june 2012 volume 8, issue 3 Advancing Biomedical Science, Education, and Health Care

Scientists honored for research unveiling molecular machines The month of May brought the good prestigious honors in science. On the Campylobacter, which together cause chains of amino acids are formed into news that two School of Medicine 29th, Arthur L. Horwich, m.d., was most of the world’s food-borne illness. three-dimensional, functional struc- scientists, each of whom have done named a winner of the Galán’s group has thoroughly tures. Misfolded proteins have been pathbreaking work on molecular ma- in Life Science and Medicine, along characterized the Salmonella “needle implicated in many diseases, including chines involved in human disease, had with his longtime scientific col- complex,” a syringe-like organelle Alzheimer’s disease and amyotrophic received high honors for their research. laborator Franz-Ulrich Hartl, m.d., through which the bacterium injects lateral sclerosis (als). On May 1 Jorge E. Galán, ph.d., dr.med., of the Max Planck Institute bacterial proteins into host cells during In 1989, Horwich’s lab, in collabo- d.v.m., chair and Lucille P. Markey of Biochemistry in Germany. infection, modulating the function ration with Hartl and his postdoctoral Professor of Microbial Pathogenesis Galán is renowned for his research of those cells for its own advantage. mentor Walter Neupert m.d., ph.d., and professor of cell biology, was elect- on the cell biology, biochemistry, im- In 2004, Galán and colleagues used discovered a specialized protein in yeast ed a member of the National Academy munobiology, and structural biology of cryoelectron microscopy to visualize called Hsp60 that acts as a protein- of Sciences (nas), one of the most the bacterial pathogens Salmonella and the three-dimensional structure of the folding machine. Horwich and col- needle complex. For his wide-ranging leagues went on to elucidate how such research, in 2011 he was awarded the machines work by studying a related Koch Prize, the leading international bacterial protein called GroEL. By 1993, scientific award in microbiology. in a collaboration with the late Yale The nas, an organization of sci- X-ray crystallographer Paul B. Sigler, entists and engineers dedicated to the ph.d., the atomic structure of GroEL— furtherance of science and its use for a “beautiful work of ,” in Hor- the general welfare, was established in wich’s words—had been deciphered. 1863. The Academy acts as an official The Shaw Prizes carry a monetary adviser to the federal government in award of $1 million (U.S.) and are any matter of science or technology. given by the Hong Kong-based Shaw Also elected to the nas in May Prize Foundation for achievement in was John R. Carlson, ph.d., of the the life sciences, astronomy, and math- Department of Cellular, Molecular, ematics. Established in 2002 by film- and Developmental Biology in Yale’s maker and philanthropist Run Run Faculty of Arts and Sciences, bringing Shaw, the awards are “dedicated to the total number of nas members at furthering societal progress, enhancing Yale to 63. quality of life, and enriching humani- harold shapiro harold Horwich, an nas member since ty’s spiritual civilization.” Horwich and Jorge Galán (left), who has studied the molecular basis of infection by Salmonella and other food- borne pathogens, was elected to the National Academy of Sciences. Arthur Horwich shares the 2003, has devoted his career to un- Hartl will receive the award in Hong Shaw Prize in Life Science and Medicine for his contributions to understanding protein folding. derstanding protein folding—how Kong in September.

Student research on heart surgery gets a boost from new endowment In the 1960s, when cardiac surgery W.L. Glenn, m.d., then chief of the heart defects—and he trained numer- was still a young field, Horace C. cardiac surgery section. ous physician-​scientists who went on to Stansel Jr., m.d., was already making “As a junior faculty colleague, head surgery departments around the his mark at Yale as a skillful, innova- I learned a great deal from Stan,” country. “Stan personified the com- tive pediatric heart surgeon. A mem- recalls John E. Fenn, m.d., now clini- mitment to life-long learning that is so ber of the School of Medicine faculty cal professor of surgery at the medical necessary to medicine,” says Fenn. until his death in 1994, Stansel built a school. “He was a skilled surgeon To carry on Stansel’s legacy, the reputation as a consummate physi- who could think on his feet. He was Stansel family recently established an cian, researcher, and educator, and a master at knowing how to get out endowment that will provide support was a mentor to generations of medi- of trouble in the operating room, to Yale medical students conducting cal students and residents. and colleagues often called on him research in cardiac surgery. Known Known as “Stan” to friends and for assistance.” as the Horace C. Stansel Jr. Research colleagues, Stansel trained with Stansel also pushed the boundaries Fund, the endowment will provide courtesy of doris stansel Ormand C. Julian, m.d., at Presby- of surgical technique—the Damus- one- and two-year fellowships to Pediatric heart surgeon Horace Stansel, seen terian St. Luke’s Hospital in Chicago Kaye-Stansel procedure is still used by students with financial need, allowing in a 1978 photo with a patient, was a widely and was recruited to Yale by William pediatric surgeons to treat congenital them to pursue research // Gift (page 8) admired physician, researcher, and educator.

Non-Profit Org. inside this issue 1 Church St., Suite 300, New Haven, CT 06510-3330 U. S. Postage www.medicineatyale.org 2 Lifelines paid Since her first foray into research on the New Haven, CT brain bases of , neurosci- Permit No. 526 entist Marina Picciotto has been “hooked.” 3 Primary care—and much more Research in Yale’s Section of General Inter- nal Medicine shapes health care worldwide. 5 Cancer: a new day Results from a clinical trial show the goal of immunotherapy may be within reach. also Advances, pp. 3, 5 Out & About, p. 4 Grants and Contracts, pp. 6–7 @YaleMed f /YaleMed lifelines New section chief to be appointed for Otolaryngology Wendell G. Yarbrough, m.d., will be Marina Picciotto’s research not only sheds light on nico- named chief of tine’s effects on the brain, the Section of but also has implications for Otolaryngology for other important health at the School of issues, such as controlling Medicine and obesity and the development Wendell of effective pain medica- Yale-New Haven Yarbrough tions that do not lead to Hospital (ynhh). drug dependence. He will also be director of the head and neck cancer program at Smilow Cancer Hospital at Yale-New Haven as well as the co-director of the molecular virol- ogy research program at Yale Cancer Center (ycc). Yarbrough, whose appoint-

Marina Picciotto michael marsland ment begins August 1, comes to Yale from Vanderbilt University, where he is professor of otolaryn- gology and cancer biology and di- Making sense of addiction rector of the Barry Baker Labora- tory of Head and Neck Oncology. transport of ions across nerve cell them,” Picciotto says. For instance, Neuroscientist is focused He is also the Ingram Professor membranes. “It was very satisfying, in 2011, she and lab member Yann S. of Cancer Research and co-leader on the brain bases of because you could actually say, ‘this Mineur, ph.d., associate research scien- of the thoracic and head and neck goes with this’ [and make] pictures tist, teamed up with colleagues in the tobacco dependence program at the Vanderbilt Ingram that made sense. But I was always Section of Comparative Medicine to Cancer Center. sneakily trying to get back to [the show that a specific type of nicotinic Marina Picciotto, ph.d., says that while Yarbrough’s research con- question], What do those molecules receptor is the crucial trigger for nico- she was growing up in Manhattan, she centrates on the identifi cation of mean for complex behaviors?” tine’s effects on appetite suppression was “one of those scattered people tumor suppressors in head and It’s a question that has driven Pic- and weight-loss in mice. The study, who did well in school but got yelled neck cancers and the understand- ciotto’s research ever since. As a post- published in Science, could lead to new at by the teachers.” In science labs, ing of tumor growth. Recently, doctoral fellow at the Institut Pasteur in strategies to treat obesity. however, “that was never a problem.” his lab has focused on identifying Paris, France, she began studying nico- Picciotto also studies galanin, a At the magnet high school she subtypes of head and neck and tinic acetylcholine receptors (nAChRs), neuropeptide that works to modu- attended, students completed gradu- salivary cancers and the use of proteins in nerve cells that are acti- late acetylcholine but also heightens ation requirements early, and took on models that the lab has developed vated by the neurotransmitter acetyl- the effects of opiate drugs—many of full-time internships as seniors. Some- to test targeted agents. choline, but also respond to chemicals which are addictive. In 2003, she pub- what by chance, she came across an “I am confi dent that Dr. Yar- like nicotine. She describes this research lished research in Proceedings of the opening in a lab at the Rockefeller Uni- brough’s experience, leadership, the way many describe their first ciga- National Academy of Sciences showing versity, where she worked on studies and goals for head and neck cancer rette: “Once I started, I was hooked.” that in addition to increasing the pain- of feeding behavior in rats that would research and care will strengthen In 1995 she joined the School of fighting effects of opiates, galanin neatly foreshadow her later career. our head and neck cancer program Medicine’s faculty as an assistant pro- also decreased their addictive proper- After earning a b.s. in biology at at Smilow Cancer Hospital at fessor. Now the Charles B.G. Murphy ties. Her lab continues to explore how , Picciotto returned Yale-New Haven,” said Thomas J. Professor of Psychiatry and professor manipulating galanin might combat to Rockefeller as a ph.d. student in Lynch Jr., m.d., director of ycc and of neurobiology and pharmacology, addiction and withdrawal symptoms. molecular neuroscience. Her mentor physician-in-chief of Smilow Cancer Picciotto studies the links between neu- “We’re never going to understand there was , ph.d., who Hospital at Yale-New Haven. would later receive the Nobel Prize for rochemical signaling and behavior. Her all the molecules necessary for an his work—a great deal of which he primary interest is the role of nAChRs in entire behavior,” Picciotto says, “but had accomplished while on the Yale brain development and function, with the overall philosophy—that you can School of Medicine faculty—explaining a special emphasis on behaviors related say something meaningful about mol- the molecular basis of communication to nicotine addiction and smoking. ecules in the brain that can inform how among nerve cells in the brain. “What’s really cool about investi- we think about the molecular basis Editor Peter Farley In Greengard’s lab, Picciotto gating nicotinic acetylcholine receptors of behavior—that’s something that’s Assistant Editor Charles Gershman studied signal transduction and the is what happens when you stimulate approachable, and it’s worth doing.” Contributors Natalie Villacorta, Sarah C.P. Williams Design Jennifer Stockwell Medicine@Yale is published five times each year by the Office of Institutional Planning and Communications, , Class of 2012 urged to give patients ‘the best possible existence’ 1 Church St., Suite 300, New Haven, CT 06510-3330 Telephone: (203) 785-5824 Fax: (203) 785-4327

At this year’s commencement ceremo- “I risked my career because I asked E-mail [email protected] ny, held May 21, graduating medical myself why I became a neurosurgeon, Website medicineatyale.org students were treated to words of and it was to give patients the best Copyright ©2012 by . All rights reserved. wisdom from pediatric neurosurgeon possible existence,” he told the 100 If you have a change of address or do not wish to receive future issues of Medicine@Yale, please write to us at the Benjamin S. Carson Sr., m.d., who members of the Class of 2012. “When above address or via e-mail at [email protected]. recounted the story of a dilemma he you tell someone their loved one is do- Postal permit held by Yale University, faced in 1985 as a young doctor. ing well,” Carson said, “that’s the best 155 Whitney Avenue, New Haven, CT 06520 In his commencement address, feeling in the world.” Carson said he believed that a hemi- Carson, director of pediatric

spherectomy—removal of half of the neurosurgery at Johns Hopkins Medi- terry dagradi Robert J. Alpern, m.d. brain—was the best way to help one of cal Institutions, received national at- Pediatric neurosurgeon Benjamin Carson Dean and Ensign Professor of Medicine his patients, a girl with severe epilepsy tention in 1987 for the fi rst separation delivered the commencement address in May. Jancy L. Houck Associate Vice President for Development and who was suffering constant seizures. of twins joined at the back of the head. Director of Medical Development (203) 436-8560 But a senior physician, a distinguished Among his many awards is the such that he and his wife established Mary Hu neurologist, disagreed. Carson, a 1973 Presidential Medal of Freedom, the Carson Scholars Fund, which has Director of Institutional Planning and Communications graduate of Yale College, decided to which he received in 2008. Carson’s awarded more than $4.5 million to perform the surgery anyway. belief in the power of education is scholars in 45 states. Printed on recycled paper ♻

2 www.medicineatyale.org advances Health & Science News Th e medical school’s ‘hidden treasure’ The fda is slow? General Internal Medicine at Yale Not so fast! is a fl ourishing research powerhouse with a diverse portfolio of projects

As is the case at most medical schools, Yale’s Department of Internal Medicine is by far its largest, with over 300 faculty members. These faculty are organized into sections, most of which carry names easily mapped onto familiar medical istockphoto specialties: Nephrology, Geriatrics, Rheumatology, and so Doctors and patients who are impa- on. But the less descriptive name of the Section of General

tient for new drugs to hit the market Internal Medicine (gim), which claims 91 of the department’s carl kaufman often get the sense that the United faculty as members, makes its role far less The more than 90 faculty members in the Section of General Internal States’ drug approval process is a long obvious, which is perhaps what leads Dean Medicine provide quality primary medical care to patients, but also and slow road. But a new study by Robert J. Alpern, m.d., to call the section advance our knowledge and shape national policy through a diverse, well-funded research portfolio. School of Medicine researchers found “a hidden treasure of Yale.” that the U.S. Food and Drug Administra- Many of gim’s activities tion (fda) actually moves faster when are quite visible: The section On the rise reviewing drug applications than its is home to the many Yale counterparts in Canada and Europe. primary care physicians The first author of the study, who work at Yale Internal Patrick O’Connor second-year Yale medical student Medicine Associates (a Nicholas Downing, and a team led by part of Yale Medical Group), Yale-New Haven Assistant Professor of Internal Medicine Hospital, the VA Connecticut Healthcare Joseph S. Ross, m.d., m.h.s., examined System in West Haven, Conn., and clinics and publically available drug applications hospitals as far afi eld as Waterbury, Conn., from 2001 through 2010 to the fda, the which together have patient visits in the tens of European Medicines Agency (ema), and thousands each year. gim is also an important Health Canada. educational resource, contributing to three de- As reported May 16 in the New Eng- partmental residency programs and numerous land Journal of Medicine, for 72 drugs medical-student teaching services, which are eventually approved by all three agen- overseen by some of the medical school’s most cies, the average review time at the fda outstanding clinician-educators. was 90 to 100 days faster than at the The more “hidden” aspect of gim is that other agencies, and most of these drugs the section is a research powerhouse, with hit the U.S. market first. For all drugs a robust and extraordinarily diverse portfo- reviewed during the nine-year period, lio. The section’s physician-scientists study the fda took 322 days on average, while such topics as targeting insulin resistance the ema averaged 366 days and Health to prevent stroke and heart attacks, hiv and Canada took 393 days. comorbid disease in aging veterans, occupational asthma Research funding for investigators in Yale’s Section of General Internal and hearing loss, and the effectiveness of health-education Medicine, mostly from federal sources, has seen a steady increase over video games. They advise the national organizations that the past eight years, and is now approaching the $22 million mark. Tight rein on glucose judge hospitals. They investigate the diffusion of surgical no boon in diabetes robot technology and develop offi ce-based treatments for Theories have swirled around the field drug addiction and alcohol dependence. They examine the being done by up-and-coming junior faculty recruited in of diabetes research that aggres- epidemiology and treatment of congestive heart failure, the last fi ve or six years. sively controlling the glucose levels of cancer, and stroke. They develop curricular guidelines that For example, Joseph S. Ross, m.d., m.h.s., who joined patients with type 2 diabetes would are used in internal-medicine residency programs nation- the section in 2008, has already been a co-author of some reduce their risk of impaired kidney wide. And, in keeping with the whole-patient philosophy 70 peer-reviewed original research papers, including some function. But a new analysis of the of general internal medicine, they study the big picture, presenting methods to use Medicare data to assess quality data by Yale researchers has found no scrutinizing patient safety, clinical effectiveness, and dis- and performance at hospitals. Ross did a postdoctoral evidence that such treatment prevents crimination in health care. fellowship at Yale, then worked in New York City before ultimate kidney failure. “In many very good places, the general medicine section is being recruited back to Yale in 2010. “I was really excited to Steven Coca, d.o., m.s., assis- simply a group of clinicians to see primary-care patients,” says come back, partly because of the community of individuals tant professor of internal medicine, Jack A. Elias, m.d., Waldemar Von Zedtwitz Professor and in the section, some of whom I’d trained with,” he recalls. Chirag R. Parikh, m.d., ph.d., associate chair of the Department of Internal Medicine. By contrast, he “It just makes it a very stimulating and provocative envi- professor of medicine, and colleagues says, Yale’s gim physicians, “while providing expert primary ronment to be around so many good thinkers.” analyzed seven previous clinical trials care, are also doing things that are going to impact patient Those thinkers include Marcella Nunez-Smith, m.d., that together included 28,065 adult care and national policy. They’re going to impact how we take m.h.s., who established the Eastern Caribbean Health Out- patients monitored for up to 15 years. care of people from impoverished and affl uent backgrounds, comes Research Network (echorn), which O’Connor calls When those patients had been alter how we take care of people with heart failure, change the “Framingham Study of the Caribbean”—a reference to the treated more aggressively—with high- how we deal with drug addiction addiction and provide im- landmark Massachusetts heart study that has been providing er doses of drugs and a lower target portant insights into ways to provide less expensive and safer crucial information on cardiovascular disease // GIM (page 7) blood glucose level than is standard— patient care. They’re at a level that almost no other section of certain markers of kidney function did general medicine is at.” improve over those in patients treated Founded in 1975, the gim ranks among the highest of the with the standard drugs and glucose Department of Medicine’s sections in research funding. And Philanthropy fuels research targets. But the more aggressive treat- keeping pace with the department as a whole, it has recently The research advances emanating from Yale’s Section of General ment plan did not reduce the patients’ enjoyed meteoric growth. In 2002, it employed 39 full-time Internal Medicine (gim) require constant and consistent funding. risk of impaired kidney function, the faculty; today there are 91. Research funding totaled a healthy Private philanthropy often provides critical early support to re- need for dialysis, or eventual death $4 million in 2004, but by 2011 it had zoomed to $21 million, searchers who wish to pursue creative but untested approaches from kidney disease, the team reports the vast majority from federal sources (see fi gure). to important questions, allowing investigators to collect the initial data needed to successfully compete for external funding. in the May 28 issue of Archives of Inter- “We’re spread thick,” says gim Section Chief Patrick Your generosity can fuel research that will lead to tomorrow’s nal Medicine. G. O’Connor, m.d., m.p.h., of the section’s varied research treatments and cures. Current-use gifts may be directed for spe- projects. “We approach each of these research areas in a “Our analysis shows that inten- cific projects, while endowments can generate perpetual support sive glycemic control may improve scientifi cally rigorous manner, and the reputation of the for investigators just launching their careers or for a senior profes- some things about the kidney that we faculty and their success at getting funding in these areas sor with a sustained record of accomplishment. To find out more measure, but did not affect patients’ through peer-reviewed federal sources speaks for itself.” about how to contribute to gim’s research projects, contact outcomes,” says Coca. Some of the most exciting work in the section, he adds, is Richard Galiette at 203-436-8529 or [email protected].

Medicine@Yale June 2012 3 out & about

March 3, 2012 Patients of the Yale Children’s Diabetes 1 March 31, 2012 The medical Program and their families attended the annual Family school’s Department of Psy- Day Symposium held at the Yale School of Nursing. The chiatry hosted Neuroscience half-day symposium included lectures, discussions, and 2012, an annual symposium interactive programs for adults and children. 1. Bryce aimed at mental health Ferguson. 2. Sasha Averko, clinical services manager professionals and consum- at Massachusetts-based Insulet Corporation, gives a ers throughout the State of demonstration of an insulin management system. Connecticut. (From left) 3. William V. Tamorlane, m.d., professor of pediatrics, John H. Krystal, m.d., the speaks to attendees. Robert L. McNeil Jr. Professor 2 3 of Translational Research and chair of the Department of Psychiatry; “Dr. Ruth”

shane seger Westheimer, ed.d., recipient of the department’s seventh annual Research Advocacy Award; and Robert E. Davidson, ph.d., president of the Connecticut chapter of the National Alliance on Mental Illness. carl kaufman (3)

May 8, 2012 Roger Daltrey, founder and lead singer of English rock band The Who, who has a long record of charitable work for teenagers and young adults with cancer, May 8, 2012 Student Research Day, an annual event, showcased medical students’ the- visited doctors and patients at the medical school and at Smilow Cancer Hospital ses, an integral part of the Yale System of medical education, and a requirement for at Yale-New Haven. 1. Daltrey signs autographs for Darrel Janis (left), manager of students since 1839. A record 92 students exhibited posters in The Anlyan Center dis- the medical school’s Marigolds Dining Service, and Joyce Brown, banquet server for playing the results of their research. 1. John M. Leventhal, m.d., professor of pediatrics, Marigolds. 2. (From left) Tara Sanft, m.d., assistant professor of medicine and medical and Jennifer Duffy ’13. 2. Students in the Medical Scientist Training Program (mstp), director of the Survivorship Clinic at Yale Cancer Center; Daltrey; Stuart E. Seropian, known informally as the m.d./ph.d. Program, with mstp Director James D. Jamieson, m.d., associate professor of medicine; Hari A. Desh- 1 m.d., ph.d., professor of cell biology (back row, second from left). (Front row, from pande, m.d., assistant professor of medicine and sur- left) Nancy Allen ’14, Ruth Wang’ondu ’15, and Katherine Uyhazi ’12. (Back row, from left) gery and assistant clinical professor of nursing; Michael Chen Wang ’14, Jamieson, Corey Frucht ’12, and Daniel Okin ’14. 3. (From left) Alice Li ’12 E. Hurwitz, ph.d., m.d., assistant professor of medicine; and Kofi-Buaku Atsina, m.d. ’11. 4. (From left) Kwame Atsina ’12 and Panos Christakis ’12. and Clifford W. Bogue, m.d., interim chair and associate professor of pediatrics, chief of the Section of Pediatric 1 2 Critical Care Medicine, and physician-in-chief at Yale- New Haven Children’s Hospital. 2

3 4 john curtis (2)

May 21, 2012 This year’s Commencement ceremony marked the end of medical school for the Class of 2012, and also set a new record: the class’s senior gift campaign raised more than $1,600 for the Alumni Fund, with 84 percent of graduating students partici- pating. 1. Mona Sadeghpour (second from right) with (from left) her mother, Maryam

terry dagradi (4) Dargahi; her brother, Mehrad Sadeghpour; and Ardavan Akhavan, m.d. 2. John Gilbert (left) and Whitney Sheen, who spearheaded the class gift effort. 3. Michael Ma (left) and Henry Park. 4. (From left) Richard Belitsky, m.d., the Harold W. Jockers Associate Professor of Medical Education, associate professor of psychiatry, and deputy dean for education; and Matthew Singleton with his son Matthew Singleton Jr.

1

2 3 4 terry dagradi

May 11, 2012 A reception was held in the Medical Historical Library marking the elec- tion of Jorge Galán, ph.d., d.v.m., chair and the Lucille P. Markey Professor of Microbial Pathogenesis, to the National Academy of Sciences (see related story, page 1). (From left) Galán; Ruslan M. Medzhitov, ph.d., the David W. Wallace Professor of Immunobiology and Howard Hughes Medical Institute investigator; , ph.d., professor of immunobiology and of molecular, cellular, and developmental biology; and Craig R. Roy, ph.d., professor of microbial pathogenesis. john curtis terry dagradi (3)

4 www.medicineatyale.org advances Health & Science News Turning on immunity to shut off cancer Tiny genomic change In multicenter trial, unleashing the makes big difference immune system’s power arrests several forms of late-stage disease

When Lieping Chen, m.d., ph.d., was training to be an oncologist in the 1980s, the lack of effective cancer treatments made it a depressing job. “That’s why I quit clinical practice,” he says. But Chen soon shifted to research, focusing on the istockphoto role of the immune system in cancer. A single regulatory region in the mam- For decades Chen and other scientists have grappled malian genome underlies a key differ- with the mystery of why our immune systems—such brave ence between mammals’ brains and warriors when it comes to other diseases—mostly sit on the those of other organisms, says a new sidelines while cancer invades the body. Though our bod- study by School of Medicine scientists. ies produce T cells, the immune system’s soldiers, in re-

A hallmark of mammalian brains is the sponse to cancer, these cells don’t seem to have much of an jerry domian corticospinal system, which, in humans, effect. Scientists have yearned to find some way to “switch (From left) Mario Sznol, Scott Gettinger, Harriet Kluger, and Lieping connects parts of the brain and the on” the immune system to attack cancer cells, an approach Chen were involved in a nine-center clinical trial of a drug that disarms spinal cord to make behaviors such as that could target the disease precisely while sparing nor- a molecular defense mechanism mounted by tumors, allowing the im- mune system to effectively attack cancer. speech and tool-use possible. mal cells, resulting in greater effectiveness and fewer of the In the new work, led by Nenad side-effects of conventional treatments. And because the Sestan, m.d., ph.d., associate professor immune system “remembers” invaders it has encountered, found that while PDL-1 is expressed in healthy tissue at low of neurobiology, Yale researchers dis- the response to immunotherapy should be long-lasting. levels during an immune response, it is over-expressed in covered that a genomic region called E4 On June 2 in the New England Journal of Medicine, a many human tumors. determines whether the corticospinal multi-center team that included Chen and two Yale colleagues “Cancer steals this mechanism,” Chen, professor of im- system emerges during development reported that in an early clinical trial of bms-936558 (a drug munobiology and medicine, says. In the presence of cancer, by exerting regulatory control over the developed by Bristol-Myers Squibb) enrolling 296 patients, an immune response is triggered properly, and T cells flock gene Fezf2, which directly mediates the tumors had regressed significantly in about one in three to to the tumor. But the T cells contribute to their own demise system’s formation. When the scien- one in five patients with non-small-cell lung cancer, kidney by releasing signaling molecules called cytokines, which tists inactivated E4 in mice, the animals cancer, or melanoma. The results, which received wide media induce the tumor to produce PD-L1. When PD-L1 binds to lacked corticospinal neurons. coverage, were presented the same day at the annual meeting PD-1 on T cells, those cells are either inactivated or die off. In mammals, the E4 region has of the American Society of Clinical Oncology in Chicago, Ill. bms-936558 prevents this immune suppression by blocking changed little over evolutionary time, For reasons that are not fully understood, the small the PD-1 binding site and keeping PD-L1 at bay. but varies considerably among other or- number of patients with colorectal or prostate cancer in the Tests on tumor samples taken from a subset of patients ganisms. The team’s results, published trial did not respond to bms‑936558. But the response in in the newly published trial revealed that tumors that did in the May 31 issue of Nature, suggest lung cancer patients is remarkable, says Professor of Medi- not express PD-L1 did not respond to treatment, while 36 that just a few small changes in the E4 cine Mario Sznol, m.d., because previously immunothera- percent of PD-L1-positive tumors showed a response, indi- region marked a crucial turning point in pies showed effectiveness only in melanoma and kidney cating that PD-L1 may be a useful biomarker for identify- the evolution of mammals. cancers. Chen points out that the patients in this trial had ing patients who will most benefit from anti-PD-1 drugs. all previously been heavily treated with therapies that likely The PD-1 pathway is only one inhibitory strategy tu- depleted their immune systems; if administered to patients mors may employ to silence the immune system. Last year Probing the cause of in earlier stages of cancer, the drug should be even more ef- the fda approved the drug ipilimumab (marketed as Yer- diabetes-related pain fective, he says. voy), which blocks another checkpoint molecule expressed Uncontrollable pain and tingling are The other exciting finding of the study, says Sznol, on the surface of T cells known as ctla-4, for the treat- all-too-familiar sensations for most who was instrumental in bringing the trial to Yale, is the ment of advanced melanoma. Ipilimumab has a response diabetics. So-called neuropathic pain consistent, durable regression of cancers: 20 of 31 responses rate of about 11 percent, but anti-PD-1 therapies have been occurs in more than half of people with lasted for at least one year, a result only rarely observed shown to be safer and more efficacious. Chen believes diabetes—and the older someone is, with traditional chemotherapy or other forms of therapy that this is due to limited PD-L1 at sites of inflammation, and the longer they’ve had diabetes, that target specific characteristics of tumors. including tumors. The ctla-4 ligand, on the other hand, the more likely they are to experience Since similar results were seen at each of the nine controls an earlier stage of immune system activation, so it. Though it often plagues the arms, centers participating in the trial, Sznol considers it highly blocking its receptor has led to severe toxicities. There are legs, hands, and feet, neuropathic pain unlikely that the drug’s effectiveness is a fluke. Scott N. side-effects of PD-1 blockage—in the current trial, three can occur in any body part. Doctors Gettinger, m.d., associate professor of medicine, who re- patients died of drug-related lung inflammation—but Chen have long struggled to understand the cruited many lung cancer patients for the trial, agrees, saying thinks they can generally be successfully managed. source of the pain, let alone treat it. the response in those patients “opens the door to looking at Jedd D. Wolchok, m.d., ph.d., of Memorial Sloan-Ket- Now scientists at the School of other solid tumors,” such as breast cancer. The majority of his tering Cancer Center, who was not involved in the current Medicine and at the VA Connecticut patients experienced few or no side effects, he says, and none trial, says that the new results are important because, along Healthcare System, in West Haven, of those typical of chemotherapy such as hair loss, a drop in with the success of ipilimumab, they are the second clear have proposed a new theory on the blood-cell counts, and fatigue. “This is probably the best drug demonstration that unleashing the immune system can origin of neuropathic pain in diabetes. I have ever given to patients with lung cancer,” Gettinger says. produce durable regressions in cancer. Previous work by Andrew Tan, The long road to these results began in 1991, when Although bms-936558 was quite effective when used ph.d., associate research scientist in Chen, then at the Mayo Clinic, discovered a protein called alone, the Yale researchers believe that it will be most use- neurology, and Stephen G. Waxman, B7-H1 that had the power to suppress the activity of T ful combined with other therapies. Sznol is currently col- m.d., ph.d., the Bridget Marie Flaherty cells. He did not know the T cell molecule responsible for laborating with Wolchok on a clinical trial that targets both Professor of Neurology, suggested this effect, but in 2000, researchers from Harvard Medical PD-1 and ctla-4, and Chen believes that adding drugs that alterations in the size, density, School’s Dana-Farber Cancer Institute and the University that block T cell checkpoints could even reverse the low and overall distribution of dendritic of Kyoto found that B7-H1 binds to another protein called success rate of cancer vaccines seen thus far. spines—signal-receiving structures that programmed death 1 (PD‑1), a “checkpoint” receptor on “We’re just at the beginning of a sort of paradigm shift project from nerve cells—may underlie the surface of T cells that suppresses their activity. in the treatment of cancer,” Sznol says, who believes that neuropathic pain that can follow nerve The B7-H1 protein is now usually called PD-L1, to immunotherapy will surpass standard treatments like and spinal cord injuries. In the May 16 reflect its role as a binding partner, or “ligand,” for PD-1. chemotherapy over the next five years. As for bms-936558, issue of The Journal of Neuroscience, Chen wondered if PD-L1 binding might be one of the Chen is hoping to see fda approval in two to three years, Tan, Waxman, and colleagues report mechanisms that allows cancer to evade an immune re- but “it should be approved tomorrow,” Sznol says: “It’s that when they gave diabetic rats a sponse, and in experiments with mice lacking the protein, better than the approved agents. I have patients who have drug that restores dendritic spines to he found that the PD-1 pathway is crucial to the normal benefited enormously from this drug. For some patients it’s a normal condition, nerve function functioning of the immune system: a prolonged immune a home run. For the field it may be a triple.” And while cur- improved and pain lessened, findings response can be very damaging to the body, so tissues rent treatments prolong life for months or a couple of years, that could lead to new treatments for express PD-L1 to turn the response off. Chen dubbed the Sznol says, “these new therapies may eventually offer the diabetes-related neuropathic pain. pathway the “peacekeeper” for its protective role, but he possibility of cure.”

Medicine@Yale June 2012 5 Finding for hiv, TB, and mdr/xdr TB in Rural 3 years, $339,250 • Pamela Chang, Jane Coffin Grants and contracts awarded South Africa, 5 years, $132,770 • Robert Sherwin, Childs Memorial Fund, Sensing Gut Microbiota nih, Yale Clinical and Translational Science Award through G-Protein Coupled Receptors, 1 year, to Yale School of Medicine Program, 5 years, $12,463,224; nih, Yale Clinical $149,500 • Tara Chaplin, Alcoholic Beverage and Translational Science Award Program, Medical Research Foundation (abmrf), Responses May–August, 2011 5 years, $3,902,930; nih, Yale Clinical and Transla- During Parent-Child Interactions and Alcohol Use tional Science Award Program, 5 years, $1,778,895 Behavior in Adolescents, 2 years, $100,000 Mark Shlomchik, nih, Transfusion of Donor Lieping Chen, Amplimmune, Inc., The Develop- Federal Effector Memory T Cells for gvl and Immune ment of New Immune Modulatory Targets for Serap Aksoy, nih, Factors in Emergence of by Ubiquitin Modifications, 3 years, $151,026 Reconstitution, 4.9 years, $2,201,362 • Warren Therapy, 3 years, $500,000 • Keith Choate, Doris New Sleeping Sickness Foci in Uganda, 3 years, Michael Hodsdon, nih, A Device for Automating Shlomchik, nih, Role of Tissue Antigen Presenting Duke Charitable Foundation, Genetics and $175,077 • Kevin Behar, nih, Ex Vivo Assay For Titration Experiments in High-Resolution nmr Cells in gvhd, 5 years, $2,101,054 • Michael Pathobiology of Disorders of Keratinization, In Situ Brain-Wide Mapping of Glutamate/gaba Spectroscopy, 3 years, $622,500 • Ralph Simons, nih, Arteriogenesis and Arterial Branch- 3 years, $486,000 • Jaehyuk Choi, Dermatology Metabolism, 3.8 years, $2,076,727 • Kathleen Hoffman, nih, Pathophysiology of Auditory Hal- ing, 3.9 years, $2,557,296 • Jody Sindelar, nih, Foundation, Transposon Insertional Mutagensis Belanger, nih, Effects of Fine Particle Composi- lucinations, 1.8 years, $1,713,285 • Yiyun Huang, Yale Training Program in Addiction, 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Sabrina Diano, American Diabetes Association, tors in Cannabis Dependence, Withdrawal, and 2 years, $446,977 • Robert LaMotte, nih, Itch solidation of Drug Memories, 11 months, $778,019 Inc., Role of Hypothalamic Prolyl Endopeptidase Abstinence, 1.9 years, $455,749 • Nihal deL- Neurons Studied In Vivo, 2 years, $456,073 Jon Vermeire, nih, Defining Target Specificity of in Glucose Homeostasis, 3 years, $339,250 anerolle, U.S. Army Medical Research Acquistion Benjamin Land, nih, Control of Cortico-Limbic Oxadiazole 2-Oxides in Ancylostoma ceylanicum, Michael DiGiovanna, Connecticut Breast Health Activity (DoD), Dissection of Macrophage Inhibi- Feeding Behavior Using Optogenetics, 2 years, 1.9 years, $269,973 • Scott Weatherbee, nih, Skin Initiative, Inc., Combination Targeting of igf-I tory Factor (mif) in Neuronal Cell Injury after $103,480 • Una Makris, nih, Understanding the Development Analysis in Mutant Mouse Lines, Receptor and her2 in Breast Cancer, 1 year, Traumatic Brain Injury 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6 www.medicineatyale.org in Depression, 2 years, $60,000 • Clayton Halde- Cancer Invasion Control Switch, 1 year, $25,000 lowship, 6 months, $4,200 • Ali Ozturk, Con- During Acute Infection, 10 months, $55,538 man, Howard Hughes Medical Institute, The Pradeep Kotapurathu Kurup, Michael J. 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Freitas, American vents Allergic Airway Hyper-Responsiveness, Nadia Ward, United Way of Coastal Fairfield Research on Schizophrenia and Depression Heart Association, Microvascular Plasticity in 3 years, $450,000 • James Rothman, Partner County, Yale-Bridgeport gear up Partnership, (narsad), Visual Cortical Neuroplasticity as a Aging and Alzheimer’s Disease, 5 months, $21,663 University Fund, Deciphering Fusion in Intracellu- 1 year, $70,000 • Kyle Williams, Massachusetts Developmental Biomarker in Schizophrenia, Xiaomei Ma, Regents University of California, lar Trafficking, 3 years, $390,999 • Margretta General Hospital, Characterization of the 2 years, $60,000 • Shinu John, Arthritis Founda- San Francisco (nih), Genome-Wide Association Seashore, Children’s Research Institute (cri), Immune Response to ivig Treatment in pandas tion, Cellular and Molecular Mechanisms by Study of Childhood Leukemia by Hispanic Status, Longitudinal Studies for Urea Cycle Disorders, Infections, 1 year, $74,548; American Academy of which tlr Regulates Lupus Disease, 2 years, 10 months, $118,796 • Stacey MacGrath, Ameri- 6 months, $23,142 • Gerald Shadel, Glenn Foun- Child and Adolescent Psychiatry, Novel Models $100,000 • Roger Jou, Nat’l Alliance for can Heart Association, The Role of Arg and Nck dation for Medical Research, Biological Mecha- of Obsessive Compulsive Disorder in Animals: Research on Schizophrenia and Depression as a Scaffold for Contract and n-was in Arp 2/3 nisms of Aging, 2 years, $60,000 • Eugene Microglia and the Neurophysiology of Compul- (narsad), The Neural Basis of Weak Central Complex-Mediated Cell Edge Protrusion, 2 years, Shapiro, Children’s Memorial Hospital (nih), sive Behavior, 1.2 years, $15,000 • Melissa Coherence in Autism Spectrum Disorders, 2 years, $44,000 • Abeel Mangi, Mount Sinai School of Long-Term Outcome of Childhood-Onset Epilepsy, Woolls, American Heart Association (Founders $52,159 • Amy Justice, Johns Hopkins University, Medicine (nih), Network for Cardiothoracic Surgi- 1 year, $732,326 • Ruth Sharf, Nat’l Alliance for Affiliate), Decoding the Molecular and Cellular North American aids Cohorts on Collaboration cal Investigations in Cardiovascular Medicine, Research on Schizophrenia and Depression Mechanisms that Regulate Hemogenic Endothe- and Design (naaccord), 5 years, $273,545; Uni- 1.9 years, $52,140 • Alexander Marzuka, Howard (narsad), Novel Approach to Understanding lium, 2 years, $44,000 • Meiyu Xu, Tourette versity of Pennsylvania (nih), Clinical Prediction Hughes Medical Institute, Evaluating the Role of Atypical Antipsychotic Induced Weight Gain, Syndrome Association, Inc., Molecular Adapta- of Hepatotoxicity and Comparative Hepatic Telomeres in Melanoma Formation and Progres- 2 years, $60,000 • Mark Shlomchik, Roche Labo- tions to Cholinergic Interneuron Ablation in a Safety of Medications, 1 year, $70,000 • Gerald sion, 1 year, $39,000 • Richard Mattson, Pfizer ratories, Inc., Investigation of Efficacy and Mech- Novel Mouse Model of Tourette Syndrome, 1 year, Kayingo, Physician Assistant Foundation, Capac- Inc., U.S. Pharmaceuticals Group, Characteriza- anism of GA101 in Lupus Mice, 1 year, $75,122 $40,000 • Ke Xu, American Psychiatric Associa- ity Building for Non-Communicable Diseases in tion of a Neural Progenitor Cell Biomarker Using Frederick Sigworth, Purdue University (nsf), tion, To Identify Susceptibility Genes for Schizo- Uganda, 1 year, $17,200 • Jun-Dae Kim, American Magnetic Resonance Spectroscopy, 1 year, idbr: High Throughput Instrumentation for Lipid phrenia: Whole Exome Sequencing Using Next- Heart Association (Founders Affiliate), Defining $20,000 • Linda Mayes, Nat’l Society for the Bilayers and Patch-Clamp, 2.9 years, $290,431 Generation Sequencing for Ketamine Associated the Function of Disabled Homolog 2 (Dab2) Medi- Prevention of Cruelty to Children, Minding the Michael Simons, Fondation Leducq, Transatlan- Psychosis, 1 year, $45,000 • Bao-Zhu Yang, Nat’l ating bmp Signaling-Induced Angiogenesis, Baby: nspcc, 1 year, $233,657 • Wang Min, Okla- tic Network on Therapeutic Arteriogenesis and Alliance for Research on Schizophrenia and 2 years, $80,000 • Sang Taek Kim, American homa Medical Research Foundation (DoD), Metabolism Modulation, 1.3 years, $191,527 Depression (narsad), Genetic Basis of Comorbid College of Rheumatology, Characterization of Epsin, a Novel Regulator in Prostate Cancer Pro- Brian Smith, American Society of Hematology, Depression and Cocaine Dependence, 2 years, Human Follicular Helper T Cells and Their Clinical gression and Metastasis, 1 year, $17,831 • Evan Clinical and Laboratory Hematology/Hematopa- $60,000 • Zhong Yun, American Heart Associa- Application, 2 years, $125,000 • Megan King, Morris, Indiana University (nih), Dopamine and thology, 2 years, $50,000 • Megan Smith, Nat’l tion, Adipose Hypoxia Signaling and Cardiomyop- Searle Scholar Program, Mechanical Coupling of Unpredicted Alcohol Delivery: Effects of Alcohol Alliance for Research on Schizophrenia and athy, 3 years, $198,000 • Hitten Zaveri, American the Nucleus and Cytoplasm, 3 years, $300,000 Consumption, 1 year, $80,190 • Mary Murphy, Depression (narsad), Effects of Maternal Depres- Epilepsy Society, Fifth Internat’l Workshop on Steven Kleinstein, Mayo Clinic College of Medi- Society for Academic Emergency Medicine, sion and Antidepressants on Children, 2 years, Seizure Prediction, 1 year, $20,000 • Lingjun Zuo, cine (nih), Bioinformatics Approach to Influenza Alcohol and Tobacco sbirt for Emergency Depart- $59,792 • Serena Spudich, aids Clinical Trial Nat’l Alliance for Research on Schizophrenia and A/H1N1 Vaccine Immune Profiling, 1 year, $28,714 ment Patients, 2 years, $150,000 • Laura Nikla- Group, actg Neurology Subcommittee, 1 year, Depression (narsad), dna Methylation of dtnbp1 Anthony Koleske, Connecticut Breast Health Ini- son, Foundation for Anesthesia Education and $59,299; University of California, San Francisco and Glutamatergic Pathway Genes in Schizophre- tiative, Inc., Developing Drugs to Target a Breast Research, faer Medical Anesthesia Student Fel- (nih), Long Term cns Consequences of Treatment nia, 2 years, $60,000

// GIM (from page 3) since 1948. Awarded other rwj Scholars programs. supportive environment for all junior country, including in Boston, Balti- a five-year, $5.3 million nih grant last “I think that having that incredible faculty, he adds. more, and Los Angeles. Mentored by fall, echorn will examine disease program here has allowed Yale to pick Emily Wang, m.d., m.a.s., as- gim senior faculty member David A. burden and conduct capacity-building the best graduates each year and get sistant professor of medicine, cites that Fiellin, m.d., professor of medicine and studies in that region in collaboration them to stay,” says Alpern, who says environment as key to her work with public health, and cardiologist Harlan with four island universities. the rwj Scholars initiative has been some of the most vulnerable patients: Krumholz, m.d., the Harold H. Hines Ross and Nunez-Smith share a a crucial ingredient in gim’s research ex-prisoners. During her internal Jr. Professor of Medicine and direc- special bond with many other gim fac- excellence. “There’s absolutely been medicine residency at the University of tor of the Yale rwj Clinical Scholars ulty members, including O’Connor: a tremendous synergy between the California-San Francisco, she cared for program, Wang has received a grant they are alumni of Yale’s Robert Wood Clinical Scholars program and the diabetic patients in the emergency de- from the National Heart, Lung, and Johnson (rwj) Clinical Scholars section,” agrees Associate Professor of partment who had lost access to medi- Blood Inst itute to study cardiovascular program. The School of Medicine is Medicine Cary P. Gross, m.d., associ- cal care after serving their sentences. disease in the formerly incarcerated. one of only four sites in the nation that ate director of the Yale program and “It seemed like a frustrating and “What I’ve always found so re- host the program, a prestigious post- an alumnus of Johns Hopkins’ rwj inefficient way to care for any popula- freshing and invigorating here is that residency fellowship for physicians program. “Because the Scholars pro- tion,” she recalls. She sought parolees’ people really want to establish new planning careers in policy, leader- gram is at Yale, we have a home-field advice, then opened a clinic there in ties and share their ideas and share ship, and/or research. In addition to advantage when it comes to recruiting 2006, which has since served 700 their resources. Faculty members here regularly hosting rwj Scholars, gim’s talented Clinical Scholars graduates to patients and provided a model not really do not want to work in silos,” faculty includes alumni of the Yale come and join us,” and the example set only for a similar clinic in New Haven, says Gross. “I’ve been here 10 years. I’ve program along with alumni of three by internist-scholars makes for a very but also for 17 other sites around the never even thought of moving.”

Medicine@Yale June 2012 7 Two Yale scientists are inducted into the Awards & Honors American Academy of Arts and Sciences

Jonathan B. Demb, ph.d., associate professor of ophthalmology Two Yale scientists have been elected and visual sciences and of cellular and molecular physiology, has to the American Academy of Arts and received the Cogan Award from the Association for Research in Vi- Sciences. Richard P. Lifton, m.d., sion and Ophthalmology. Demb was honored for his “outstanding ph.d., chair and Sterling Professor of contributions to vision science in the retina and in the central visual Genetics and Howard Hughes Medi- pathways emphasizing three areas of visual science: quantitative cal Institute investigator, and John R. psychophysics, retinal microcircuitry, and molecular synaptic mecha- Carlson, ph.d., the Eugene Higgins nisms,” according to the association’s website. Demb joined the Yale Professor of Molecular, Cellular, and faculty in 2011. Jonathan Demb Developmental Biology, were named John Carlson Richard Lifton fellows of the Academy in April, and will be formally inducted at an Octo- of a free, independent, and virtuous ber ceremony in Cambridge, Mass. people.” Today it is an international Jack A. Elias, m.d., the Waldemar Von Zedtwitz Professor of Medicine The Academy was founded in 1780 society whose 4,600 fellows and 600 and chair of the Department of Internal Medicine, delivered the J. Burns during the American Revolution by foreign honorary members are drawn Amberson Lecture at the American Thoracic Society International Con- John Adams and other leaders of the from multiple disciplines. The current ference in May. The lecture is given by individuals who have made major new nation, to “cultivate every art and membership includes more than 250 lifetime contributions to pulmonary research or clinical practice. Elias science which may tend to advance the Nobel laureates and more than 260 studies the cellular and molecular biology of processes related to lung interest, honor, dignity, and happiness Pulitzer Prize winners. injury and repair. His work established current concepts of the inflamma- tory mechanisms of lung diseases, including asthma, chronic obstructive pulmonary disease (copd), acute lung injury, and pulmonary fibrosis. Jack Elias

Medical school immunobiologist honored for Tamas L. Horvath, d.v.m., ph.d., Jean and David W. Wallace Profes- contributions to understanding of antigens sor of Biomedical Research and chair of the Section of Comparative Medicine, has been honored by the Endocrine Society with the 2012 Ernst Oppenheimer Award, one of the society’s Laureate Awards. The American Association of Im- Scientist Award Horvath, also professor of neurobiology and of obstetrics, gynecol- munologists (aai) has awarded the from the American ogy, and reproductive sciences, is director of the Yale Program on 2012 aai-Life Technologies Meritori- Society for Histo- Integrative Cell Signaling and Neurobiology of Metabolism. His work ous Career Award to Peter Cresswell, compatibility and has played a key role in the development of the current model of ph.d., the Eugene Higgins Professor Immunogenetics, a neuroendocrine regulation of energy balance. Tamas Horvath of Immunobiology, professor merit Award from of cell biology and dermatology, the National In- and Howard Hughes Medical Insti- stitutes of Health, tute investigator. Peter Cresswell and the 2010 Alexandra J. Lansky, m.d., associate professor of medicine and direc- Cresswell was honored for “his Buchanan Medal, presented by the tor of the Yale Cardiovascular Research Group and the Yale Valve groundbreaking contributions to the Royal Society in the U.K. for distin- Program, has received the Wenger Award for Excellence in Medical field of immunology in the area of anti- guished contributions to the medical Leadership. Lansky was honored “for her longtime commitment to gen processing and presentation.” sciences, among other honors. pursuing gender-based outcomes research and teaching interven- Prior to joining the Yale faculty He is a member of the U.S. tional cardiology and prevention,” according to a press release. The in 1991, Cresswell was on the faculty National Academy of Sciences and Wenger Awards are given by WomenHeart: The National Coalition at the Duke University Medical the American Academy of Arts and for Women with Heart Disease to recognize those who have set Center. His past honors include Sciences, and is a Fellow of the precedent in advancing women’s heart health. Alexandra Lansky the 1995 Rose Payne Distinguished Royal Society.

explore milestones in our // Gift (from page 1) projects in both labo- the heart is an extremely complex 200-year history on Facebook Timeline ratory and clinical settings. machine. “We need a dynamic model “Medical school was a struggle for to predict how a heart will behave facebook.com/YaleMed Stan financially,” says Stansel’s widow, after a surgical intervention, so we Doris Stansel. “He was very dedicated use advanced imaging techniques to to his students and would be pleased build computer models of the beating to know that we are helping to make heart. The many variables, including these opportunities available to them.” mechanical and fluid dynamics as well Dean Robert J. Alpern, m.d., says as human tissue properties, require an that the new fund provides important interdisciplinary research group, with backing for the unique “Yale system” students playing an important role.” of medical education, which places Or students may work with great emphasis on original research Pramod N. Bonde, m.d., who is de- by students. veloping wireless power supplies for For example, with David D. Yuh, cardiac assist devices. Some patients m.d., chief of the Section of Cardiac with failing hearts are outfitted with Surgery, students are working at the a mechanical pump, with a power frontiers of surgical research. “Advanc- cord routed through the abdomen. es in mechanical, computational, and To eliminate the cord—a frequent biomedical engineering have led to sur- source of infection—Bonde is testing gical therapies until recently thought charging technologies that transmit unattainable,” Yuh says. “My section is energy to an internal battery via elec- engaged in exploring minimally inva- tromagnetic waves. sive and even nonsurgical techniques to “Yale faculty break new ground replace or repair diseased heart valves, every day, and students in our pro- and a new generation of devices to gram engage directly in generating replace failing hearts functionally are this new knowledge,” Alpern says. already in clinical trials.” “I am grateful that the Stansel family Research to advance cardiac is supporting a program we see as a surgery is a particularly complex critical component in the education of undertaking, explains Yuh, because tomorrow’s physician-scientists.”

8 www.medicineatyale.org