathway emphasizes biomedical and structural approaches to uncover mechanistic principles that underlie normal and pathogenic signaling.

Honors and AwardsJohn D.E. Gabrieli, PhD, has been elected

to fellowship in the American Association for the Advancement of Science. He was recognized for “penetrating analyses of the nature of human memory, its neural substrates, its development, and its problems.” Gabrieli is the Grover Herman Pro-fessor of HST and Professor of Brain and Cognitive Sciences at MIT, and the Associate Director of the Martinos Center for Biomedical Imaging.

Elazer R. Edelman, MD ’83, PhD ’84, the Thomas D. and Virgina W. Cabot Profes-sor of Health Sciences and Technology at MIT, Professor of Medicine at HMS and BWH, and Director of the Harvard-MIT Biomedical En-gineering Center at HST, has received the 2009 Jeffrey M. Hoeg Arteriosclerosis, Thrombosis and Vascular Biology Award for Basic Science and Clinical Research. This award from the American

hst news

Heart Association’s Council on Arteriosclerosis, Thrombosis and Vascular Biology recognizes an established investigator in the prime of his or her career who has made an outstanding contribution to furthering understanding of the pathophysiol-ogy of arteriosclerosis and/or the development of treatment strategies. The award will be presented at the Annual Conference of the Council in Wash-ington DC in April, at which time he will make a 30-minute presentation.

Sangeeta Bhatia, PhD ’97, MD ’99, Pro-fessor of Health Sciences and Technology and of Electrical Engineering and Computer Sciences, at MIT, was named one of the 10 “Women to Watch” by the Mass High Tech: The Journal of New England Technology on January 23. A member of the David H. Koch Institute for Integrative Cancer Research at MIT, as well as a Howard Hughes Medical Investigator, Bhatia was cited for leading her field and for outstanding dedication to technology, entrepreneurship, lifelong learning and civic responsibility.

Matthew P. Frosch, MD, PhD ’87, Associ-ate Professor of Pathology, has also been appointed as Associate Professor of Health Sciences and Tech-nology. His research focuses on cerebral amyloid angiopathy, using in vivo kinetic measurements via muliphoton imaging in mouse models.

Viviany R. Taqueti, MD ’07, clinical fel-low in medicine at HMS and MGH, received honorable mention for her poster on “Octoge-narian with Aids, Lymphoma, and Multiple Op-

On page 2 of the Winter 2008-09 issue, Sangeeta N. Bhatia, MD, PhD, was mistitled. She is Professor of HST and of EECS at MIT.

E R R A T U M

The Connector is going green!In an effort to save paper and preserve funds, this will be the last print issue of The Connector. Future issues will be available only on our website. To stay connected, sign up today!

Give us your email so that we can let you know when a new issue is available. To confirm your email address or to update your contact information, email [email protected]. Please include your name, current address and phone numbers. HST alumni/ae should also include their degree(s) and graduation year(s).

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portunistic Infections Presenting with Failure to Thrive” at the Annual Scientific Meeting of the Massachusetts Chapter of the American College of Physicians.

Match Day Most RewardingAll of the 38 HST students expected to

graduate with MD degrees this year have suc-cessfully completed their plans for the next academic year(s). Internal Medicine attracted the largest number (9), followed by Primary Medicine leading to Radiology (5), Neurology (2), Anesthesiology (1) and Dermatology (1). Five students are headed for Pediatrics, three for Orthopedic Surgery, two for General Surgery, two for Neurosurgery, two for Research, and one each for Urology, Otolaryngology, Clinical Pathology, and Psychiatry. Two graduates are headed for McKinsey & Co.

Save the Date for GraduationHST’s Class of 2009 will be recognized and

celebrated on Wednesday, June 3, from 9 a.m. to noon at the Harvard Club of Boston, 374 Com-monwealth Avenue. Watch for more information about the keynote speaker and other details in the coming month.

Elazer Edelman

Lora

Mau

rer

4 Spring 2009

hst news

At this time last year, I found myself rum-bling down a dirt road in rural Swaziland, my truck kicking up dust as I swerved around potholes and made my way to a remote drug warehouse. The warehouse normally supplied anti-retroviral (ARV) drugs for HIV patients at a nearby clinic. On that day, however, the depot ran out of certain drugs. The government of Swaziland asked me to help figure out why.

That experience was quite different from how I currently spend my days as a first-year HST MD student. After graduating from MIT in 2006, I spent two years working for the Clinton Founda-tion HIV/AIDS Initiative (CHAI) based out of Ethiopia and Swaziland. My division within CHAI applied operations research to healthcare systems in developing countries, which is to say that we looked for low-cost and high-impact ways to help governments deliver better HIV treatment.

We faced quite a challenge in Swaziland. The small country stands out for many reasons: It has been called the Switzerland of Africa because of its stunning beauty, it boasts a strong and rich culture, and its people are truly some of the nicest I’ve ever met. Unfortunately, Swaziland also stands out for having the world’s highest HIV prevalence and the lowest life expectancy, which means that the challenges facing its healthcare system are among the most difficult in the world.

What brought me to that remote drug warehouse a year ago was a project that focused on quantifying Swaziland’s ARV needs. CHAI and the Swaziland government set out to ensure

that the country’s patients would have the drugs they needed, when they needed them. There are many steps in this process — ordering drugs

from reputable suppliers, distributing them, etc. — but it all starts with accurately forecasting the quantity of drugs. Getting this number right has serious implica-tions: If you under-quantify, then patients won’t be able to take their life-saving medica-tions; if you overestimate, then the excess drugs may sit on shelves until they expire, wasting thousands or even millions of dollars in a coun-try where over 75 percent of the population lives on less than two dollars a day.

I spent much of my time working to get that

number right. I took trips to warehouses and clinics to investigate where the system was break-ing down. I worked with colleagues in CHAI to build a computerized tool for forecasting drug

As part of his work with the Clinton Foundation HIV/AIDS Initiative in Swaziland, Adam Was participated in a “Walk Across the Nation” event to raise awareness for HIV.

A Journey from Swaziland to HST

needs. And most importantly, I worked with Swazi clinicians and government employees to add safe-guards against mistakes and to improve the overall drug quantification process. It was an incredibly rewarding project, and yet it was just one example of the work done in CHAI and Swaziland.

However, I wanted to be able to do more — to interact with patients, introduce new healthcare policy or lead a research project — that simply are not possible without more training. This is ultimately what led me to join the HST MD program. HMS has amazing resources for global health and clinical training, while HST takes a rigorous approach to medical education with a fo-cus on research. The strengths of HST are perhaps best exemplified by my research assistantship op-portunity, where I have joined a fantastic team of researchers from HMS, MIT, HSPH, and MGH to develop a new diagnostic device for detecting multi-drug resistant tuberculosis.

I’m proud of what CHAI accomplished in Swaziland. My hope is that the unique opportu-nity I’ve been given in HST will allow me to make a far greater impact when I return to Swaziland as a clinician and research scientist.

—Adam Was (MD ’12)

Eli Anderson

Swaziland has been called the Switzerland of Africa, both for its small size and stunning mountains. It also has the world’s highest rate of HIV/AIDS.

Quest for global health

Adam Was (second from left) and friends in the mountains of Swaziland.

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The Connector 5

faculty profile

Jennifer Melcher counsels graduate students who are looking for a thesis topic or deciding which laboratory to join: “Follow your pas-

sion.” She suggests that they consider what excites them most and in this process “the thesis topic or the laboratory will find you.” Perhaps it can be said that she has followed the same advice which might have been inspired by her father, James Russell Melcher, who won many teaching awards and was a Professor of Electrical Engineering and Computer Science (EECS) at MIT.

Melcher was born in Boston and has lived in the area nearly all her life. She received her SB, SM and PhD in EECS. After a two-year post-doctoral fellowship at the Eaton Peabody Laboratory at MEEI, she joined the faculty of HSM in the Department of Otology and Laryngology. She is an Associate Professor at HMS and also of HST. She teaches in several classes, including HST 722: Brain Mechanisms for Hearing and Speech, and HST 583: Functional Magnetic Resonance Imaging.

“I’m fond of saying I’ve gone nowhere in life. But the truth is I’ve always had the opportunity to do exactly what I want to do without leaving Boston. I had wonderful PhD and postdoctoral experiences in EPL where I used a combination of neuroanatomical, neurophysiological and neuronal modeling techniques to identify specific neuronal populations generating a widely mea-sured, but poorly understood brainstem evoked response. The work was performed in animals, but had direct implications for how we (humans) perceive sound. These implications seeded my interest in how the brain determines what we (listening humans) hear.”

She finished her graduate school and post-doctoral training at a fortuitous time in the advancement in biomedical imaging, especially some work at the MGH NMR Center (now the HST-Martinos Center) where functional magnetic resonance imaging was discovered.

Melcher puts it this way: “As luck would have it, EPL was interested in bringing aboard an investigator interested in using fMRI to un-

derstand human listening. I was quick to seize this opportunity and formed an auditory imaging research group based at EPL, with close ties to the Martinos Imaging Center.” For the next nine years her group, including many HST students, investigated the neural bases of human sound perception.

A couple of years ago, Melcher found an-other great opportunity in her career. “Thanks to several benefactors I was able to move my research in a translational direction and focus on the clinical problem of tinnitus, a condition commonly called ‘ringing in the ears.’ One goal of our work is to use neuroimaging, diagnostics of auditory peripheral function, and measurements of auditory perception to discern whether there are different physiological types of tinnitus that might be responsive to different treatments.”

She describes tinnitus as the “perception of

sound in the absence of a physical sound source. Almost everyone has experienced tinnitus of some sort — a ringing in the ears after a loud concert, buzzing in the head during the quiet dead of night, or the occasional tone heard in one ear for no apparent reason. In these examples, tinnitus might be considered more a curiosity than anything else. But now imagine that the sound never goes away. This is the situation for about 10 percent of people. Of this percent about half has tinnitus that interferes with their ability to lead a normal life because they can’t sleep or concentrate. Unfortunately tinnitus is a growing problem since our ears are bombarded by increasing amounts of acoustic noise and, as a population, we are aging.”

“I became interested in tinnitus,” Melcher says, “when I realized how much cool neuroscience there is behind it. Tinnitus is commonly viewed as an ‘ear problem,’ but there is good evidence that tinnitus involves plastic changes in the brain as well as peripheral auditory pathology, that it involves the somatosensory system as well as the auditory system, and that the clinical problem of tinnitus is as much (if not more) about the abnormal engagement of brain centers mediating our emotions as it is about hearing a sound that isn’t actually present.” Since she has trained in the basic neurophysiology of hearing, and much of her graduate training emphasized the “hard sciences,” the transition to tinnitus might seem like somewhat of a challenge.

Actually, she says, “I think my formal back-ground is a good fit, especially since it’s augmented by the tremendous amount I’ve learned from cog-nitive neuroscience, neurologist and psychiatrist colleagues in the intellectual mixing pot that is the Martinos Center.”

Melcher is raising two young twin boys, which can make the work-life balance a challenge. “I’m incredibly lucky to have my wonderful hus-band and equal partner in raising the boys — not to mention my indispensable mother, who helps make it all work,” she says. However, she adds,

by Steven Stufflebeam, MD ’94

Inge Knudson

Jennifer Melcher

(continues on page 11)

6 Spring 2009

faculty profile

L ee Gehrke wears many hats in the Boston-Cambridge educational milieu. Though varied, these hats are woven from a common

thread of commitment — to students, to teaching, to science, to HST.

Familiar to generations of HST students since the 1980s as teacher of anatomy and to HST faculty as a leader, Gehrke, Professor of Health Sciences and Technology at HMS and MIT and Professor of Microbiology and Molecular Genet-ics at HMS, has recently undertaken a new role that many may not know about: housemaster of Quincy House at Harvard College. Gehrke and his wife, Deb, have served as Quincy master and co-master, since 2006.

“Our two kids were grown and out of the house, and we wondered what our next challenge would be. [Housemastering] is great — it’s refresh-ing — and we get to do it together.” And, always looking out for HST’s interests, Gehrke says this is a good position from which to direct outstanding undergraduates to HST’s programs.

No one who knows the Gehrkes would have any question about their fit for the housemaster role. Their goals are to create a sense of community such that the house becomes the center of the stu-dents’ social and academic lives. Characteristically underplaying his part, Gehrke credits his friendly, outgoing, artist wife for their success.

“Deb is a natural housemaster. She is very skilled at making connections with students in ways I don’t know how to do … It’s a big challenge because the students are extremely over-scheduled and trying to involve them requires a lot of face time. She has ways of making them feel at ease, whether inviting them to her painting studio or to open houses in our quarters.”

As housemaster, Professor Gehrke supervises 22 resident tutors — graduate students or post-

grads who live on the floors with the students and offer their academic expertise as needed. In addition, he serves on Harvard’s House Program Planning Committee (HPPC), where he is chair of the subcommittee on academic and social spaces. Many of Harvard’s residences for undergraduate students were built in the 1930s and need renova-tion. The HPPC is asking how space should be formulated to meet the needs of current and future students. “Our sister institutions have already done this,” says Gehrke. “We are in the planning stages.” In keeping with today’s economic realities, it is more cost-effective to plan ahead than to ap-proach renovation needs with ad hoc “band-aid” interventions.

Gehrke draws a parallel between Harvard’s college house system and its medical school soci-eties, of which the Irving M. London Society of Health Sciences and Technology is one. Some of the terminology is the same, insofar as the heads of the societies and the houses are both “masters.” “And each system divides a large group into smaller units,” he says, “where there can be closer interactions among students and faculty.”

Respected and treasured for his own close interactions with HST students, Gehrke began teaching anatomy in HST in 1982. He had been a postdoctoral fellow in MIT’s Biology Depart-ment when his thesis advisor from Case Western Reserve called and told him that a friend, Irving London, HST’s founding director, was looking for someone to teach anatomy and that the two should meet.

“I had studied and taught anatomy as a graduate student,” Gehrke explains, “but never thought I’d do it again because I was focusing on virology.” As fate would have it, Gehrke contacted London, who arranged for him to meet Farish Jenkins, director of HST’s anatomy course. “This

was one of the most memorable moments of my life,” he continues. “I was shaking going in and shaking going out. I had never considered the possibility of being a Harvard faculty member. I hit it off with Farish and was fortunate enough to get the job.”

Professor Gehrke feels he owes his success at Harvard to Professor Jenkins’s mentoring. He elaborates: “Farish was intimidating to me at that time…a dear, dear man, but with a formal demeanor in his starched white shirt, and he had a reputation as a world-class paleontologist. He’s been an unbelievable mentor: He gave me the op-portunity to learn about teaching from a master, but also to learn about life as a university professor, how to run a lab, have a family. It’s too bad that everyone can’t be so lucky as to have a mentor like I’ve had in Farish Jenkins.”

Gehrke taught HST anatomy with Jenkins for more than 20 years, and when the latter stepped down as course director, it was natural for Gehrke took over.

“Farish’s style of teaching anatomy using chalk drawings is something I’ve always tried to emulate,” Gehrke continues. “This contrasts with the usual way of teaching anatomy today, with PowerPoint slides, where everything goes by so quickly. In HST, the students are drawing and labeling along with me. This is a very effective way to make sure the students are keeping pace. Farish’s drawings are something I’ve never been able to match. He used to go in at 4:00 a.m. to put up his drawings. I go in a couple hours ahead. I do the best I can.”

HST students learn functional anatomy, as opposed to simply structural anatomy. “We en-courage students to think about how things work physically rather than just memorize the structure. We have a laboratory in which we think about the

the HST Phenotype

by Lora Maurer

The Connector 7

embryology of the lower extremities, for example, where students are encouraged to consider how the lower extremities develop. On an exam, we’d never ask students to name all the bones of the lower extremities. We might ask, ‘When a sensory nerve has been damaged, what would the deficit be in the lower extremities? What movements would you be able to make or not make?’” Of course, he says, “There is a baseline of structural information you have to learn. I tell the students it’s like learning a new language. You have to know how to conjugate all the verbs because they are not all the same.”

HST’s anatomy course is required of all HST MD and PhD students. Gehrke says that he can’t tell the difference between them.

“At the beginning of the course, when I’m learning everyone’s name, I make it a point not to learn which program the students are in. What I see is that students who have different kinds of training have different ways of solving problems; they learn from one another and they all benefit. It’s one of the great strengths of the course to have a heavy concentration of both MD and PhD students.”

People often ask Gehrke — who started col-lege as an English major until he found his home in molecular biology — how anatomy is related to his research interest in virology. He tells them he’s interested in both the structure and function

of the viruses. “It’s just studying structure and function at a different level.” In short, Gehrke’s lab has been trying to understand how viruses “hijack cells” for their own reproduction. “We work on flaviviruses, such as West Nile, dengue and yellow fever — also on hepatitis C, a related virus,” he says. “These are all RNA viruses and ‘positive-strand’ viruses. The first three are spread by mosquitoes and are typically found in tropical areas. The infected mosquitoes are now moving north and even into the U.S.”

Since the beginning of his teaching in HST — and, perhaps, setting the stage for his future leadership role — Gehrke has been one of those rare faculty members to be employed and paid by both Harvard and MIT.

“Both institutions have been very good to me,” he says with obvious gratitude. It’s been beneficial, he feels, to have a presence in both communities.

“HST is inter-institutional. My lab has al-ways been at MIT, and I teach at HMS. Having tangible links to both universities has been useful in helping me understand how to support HST when each institution has very different admin-istrative structures, approaches and policies.” This benefit has also served him in his new role as housemaster, and the housemaster role has, in turn, served HST.

Over the years, Gehrke’s role in HST leader-

ship has grown. He sees this as a way of repaying the community:

“[Taking a leadership role] seems appropriate from the perspective that I’m one of the few faculty members to have a primary appointment in HST at HMS.” In addition to directing the anatomy course, Gehrke served on the MD Admissions Committee for a long time, as well as on the MD-PhD Admissions Committee and the MD Board of Advisors. During Roger Mark’s tenure as HST director in the mid-1980s, Gehrke started the HST Forum to emphasize HST’s research focus and integrate it more fully into the divi-sion. Recent directors Martha Gray and Joseph Bonventre enlisted Gehrke as chair of the HST faculty search committee and later appointed him associate director for faculty. Most recently, he was called on to serve as interim HST director at MIT between Professor Gray’s stepping down and the appointment of Ram Sasisekharan.

HST faculty members are fond of identify-ing likeminded souls as embodying the “HST phenotype.” As teacher, mentor, scientist and leader, Professor Lee Gehrke exemplifies the phe-notypical, interdisciplinary spirit of HST — the scientist whose genetic makeup and sincere efforts allow him to interact in many different environ-ments with ease and grace, always to the benefit of those he touches.

Lee and Deb Gehrke serve as masters of Quincy House at Harvard College.

Marisa Flavin

8 Spring 2009

research newsApiAP2 Proteins May Play an Essential Role in Malaria Parasite Development

Martha Bulyk, PhD, Associate Professor of Medicine and Pathology and Health Sciences and Technology at HMS and BWH, is co-author of “Specific DNA-binding by apicomplexan AP2 transcription factors.”

Authors’ Abstract: Malaria remains one of the most prevalent infectious diseases worldwide, affecting more than half a billion people annually. Despite many years of research, the mechanisms underlying transcriptional regulation in the malar-ia-causing Plasmodium spp., and in Apicomplexan parasites generally, remain poorly understood. In Plasmodium, few regulatory elements sufficient to drive gene expression have been character-ized, and their cognate DNA-binding proteins remain unknown. This study characterizes the DNA-binding specificities of two members of the recently identified Apicomplexan AP2 (ApiAP2) family of putative transcriptional regulators from Plasmodium falciparum. The ApiAP2 proteins contain AP2 domains homologous to the well characterized plant AP2 family of transcriptional regulators, which play key roles in development and environmental stress response pathways. We assayed ApiAP2 protein-DNA interactions us-ing protein-binding microarrays and combined these results with computational predictions of coexpressed target genes to couple these putative trans factors to corresponding cis-regulatory mo-tifs in Plasmodium. Furthermore, we show that protein-DNA sequence specificity is conserved in orthologous proteins between phylogenetically distant Apicomplexan species. The identification of the DNA-binding specificities for ApiAP2 proteins lays the foundation for the exploration of their role as transcriptional regulators during all stages of parasite development. Because of their origin in the plant lineage, ApiAP2 proteins have no homologues in the human host and may prove to be ideal antimalarial targets (EK DeSilva et al., Proc Natl Acad Sci USA; 2008;105(24):8393-8).

Advances in Successful Air Transport and Critical Care of War Casualities

James S. Eadie, MD ’00, is co-author of “Prospective Observational Study of United States Air Forces Critical Care Transport Team Opera-tions in Iraq.”

This report analyses all patients transported by three Critical Care Air Transport Teams (CCAT), each comprising one physician, one nurse and one respiratory therapist, from Balad Air Base, Iraq, to Germany, over one year. A total of 133 patients were evacuated on 61 flights. Trauma was present in 65%, lower extremity injuries being the most prevalent. Cardiac condi-tions were the most frequent diagnoses among medical patients. Fifty-seven percent of patients were ventilated mechanically. The most frequent in-flight complication was hypotension, seen in 17%. No patients died during the flights or the ensuing 24 hours. Thus, US Air Force CCAT

teams could safely transport critical patients over long distances while providing intensive care (PE Mason et al., J Emerg Med; 2008 Dec 4 [E pub ahead of print]).

Capt. Eadie, USAF MC, was a CCAT team leader of the 332nd Expeditionary Air Evacuation Squadron at the Balad Air Base, Iraq, during this study. He is now an Emergency Medicine physi-cian at Wilford Hall Medical Center, the major Air Force hospital located in San Antonio, TX.

The Challenge of Personal Health Records

John D. Halamka, MD, SM ’98, is first au-thor and Kenneth D. Mandl, MD, MPH, is co-author of “Early experiences with personal health records.” The authors present three case studies of personal health record projects: MyChart at Palo Alto Medical Foundation, PatientSite at BIDMC, and Indivo at Children’s Hospital Boston.

Conclusions: “The increasing prevalence of personal health records over the next five years will create many policy and technical challenges for healthcare institutions, payers, and employ-ers. However, it may also provide a great oppor-tunity. Providing patient control of healthcare information exchange is appealing, since it solves many of the privacy and consent issues faced by organizations desiring to exchange data today. By placing the patient at the center of healthcare data exchange and empowering the patient to become the steward of their own data, protecting patient confidentiality becomes the personal responsibility of every participating patient. This may accelerate healthcare information exchange as it simplifies consent models among producers and consum-ers of healthcare data. Our experience to date at three institutions demonstrates that personal health records which share data among patients and providers can successfully be deployed, but require careful attention to policy around privacy, security, data stewardship, and personal control” (J Am Med Inform Assoc 2008; 15: 1-7).

Halamka is Associate Professor of Medicine at HMS and BIDMC, and Chief Information Officer at HMS. Mandl is Associate Professor of Pediatrics, at HMS and CHB, and member of the HST affiliated faculty.

Simulation of Effects of Blood Flow on Deposition of Drugs by Endovascular Stents

Vijaya B. Kolachalama, PhD, postdoctoral research associate at HST, is first author and Elaz-er R. Edelman, MD ’83, PhD ’84, the Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology at MIT and Professor of Medicine at HMS and BWH, is senior author of “Luminal flow patterns dictate arterial drug deposition in stent-based delivery.”

Authors’ Abstract: Endovascular stents reside in a dynamic flow environment and yet the impact of flow on arterial drug deposition after stent-based delivery is only now emerging. We employed

computational fluid dynamic modeling tools to investigate the influence of luminal flow patterns on arterial drug deposition and distribution. Flow imposes recirculation zones distal and proximal to the stent strut that extend the coverage of tissue absorption of eluted drug and induce asymmetry in tissue drug distribution. Our analysis now explains how the disparity in sizes of the two recirculation zones and the asymmetry in drug distribution are determined by a complex interplay of local flow and strut geometry. When temporal periodicity was introduced as a model of pulsatile flow, the net luminal flow served as an index of flow-mediated spatio-temporal tissue drug uptake. Dynamically changing luminal flow patterns are intrinsic to the coronary arterial tree. Coronary drug-eluting stents should be appropriately considered where luminal flow, strut design and pulsatility have direct effects on tissue drug uptake after local delivery (J Control Release 2009; 133:24-30).

Bariatric Surgery Reduces Adverse Maternal Outcomes

Melinda A. Maggard, MD ’94, is first author of “Pregnancy and fertility following bariatric surgery: a systematic review.” In order to assess pregnancy outcomes and fertility after bariatric surgery, the authors searched a nation-wide in-patient sample (1998-2005) and multiple electronic databases to identify articles (1985-2008) on bariatric surgery among obese women of reproductive age. Data from 75 articles were analyzed. Three matched cohort studies revealed lower maternal complications rates after bariatric surgery than unoperated obese women, approach-ing rates found in nonobese controls. The effect of bariatric surgery upon neonatal outcomes were less clear (JAMA 2008; 300[19]:2286-96).

Maggard is Associate Professor of Surgery at the David Geffen School of Medicine at UCLA. She also serves as deputy director of the Center for Surgical Outcomes and Quality at UCLA.

Tracking Patients’ Preoperative Progress Mark A. Meyer, MD, MPH, SM ’06, is

first author of “Automatic time-motion study of a multistep preoperative process.”

Authors’ Abstract: Hospitals use time-mo-tion studies to monitor process effectiveness and patient waiting. Manual tracking is labor-intensive and potentially influences system performance. New technology known as indoor positioning systems (IPS) may allow automatic monitoring of patient waiting and progress. The authors tested whether an IPS can track patients through a multistep preoperative process.

Methods: The authors used an IPS between Oct. 14, 2005, and June 13, 2006, to track pa-tients in a multistep ambulatory preoperative pro-cess: needle localization and excisional biopsy of a breast lesion. The process was distributed across the ambulatory surgery and radiology departments of a large academic hospital. Direct observation of the process was used to develop a workflow

The Connector 9

research news

Imaging SchizophreniaJohn Gabrieli, PhD, the Grover Herman Professor of HST and Professor of Brain and

Cognitive Sciences at MIT, and Associate Director of the Martinos Center for Biomedical Imaging, is part of the research team for a study called “Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizo-phrenia.”

The traditional view of schizophrenia is that the disturbed thoughts, perceptions and emotions that characterize the disease are caused by disconnections among the brain regions that control these different functions. But this study found that schizophrenia also involves an excess of connectivity between the so-called default brain regions, which are involved in self-reflection and become active when we are thinking about nothing in particular, or thinking about ourselves, but generally suppressed when performing challenging tasks.

The researchers studied three matched groups of 13 subjects each: schizophrenia patients, nonpsychotic first-degree relatives of patients, and healthy controls. The subjects were scanned by functional magnetic resonance imaging (fMRI) while resting and while performing easy or hard memory tasks.

Whereas the control subjects exhibited task-related suppression of activities of the default network, in the schizophrenia patients the default system was both hyperactive and hypercon-nected during rest, and it remained so as they performed the memory tasks. The less the sup-pression and the greater the connectivity, the worse they performed on the hard memory task, and the more severe their clinical symptoms. The default system is also overactive, though to a lesser extent, in first-degree relatives of schizophrenia patients who did not themselves have the disease. This suggests that overactivation of the default system may be linked to the genetic cause of the disease rather than its consequences (S. Whitfield-Gabrieli et al., Proc Natl Acad Sci USA 2009; 106: 1279-1284).

template. The authors then developed software to convert the IPS data into usable time-motion data suitable for monitoring process efficiency over time.

Results: The authors assigned tags to 306 patients during the study period. Eighty patients never underwent the procedure or never had their tag affixed. One hundred seventy-seven (78%) of the remaining 226 patients successfully matched the workflow template. Process time stamps were automatically extracted from the successful matches, measuring time before radiology (mean +/- SD, 77 +/- 35 min), time in radiology (105 +/- 35 min), and time between radiology and operating room (80 +/- 60 min), which summed to total preoperative time (261 +/- 67 min). CON-CLUSIONS: The authors have demonstrated that it is possible to use a combination of IPS technol-ogy and sequence alignment pattern matching software to automate the time-motion study of patients in a multidepartment, multistep process with the only day-of-surgery intervention being the application of a tag when the patient arrives (Anesthesiology 2008; 108:1109-16).

Meyer is a PhD candidate in EECS’s Com-puter Science and Artificial Intelligence Labora-tory at MIT.

Soluble Abeta Oligomers Extracted from Alzheimer’s Brains Impair Synapse Structure and Functions

Bernardo Luis Sabatini, MD ’99, PhD, Associate Professor of Neurobiology at HMS, is co-author of “Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory.”

Authors’ Abstract: Alzheimer’s disease con-stitutes a rising threat to public health. Despite extensive research in cellular and animal models, identifying the pathogenic agent present in the hu-man brain and showing that it confers key features of Alzheimer’s disease has not been achieved. We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer’s disease. The oligom-ers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. Soluble Abeta from Alzheimer’s disease brain also disrupted the memory of a learned behavior in normal rats. These various effects were specifically attributable to Abeta dimers. Mechanistically, metabotropic glutamate receptors were required for the LTD enhance-ment, and N-methyl D-aspartate receptors were required for the spine loss. Co-administering antibodies to the Abeta N-terminus prevented the LTP and LTD deficits, whereas antibodies to the midregion or C-terminus were less effective. Insoluble amyloid plaque cores from Alzheimer’s disease cortex did not impair LTP unless they were first solubilized to release Abeta dimers, sug-gesting that plaque cores are largely inactive but

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Task-related suppression in default network regions. (A) Greater activation during rest than task (2-back WM) in PCC/precuneus and MPFC for controls (CON), relatives (REL), and patients (SZ). (B) MPFC region (peak: [12, 57, 6]) showing significant task-related suppression differences among groups. (C) Task-related suppression (with 95% confidence intervals) of MPFC region during 2-back and 0-back conditions. There was significantly more task suppression for controls than for relatives and patients on both WM tasks. The [x, y, z] locations are listed in Montreal Neurological Institute coordinates.

10 Spring 2009

sequester Abeta dimers that are synaptotoxic. We conclude that soluble Abeta oligomers extracted from Alzheimer’s disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species (GM Shanker et al., Nat Med 2008; 14:837-42).

What Contributed to the Transmissibility of the 1918 Influenza Virus?

Ram Sasisekharan, PhD, is co-author of “Human HA and polymerase subunit PB2 pro-teins confer transmission of an avian influenza virus through the air.”

Authors’ Abstract: The influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. The rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. Here, we used a series of human 1918-avian H1N1 in-fluenza reassortant viruses to identify the genetic determinants that govern airborne transmission of avian influenza viruses. We have demonstrated that the 1918 HA gene was necessary for efficient direct contact transmission, but did not allow respiratory droplet transmission between ferrets of an avian influenza virus possessing an avian polymerase subunit PB2. The 1918 PB2 protein was found to be both necessary and sufficient for airborne transmission of a virus expressing the 1918 HA and neuraminidase. Also, it was found that influenza viruses that were able to transmit efficiently in ferrets were able to replicate ef-ficiently at the lower temperature (33 degrees C) found in the environment of mammalian airway. These findings demonstrate that the adaptation of the HA and PB2 proteins are critical for the development of pandemic influenza strains from avian influenza viruses (N Van Hoeven et al., Proc Natl Acad Sci USA 2009; 106:3366-71).

Sasisekharan is the Edward Hood Taplin Professor of Health Sciences and Technology and Biological Engineering, as well as Director of HST.

Predicting Risk of Stroke after TIAA. Gregory Sorensen, MD ’89, Associate

Professor of HST and Radiology, HMS, and Associate Director of the Athinoula A. Martinos Center for Biomedical Imaging, is senior author and Lee H. Schwamm, MD, Associate Professor of Neurology at HMS and MGH, and Associate Director of the Clinical Research Center at MIT, is co-author of “Clinical and Imaging-based Pre-diction of Stroke After Transient Ischemic Attack. The CIP Model.”

In an effort to improve the prediction of risk of stroke after a transient ischemic attack (TIA), 601 consecutive patients with TIA fol-lowed by an MRI within 24 hours of onset of symptoms were studied. A logistic regression model was developed, using stroke within seven

research newsdays as the criterion of response. A subsequent stroke occurred in 25 patients (5.2%). Combin-ing the diffusion-weighted imaging findings with a clinical score integrating age, blood pressure, diabetes, duration of symptoms and neurological findings yielded a prediction of high sensitivity and specificity. This approach to stratification of risk is expected to permit early implementation of therapeutic measures. (H Ay et al., Stroke 2009; 40:181-6).

New Potential Therapy for SepsisRobert A. Star, MD ’80, is co-author of

“Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production.”

Authors’ Abstract: Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs, also known as mesenchy-mal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated mac-rophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like recep-tor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BM-SCs (activated by LPS or TNF-alpha) reprogram macrophages by releasing prostaglandin E(2) that acts on the macrophages through the prostaglan-din EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups (K Németh et al., Nat Med 2009; 15:42-9).

Star is Director of the Division of Kidney, Urol-ogy and Hematology Research, National Institute of Diabetes and Digestive and Kidney Diseases.

Regulation of Cardiomyocyte Growth in Cardic Hypertrophy

Susan F. Steinberg, MD ’76, is senior author of “p66Shc Links {alpha}1-Adrenergic Re-ceptors to a Reactive Oxygen Species-Dependent AKT-FOXO3A Phosphorylation Pathway in Cardiomyocytes.”

Authors’ Abstract: p66Shc is an adapter protein that is induced by hypertrophic stimuli and has been implicated as a major regulator of reactive oxygen species (ROS) production and cardiovascular oxidative stress responses. This study implicates p66Shc in an alpha1-adrenergtic

receptor (alpha1-AR) pathway that requires the cooperative effects of protein kinase (PK)Cep-silon and PKCdelta and leads to AKT-FOXO3a phosphorylation in cardiomyocytes. alpha1-ARs promote p66Shc-YY(239/240) phosphorylation via a ROS-dependent mechanism that is localized to caveolae and requires epidermal growth factor receptor (EGFR) and PKCepsilon activity. alpha1-ARs also increase p66Shc-S(36) phosphorylation via an EGFR transactivation pathway involving PKCdelta. p66Shc links alpha1-ARs to an AKT signaling pathway that selectively phosphorylates/inactivates FOXO transcription factors and down-regulates the ROS-scavenging protein manganese superoxide dismutase (MnSOD); the alpha1-AR-p66Shc-dependent pathway involving AKT does not regulate GSK3. Additional studies show that RNA interference-mediated downregulation of endogenous p66Shc leads to the derepression of FOXO3a-regulated genes such as MnSOD, p27Kip1, and BIM-1. p66Shc downregulation also increases proliferating cell nuclear antigen expression and induces cardiomyocyte hypertro-phy, suggesting that p66Shc exerts an antihyper-trophic action in neonatal cardiomyocytes. The novel alpha1-AR- and ROS-dependent pathway involving p66Shc identified in this study is likely to contribute to cardiomyocyte remodeling and the evolution of heart failure (J Guo et al., Circ Res 2009; 104:660-9).

Steinberg is Professor of Pharmacology and Medicine in the Center for Molecular Therapeu-tics, Department of Pharmacology, College of Physicians and Surgeons, Columbia University.

Basis of the Autoimmune Susceptibility of Turner Syndrome PAtients

Maureen A. Su, MD ’00, Assistant Adjunct Professor in Pediatric Endocrinology at the Univer-sity of California San Francisco, is first author of “The Role of X-linked FOXP3 in the autoimmune susceptibility of Turner Syndrome patients.”

Authors’ Abstract: Turner Syndrome patients have an absent second sex chromosome and a pre-disposition to autoimmune disease. We hypothe-sized that the autoimmune susceptibility in Turner Syndrome may be due to an alteration in the expression of the X-linked FOXP3 gene. FOXP3 is important in the development of regulatory T cells, and complete loss of FOXP3 expression has been shown to result in severe autoimmunity. To test this hypothesis, we characterized the regula-tory T cells and performed immunophenotyping on the peripheral blood leukocytes of a cohort of Turner Syndrome patients. These patients retained regulatory T cell frequency and function despite an increased prevalence of autoimmunity. Immu-nophenotyping revealed a decrease in the ratio of CD4 to CD8 lymphocytes. These findings suggest that the autoimmune predisposition in Turner Syndrome is not due to alterations in regulatory T cells but may be associated with a change in the proportion of T cell subsets (Clin Immunol 2009 Jan 14. [E pub ahead of print]).

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The Connector 11

alumni news1980s

Toren Finkel, MD ’86, PhD, Principal Investigator in the Cardiology Branch, Molecular Biology Section of the National Heart, Lung and Blood Institute of the NIH, has been elected to membership in the prestigious Association of American Physicians.

1990s

David A. Shaywitz, MD ’99, PhD, gave a seminar on “Found in Translation: Challenges and Opportunities in Translational Research” on February 18 at the Tosteson Medical Education Center at HMS. A past Associate Director in the Department of Experimental Medicine at Merck, he is now a member of the Healthcare Practice of Boston Consulting Group.

2000s

Howard Y. Chang, MD ’00, PhD, has been promoted to Associate Professor of Dermatology (with tenure) at Stanford University. His research is focused on gene regulation in skin patterning, cancer, and aging. He is the recipient of the inau-gural Vilcek Prize in Creative Promise.

Atul J. Butte, PhD ’04, Assistant Professor of Medicine (Medical Informatics) at Stanford University School of Medicine, and Director of the Center for Pediatric Bioinformatics at Lucile Packard Children’s Hospital, proudly reports that two high-school students who had done research

in his laboratory were among the 300 semi-final-ists in the Intel Science Talent Search. Densil Sikka and Rohan Chakicherla will each receive $1,000, as will their respective high schools.

Anna Greka, MD-PhD ’04, has been ap-pointed to the faculty at HMS as Instructor in Medicine as of July 2008. Greka was also named the recipient of the Young Investigator Grant of the NephCure Foundation. Worth $100,000 annually for three years, the grant supports basic science research aimed at identifying the cause, treatments and potential cures for focal segmental glomerulosclerosis (FSGS) and nephrotic syn-drome. She plans to study how changes in cell calcium signaling in kidney glomeruli may lead to destruction of the filtration barrier leading to proteinuria. Currently, Greka is completing her residency in Medicine at MGH.

Blanca E. Himes, PhD ’07, and Nathan C. Himes, MD ’08, announce the birth of Sylvia Alexandra on December 7, 2008. Blanca is an HST research fellow at the Children’s Hospital Informatics Program. Nate is completing his tran-sitional year and will begin his radiology residency at BWH in June.

Two Alumni Elected AAAS OfficersJudy Lieberman, MD ’81, PhD, Professor

of Pediatrics at HMS and CHB, is the Chair-Elect of the Section on Medical Sciences.

Jennifer M. Puck, MD ’75, is the section’s Council Delegate. She is Professor in the De-partment of Pediatrics and Institute for Human Genetics at UC San Francisco.

HST Alumni Round TablesRecent HST Alumni Round Tables in-

cluded Tina Stankovic, PhD ’98, MD ’99, who discussed life as a surgery research-clinician; and Steven Stufflebeam, MD ’94, who covered the topic of biomedical researchers working with clinicians. Chuck Stearns, PhD ’90, met with a group of PhD candidates over dinner at Legal Seafoods to discuss PET imaging research in in-dustry, as well as his personal HST experience.

Stankovic is a Clinical Fellow in Otology and Laryngology at HMS and MEEI. Stuffle-beam is an Instructor in Radiology at HMS and MGH, and a member of the HST affili-ated faculty. Stearns currently works with GE Healthcare in Milwaukee as Principal Engineer at PET Systems.

HST Social Networking MingleThe Second HST Social Networking Min-

gle was held on March 30 at Brick Oven Pizza in the Longwood Medical Area. This event was a way for the HST Alumni Association to reach out to current HST students and to allow all HST students from the PhD and the MD programs to get to know each other and alumni. These larger Social Mingles supplement the smaller, more focused HST Alumni Roundtable events (see above).

One important topic covered at the Mingle is that the HST Alumni Association is attempting to cover the shortfall in the current funding for the HST Student Life Fund. It is hoped that this will allow the continuation of a number of social events, such as the yearly ski retreat, which build camaraderie and improve student life.

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Lemelson Prizelike the immune system, where cells interact to create a network that can quickly detect illnesses and other abnormalities. Von Maltzahn hopes to implement the same network principles with his tumor-detecting nanoparticles: If one particle detects a tumor, then all other particles will also know the location of that tumor.

One of his systems involves benign “scout” particles that initially locate the tumor and, once inside, send powerful signals to recruit secondary, ‘assassin’ particles that contain the therapeutics. In preclinical trials, this system has been able to deliver more than 40 times stronger doses of therapeutics to tumors in mice, in comparison to non-communicating control nanoparticles.

“This concept of engineering systems of nanoparticles that collectively outsmart disease barriers has many potential applications in medi-cine, from improving regenerative medicines to ultra-sensitive diagnostics,” said von Maltzahn.

Von Maltzahn has won several other awards for his research, including MIT’s Outstanding Undergraduate Research Mentor Award, the National Science Foundation Graduate Research

Fellowship, and the Biomedical Engineering Soci-ety Graduate Research award. He is also an active participant in MIT’s Undergraduate Research Opportunities Program (UROP), supervising 14 undergraduates and helping them get involved in cancer therapy treatments.

“In addition to the long hours spent in the lab, finishing up his PhD, and founding two companies, Geoff mentored 14 undergraduate students, taking them out of the classroom setting and inspiring them to make the link from science to the real world,” says Joshua Schuler, executive director of the Lemelson-MIT Program. “Geoff is not only a mentor for aspiring scientists, but also a shining example of bridging the gap between technological invention and entrepreneurship.”

Every year, the Lemelson-MIT Program recognizes an MIT senior or graduate student who has demonstrated innovation and invention in his or her field. A diverse panel of MIT alumni specially selected by the Lemelson-MIT program determines the winner of the $30,000 award.

Past HST student winners include Timothy K. Lu, PhD ’03, who is currently pursuing his MD at HST. Lu was 2008’s recipient, recognized for

his work on eradicating biofilms and enhancing the effectiveness of antibiotics. David Berry, MD ’06, was named the Student Prize winner in 2005 for his innovations in both stroke and cancer treat-ments, and Daniel DiLorenzo, SM, MD ’99, was awarded the prize in 1999 for his development of medical electronic devices.

—Laurie Pass

“Anyone who works or lives with me knows I like things to be a little bit out of control. Having life filled in every corner is a good way to keep things that way. There’s simply no time to focus on anything but big picture stuff that really matters – family, research that might help someone, training the next generation of scientists. So you might say there is no ‘balance’ — more like a constant state of imbalance that makes the ride fun.”

Through her pioneering work in functional neuroimaging of hearing, mentoring HST stu-dents, and balancing family, Jennifer Melcher continues to follow her passion.

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Melcher profile

12 Spring 2009

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At the semi-annual meeting of The Connector’s Editorial Board, held on March 11, the dominant topic of discussion was the impact of the financial crisis on next year’s budget for this publication. Al-though the informal feedback and the results of a recent email survey that we received from you, our readers, are generally positive to highly laudatory with regard to the content, format and distribution, HST simply cannot afford to continue to outsource the production, print-ing and mailing of four issues per year during this time of difficult financial choices.

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Some of us on the Editorial Board believe that converting to an electronic format is also a way to support Harvard and MIT’s shared mission to “go green”: reduce paper usage and move toward new com-munications options offered by the Internet. We would be interested to hear from you about your impressions of this new format.

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For those of you who were asked to participate in our recent online survey and responded, we thank you for your comments and sugges-tions. We welcome your feedback as we work through this transition, and hope to make this publication ever more responsive to your needs and interests.

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