may/june 2010 volume 6, issue 2 Advancing Biomedical Science, Education, and Health Care

Yale’s new Research Accelerator will bring scientists together As a pulmonologist who conducts a methods—searching the literature or people over age 40 find meaningful great deal of translational research on Internet, for instance—are often inef- work in a tough economy. diseases of the airway and lungs, ficient. “There may be people in my Chupp and Greenberg built a Geoffrey L. Chupp, m.d., associate own building that I don’t even know prototype, which they demonstrated professor of medicine and director of about whom I could work with or get for Robert S. Sherwin, m.d., the the Yale Center for Asthma and Airway information from,” Chupp says. C.N.H. Long Professor of Medi- Disease, often finds himself in unfa- Chupp hatched an idea for a cine. As director of the Yale Center miliar scientific territory. “I’ll find a Web-based resource that would make for Clinical Investigation (ycci), molecule that’s interesting or I’ll come interdisciplinary scientific collabora- Sherwin oversees many of the School william sacco upon some piece of data where I don’t tion quicker and easier. In 2008, he of Medicine’s efforts to accelerate With the backing of the Yale Center for really know what I’m dealing with,” approached longtime friend Steven the pace of clinical and translational Clinical Investigation (ycci) and ycci Director Chupp says. Greenberg, a Westport, Conn.-based research. Robert Sherwin (right), Steven Greenberg But in the fast-moving world of journalist and attorney who recently “We presented our site to Dr. (left) and Geoffrey Chupp (middle) have launched the ycci Research Accelerator, a new biomedical research, finding people launched Jobs4.0, an online em- Sherwin because we felt that the Web-based platform that makes collaboration with specific expertise using traditional ployment resource designed to help goals of ycci and // Chupp (page 4) easier for Yale scientists.

Homecoming for Ten years on: a new genomic revolution a top cell biologist A decade after the first human genome map, is packed to rafters Yale’s new dna sequencing facility provides a For several years, the School of wealth of information at unprecedented speed Medicine’s Department of has invited a distinguished In June 2000, the human genome revolution began with a scientist to Yale each year to deliver bang. At a White House ceremony, genome pioneers Francis the George Palade Lecture, named S. Collins, m.d., ph.d., and J. Craig Venter, ph.d., joined in honor of a beloved former Yale then-president Bill Clinton and British Prime Minister Tony faculty member and Nobel Prize Blair to announce the completion of a “working draft” of winner whose integration of the 3 billion base pairs of Dna that comprise our genetic electron microscopy and biochem- endowment. That effort took 10 years, $3 billion, and the istry helped lay the foundation of work of 900 automated Dna sequencing machines scattered modern cell biology. in laboratories around the world. Following Palade’s death at age Ten years later, one technological advance after another 95 in 2008, the department decided has driven the speed of genomic analysis up and the cost to “elevate the status of the lecture- down: the latest Dna sequencing technology is eight orders ship to a university-wide event, of magnitude faster than that used in 1987; over the last michael marsland a major international lectureship decade, costs have plummeted 14,000-fold. In a recent issue Shrikant Mane (left), director of the Yale Center for Genome Analy- renamed the George E. Palade sis (ycga) and Kira Fitzsimons, biotechnology assistant, discuss data of the journal Nature that marked the 10th anniversary of produced by the ycga’s latest gene sequencers, which can sequence the Memorial Lectureship in Cell Biol- the human genome’s first draft, Collins, now director of the equivalent of more than 300 complete human genomes per month. ogy,” says Chair James E. Roth- National Institutes of Health, provided a vivid description man, ph.d., the Fergus F. Wallace of what these developments mean for biomedical research. discovery—every life scientist seems to be making use of it in Professor of Biomedical Sciences. “For example,” Collins writes, “the search for the cystic one way or another, and it is hard for those who oversee se- In a fitting tribute, on April 4, fibrosis gene finally succeeded in 1989 after years of effort quencing facilities to keep up with the demand. For research- the inaugural Palade Memorial by my lab and several others, at an estimated cost of ers today, a single human genome won’t do—they want many, Lecture was given before a stand- US$50 million. Such a project could now be accomplished and they want to be able to compare them in detail. ing-room-only crowd by world- in a few days by a good graduate student with access to At Yale, scientists can now obtain this 21st century renowned cell biologist Marilyn G. the Internet, appropriate dna samples, some inexpensive research staple from the Yale Center for Genome Analysis Farquhar, ph.d., Palade’s widow reagents, a thermal cycler and a dna sequencer.” (Ycga), a new high-speed sequencing facility that opened and his frequent scientific collabo- As a result of this stunning progress, Dna sequence in January. Housed in a newly renovated space perched atop rator, now Distinguished Professor information has become a common currency for scientific a hill at Yale’s West Campus, the Ycga is // YCGA (page 5) of Molecular and // Palade (page 7)

Non-Profit Org. inside this issue 300 George St., Suite 773, New Haven, CT 06511 U. S. Postage www.medicineatyale.org 2 Lifelines paid Diabetes researcher Gerald Shulman New Haven, CT probes the mysteries of insulin resistance Permit No. 526 3 Dangerous pairings Yale researchers find that separate cells can team up to fuel cancer 5 Old pals, warm memories Two lifelong friends from the Class of 1956 give back to the School of Medicine also Advances, pp. 3, 5 Out & About, p. 4 Grants and Contracts, pp. 6–7 lifelines Diabetes expert is named head

Gerald Shulman has mapped of endocrinology out the metabolic disruptions at Robert S. Sher- the root of type 2 diabetes. Until recently, this disease was mostly win, m.d., an diagnosed in those over 40, but internationally there has been a sharp increase in renowned dia- type 2 diabetes in younger adults betes researcher and in children. The illness is also on and director of the rise in China and India, and it is estimated that it will affect more the Yale Cen- that a third of a billion individuals ter for Clinical Robert Sherwin in the world by the year 2020. Investigation (ycci), has been appointed chief of endocrinology in the depart- ment of internal medicine at Yale- New Haven Hospital (ynhh) and . The Gerald Shulman endocrinology section at ynhh harold shapiro provides diagnosis and therapy to people with hormonal and meta- bolic diseases. Sherwin, the C.N.H. Long Turning the tide on type 2 diabetes Professor of Medicine, has been an Work on insulin resistance animals, such as those he had done synthesis. On the other hand, increased attending physician at ynhh since at Vanderbilt. synthesis of glucose from amino acids 1974, as well as a consulting physi- sparks researcher’s hopes Fortuitously, magnetic resonance and lactate in the liver is the main cause cian at the VA Connecticut Health- for prevention and a cure spectroscopy (mrs) was just begin- of the fasting hyperglycemia seen in care System in West Haven, Conn. ning to blossom. Based on the same type 2 diabetes. In addition to his role at ycci, Gerald I. Shulman, m.d., ph.d., a world- principles as mr imaging, mrs allows In a novel unifying hypothesis of Sherwin directs the medical school’s renowned authority on diabetes, says he scientists to noninvasively create precise, insulin resistance, Shulman and col- Diabetes Endocrinology Research can’t remember a time when he wasn’t real-time chemical profiles of small leagues have proposed that an imbal- Center, and he has served as the interested in science and medicine. regions of tissue in live animals, includ- ance between the delivery and oxidation program director of Yale’s General He was partly inspired by his father, ing humans. For Shulman, who was of fatty acids in liver and muscle cells Clinical Research Center. a Detroit physician who occasionally searching for a noninvasive method to causes biochemical changes that block Sherwin received his under- took the younger Shulman on hospital study intracellular metabolism in living insulin signaling. Recently his group iden- graduate degree from Union rounds. But as a biophysics major at the systems, mrs was the answer. In 1984 he tified two common genetic variants that College in Schenectady, New York, University of Michigan, Shulman “fell persuaded his Mass General mentors to predispose individuals to nonalcoholic and his m.d. from Albert Einstein in love with physics and biochemistry,” let him travel to Yale to complete his fel- fatty liver disease (nafld) and insulin College of Medicine. He did his he says, and knew that research would lowship, since Robert G. Shulman, ph.d. resistance, providing new insights into residency at Mount Sinai Hospital figure prominently in his career. (no relation), an mrs pioneer, had just gene–environment interactions that and was a clinical associate at the After his second year of medical joined the faculty. “It’s been 25 years,” promote the development of type 2 nih before becoming a fellow in school at Wayne State University, jokes Shulman, who has been at Yale diabetes. His work is revealing new drug medicine (metabolism) at Yale. Shulman took a break to study in the ever since, and is now the George R. targets and exercise and dietary strate- He is a former president of laboratory of Alan D. Cherrington, ph.d., Cowgill Professor of Physiological Chem- gies to “melt fat away” from liver and the American Diabetes Associa- at Vanderbilt University School of Medi- istry. “And they keep asking me when muscle, which will reverse insulin resis- tion (ada) and a winner of the cine. There, Shulman administered the I’m coming back.” tance and prevent type 2 diabetes. ada’s Banting Medal for lifetime newly discovered hormone somatosta- In two decades of research that has Shulman is optimistic that type 2 scientific achievement in diabetes. tin to animals to suppress the pancre- earned him election to the National diabetes—an illness that is the leading He has published over 300 papers atic secretion of glucagon and insulin, Academy of Sciences and many other cause of blindness, end-stage renal in scientific journals, edited text- allowing him to eliminate the effects honors, Shulman, also professor of medi- disease, and nontraumatic loss of limbs books and book chapters related of these two hormones and show that cine and of cellular and molecular physi- in the U.S., currently costing the U.S. to diabetes, and has served on the amount of glucose produced by the ology, and a Howard Hughes Medical economy more than $180 billion annu- national professional committees liver can be affected by changes in blood Institute investigator, has combined mrs ally—will be beaten. “Just about every for the past 30 years. glucose levels alone. studies of patients with experiments drug that we currently have to treat Following a residency in internal using transgenic mice to elucidate the type 2 diabetes was discovered seren- medicine at Duke University Medical mechanisms of insulin resistance, the dipitously,” he says, “and just treats the Center, Shulman did his endocrine metabolic dysfunction at the core of symptom of diabetes: hyperglycemia. Managing Editor Peter Farley fellowship training at Massachusetts type 2 diabetes. Now that we are beginning to under- Assistant Editor Charles Gershman General Hospital. During the research His group has found that insulin stand the cellular mechanisms of insulin Contributors Helen Dodson, William Hathaway, Pat portion of the fellowship, he studied resistance in muscle is mainly caused resistance, which is at the root of type McCaffrey, Kara Nyberg, Karen Peart Jennifer Stockwell the insulin receptor but he was keen by defective insulin-stimulated glucose 2 diabetes, we have better therapeutic Design Medicine@Yale is published five times each year by the to return to studies of metabolism in transport, which reduces glycogen targets, and I’m quite excited about it.” Office of Institutional Planning and Communications, Yale School of Medicine, 300 George St., Suite 773, New Haven, CT 06511 Telephone: (203) 785-5824 Fax: (203) 785-4327 E-mail [email protected] Insulin pump innovator receives high honor for diabetes research Website medicineatyale.org Copyright ©2010 by Yale School of Medicine. The American Diabetes Association continuous glucose Leadership Award for his extraordinary All rights reserved. If you have a change of address or do not wish (ada) has selected William V. Tambor­ monitoring, sensor- lifetime accomplishments in diabetes to receive future issues of Medicine@Yale, please lane, m.d., to receive its Outstanding augmented pumps, research and technological innovation. write to us at the above address or via e-mail at [email protected]. Physician Clinician Award, one of the and, most recently, Also in 2009, Tamborlane was Postal permit held by , highest honors bestowed by the ada designing a proto- one of six members of the ysm faculty 155 Whitney Avenue, New Haven, CT 06520 each year. type of an artificial elected to the Connecticut Academy of Yale School of Medicine A professor of pediatrics and a pancreas. Science and Engineering, in recognition Robert J. Alpern, m.d. world-renowned figure in the un- Tamborlane has of his original contributions to “theoreti- Dean and Ensign Professor of Medicine William Jancy L. Houck derstanding and treatment of child- Tamborlane also demonstrated cal or applied science or engineering.” Associate Vice President for Development and Director of hood diabetes, Tamborlane is chief of the role of insulin re- Tamborlane will be presented Medical Development 203 436-8560 Mary Hu pediatric endocrinology at the School sistance in pediatric metabolic disorders, with the award at the annual ada Director of Institutional Planning and Communications of Medicine. including obesity and type 2 diabetes. meeting in Orlando, Fla., in June. Michael Fitzsousa Director of Communications Tamborlane’s major achievements In late 2009, Tamborlane was Printed on recycled paper have included pioneering work in the honored by the Diabetes Technology Yale Netcast ♻ “The Littlest Volunteers ” This issue follows Volume 6, Issue 1 (January/Febru- development of insulin pump therapy, Society with the Diabetes Technology Available on iTunesU or at medicineatyale.org ary 2010). A March/April 2010 issue was not published.

2 www.medicineatyale.org advances Health & Science News Cellular ‘neighbors’ spur cancer’s spread Immune system fights Genetic flaws in separate cells stem cells’ dark side interact with one another to form If proteins were celebrities, oct4 would be on the A-list. In 2007, in a dramatic tumors, Yale researchers find advance, several researchers showed that inserting the gene for oct4 and One reason cancer is so difficult to understand and to treat just a few other genes transformed is that tumors are a genetic muddle. A cell can become adult skin cells into stem cells capable cancerous via a number of pathways, so the cancer-causing of generating any tissue in the body. mutations found in one tumor cell may be quite different But in addition to the vast healing from those found in neighboring cells. One consequence of potential of stem cells, some fear that this genetic heterogeneity is that a treatment that success- using them for fully kills some cells may be ineffective against others. As therapy may these surviving cells proliferate, the tumor may become cause tumors, resistant to treatment. and others Cancer researchers are beginning to decipher how genetic believe that tu- defects interact within individual cells and lead them awry. mors regrow in However, very little is known about the far more daunting question of whether, in the complex biological milieu that sci- istockphoto.com cancer patients when a tiny entists call the “tumor microenvironment,” mutations in one number of stem cells in tumors survives cell can interact with those in other cells to promote cancer. therapy and continues regenerating. In an article in Science published in 2003, Tian Xu, ph.d., oct4 is commonly expressed in vice chair and professor of genetics, and colleagues noted germ-cell tumors (gcts) such as testicu- that tumors in the fruit flyDrosophila melanogaster “display lar cancer and some ovarian cancers. In many characteristics observed in human cancers.” In order the April 17 online edition of Proceedings to emulate the genetic patchwork of human tumors, Xu and of the National Academy of Sciences, School of Medicine colleagues have created a “mosaic” form of

a team led by Madhav V. Dhodapkar, Drosophila in which a tiny number of cells with mutant genes harold shapiro can exist in a fly with mostly normal cells. In an elegant series m.d., the Arthur H. and Isabel Bunker 1 2 3 4 Professor of Hematology, found that of experiments reported in the journal Nature in January, Xu the immune system commonly targets and colleagues used this model to demonstrate that interac- this protein and that this immune tions between separate cells carrying different mutations are response correlates with the develop- indeed possible, and that they can have a profound effect on

ment of GCTs. Only 35 percent of newly how cancers grow and metastasize. courtesy of tian xu diagnosed gct patients had an immune In the new studies, Xu, along with graduate student Ming (Top) Tian Xu (seated) and (standing, from left) postdocs José Carlos response to oct4, compared to more Wu, ph.d., and postdoctoral fellow José Carlos Pastor-Pereja, Pastor-Pereja and Ming Wu discovered that distinct genetic mutations than 80 percent of healthy humans. ph.d., the lead authors, first created mosaic flies in which a occurring in different cells can cooperate to fuel cancer. (Bottom) In the Interestingly, after chemotherapy, an well-known cancer-causing gene known as Ras is expressed fruit fly brain, cells carrying a cancer-promotingRas mutation alone (pan- in some cells along with a mutant, non-functional form of el 1, green) show moderate overgrowth, while a mutant scribbled gene anti-oct4 immune response was seen alone (2) has little effect. When Ras and mutant scribbled are together in in 83 percent of the gct patients. scribbled (abbreviated scrib), a tumor-suppressor gene. To track cells, tumors invade the entire brain (3), an effect also seen when these The work could lead to trials of im- the effects of these manipulations, these cells were tagged genes are each expressed alone in different, but adjacent, cells (4). mune therapies for cancer that target with green-fluorescent protein gfp)( . pathways involving stem cells. The result was explosive: gfp-tagged tumors soon en- findings of other researchers, who have shown that tumors gulfed the normal cells in the flies’ brains, and spread to adja- and wounds have similar traits, and that there is a close rela- cent tissues as well. In these cells, the presence of mutant scrib tionship between chronic inflammation and cancer. Zeroing in on genes to signals that the cells are damaged, which activates a stress- Xu believes that his group’s findings on cell–cell interac- head off aneurysms related signaling pathway called jnk (pronounced “junk”). If tion in tumors are a powerful demonstration of how the the cells had been carrying mutant scrib alone, the activation precise genetic control offered by Drosophila can shed new In a massive new genomic study, an of the jnk pathway would have caused the cells to die, while light on the biology of cancer. “The bad news is that it is international team led by School of simultaneously triggering another pathway in adjacent cells much easier for a tissue to accumulate mutations in differ- Medicine researchers has identified known as jak-stat, which promotes proliferation. This ent cells than in the same cell,” says Xu, a Howard Hughes three new regions, or loci, containing makes up for the loss of the lost scrib mutant cells in a process Medical Institute investigator and director of the Institute genetic variants that increase the risk known as compensatory proliferation. However, the presence of Developmental Biology and Molecular Medicine at Fudan of intracranial aneurysms, weaknesses of Ras and the scrib mutation together in the same cells over- University in Shanghai, China. “Better understanding of in the brain’s blood vessels. Ruptured rides the jnk cell-death signal, while preserving the jak- the underlying mechanism causing cancer always offers new aneurysms occur in 500,000 people stat proliferation signal, putting the Ras carrying cells on a tools to battle the disease.” worldwide each year, causing hem- path to tumor development and progression. orrhagic stroke, but most have no The most intriguing observation, however, was that when Special pre-publication offer symptoms. Rupture is fatal in up to 40 Ras was expressed alone in some cells, and the scrib mutation percent of cases, and survivors usually alone in other, adjacent cells (with most cells being normal, Medicine at Yale as before), rampant tumor growth and metastasis was seen have severe neurological damage. The First 200 Years The team compared nearly again, just as when the two mutants occurred together in the 900,000 variable spots in the genomes same cells (see photo). Kerry L. Falvey of almost 6,000 aneurysm patients This phenomenon had never been observed, and indicated With essays by Thomas P. Duffy, m.d., with those of 14,000 healthy subjects. that some intercellular interaction between Ras and scrib Sherwin B. Nuland, m.d., and John Harley Warner, ph.d. In the May issue of Nature Genetics, mutant cells could fuel the growth and spread of cancer. The they describe the new loci and confirm researchers discovered that the jnk pathway is activated as Founded in 1810, the Yale School of that two previously identified loci are usual in the scrib mutant cells, causing them to die, but jnk Medicine was among the nation’s first medical schools. Over signaling in these cells is also somehow propagated to ad- the past 200 years it has grown and evolved to become a world- strongly associated with aneurysms. A class institution for research, education, and patient care, as person carrying variants in all five loci jacent cells carrying Ras. In those cells, jnk activates the jak- well as a hub of medical innovation and discovery. By setting is five to seven times more likely to de- stat proliferation pathway, causing tumors and metastasis. the development of the institution in the context of changes in velop an aneurysm than an individual As noted above, jnk signaling is induced by stress, such American culture and advancements in science, this full-color, beautifully illustrated volume portrays the evolution of medicine carrying none. as when tissue is wounded. When the researchers dam- in America through the lens of the eventful history of the school. “These five findings explain about aged wing discs in Drosophila larvae with cells carrying Ras, Available November 2010. 10 percent of the genetic risk,” says tumors resulted, indicating that stress-induced jnk signaling 240 pp. 350 illus. 9 1/2 x 12 $50.00 lead author Murat Günel, m.d., the alone is sufficient to turn cells carryingRas toward cancer. Special offer: pre-order by July 31, 2010 via YaleBooks.com/YSM200 Nixdorff-German Professor of Neuro- “A lot of different conditions can trigger jnk stress and receive Medicine at Yale at the special 25% discount price of $37.50. surgery. “This is 10 percent more than signaling,” says Xu. “Physical stress, emotional stress, infec- tions, inflammation – all these things.” The Xu team’s view we understood just a couple of years university press YaleBooks.com ago, but there is a long way to go.” of stress-induced tumor growth is consistent with recent

Medicine@Yale May/June 2010 3 out & about

January 21 The Status of Women in Medicine (swim) held a reception celebrating the con- January 29 John Allen Jones, an alumnus of Yale College and the Graduate School of tributions of women to the School of Medicine. From left: Merle Waxman, m.a., associate Arts and Sciences, made a major gift in support of the student-run haven Free Clinic. dean for academic development, ombudsperson of the School of Medicine, and director The clinic, which opened in 2005, offers medical services to uninsured patients in the of the Office of Women in Medicine; swim co-chair Paula B. Kavathas, ph.d., professor of Fair Haven neighborhood laboratory medicine, genetics, and immunobiology; swim co-chair Jennifer M. McNiff, m.d., of New Haven. From left: professor of dermatology and ; Robert J. Alpern, m.d., Dean and Ensign Professor haven student leaders of Medicine; swim co-chair Joann B. Sweasy, ph.d., professor of therapeutic radiology and Rachel Jamison ’15; Sara Cra­ genetics; Carolyn M. Mazure, ger ’12; Audrey Provenz­ ph.d., professor of psychiatry ano ’10; Jones, Richard and psychology, associate dean Belitsky, m.d., Harold W. for faculty affairs, and director Jockers Professor of Medi- of Women’s Health Research cal Education, deputy dean at Yale; and Nancy H. Ruddle, for education, and associ- ph.d., the John Rodman Paul ate professor of psychiatry; Professor of Epidemi­ology and and Olatokunbo “Toks” jerry domian professor of immunobiology. courtesy of jancy houck Famakinwa ’11.

February 19 and 20 The Class of 2012 1 4 affectionately mocked faculty while carrying on a 61-year-old tradition at this year’s Second Year Show, entitled “Love in the Time of Swine Flu.” 1. The show’s finale featured the full cast. 2. Whitney Sheen ’12 portrayed Nancy R. Angoff, m.p.h., m.d., associate dean for student affairs. 3. Julius Oatts ’12, the show’s director, as star-crossed lover 2 3 Steven. 4. Alyssa Nylander ’12 (in red), the director of choreography, and Oatts (with bow tie) lead a dance number in the Cadaver Ball scene that accompa- nies the song “Thriller,” choreographed by Carina Preskill ’12 (not pictured). john curtis (4)

1 2 March 18 Each year, fourth-year medical students experi- ence a welcome sense of relief on Match Day, when they receive word of acceptance in residency training programs. Students from the Class of 2010 matched at top programs across the country, including at Harvard-affiliated hospi- tals; Yale-New Haven Hospital, the University of California– San Francisco; the Hospital of the University of Pennsyl- 3 vania; Memorial Sloan-Kettering Cancer Center; Stanford University; New York Presbyterian Hospital; Columbia Uni- versity; the Hospital of St. Raphael; Johns Hopkins Hospital; and the University of Southern California. 1. Frederick Wang ’10 and Leah McNally ’10. 2. Stephanie Nguyen ’10 (left) and Laura Cooney ’10. 3. Matty Vestal ’10 (left) and Andres Martin, m.d., m.p.h., Riva Ariella Ritvo Professor of Pediatric

john curtis (3) Oncology Psychosocial Services.

// Chupp (from page 1) Yale’s Clinical Yale is the first institution to have potential collaborators on the basis Center’s Executive Council. Hili- and Translational Science Award— full access to this type of technol- of a mutual interest in the substance brand’s son David has both scoliosis collaboration, breaking down barriers ogy for scientific collaboration and of the data or reagents, not on purely and autism. “Autism, for instance, is and resource sharing—were remark- resource sharing. The RA offers Yale social factors.” [connected with] learning disabilities ably well aligned with the focus of scientists a comprehensive online Greenberg notes there is great and obsessive-compulsive disorder. our new platform,” Greenberg says, tool they can use to share and discuss flexibility built into the website, so And those may also be worked on in and Sherwin agreed. “Our goal is to research projects, data, lab protocols, that each scientist can use it in his multiple departments.” Technologies more effectively link scientists across results, news of clinical trials, and or her own way, and each scientist like the RA “will help research at the the Yale campus to promote new advances in clinical care. can choose his or her own level of university become better-integrated interdisciplinary research collabora- “A cancer researcher studying a disclosure. In addition, the site can be and more effective.” tions,” Sherwin says. particular gene has no systematic way customized for other institutions, and “We’ve had listings from a wide Sherwin provided support that of finding other researchers, say in many institutions can be linked to- range of Yale scientists who are shar- allowed Greenberg and Chupp to immunology, asthma, or even botany, gether, so the RA can allow scientists ing data, reagents, antibodies, human proceed on their project, and two who might be studying the same to reach beyond Yale to forge new samples, research projects, and more. years of discussions, consultations, gene,” Greenberg says. “The ycci research connections. The response has been extremely and testing followed. “We spoke to Research Accelerator is designed to But for the site to be valuable to strong. We’re also about to post dozens of researchers and clinicians, facilitate those potentially rewarding members of the Yale community, information on over 90,000 peptides from lab assistants to department collaborations.” Greenberg says, scientists need to available from the Keck Lab,” Green- chairs, to make the platform as valu- The service uses a novel system log on and post data. He and Chupp berg says, referring to one of Yale’s able as possible to the entire Yale called data-driven collaboration to are encouraging all Yale researchers main centers for protein analysis. scientific community,” says Chupp. quickly and easily identify potential across the university campus to join “Much more is in the works.” Finally, in March, Chupp saw his research partners, Chupp explains. the RA community. The RA is secure, password- concept made real, as the new resource— “Other software programs allow “The real benefit of having this protected, and free of charge for all dubbed the ycci Research Accelerator researchers to easily find published type of technology is that it will help Yale users. To learn more about using (RA)—was launched. Since then, more papers or biographical information,” communication about complex dis- this powerful new tool for scientific than 300 members of the Yale commu- he says, “but we wanted to create eases and disorders,” says Debbie Hil- collaboration, visit ycci.researchac- nity have registered to use the RA. the first-ever platform that identifies ibrand, chair of the Yale Child Study celerator.org.

4 www.medicineatyale.org advances Health & Science News Lifelong friends, also joined in giving Two members of the Class of 1956 who fondly recall their Yale years make gifts to the medical school

getty images Rear Admiral William M. Narva, mc, usn, and Captain Mitchell Edson, mc, usn, met as members of the School An engineered tissue’s of Medicine’s Class of 1956, and have remained friends throughout their adult lives. More than 50 years later, with surprising development their medical school years firmly etched in memory and Christopher K. Breuer, m.d., and Toshi- their careers largely behind them, they still speak on the haru Shinoka, m.d., ph.d., have been phone regularly. studying the use of tissue-engineered The two met, Narva says, because “the class was an vascular grafts (tevgs) to treat congeni- intimate class. The whole community was very close.” Narva tal heart defects. tevgs—created by and Edson’s first days on Cedar Street in the fall of 1952 seeding a biodegradable scaffold with coincided with the arrival of Dean Vernon W. Lippard, m.d. a patient’s bone marrow cells (bmcs) — “His pitch was, ‘I’m a freshman like you are, I’m just starting make living vessels that will grow as a like you. You’re my class—we’re going to do this together,’ ” courtesy of mitchell edson child grows and could last a lifetime. Narva recalls. “Everybody at Yale was on your side.” Breuer and Shinoka, both associate The two old friends have also joined together in giv- In 1963, both William Narva (left) and Mitchell Edson professors of surgery and pediatrics, ing back to Yale. Edson has generously contributed to the were stationed in Oakland, Calif., but Edson soon and Yale colleagues explored how bmcs Annual Fund for years, and he added to this long record of received orders to head to the U.S. military base at Okinawa, Japan, where many American soldiers are transformed to vessels in tevgs. support in 2005 by establishing the Mitchell Edson, m.d., and Marines received training before joining forces bmcs are stem cells, so many scientists Endowment for International Clinical Rotations. At that in Vietnam. From 1963–64, Edson (above) was thought that bmcs differentiate into time, Edson was the gift chair for his 50th reunion, and Commanding Officer, Third Medical Battalion, Third the endothelial and smooth-muscle discussions with Narva planted the seed for Narva making courtesy of william narvaMarine Division, Okinawa. cells that comprise blood vessels. a new $200,000 bequest in honor of his and Edson’s 55th But in the March 9 issue of Proceed- reunion next spring. In happy coincidences, that event falls States Congress. Edson, also a career Navy man, completed ings of the National Academy of Sciences, at the close of the School of Medicine’s Bicentennial celebra- residencies in surgery and urology at the St. Albans Naval the group reports that bmcs were tion and at the conclusion of the University’s five-year “Yale Hospital in New York City, where he eventually became undetectable soon after tevgs were Tomorrow” fundraising campaign. chief of urology in 1966. Edson subsequently became chair implanted into mice. Instead, the graft After medical school, Narva interned at the National of the Department of Urology at the nnmc, and then at appeared to initiate an inflammatory Naval Medical Center (nnmc) in Bethesda, Md. He then Washington Hospital Center in Washington, D.C., where at response that drew white blood cells to completed a three-year residency in dermatology that 82 he still practices four days a week. the scaffold, replacing the bmcs. These included stints at the U.S. Naval Hospital in San Diego and Although their military careers took them on different cells were also soon replaced, with the Los Angeles County General Hospital. From 1966 to 1986, courses, the friends’ paths did cross. When Narva was as- mouse’s own blood vessel cells. as a medical officer in the Navy, he was a consulting physi- signed to the U.S. Naval Hospital in Oakland, Calif., Edson, This “better understanding of cian to the White House and the United States Congress, having finished his residency, joined the Department of how tevgs develop in vivo will lead to and in 1986 he became Attending Physician of the United Urology there. Edson and Narva met again // Narva (page 8) improved second-generation tevgs,” the authors write. // YCGA (from page 1) home to 13 technologies, to support research by an important new state-of-the-art sequencers that churn investigators across the entire campus. milestone in person- out more than 900 billion base pairs of Mane was named to head the new alized medicine. New pathways toward new information every 30 days, or the facility. He moved rapidly to acquire The investment growing new arteries equivalent of more than 300 complete seven new Illumina Genome Analyz- in large-scale se- human genomes per month. ers, three machines at various campus quencing has also Stimulating arteriogenesis, the “Advancing science in these areas locations, and three sequencers housed enabled a raft of now requires the ability to produce at the Keck facility, and to consolidate new research proj- growth of new arteries, in adults Richard Lifton with cardiovascular disease is a holy very large volumes of sequence data all the equipment at the West Cam- ects. In last year’s grail of cardiology. Many efforts have and analyze them efficiently,” says pus. But that was just the beginning. competition for research funds under focused on vascular endothelial growth Richard P. Lifton, m.d., ph.d., chair “Scaling up an operation of this size the American Recovery and Reinvest- factor (vegf), which creates new blood and of Genetics, by a factor of at least 100 in data out- ment Act, Yale received five majornih vessels during embryonic development. who chairs Ycga’s Advisory Board. put over the course of several months awards totaling $21 million, all depen- However, vegf has shown little success “The Ycga permits us to do this at a is a Herculean task,” Lifton said. The dent on the resources of the Ycga. in adults, especially in those with car- scale that has been matched by few job included building “wet bench” In his 25 years in science, Mane has diovascular disease or diabetes. places in the country.” infrastructure to prepare samples as not witnessed the level of enthusiasm A team led by Michael Simons, The immense computational well as other building modifications to among researchers for any technology m.d., the Robert W. Berliner Profes- power of the medical school’s newest accommodate high-performance com- as he sees now for large-scale sequenc- sor of Medicine and Cell Biology, and sequencers is belied by the machines’ puting; hiring and training new per- ing. “When I wrote a grant to pur- chief of Yale’s Section of Cardiovascular quiet operation and unremarkable sonnel; and developing and refining chase our first genome analyzer back Medicine, focused instead on two appearance. Lined up behind a glass bioinformatics techniques and soft- in 2005, I had 38 investigators sign on. interacting signaling pathways, erk1/2 wall, through which Ycga Director ware. With round-the-clock efforts Now, for my latest grant I have 150 and PI3K. erk1/2 is activated in growing Shrikant Mane, Ph.d., keeps a watch- from Mane and his staff, the pieces fell interested. That kind of response tells arteries and suppressed in quiescent ful eye, these multimillion dollar into place quickly, and the facility was you how important this technology is. vessels, so the group searched for some marvels could be mistaken for a group up and running within two days after It’s the most exciting thing I’ve ever PI3K inhibitory factor. In the April issue of blue dorm fridges. the move to West Campus. been involved in.” of The Journal of Clinical Investigation, The Ycga had its beginnings in These labors have already yielded In just a few years, researchers pre- they name the culprit, a PI3K-regulated a much smaller Dna sequencing core a significant scientific payoff. In a pilot dict, it will take only 15 minutes and enzyme known as Akt1. Suppressing Mane launched at Yale’s Keck Founda- project last fall, Lifton and Mane used a few hundred dollars to decode an Akt1 released the PI3K brake on erk1/2 tion Biotechnology Resource Lab in whole-exome sequencing—a genomic individual’s genome. Sequencing will and successfully activated growth of 2006. Through the Keck facility, for shortcut in which researchers sequence be a routine part of medical care, and new arteries in mice and zebrafish. which he remains director of microar- only the few percent of a person’s Dna doctors will use genetic information to “Because we’ve located this inhibi- ray services, Mane provided sequenc- that actually encodes proteins, where drive the diagnosis and treatment of tory pathway, this opens the possibility ing services to Yale researchers using disease-causing mutations are most many diseases. As Lifton sees it, “We of developing a new class of medication just three automated machines. likely to occur—to pinpoint the cause have already had innumerable new to grow new arteries,” Simons says. Last fall, Yale University made of a baby’s rare kidney disease. Their insights into disease biology from hav- “The next step is to test this finding in a the decision to invest significantly success marked the first use of whole- ing the genome sequence, but I think human clinical trial.” in large-scale Dna sequencing exome scanning to diagnose a patient, the best is yet to come.”

Medicine@Yale May/June 2010 5 Grants and contracts awarded Multidisciplinary Sensory Data, 5 years, Radiation Oncology, Targeting N-Linked $3,523,649 • Robert Sherwin, nih, Diabetes Glycosylation to Radiosensitize Malignant Mellitus and Disorders of Metabolism, 5 years, Gliomas, 2 years, $250,000 • Neera Dahl, to Yale School of Medicine $1,637,270 • Frederick Sigworth, nih, Fluctu- Plexxikon, Inc., A pkd Patient Registry, 1 year, ations in Ionic Current through Membrane $64,940 • Charles Dela Cruz, Flight Atten- July/August, 2009 Channels, 4 years, $1,710,451 • Rajita Sinha, dant Medical Research Institute, Mecha- nih, Development of Guanfacine to Decrease nisms of Synergy between Cigarette Smoke Drug Craving, Anxiety and Cocaine Relapse and rsv, 3 years, $325,500 • Kavita Dhodapkar, Federal Risk, 3 years, $1,056,114 • Carla Stover, nih, Doris Duke Charitable Foundation, Regula- Serap Aksoy, nih, Tsetse Fecundity Reduction 5 years, $1,863,470 • Susan Kaech, nih, Tran- Integrated Treatment for Fathers Who Perpe- tion of Fc Gamma Receptors in Immune for Tryopanosomiasis Control, 5 years, scriptional Control of IL-7 receptor (IL-7R) in trate Domestic Violence, 5 years, $784,663 Thrombocytopenic Purpura, 3 years, $2,064,820 • Karen Anderson, nih, Exploring T Cells, 3 years, $166,476 • Mustafa Khokha, Stephen Strittmatter, nih, Molecular Deter- $405,000 • Antonette Dulay, Society for Novel Targeting Strategies for aids Protozoal nih, Developing Transposon Methods for minants of Adult cns Axon Growth, 2 years, Maternal-Fetal Medicine, A Role for Soluble Pathogens, 1 year, $413,750 • Robert Beech, Insertional Mutagenesis in Xenopus, 2 years, $963,898 • Scott Strobel, nsf, ires: U.S./ Modulators of Innate Immunity in Regulating nih, Stress-Related Changes in Gene Expres- $455,125 • Kenneth Kidd, nsf, alfred: Ecuador/Peru/International: Undergraduate the Intra-Amniotic Inflammatory Response to sion as Biomarkers of Relapse Vulnerability, Ongoing Growth of an Anthropological Rainforest Expedition and Laboratory, 3 years, Infection, 3 years, $300,000 • Stephanie 2 years, $453,547 • Vineet Bhandari, nih, Role Resource, 3 years, $731,577 • Robert LaMotte, $115,065 • Bindu Sukumaran, nih, Character- Eisenbarth, College of American Patholo- of Angiogenic Agents in Alveolar Maturation nih, Neural Mechanisms of Itch, 5 years, ization of an Anaplasma phagocytophilum gists Foundation, Evaluating the Role of IL- and Injury, 2 years, $827,500 • James Boyer, $6,256,393 • Brian Leaderer, nih, Traffic and Protein Interfering with Eukaryotic Vacuolar 1beta in the Generation of Immunity Follow- nih, Silvio O. Conte Digestive Diseases Respiratory Morbidity in the Northeast, Transport Pathway, 2 years, $165,500 • Jane ing Nalp3 Inflammasome Activation by Alu- Research Core Centers, 10 months, $296,930 5 years, $3,179,812 • Qiang Leng, nih, Identifi- Taylor, nih, Motivation in Addiction: pka minum Adjuvants, 1 year, $25,000 • Jack Richard Bucala, nih, mif and the Host cation, Characterization and Regulation of Mechanisms, 5 years, $1,399,507 • Mary Elias, Flight Attendant Medical Research Response to Infection, 5 years, $2,068,750 Intermediate Conductance K Channels in the Tinetti, nih, Universal Outcomes as a Institute, Cigarette Smoke and rig-Like Heli- David Calderwood, nih, Structure and Func- Kidney, 5 years, $1,559,347 • Becca Levy, nih, Common Metric across Multiple Diseases in case Innate Immunity, 3 years, $325,500 tion of the ipp Complex, 4 years, $1,390,200 Positive Age Stereotypes across the Life Span, Elders, 2 years, $373,203 • Flora Vaccarino, Eran Elinav, Cancer Research Institute, Role Michael Caplan, nih, Ion Pump Partners: Reg- 2 years, $826,221 • Chiang-Shan Li, nih, nih, Environmental Enrichment and Neuronal and Mechanism of Inflammasome Dysregula- ulators of Sorting and Function, 10 months, Thalamic Processes of Self-control in Cocaine Turnover in the Brain, 2 years, $331,000 • Fei tion in Autoimmunity, 3 years, $145,500 $566,331 • Herta Chao, nih, Imaging the Dependence, 22 months, $383,635; nih, Wang, nih, Frontotemporal Neural Systems Ada Fenick, The Children’s Fund of Connecti- Effects of Androgen Deprivation Therapy on Imaging Cognitive Control in Cocaine Depen- in Bipolar Disorder and Schizophrenia, 5 years, cut, Enhancement of Developmental Screen- Cognitive Functions in Patients with Non- dence, 5 years, $639,090 • Brett Lindenbach, $897,352 • Tong Wang, nih, Axial Flow ing in the Medical Home, 20 months, Metastatic Prostate Cancer, 2 years, $130,400 nih, Molecular Determinants of Hepatitis C Effects in Proximal Tubule, 5 years, $2,050,925 $115,000 • Liana Fraenkel, American College Lauren Cohn, nih, Immune Regulation in the Virus Infectivity, 4 years, $1,655,000 Anne Williamson, nih, Glutamate–Gluta- of Rheumatology, Improving Risk Communi- Respiratory Tract by the Epithelial Protein Shuangge Ma, nih, Effective Clustering mine Metabolism in Primary Human Brain cation and Decision Making in RA, 2 years, plunc, 2 years, $455,125 • Michael Crair, nih, Penalized Methods for Genomic Biomarker Tumors, 2 years, $455,125 • Lawrence Young, $400,000 • Xiao-Bing Gao, Foundation for Mechanisms of Visual Map Development in Selection, 2 years, $173,605; nsf, Novel nih, amp-Activated Protein Kinase in the Prader-Willi Research, Hypocrelin/Crexin the Superior Colliculus, 4 years, $2,388,716 Methods for Pharmacogenomic Data Analysis Ischemic Heart, 4 years, $1,655,000 • Dejan Deficiency in Prader-Willi Syndrome Animal Gary Desir, nih, The Molecular Physiology of using Gene Clusters, 3 years, $99,998 Zecevic, nih, Voltage-Sensitive Dye Imaging Models, 1 year, $50,000 • Arnar Geirsson, Renalase, 22 months, $645,588 • Kavita Dho- Suzanne Macari, nih, Perceptual Factors from the Nervous System, 4 years, The Thoracic Surgery Foundation for dapkar, nih, fcy Receptor–Mediated Regula- Affecting Social Attention in Autism Spec- $1,446,842 • Caroline Zeiss, nih, Building a Research and Education, Role of Microrna in tion of Dendritic Cell Function, 4 years, trum Disorders, 2 years, $165,500 • Arya Better amd Mouse, 2 years, $455,125 • Tong- Cardiac Ischemia and Heart Failure, 2 years, $1,655,000 • Ralph DiLeone, nih, Leptin Mani, nih, Investigation of Genetic and Physi- zhang Zheng, nih, Research Training for $100,000 • Jonathan Grauer, Stryker Spine, Receptor Signaling and Function in Dopamine ological Causes of Inherited Vascular Cancer Epidemiology and Biostatistics in Biochemical Comparison of Uniaxial Screws Neurons, 4 years, $1,294,726 • Hester Doyle, and Metabolic Diseases, 5 years, $2,068,750 China, 5 years, $1,107,087 and Monoaxial Screws, 8 months, $26,685 nih, The Contribution of Protein Methylation John McCormack, nih, The Role of ssd1 in Hamada Hamid, Epilepsy Foundation of to the Development of sle, 2 years, $164,912 Handling of Oxidized rnas in Saccharomyces Non-Federal America, Characterizing Hippocampal– Jack Elias, nih, Cigarette Smoke, rig-Like Heli- cerevisiae, 3 years, $148,974 • Eric Meffre, Neil Aggarwal, American Psychiatric Associ- Frontal Circuits in Epilepsy and Depression, cases and Alveolar Remodeling, 4 years, nih, Loss of B Cell Tolerance in Rheumatoid ation, apa/samhsa Minority Fellowship, 1 year, $40,000; Nat’l EpiFellows Foundation, $1,655,000 • Americo Esquibies, nih, Role of Arthritis, 2 years, $788,236 • Alexandra 1 year, $32,895 • Diego Alvarez, Pew Medical White Matter Changes in Epilepsy and vegf in Lung Development and Hyperoxic Miller, nih, A Role for Migrating Olfactory Fellowships, The Cell Biology of Hepatitis C Depression, 1 year, $20,000 • Marc Hammar- Injury, 5 years, $665,550 • Lynn Fiellin, nih, Placode Cells in Olfactory Nerve Develop- Virus Entry, 3 years, $90,000 • Marc Auer- lund, Arnold and Mabel Beckman Founda- An Interactive Video Game for hiv Prevention ment, 2 years, $90,254 • Andrew Miranker, bach, R Baby Foundation, A Multi-Center tion, Strategies to Study the Function of in At-Risk Adolescents, 5 years, $3,983,099 nsf, Protein–Protein Recognition Motifs Study to Evaluate the Effectiveness of Simula- Essential Genes in Neurons, 3 years, $300,000 Brian Forsyth, nih, Addressing Adherence to Based on Solenoid Display, 3 years, $450,000 tion of Patient Outcomes, 1 year, $90,000 Jamie Harrington, Howard Hughes Medical pmtct and Early Care of Women and Infants Alan Morrison, nih, The Rac2-Induced Macro- Henry Binder, Bill and Melinda Gates Foun- Institute, Evaluation and Characterization of in South Africa, 2 years, $348,450 • Alison phage Proteome and Vascular Pathology, dation, Planning for the Delivery of a More Nanomaterials for Noninvasive Monitoring Galvani, nsf, Dynamic Risk Perceptions about 3 years, $165,858 • Michael Nathanson, nih, Effective Oral Rehydration Solution to of Human Embryonic Stem Cell–Based Tissue Mexican Swine Influenza, 1 year, $57,125 Investigative Training in Hepatology, 5 years, Improve Diarrhea Control Worldwide, 2 years, Engineered Vascular Grafts, 22 months, Charles Greer, nih, Genetic Determinants of $1,249,731 • Alexander Neumeister, nih, $1,803,724 • Elizabeth Bradley, Common- $38,000 • Lyndsay Harris, calgb Foundation, Local Circuit Organization, 5 years, $1,758,440 Serotonin 1B Receptor Imaging in Pathological wealth Fund, Hospital Variation in Survival Biomarker Incubator to Define and Validate Yongtao Guan, nsf, career: New Statistical Gambling and Alcohol Dependence, 2 years, Rates after Acute Myocardial Infarction, Predictors of Response to Paclitaxel and Methods for Massive Spatial, Temporal and $355,679 • Laura Niklason, nih, Research 2 years, $203,185; South Essex Partnership Trastuzumab, 1 year, $44,967 • Kevan Herold, Spatial-Temporal Process, 5 years, $400,000 Training in Anesthesiology, 5 years, $843,747 nhs Foundation Trust, Leadership Workshop, American Diabetes Association, Inc., Beta Seth Guller, nih, Targeting Placental Patho- Kevin Pelphrey, nih, Neuroimaging of the 14 months, $140,000 • Christopher Breuer, before Alpha: The Importance of Residual physiology in iugr and Preeclampsia, 2 years, Development of Neural Mechanisms for Advanced Technologies and Regenerative Beta Cell Function for Alpha Cell Secretion $827,500 • Ann Haberman, nih, In Vivo Social Cognition, 2 years, $999,085 • Kitt Medicine, llc, Development of a Murine of Glucagon in Response to Hypolycemia, Imaging of T and B Interactions in Germinal Petersen, nih, Mechanisms of Insulin Resis- Model for Evaluating Tissue Engineered Vas- 2 years, $150,000; Juvenile Diabetes Center Initiation, 4 years, $1,655,000 • Marc tance in the Aged, 1 year, $413,750 • Anna cular Graft (Aortic Interposition Model), Research Foundation Int’l, Preclinical Studies Hammarlund, nih, Horseman, Pass By: Rhoades, nsf, Single-Molecule Studies of 1 year, $63,765 • Natalia Buza, Cap Founda- of Anti-CD3 mAb and IL-1 Antagonists, Finding Post-Development Functions of Tau Conformations and Dynamics, 5 years, tion Scholars Program, Scholars Research Fel- 2 years, $324,020 • Hoby Hetherington, Essential Genes, 4 years, $1,324,000 • Jonas $761,404 • David Rimm, nih, Optimal Predic- lowship, 1 year, $25,000 • Ilana Chefetz- Resonance Research, Inc., Optimization of Hannestad, nih, Validation of Beta2-Containing tors of Response to Trastuzumab, 2 years, Menaker, Life Sciences Research Foundation, Human Head mri and mrs using High Order Nicotinic Acetylcholinergic Receptors as a $1,172,590 • Marc Rosen, nih, Abstinence- Identification and Characterization of Shim Insert, 6 months, $54,968 • Narutoshi Potential Therapeutic Target in Bipolar Disor- Linked Money Management, 4 years, Ovarian Cancer Stem Cells, 3 years, $168,000 Hibino, American Heart Association, Found- der, 22 months, $382,516 • Hoby Hethering- $2,017,242 • Bruce Rounsaville, nih, Psycho- Hyung Chun, Howard Hughes Medical Insti- ers Affiliate, Nanomaterials for Noninvasive ton, nih, B1-Based Localization for mrsi of therapy Development Research Center, tute, Role of the Apelin-APJ Pathway in Vas- Monitoring of Mouse Induced Pluripotent Human Brain at 7T, 4 years, $2,001,728 5 years, $11,029,918 • Eric Rubenstein, nih, cular Wall Disease, 4 years, $307,663 • Oscar Stem Cell–Based Tissue Engineering Vascular Minoti Hiremath, Dept of Defense (US), Role Nuclear Localization and Function of the Colegio, Dermatology Foundation, Defining Graft, 2 years, $87,000 • Theodore Holford, of pthrP and Mesenchymal Wnt Signaling Transmembrane doa10 Ubiquitin Ligase, the Role of the Innate Immune System in MD Anderson Cancer Center, Microsimula- in Mediating the Effects of pthrP in the 3 years, $148,974 • Nancy Ruddle, nih, Lym- Tumor Progression and Metastasis, 1 year, tion of Longitudinal Smoking and Lung Mammary Gland, 3 years, $243,000 • Jean- photoxin: Regulation and Biologic Function, $55,000; Damon Runyon Cancer Research Cancer Risk, 2 years, $250,241 • Henry Huang, nette Ickovics, nih, Interdisciplinary hiv Pre- 4 years, $839,245 • Gerard Sanacora, nih, Foundation, Defining the Role of the Innate University of Montana, pet Imaging Tracers vention Training Program, 5 years, $2,240,148 Effects of Stress and Glutamatergic Agents Immune System in Tumor Progression and to Quantify Norepinephrine Transporter in Jessica Illuzzi, nih, Duration of Intrapartum on Glutamate Cycling and Behavior, 5 years, Metastasis, 3 years, $275,667 • Daniel Colón- the Brain, 1 year, $138,439 • Beth Jones, Uni- Antibiotic Prophylaxis for Group B Streptococ- $1,903,013 • Richard Schottenfeld, nih, Pain Ramos, Esther and Joseph Klingenstein versity of Miami, Effectively Communicating cus, 2 years, $158,175 • Karl Insogna, nih, Core and Opioid Dependence (pod), 4 years, Fund, Inc., Molecular Factors Directing Mammography Results to Underserved Center for Musculoskeletal Biology and Medi- $1,484,772 • Nenad Sestan, nih, Develop- Orchestrated Circuit Formation during the Women, 1 year, $3,333 • Kaveh Khoshnood, cine, 5 years, $3,310,000 • Melinda Irwin, ment and Organization of the Human Frontal Development of the Thermotaxis Circuits in China cdc, Multidisciplinary hiv and TB nih, rct of Exercise on Aromatase Inhibitor Cortex, 5 years, $5,707,948; nih, Molecular C. clegans, 3 years, $150,000 • Eve Colson, Implementation Sciences Training in China, Side Effects in Breast Cancer Survivors, Control of Cortical Projection Neuron Identity Boston University, Study of Attitudes and 9 months, $129,983 • Felix Knauf, Amgen, 4 years, $2,542,898 • Yasuko Iwakiri, nih, and Connectivity, 5 years, $1,810,155 • Gordon Factors Affecting Infant Care, 1 year, $56,244 Inc., Role of Transporter slc26A2 in Oxalate Arterial Remodeling in Chronic Liver Disease, Shepherd, nih, Sense Lab: Integration of Joseph Contessa, American Society for Homestasis, 1 year, $40,000 • Christine Ko,

6 www.medicineatyale.org Dermatology Foundation, Comparison of (clams), 1 year, $94,795 • , G. // Palade (from page 1) Cellular Medicine recently discovered in her lab which Squamous Cell Carcinoma and Keratoacan- Harold and Leila Y. Mathers Charitable Foun- at the University of California–San appears to play a role in cancer growth thoma, 1 year, $20,000 • Peter Krause, Tufts dation, Regulation of Vesicle Transport Path- Diego (ucsd). and metastasis. University, Xenodiagnosis of Lyme Disease, ways Established by Genome-Scale Function In 1973, Farquhar came to Yale with giv binds to Gai, a member of a 1 year, $37,569 • Harlan Krumholz, Robert Scans, 1 year, $197,068 • Lauren Saunders, Palade and with James D. Jamieson, family known as G proteins, which are Wood Johnson Foundation, Clinical Scholars American Heart Association, Nat’l Center, m.d., ph.d. (now professor of cell biol- usually found on cells’ outer mem- Program, 1 year, $93,543; Robert Wood Characterization of Autotaxin, a Lysophos- ogy and director of the medical school’s branes, where they act as middlemen Johnson Foundation, Clinical Scholars pholipase D, 2 years, $42,000 • Montrell m.d./ph.d. Program) to establish a between receptors that detect extracel- Program, 2 years, $1,085,855 • Rachel Seay, United Negro College Fund, uncf- Lampert, Emory University, Mechanisms Merck Postdoctoral Fellow, 18 months, new Section of Cell Biology, ultimately lular signals and effectors that induce Linking Depression to Cardiovascular Risk, $85,000 • Hua Shen, International Society spending 17 years on the faculty and actions inside the cell. By contrast, 1 year, $18,423 • Adam Lazorchak, The Leuke- for Heart and Lung Transplantation, The rising to Sterling Professor. Farquhar’s group and others found mia & Lymphoma Society, The Role of mtor Impact of CD14 and CD36 Signaling in For Farquhar, the occasion was Gai to be abundantly expressed in Signaling in the Regulation of rag Recombi- Costimulatory Blockade Extension of suffused with nostalgia, with many the Golgi apparatus, an intracellular nase Expression, 3 years, $146,510 • Patty Lee, Allograft Survival, 1 year, $40,000 • Anushree familiar faces dotting the capacity structure, with no associated receptor; Flight Attendant Medical Research Institute, Shirali, Nat’l Kidney Foundation, Nanoparticle- crowd at the medical school’s Anlyan when Gai was localized with a red tlr-Mediated Emphysema: Role of Aging and Encapsulated Delivery of Immunosuppression Center auditorium. For her listeners, fluorescent protein, explained Farqu- Gender, 3 years, $325,500 • Seung Lee, Rotary during Transplantation, 2 years, $100,000 the lecture was a tour de force of sci- har, underscoring a vivid micrograph International District 3690 Club of Korea, Mark Shlomchik, Boston University, Activa- entific exposition by a researcher with projected behind her, the Golgi “lit up Therapeutic Implication of pkd, Histone tion and Regulation of Autoimmunity by five decades’ experience in the lab. like a Christmas tree.” Deacetylase Inhibitors, 1 year, $56,802 • Ralf Innate Immune Sensing Pathways, 5 years, Leonhardt, Cancer Research Institute, Char- $2,293,327 • Gerald Shulman, American Dia- In a pair of classic 1957 papers that Further studies of this peculiar acterization of tap- and Tapasin-Independent betes Association, Inc., Mentor Based Award, she published as a postdoctoral fellow protein led to the discovery that giv mhc Class-1 Restricted Melanoma Epitope, 4 years, $144,000 • Frederick Sigworth, at the in col- regulates and activates Gai: when Gai 3 years, $145,500 • Chiang-Shan Li, Tourette Princeton University, Improved Algorithms laboration with Robert A. Good, m.d., is in an active state, cells tend to mi- Syndrome Association, Inc., Imaging Cogni- for Macromolecular Structure Determination and Robert L. Vernier, m.d., Farquhar grate, whereas inactive Gai prompts tive Motor Control in Tourette Syndrome, by Cryo-EM + nmr Spectroscopy, 5 years, used electron microscopy to examine cells to divide. Because unregulated 1 year, $75,000 • Susan MacLauchlan, Ameri- $500,000 • Mark Solomon, American Heart biopsies from children with kidney cell migration and division are hall- can Heart Association, Founders Affiliate, Association, Nat’l Center, Pseudosubstrate diseases and made the first descrip- marks, respectively, of the metastasis Thrombospondin 2 Regulation by Nitric Oxide Inhibition of the Anaphase-Promoting tions of the structural abnormalities and rampant proliferation seen in Levels in Wound Angiogenesis, 2 years, Complex, 3 years, $198,000 • Ajay Srivas- $42,000 • Praveen Mannam, American tava, American Society of Nuclear Cardiol- Heart Association, Nat’l Center, Endothelial ogy, Determining Myocardial Blood Flow mkk3 Mediates Sepsis and Lung Injury, 1 year, Reserve in Cardiac Transplant Recipients by $65,000 • Linda Mayes, Hope for Depression 82-Rb pet, 1 year, $30,000 • Gary Stack, Research Foundation, Understanding Abnor- College of American Pathologists Founda- mal Cortical Activation in Infants of tion, Delayed Hemolytic Transfusion Reac- Depressed Mothers, 2 years, $110,000 tions, 1 year, $10,000 • Hanna Stevens, Carolyn Mazure, Maximilian E. & Marion O. American Psychiatric Institute for Research Hoffman Foundation, Inc., Women’s Health and Education, Wyeth Research Fellowship, Research at Yale, 2 years, $50,000 • Brannon 1 year, $45,000 • Michael Strambler, Nat’l McCullough, American Heart Association, Research Council, Diversity Fellowship, 1 year, Nat’l Center, Mechanics of Cofilin-Induced $41,500 • Stephen Strittmatter, Craig H. Actin Filament Severing, 2 years, $42,000 Neilsen Foundation, Screening the Genome Thomas McGlashan, University of Oslo, for Axonal Regeneration Control, 2 years, Collaborative Research Agreement, 1 year, $250,000 • Patrick Sung, New York Univer- $37,000; Stavanger University Hospital, sity, Mechanisms of dna Motor Proteins in Collaborative Research Agreement, 1 year, Homologous Recombination, 10 months, $18,500 • Carsten Mim, Cancer Research $99,176 • Hugh Taylor, The John B. Pierce Institute, Structural Studies on bar-proteins Laboratory, Inc., Compromised Microcircula- chris volpe and their Role in Membrane Remodeling, tion in Women with Polycystic Ovary Syn- The inaugural George E. Palade Memorial Lecture, sponsored by the Department of Cell Biology, 3 years, $145,500 • Wang Min, Oklahoma drome, 1 year, $20,421 • David Tuck, Philips was delivered to a capacity crowd by Marilyn Farquhar of the University of California–San Diego. Medical Research Foundation, Epsin in Medical Systems, Integration of Imaging and Farquhar, a distinguished scientist whose career spans more than 50 years, is the widow of Palade, Angiogenesis and Vascular Remodeling, Genomic Data in Breast Cancer, 2.5 years, a Nobel Prize winner whose integration of electron microscopy and biochemistry helped to launch 1 year, $13,659 • Sukanya Narasimhan, L2 $475,662 • Flora Vaccarino, Tourette Syn- the modern era of cell biology. Farquhar and Palade (along with James Jamieson, now director of Diagnostics, llc, Nanoparticle-Based Vac- drome Association, Inc., Interneuron Deficit Yale’s m.d./ph.d. program) came to the School of Medicine in 1973 to establish the Section of Cell cines against Flaviviruses, 1 year, $34,401 and Functional Compartments of the Stria- Biology, now a full-fledged department, and were members of the Yale faculty for 17 years. Abhinav Nath, American Heart Association, tum in Tourette Syndrome, 1 year, $71,892 Nat’l Center, Single-Molecule Insights into Vivian Vlamakis, American College of Rheu- that compromise renal function in cancer, Farquhar’s team next explored Detoxification Catalysis and the Response to matology, An Analysis of CD4 T-Cell Subsets these patients. the potential role of giv–Gai interac- Oxidative Stress, 2 years, $78,000 • Ali in Patients with sle, 3 years, $150,000 • Fei After joining Palade’s cell biology tions in human cancers. Ozturk, Congress of Neurological Surgeons, Wang, The Klingenstein Third Generation lab at The in The scientists’ analysis of speci- Genetics of Intracranial Aneurysms, 1 year, Foundation, The Neural Circuitry of Adoles- $25,000 • Anisha Patel, Endocrine Fellows cent Major Depressive Disorder: A Multi- 1959 as a postdoctoral fellow, Farqu- mens from rapidly spreading cancers Foundation, Obesity and Metabolic Changes Modality Magnetic Resonance Imaging Study, har continued her work on kidney versus those from localized cancers re- Associated With Transgenic Marshmallow 2 years, $60,000 • Stuart Weinzimer, Juve- structure and function. In 1963 she vealed that giv was far more abundant Mice, 1 year, $20,000; Lawson Wilkins Pediat- nile Diabetes Research Foundation Int’l, Pre- discovered tight junctions, crucial sites in the former than the latter, findings ric Endocrine Society, Obesity and Metabolic vention of Nocturnal Hypoglycemia with of cell–cell interactions, and in her that were replicated in pancreas, colon, Changes Associated with Transgenic Marsh- Automatic Pump Suspension, 1 year, $241,873 subsequent work at the University of and breast cancers. mallow Mice, 1 year, $50,000 • Kevin Pel- Sherman Weissman, American Society of California–San Francisco, Rockefeller, Taken together, the results indicate phrey, University of Pittsburgh, Biological Hematology, A Biochemical Approach to Yale, and ucsd she has made seminal that drug compounds that target giv and Information Processing Mechanisms Isolate Extracellular and Intracellular contributions to our understanding of and prevent activation of Gai may Underlying Autism, 7 months, $44,238 Interacor(s) of the Stem Cell Antigen CD34, membrane trafficking, the process by slow the metastatic progression that Salley Pels, Nat’l Hemophilia Foundation, 6 months, $4,000 • Carol Weitzman, Lulac which proteins and other materials are proves lethal in many cases of cancer, Clinical Hemostasis Fellowship, 2 years, Head Start Inc., Head Start, 1 year, $30,000 $192,498 • Kitt Petersen, American Diabetes Dawn Wetzel, Pediatric Infectious Diseases transported within and between cells. a direction now being pursued by Association, Inc., Distinguished Clinical Scien- Society, Phagocytosis and Leishmania Inva- This diverse body of work has earned Farquhar’s trainees. tist Award, 4 years, $760,000 • Yibing sion, 2 years, $90,000 • Bruce Wexler, Nat’l Farquhar many accolades, including Farquhar summed up her talk with Qyang, American Heart Association, Nat’l Inst. of Mental Health & Neurosciences, fmri the A.N. Richards Award from the a straightforward acknowledgment of Center, Wnt Signaling and Functional Char- during Simulated Social Interactions in International Society of Nephrology, the remaining mysteries in this latest acterization of Isl+ Cardiovascular Progenitor Schizophrenia: Emotion- and Cognition- the Homer W. Smith Award from the research, and with thanks to the many Cells, 4 years, $308,000 • Lynne Regan, Mary Related Brain Activations, 3 years, $965,500 American Society of Nephrology, the young scientists who have helped her Kay Ash Charitable Foundation, Develop- Dianqing Wu, University of Connecticut, E.B. Wilson Medal from the American probe these questions in the lab. ment of a Novel Class of Hsp90 Inhibitors as Interactive Signaling Modules and Vascular Society for Cell Biology, and member- Then, with the wisdom gained Anti-Cancer Therapeutics, 2 years, $100,000 Phenotypes, 10 months, $409,069 • James ship in the National Academy of Sci- during a life in science, she elegantly Robert Rosenheck, The Feinstein Institute Yue, Depuy Spine, Inc., Clinical Spine Fellow- ences and the American Association of tied a bow around both sentiments. for Medical Research, Recovery after an ship, 1 year, $80,000; Medtronic Spinal and Initial Schizophrenic Episode (raise): Schizo- Biologics, Charitable Spine Fellowship, 1 year, Arts and Sciences. “After all, these young people all need phrenic Episode Recovery, 6 months, $94,795; $80,000 • Hitten Zaveri, itn Energy In her April lecture at Yale, Far- something to do,” she said. “So we Duke University, Comparison of Long-Acting Systems, Inc., Wireless Multimodal Brain quhar crisply presented a new line need to leave some questions on the Antipsychotic Medications for Schizophrenia Monitoring, 2 years, $265,341 of work centered on giv, a protein table for them.”

Medicine@Yale May/June 2010 7 Expert on autoimmunity is appointed Paul Beeson Professor Joseph E. Craft, m.d., newly named as at Yale-New Haven Craft has served numerous na- Chapter of the Lupus Foundation the Paul B. Beeson Professor of Medi- Hospital (ynhh) tional research organizations, includ- of America. cine, is an internationally recognized and a fellowship in ing as chair of two standing study The professorship was established expert on the pathogenesis of systemic rheumatology. He sections at nih and on the scientific in 1981 by the late Elisha Atkins, m.d., autoimmune diseases, including lupus became a professor advisory board of the Alliance for Lu- to honor his colleague Paul B. Beeson, and rheumatoid arthritis. of medicine in 1997, a pus Research. He is a member of the m.d., a beloved clinician, researcher, He and his research team seek to professor of immu- Board of Scientific Counselors at the and teacher who served as chair of define the mechanisms of loss of self- nobiology in 1999. nih’s National Institute of Arthritis, Yale’s Department of Internal Medi- Joseph Craft tolerance and activation of autoreac- The chief of the Musculoskeletal, and Skin Diseases cine from 1952 to 1965. An expert in tive T cells in systemic autoimmune Section of Rheumatology since 1991, (niams), and he is a member of the infectious disease, Beeson provided an diseases, and the differentiation and Craft has also directed the Yale Investi- boards of the Arthritis Foundation ideal by which Yale medical students, regulation of T cells in normal immune gative Medicine Program since 2004. He and the Lupus Clinical Trials Consor- residents, and faculty members have responses. His research has been con- is chief of rheumatology at ynhh. tium. Craft is a co-founder and serves measured themselves for decades. tinually funded by the National Insti- Craft won the School of Medicine’s on the board of L2 Diagnostics, a bio- Upon his retirement from academia in tutes of Health (nih) since 1985, and he Charles W. Bohmfalk Teaching Prize technology company in New Haven. 1981, his two chief residents summa- is the current recipient of an nih merit in Basic Sciences in 2004. He has been An associate editor of Arthritis & rized Beeson’s legacy: “In short,” they Award and directs an nih-funded center elected a fellow of the American As- Rheumatism, Craft also serves on the said, “he is the kind of physician all of in the rheumatic diseases. sociation for the Advancement of Sci- editorial board of Autoimmunity. He us aspire to be.” Craft joined the School of Medicine ence and to the American Society for is active in a number of community Yale Netcast as an assistant professor in 1985 after Clinical Investigation, among other service endeavors, including serving “Is There a Doctor in the Lab?” completing an internship and residency professional honors. as a volunteer for the Connecticut Available on iTunesU or at medicineatyale.org

Ritvo Professor to address psychosocial needs of children with cancer Andrés S. Martin, m.d., m.p.h., a cancer affects not only children’s important clinical Martin has helped develop a child and adolescent psychiatrist on physical health, but can threaten their interface between medical student mentorship program the faculty of the Yale Child Study social and emotional adjustment, the ycsc and the in child psychiatry that has been rep- Center (ycsc), has been named the educational performance and cogni- hospital. In addi- licated at 10 other institutions across inaugural Riva Ariella Ritvo Profes- tive abilities. tion to providing the nation, and a separate interna- sor of Pediatric Oncology Psychoso- After receiving his medical degree clinical care, the tional mentorship program for early cial Services by the Yale Corporation. from Anahuac University in Mexico cpis has evolved career academic psychiatrists. The new professorship was estab- City in 1990, Martin completed a fel- into a model train- Martin is editor-in-chief of the Andrés Martin lished in September 2009 with a gift lowship and residency in psychiatry ing facility for Journal of the American Academy of from Riva Ariella Ritvo, ph.d., an at Harvard Medical School, followed house staff and for medical students Child and Adolescent Psychiatry. He autism expert and clinical instructor by a residency in internal medicine from Yale and other institutions. is co-editor of the fourth edition of at the ycsc, and her husband, Alan at the University of Miami’s Miller Martin is director of medical Lewis’s Child and Adolescent Psychia- B. Slifka, m.b.a., a noted philanthro- School of Medicine. He received his studies at the ycsc. He is also associ- try: A Comprehensive Textbook; the pist and member of the Yale College m.p.h. degree from the Yale School of ate training director of both the child forthcoming second edition of Pedi- Class of 1951. Public Health. and adolescent psychiatry program atric Psychopharmacology: Principles The professorship was created to Since 2002, Martin has been and an innovative program in child and Practice; and of Life Is with Others: hasten the pace of ycsc research in medical director of the Children’s psychiatry funded by the National Selected Writings in Child Psychiatry, this area, with the aim of creating a Psychiatric Inpatient Service (Cpis) at Institute of Mental Health that inte- which features essays by his late model of comprehensive psychoso- Yale-New Haven Children’s Hospital, grates clinical and research training. mentor and father-in-law, Donald cial care for children diagnosed with which serves children with serious The latter program has served as a J. Cohen, m.d., who served as ycsc cancer and their families. Childhood neuropsychiatric disorders and is an model for other teaching institutions. director from 1983 to 2001.

// Narva (from page 5) in Washington. Narva had moved from Oakland to Awards and Honors San Diego when, “out of nowhere, I Daniel A. Colón-Ramos, ph.d., Mark B. Gerstein, ph.d., Albert L. Williams Pro- got a set of orders after eight months assistant professor of cell biology, fessor of Biomedical Informatics; G. Shirleen to go back to be the chief of dermatol- has won a two-year Sloan Founda- Roeder, ph.d., Eugene Higgins Professor of ogy at the nnmc in Bethesda,” Narva tion Fellowship for “outstanding gerstein roeder shulman Molecular, Cellular, and Developmental Biolo- says. Soon afterwards, Edson also was promise.” Colón-Ramos studies how gy; and Gerald I. Shulman, m.d., ph.d., George assigned to Bethesda, initially to serve neuronal circuits form during devel- R. Cowgill Professor of Physiological Chemistry and professor of medicine as assistant chief of urology. opment. The awards, given annually and of cellular and molecular physiology, have been elected Fellows of the In Washington, Narva saw and by the Alfred P. Sloan Foundation to American Association for the Advancement of Science (aaas). aaas is an treated members of Congress, the Su- 118 early-career researchers, include international nonprofit organization dedicated to advancing science around preme Court, and five U.S. presidents, funding of $50,000. the world. Among other activities, aaas publishes the journal Science. and Edson once had President Richard Nixon as a patient. Narva “was never David A. Hafler, m.d., Gilbert H. Gla- intimidated by any of these folks,” he ser Professor and chair of Neurology, says. “Every one of them was very ap- has been awarded the John J. Dystel preciative and compliant.” But he soon Prize for Multiple Sclerosis Research caplan cappello carson fish hafler insogna mazure mayne roeder corrects himself: “Lyndon Johnson was from the American Academy of Neurology. The Prize recognizes out- Michael J. Caplan, m.d., ph.d., chair and C.N.H. Long Professor of Physiology truly an intimidating personality.” and professor of cell biology; Michael Cappello, m.d., professor of pediatrics, Edson, who attends class reunions at standing contributions to research in the understanding, treatment, or microbial pathogenesis, and epidemiology; Richard E. Carson, ph.d., profes- Yale every five years, says of himself and prevention of multiple sclerosis. sor of diagnostic radiology and biomedical engineering; Durland Fish, ph.d., Narva, “It was a very exciting time for professor of epidemiology; David A. Hafler, m.d., Gilbert H. Glaser Professor us. And that’s why we feel so strongly and chair of the Department of Neurology; Karl L. Insogna, m.d., professor that we should continue to support the John H. Krystal, m.d., the Robert L. of medicine; Susan T. Mayne, ph.d., professor of epidemiology; Carolyn M. School of Medicine, financially and in McNeil Jr., Professor of Translational Mazure, ph.d., professor of psychiatry and psychology, associate dean for fac- other ways.” Research and chair of the Depart- ulty affairs, and director of Women’s Health Research at Yale; and G. Shirleen Narva, of course, agrees: “Every- ment of Psychiatry, has received the Roeder, ph.d., Eugene Higgins Professor of Molecular, Cellular, and Develop- Stanley Dean Research Award from mental Biology and professor of genetics, have been elected members of the body was so receptive. Everybody was the American College of Psychiatrists Connecticut Academy of Science and Engineering (case). Founded in 1976 and so supportive. It really was a pleasant, for research leading to “promising patterned after the National Academy of Sciences, case is a private, nonprofit warm experience. That’s what I con- new approaches to the neurobiology institution devoted to advising state government and industry “in the applica- jure up every time I think about New and treatment of schizophrenia.” tion of science and engineering to the economic and social welfare.” Haven and the medical school.”

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