july/august 2010 volume 6, issue 3 Advancing Biomedical Science, Education, and Health Care

Gift will support troops still troubled after the battle ends Described in Homer’s Iliad and called with deep psychological scars left by research on ptsd, concluded that many had been misdi- by a succession of names ever since— those conflicts. For Greenberg’s wife, he “was not ap- agnosed with maladies ranging from from mere “exhaustion” to “shell shock” Linda Vester, who had worked for years preciative of the alcoholism to schizophrenia. In 1973, and “battle fatigue”—the distinctive as a war-zone correspondent for nbc long history of really Blank, now a psychiatrist in Bethesda, condition that often afflicts soldiers News, the cluster of symptoms that original work,” he Md., invited those men to a therapy after stressful wartime experiences, make up ptsd were all too familiar. says, and he soon group at the veterans hospital in West now known as post-traumatic stress “She also came back with stress decided to help con- Haven, Conn. (now the vachs), disorder (ptsd), still carries a strong disorder,” Greenberg says, “and she told tinue that work with which helped to lay the groundwork Glenn Greenberg social stigma. And scientists still have me how debilitating it was, such that a major gift that for ptsd’s eventual acceptance as an much to learn about its psychological when there was a thunderstorm she’d establishes the Greenberg Professorship official psychiatric diagnosis in 1980. and physiological underpinnings. dive under the dining room table—lit- in Psychiatry, Post-Traumatic Stress Soon after, Yale recruited Walter Reed Though the investment firm erally, with her family there.” Disorder, and Resilience. Army Medical Center endocrinologist headed by Yale College alumnus The School of Medicine, in partner- In the mid-1960s, after complet- John W. Mason, m.d., who led the first Glenn H. Greenberg, m.a., m.b.a., ship with the VA Connecticut Health- ing a residency in psychiatry at Yale, studies of disturbances in stress-related is known as Brave Warrior Advisors, care System (vachs), has been in the Arthur S. Blank Jr., m.d., saw the hormones in soldiers with ptsd. In Greenberg knew little about ptsd vanguard of ptsd research and treat- Vietnam War first hand, working in 1989, Yale became home to the Clinical until he began hearing that increasing ment for decades. When Greenberg, a hospitals in Long Binh and Saigon. Neurosciences Division and the Health numbers of veterans of the wars in Iraq member of the Class of 1968, contacted Soon after the war ended, Blank Services Division of the VA National and Afghanistan had returned home his alma mater to find out about Yale reviewed the charts of 60 veterans and Center for ptsd, // Greenberg (page 8)

Innate immunity Cell biologist awarded top science prize innovator joins 2010 Kavli Prize in Neuroscience honors National Academy researcher’s deciphering of membranes’ role In April, Yale in shuttling proteins within and between cells immunobiologist Ruslan Med- On June 3, James E. Rothman, ph.d., the Fergus F. Wal- zhitov, ph.d., lace Professor of Biomedical Sciences and chair of the received one medical school’s Department of Cell Biology, was named of the highest a recipient of the 2010 Kavli Prize in Neuroscience. The honors bestowed biennial $1 million award, which has become one of the on American Ruslan Medzhitov most prestigious in science, was established in 2008 by a scientists when partnership of the Norwegian Association of Science and he was elected to the National Letters, the U.S.-based Kavli Foundation, and the Norwe- Academy of Sciences (nas), the elite gian Ministry of Education and Research. corps of researchers from the na- Rothman is one of the world’s foremost experts on tion’s top scientific institutions. membrane trafficking, the means by which proteins and courtesy of columbia university The David W. Wallace Professor other materials are transported within and between cells. James Rothman, winner of this year’s Kavli Prize in Neuroscience. of Immunobiology and a Howard The Kavli Prize highlights his contributions to the un- Hughes Medical Institute investiga- derstanding of exocytosis, a form of trafficking in which cell biology experiments that have revealed the molecular tor, Medzhitov has done pioneering spherical sacs called vesicles fuse with cell membranes to machinery of membrane trafficking in fine detail. Much of research on the innate immune deliver their contents outside the cell. this work was done using a “cell-free” approach, in which system, an evolutionarily ancient This process is ubiquitous in biology—it is essential to Rothman sidestepped the complexities of working with physiological system that launches cell division and insulin secretion, for example—but exocy- complete cells by isolating the intracellular components rapid first-line defenses against tosis plays a particularly crucial role in the nervous system. crucial to membrane trafficking. This strategy allowed bacteria and viruses. In neurons, vesicles carrying neurotransmitters fuse with him to propose that complexes of membrane-associated “We are all delighted by Rus- cell membranes at synapses, emptying their cargo to pass proteins known as snares are required for vesicles to fuse lan’s election to the nas, which on the chemical messages that govern movement, percep- with membranes. honors his seminal research on tion, cognition, memory, and mood. For three decades, Rothman shares the Kavli Prize with Thomas Süd- innate immunity,” says Carolyn W. Rothman has performed elegant, focused biochemical and hof, ph.d., of the Stanford School of // Rothman (page 8) Slayman, ph.d., // Medzhitov (page 8)

Non-Profit Org. inside this issue 300 George St., Suite 773, New Haven, CT 06511 U. S. Postage www.medicineatyale.org 2 Lifelines paid Ophthalmologist James Tsai brings New Haven, CT unbridled energy to his work. Permit No. 526 4 An actor’s voice Yale alumnus David Hyde Pierce is a passionate backer of Alzheimer’s research 5 Beat deer ticks with your phone New Lyme disease application for iPhone helps users avoid ticks, deal with bites. also Advances, pp. 3, 5 Out & About, p. 4 Grants and Contracts, pp. 6–7 lifelines VA hospital with Yale affiliation gets top marks for care

In addition to leading the The U.S. Depart- medical school’s ophthal- ment of Veterans mology department and Affairs (VA) caring for his many patients, has ranked the James Tsai is an active re- searcher on topics including VA Connecti- patient adherence to glau- cut Healthcare coma medication regimens, System (vachs) the development of new in West Haven, diagnostic technology, and Gary Desir Conn., first in the the application of molecu- lar biology to regenerate country among the system’s tertiary damaged retinal nerve cells facilities for its clinical care. in glaucoma and other eye “We’re not one of the largest or diseases. most well-funded facilities, but we tend to be very efficient and provide outstanding care,” says Gary Desir, m.d., professor of medicine and chief of medical services at the James Tsai vachs. “The challenge is going to terry dagradi be that our patient population is increasing yet our funding is not, so we have to maintain the same level of care but with fewer resources.” Leading with vision The vachs, one of 153 VA Yale glaucoma specialist Characterized by elevated pressure eldest daughter underwent chemo- hospitals nationwide, achieved a of fluid inside the eye, glaucoma can therapy and surgery for liver cancer. perfect score in performance mea- is also helping to bring damage the optic nerve and cause irre- (She is now a healthy and athletic sures in three of nine categories: eye cancers into the light versible vision loss. But in as many as 12-year-old.) acute myocardial infarction, to- one-third of cases, low to normal pres- This history inspired Tsai to raise bacco screening, and heart failure. Patients go out of their way to see Yale sure measurements (a thin cornea can the profile of ocular oncology at Yale. For behavioral health screening, ophthalmologist James C. Tsai, m.d., skew test results) can leave glaucoma Though little-known, eye cancer can community-acquired pneumo- m.b.a. One traveled four-and-a-half undiagnosed until there is significant cause blindness and can even be fatal. nia, and surgical complications it hours from Long Island. Another takes visual damage. Whall’s undiagnosed Metastasizing breast cancers often achieved a rating of “exceptional.” a car service each week from Garden glaucoma was affecting her ability to reach the eye, and the most common For diabetes, ischemic heart City, N.Y., for post-operative care. For his do basic tasks as a mother and interior cancer that originates in the eye, disease, and heart-disease pre- weekly follow-ups, a Wall Street trader designer. After a proper diagnosis, a choroidal melanoma, can spread to vention, the vachs, which has a journeys to New Haven each Wednesday New York surgeon performed pressure- the liver, lungs, and brain. The recent long-standing affiliation with the on the Metro-North Railroad. reducing surgery on her left eye, but it opening of Smilow Cancer Hospital at School of Medicine, also had very Tsai, an expert in glaucoma research yielded only short-term results. Medi- ynhh helped Tsai to recruit “the first high ratings. and treatment, came to Yale in 2006 cation to lower pressure in her right fully trained ophthalmic oncologist in There are more than 200,000 from Columbia University College of eye had severe side effects. the state of Connecticut,” Miguel A. visits to vachs clinics each year. Physicians and Surgeons, where he was Whall consulted Tsai, who sug- Materin, m.d., assistant professor of The hospital offers a full range of director of the Edward S. Harkness Eye gested “revising” the previous surgery ophthalmology and visual science and medical, surgical, and psychiatric Institute. Now chair and Robert R. Young on her left eye, and advised against director of ocular oncology. services to veterans, with particu- Professor of Ophthalmology and Visual surgery on her right eye altogether. In his personal life, Tsai’s abun- lar strengths in epilepsy, stroke, Science at the School of Medicine, Tsai is Today, with glasses, the combined dant energy fuels a passion for tennis. rehabilitation for the blind, post- also chief of ophthalmology at Yale-New vision of Whall’s eyes is 20/20. A recent bout of tendonitis, which traumatic stress disorder, alcohol- Haven Hospital (ynhh) and director of Born in Taiwan and delivered by brought him to a physical therapist, ism, schizophrenia, and virology. the Yale Eye Center. his grandmother, an obstetrician, Tsai was a worthwhile result of winning a In addition, its medical research Liz Whall, one of his patients, is a fourth-generation physician. But match against his coach. “The physical program is the second-largest in says Tsai’s stamina is matched by his there is also a darker family legacy. therapist asked, ‘How did you do this?’ the VA system. empathy: “I don’t know how he has “I’m in a family where there definitely And I said, ‘I tried to learn a kick serve,’ time to take care of so many people is a cancer gene,” says Tsai. As a teen- and he said, ‘Yeah, but you’re not in and still stop and listen.” But for Tsai, ager, he watched his father fight lung your twenties anymore!’ ” listening is key. “You have to tailor cancer; three decades later, his father Yale Netcast “A Discussion of the every treatment for every individual,” is being treated at Yale for a brain Importance of Glaucoma Screening” Peter Farley he explains. “It’s not one size fits all.” tumor. At just 5 months old, Tsai’s Available on iTunesU or at medicineatyale.org Managing Editor Assistant Editor Charles Gershman Contributors Sonya Collins, William Hathaway, Jill Max, Karen Peart Design Jennifer Stockwell Expert on causes of kidney disease will lead physiology department Medicine@Yale is published five times each year by the Office of Institutional Planning and Communications, Yale School of Medicine, Michael J. Caplan, m.d., ph.d., who colleagues study professor in 1988 and was promoted 300 George St., Suite 773, New Haven, CT 06511 studies how membrane proteins find the cellular and to full professor in 1998. Telephone: (203) 785-5824 Fax: (203) 785-4327 their proper location on the cell sur- molecular pathways In April, Caplan was named as E-mail [email protected] face, and disruptions in this process respon­sible for this the first recipient of Yale’s Postdoctor- Website medicineatyale.org Copyright ©2010 by Yale School of Medicine. that are associated with polycystic process. They have al Fellows Mentoring Award. He has All rights reserved. kidney disease (pkd), has been made the surpris- been given numerous other honors, If you have a change of address or do not wish to receive future issues of Medicine@Yale, please write to us at the named chair of the Department of ing discovery that including the School of Medicine’s above address or via e-mail at [email protected]. Cellular and Molecular Physiology. many receptor and Charles W. Bohmfalk Teaching Prize, Postal permit held by Yale University, Michael Caplan 155 Whitney Avenue, New Haven, CT 06520 Caplan, the C.N.H. Long Professor signaling proteins the Young Investigator Award of the of Cellular and Molecular Physiology involved in the sense of smell are also American Society of Nephrology, Robert J. Alpern, m.d. and professor of cell biology, also serves expressed in the kidney, a finding and the Henry P. Bowditch Award Dean and Ensign Professor of Medicine as associate director for basic research that suggests that olfactory signaling Lectureship of the American Physi- Jancy L. Houck Associate Vice President for Development and Director of for the School of Medicine’s m.d./ mechanisms may play an important ological Society. Medical Development (203) 436-8560 ph.d. Program. role in regulating kidney function in Caplan has served as interim chair Mary Hu In pkd, a common genetic response to chemosensory cues. since the death of his colleague Steven Director of Institutional Planning and Communications Michael Fitzsousa disease, the normal architecture Caplan earned his m.d. and ph.d. C. Hebert, m.d., a distinguished neph­ Director of Communications of kidney tubules is replaced by degrees at Yale School of Medicine rologist and kidney researcher who large, fluid-filled cysts. Caplan and in 1987. He became an assistant served as chair from 2000 to 2008. Printed on recycled paper ♻

2 www.medicineatyale.org advances Health & Science News A big shift in our knowledge of smallrna s New pathway found for micrornas, powerful

kuakarun krusong and versatile regulators Faulty histamine gene Lively, hardy, and inexpensive, the zebra­ fish is a popular species for beginning is a factor in Tourette’s tropical-fish hobbyists. An attractive Best known for triggering symptoms small fish native to the Ganges River and of hay fever, histamine also acts as a other freshwater sites in South Asia, it neurotransmitter in the brain. A new is also a darling of developmental biolo- genetic study led by Matthew W. gists because, in addition to being easy State, m.d., ph.d., the Donald J. Cohen to maintain in large numbers, zebra­ Associate Professor of Child Psychiatry, fish develop rapidly—their major organ suggests that histamine plays a role in systems undergo substantial development Tourette’s syndrome. in just 24 hours—a phenomenon made all As reported in the May 20 issue of the more remarkable by the transparency The New England Journal of Medicine, in of the fish’s embryos. Through a micro- a rare family in which the father and all scope, says zebra­fish specialist Antonio J. terry dagradi eight children, but not the mother, have Giraldez, ph.d., scientists have an intimate, clear view as the Antonio Giraldez (center), leader of a study that revealed a new pathway Tourette’s, affected family members fish’s adult form swiftly unfolds. for microrna processing, in the medical school’s zebrafish facility with co- all carried the same mutation in hdc, a Some basic principles of molecular biology have lately authors (from left) Heather Patnode (research assistant), Daniel Cifuentes seemed to change just as dramatically. The wholly unexpected (postdoctoral fellow), Huiling Xue (postdoctoral fellow), and David Taylor gene involved in histamine synthesis. (graduate student in molecular biophysics and biochemistry). Normally, hdc molecules pair up discovery about 20 years ago that short stretches of genetic in a symmetrical complex (above left) material called micrornas (mirnas) exert profound and per- to synthesize histamine. The muta- vasive control of gene expression is a case in point. The study the normal production of red blood cells. In the new research, tion, which truncates the hdc protein, of mirnas has since become one of the fastest-growing areas published in the June 25 issue of the journal Science, Giraldez is found on only one of two chromo- in biology, and now, by taking advantage of the zebrafish’s and colleagues expanded on his earlier work with zebra- somes, and inhibits the enzymatic unique qualities, research in the laboratory of Giraldez, assis- fish mutants. After introducing a mutation to suppress the activity of the normal copy by forming tant professor of genetics and the Lois and Franklin H. Top, Jr. activity of Dicer, the researchers looked to see whether any an abnormal complex (above right). Yale Scholar (see box below), is prompting scientists to rethink functional mirnas were present in these mutant fish. Using Histamine-boosting drugs reduce strongly held ideas on how mirnas are formed. high-throughput genomic sequencing tools, the group found Tourette’s-like behaviors in mice lacking Until the early 1990s, it was thought that, for the most that several mirnas had indeed been successfully processed. hdc, and several are in human clinical part, genes are activated or suppressed by transcription factors, Giraldez recalls that, because the belief that Dicer is essential trials for neuropsychiatric conditions, which bind to dna to promote or inhibit the transcription to mirna processing was so firmly established, he and his says State, also co-director of the Yale of genes into messenger rna (mrna), and hence determine team found this result “extremely weird, and in fact it took us Neurogenetics Program. “This may which genes are ultimately translated into proteins. But while almost two years to believe it,” during which time the group mean that we have the opportunity to studying the development of the microscopic roundworm conducted every imaginable experiment until they were satis- go directly from a rare genetic finding Caenorhabditis elegans (another handily transparent organism), fied that the finding held up. to a trial of a new approach to treat- Victor Ambros, ph.d., then at Harvard University, made the Eventually, they concentrated on one Dicer-independent ment. In our field, that would be very startling discovery that a tiny stretch of rna, only 22 genetic mirna called miR-451, because it is present in many species unusual, and very exciting,” he says. letters long, switched off a crucial gene that orchestrates the (in March, for example, researchers at Ohio State University timing of developmental events in C. elegans. proposed that miR-451 may regulate the growth of brain tu- A new sort of stem cell Over the next 10 years, scientists determined that small mors in humans), and because its distinctive configuration is is aimed at Parkinson’s rnas like that discovered by Ambros are a ubiquitous, funda- a bad structural match for Dicer processing, which suggested mental regulator of gene expression throughout the plant and that some other pathway was at work. Parkinson’s disease, which degenerates animal kingdoms. More than 700 mirnas have been identi- In typical mirna processing, once Dicer has cut mirna motor function and speech, results from fied in humans, each of which may regulate hundreds (or even precursor strands to a proper-length mirna, the strands are a loss of dopamine-producing brain thousands) of genes; with such wide reach, mirnas may inter- loaded into a molecule known as the rna-Induced Silencing cells. Drug treatments cannot always act with more than 60 percent of our genome. These findings Complex (risc), where the business of gene-silencing actually relieve the tremor and loss of balance have revealed that mirnas “have deep implications not only in takes place. Inside risc, a second enzyme called Argonaute 2 caused by the disorder. how humans and animals are made, but in the development (Ago2) slices up any mrna strand containing a sequence that Embryonic stem cells (escs) have of human diseases,” says Giraldez, also a member of the Yale exactly matches the loaded mirna, // Giraldez (page 7) shown promise as a means of regener- Stem Cell Center. In 2006, the Nobel Prize in Physiology or ating the lost cells, but scientists have Medicine was awarded to two American scientists for elucidat- been on the lookout for alternatives to ing one of the main mechanisms by which mirnas silence escs that can be easily obtained from genes, an extraordinary turn of events considering that just 15 adult patients. years earlier mirnas were not even known to exist. Yale Scholars: a gift that yields scientific dividends In experiments reported online in Scientists have revised many of their ideas over the past In 2007, medical school alumnus the April issue of the Journal of Molecu- 20 years regarding how mirnas work and how they are Frank Top, m.d., and his wife, Lois lar and Cellular Medicine, Yale research- formed, but one character in the mirna story has remained (right), made a $2.5 million gift to ers led by Hugh Taylor, m.d., professor unchanged: Dicer, an enzyme that, as its name implies, snips the School of Medicine to establish of obstetrics, gynecology, and reproduc- complex precursors into the 21- to 23-nucleotide length that a Yale Scholar endowment, a fund tive sciences, explored the therapeutic characterizes functional mirnas. In addition to the zebra­ that smooths the way for a promis- potential of cells from the lining of fish’s other attributes, the species is also amenable to precise ing young scientist beginning his or the uterus, or endometrium. Regularly genetic manipulations. In recent work with zebrafish mutants, her career. Yale Scholars receive four regenerated after menstruation, this Giraldez has confirmed Dicer’s central role, showing that fish years of research funding; by year five, when a researcher generally tissue is a rich source of stem-like cells in develop abnormally if the enzyme’s function is compromised. has independent grant funding, the award passes on to another adults. In a mouse model of Parkinson’s, Though diagrams in journals and textbooks have varied in top recruit. Exciting new work by Antonio Giraldez, the Lois and transplanted endometrial cells migrated their depictions of the early and intermediate steps of mirna Franklin J. Top, Jr. Yale Scholar, is described on this page. “To take tal- to damaged brain tissue and differenti- maturation, up to now Dicer has always stood toward the end ent that’s already been recognized in a postdoctoral program and ated into dopamine-producing neurons, of the line, the enzymatic gateway through which all precur- let that person run with it makes an awful lot of sense,” says Frank, significantly raising dopamine levels. sors must pass to become mirnas. and Lois agrees. “It’s really time-consuming to pursue a research “Endometrial tissue is probably But mirnas continue to surprise. Giraldez and Yale col- career,” she says, “and you can use all the help you can get.” the safest, most easily attainable leagues, collaborating with scientists from Massachusetts to A named Yale Scholar position can be endowed with a gift of source of stem cells currently avail- Japan, have now shown that some mirnas can be processed $2.5 million, which is matched dollar for dollar by Yale University, able,” says Taylor. “I think this is just by an alternative pathway that does not require Dicer. More- creating a $5 million endowment. Donors receive Yale Tomorrow the tip of the iceberg for what we will over, the researchers provide evidence that miR-451, a Dicer- campaign and reunion credit for the full amount. For more infor- be able to do with these cells.” independent mirna they analyzed in depth, is necessary for mation, contact Jancy Houck at (203) 436-8560.

Medicine@Yale July/August 2010 3 A familiar voice speaks up for Alzheimer’s patients, research It began with a sweatshirt. In Decem- Alpern has made the expansion of on neuropsychiatric ber 2007, when Tony- and Emmy- research on neurodegenerative diseases disease. To lead off the Award-winning actor David Hyde a touchstone of his tenure as dean, he talks, Associate Profes- Pierce appeared on the Today show invited Hyde Pierce to visit the School sor of Pharmacology Ya to promote Curtains, the Broadway of Medicine to learn about the school’s Ha, ph.d., whose team comedy in which he was then appear- diverse research efforts in AD. published the first-ever ing, an alert viewer in New Haven “Statistically, this is a disease that’s crystal structure of an noticed that the illustrious Yale going to affect everybody in one way enzyme that acts inside College alumnus wore a sweatshirt or another,” Hyde Pierce says, and this cell membranes in bearing the name of An Important trend has been borne out in his own 2007, discussed how his Medical School That Is Not Yale. life. The disease killed his beloved work relates to human A package was soon delivered to grandfather, and advancing dementia gamma-secretase, the Hyde Pierce’s dressing room at the Al would likely have claimed his father enzyme that creates the

Hirschfeld Theater with a tongue-in- but for a fatal bout with pneumonia. amyloid fragments in- terry dagradi cheek note from Dean Robert J. Alpern, “When he died, he still knew us,” says volved in AD. Stephen m.d., that read, in part, “I have been the actor, a former national board M. Strittmatter, m.d., ph.d., the Actor and Yale alumnus David Hyde Pierce of Frasier fame joined researchers Stephen remiss in not providing you with the member (now an honorary member) of Vincent Coates Professor of Neu- Strittmatter (left) and John Krystal (right) at a relevant clothing associated with your the Alzheimer’s Association. rology and co-director of the Yale Yale Club session on Alzheimer’s disease. alma mater . . . and am enclosing a Yale Hyde Pierce took Alpern up on Program in Cellular Neuroscience, School of Medicine sweatshirt, hat, his offer to visit New Haven, and met Neurodegeneration, and Repair, then frame most of his talks on the sub- and scarf.” The hat, a baseball cap, was with scientists exploring AD on every presented his surprising recent find- ject. It is essential, he says, to “keep a hit: Hyde Pierce, best-known for his front in the search for new treatments. ings on how the amyloid-beta (A-b) hope alive and let people know there’s portrayal of the cultured, persnickety “When you see these bristling intel- protein that comprises the “plaques” progress,” but also to drive home the Niles Crane, m.d., ph.d., in the long- lects working on this thing, and how found in AD patients’ brains may begin urgency of the current situation. “We running cbs sitcom Frasier, says he much has been done,” Hyde Pierce the destructive cascade that eventually have no treatments, and we need to wears the cap “religiously.” (The fic- says, “it gives you hope.” He was erases memories (see related story, p. be candid about this disease.” tional Crane earned his undergradu- “pleased and proud, having gone to 5). Finally, Christopher H. van Dyck, The prolific Hyde Pierce has ate, m.d., and ph.d. degrees at Yale.) Yale, to find out about the medical m.d., professor of psychiatry and received many accolades since he But Alpern’s letter also had a seri- school’s vibrant neurodegenerative neurobiology and director of Yale’s graduated from Yale College in 1981, ous purpose. During his career, Hyde research community,” and this past Alzheimer’s Disease Research Unit, including a Tony Award in 2007 for Pierce has lent his voice to animated March he joined Alpern and a group reported on progress using imaging his work in Curtains, and four Em- characters as various as The Simpsons’ of School of Medicine scientists at the techniques such as positron emission mys for Frasier. But earlier this year Cecil Terwilliger and Slim the stick- Yale Club of New York for a presen- tomography (pet) to measure brain he brought home a different sort of insect in A Bug’s Life. But for 15 years, tation of the School of Medicine’s levels of A-b, which may soon achieve prize, one that is particularly appro- he has also been one of the most visible Alzheimer’s disease research. the elusive goal of early AD diagnosis, priate for a man who has made his and articulate spokesman for The The session was moderated by providing doctors with enough time for name as both actor and advocate: the Alzheimer’s Association, raising aware- John H. Krystal, m.d., the Robert treatments to make a difference. Tony Awards’ 2010 Isabelle Stevenson ness of the urgent need for better di- McNeil Professor of Translational In his own remarks, Hyde Pierce Award, which honors his “substan- agnostic tools and effective treatments Research, chair of the Department navigated “the twin horns of the tial contribution” to the Alzheimer’s for Alzheimer’s disease (AD). Because of Psychiatry, and an authority Alzheimer’s dilemma” that he says Association. out & about

April 15 During their annual visit to the medical school’s Center for Neuroscience and May 11 At the School of Medicine’s annual Student Research Day, held in the atrium Regeneration Research (cnrr), members of the Paralyzed Veterans of America (pva) had of the Anlyan Center, m.d./ph.d. student Daniel Balkin, one of 71 students who dinner with cnrr scientists in Branford College’s Common Room and received scientif- presented original research, discussed his work with Associate Research Scientist ic updates at cnrr labs the follow- Zhi-Jia Ye, ph.d., and ing day. From left: Yale University Associate Professor of President Richard C. Levin accepts Medicine Arya Mani, a pva donation of $300,000 from m.d. The Farr Lecture, Gene A. Crayton, national presi- the culminating event dent of pva, joined by Stephen G. of Student Research Waxman, m.d., ph.d., cnrr director Day, was delivered and Bridget Marie Flaherty Profes- by Lewis Landsberg, sor of Neurology, Neurobiology, m.d., Irving S. Cutter and Pharmacology. pva has been Professor of Medicine a steadfast supporter of the cnrr and dean emeritus of for over 20 years, and has made Northwestern Univer- donations totaling millions of dol- sity’s Feinberg School lars to fund the center’s research. chris volpe terry dagradi of Medicine.

May 24 The members of the Class of June 3–6 Medical school alumni 2010 launched their careers as physi- turned out in droves for Alumni Week- cians at this year’s Commencement end, which featured symposia on ceremonies. Graduate David Myles ’10, “Doctor as Patient” and “When Illness who will join the Pediatric Residency Strikes the Leader”; an academic re- Program at Johns Hopkins Children’s view of the legacy of pioneering neu- Center, celebrated with his family. rosurgeon Harvey Cushing, m.d.; and This year’s Commencement address guided tours of the Medical Library, was given by Donald M. Berwick, m.d., campus improvements, the new m.p.p., professor at the Harvard School john curtis Smilow Cancer Hospital, and the 136- of Public Health, newly appointed by acre West Campus. Saturday marked President Obama to head the Centers the dedication of the new Harvey Cushing Center, which includes a dramatic display of for Medicare and Medicaid Services. Cushing’s whole-brain specimens, clinical drawings and photographs, and memorabilia. Many students graduated with joint Class Dinners, including one in honor of the Class of 1960’s 50th reunion, took place at terry dagradi degrees at this year’s Commence- New Haven–area restaurants. Members of the Class of 2000, including (from left) Carl J. ment: 15 received m.d./ph.d. degrees; 22 received m.d./m.h.s. degrees; one received an Seashore, m.d., Daniel Jacoby, m.d., Linda Maxwell, m.d., John D. Mahoney, m.d., Darren L. m.d./m.b.a.; and one received an m.d./m.p.h. Lish, m.d., and Felix Adler, m.d., celebrated their 10th reunion.

4 www.medicineatyale.org advances Ixodes scapularis? There’s an app for that! Health & Science News Getting ‘pumped’ aids Yale-designed iPhone application kids’ diabetes control provides Lyme disease information, employs user’s location to assess risk

Thanks to faculty and students at the Yale School of Public Health (ysph), users of Apple’s popular iPhone can better protect themselves against Lyme disease, the most prevalent insect-borne disease in the United States. The new application presents data on the abundance of In type 1 diabetes, autoimmune dam- infected ticks at the location of the user anywhere within age to insulin-producing cells in the the U.S., based on information from the phone’s Global pancreas causes abnormally high levels Positioning System (gps) hardware. If ticks are determined of glucose in the blood. Unchecked, to be present, the user is given a list of precautions to avoid diabetes can cause blindness, kidney bites. A chart with life-size photos is provided to aid in the failure, and heart disease. identification of black-legged ticks Ixodes( scapularis, also To keep harmful hyperglycemia at known as deer ticks) at each life stage, useful information harold shapiro (2) because these ticks cannot transmit Lyme disease during bay, patients rely on dietary adjustments Along with Maria Diuk-Wasser (right), and injections of insulin. But successfully some stages. If the user has been bitten, the program pro- assistant professor of epidemiology, and managing blood sugar using current vides instructions on how to properly remove a tick, along Francesica Tizard (left), senior admin- methods of self-testing and multiple with a narrated video. istrative assistant at the Yale School of daily insulin injections is difficult. In “This is the first health application for smartphones that Public Health, Durland Fish (seated) has could have an immediate impact on a major disease” said crafted a new Lyme disease application adults, continuous glucose monitoring for the Apple iPhone. The software uses technology and insulin pumps (see pho- Durland Fish, ph.d., professor of epidemiology at ysph, location-based services to inform users to) have each proven to better control who oversaw the development of the application. of the presence of deer tick populations, blood sugar, but these approaches have Lyme disease can be transmitted after 48 hours of feeding and also includes clear depictions of not worked as well in children. by an infected tick, and most physicians will treat patients ticks at various life stages (left), which who experience such bites with a short course of antibiotics to can help determine whether tick bites In a year-long, randomized, multi- require quick medical attention. center trial known as star 3, led at prevent the disease. To help users determine when they were the School of Medicine by William V. bitten, the application depicts ticks at various stages of blood Tamborlane, m.d., professor of pedi- engorgement and advises patients to seek medical attention if certain amount of time,” says Fish. “Information provided by atrics and chief of that department’s the photos suggest that a removed tick had been attached for this app should help many people prevent Lyme disease.” Section of Pediatric Endocrinology and 48 hours or longer. A panel of photos of skin rashes character- Content for the application is provided by Lyme disease Diabetes, sensor-augmented insulin istic of Lyme disease along with a list of other symptoms also researchers at the School of Medicine—where Lyme disease pumps, which combine insulin infusion prompts users to seek immediate medical attention if they was first identified—in cooperation with the U.S. Centers for with continuous glucose monitoring, believe they are infected. To help users obtain medical care Disease Control and Prevention, the American Lyme Dis- better controlled blood sugar in type 1 in unfamiliar locations, a gps-based physician locator finds ease Foundation, and IntuApp, an applications development diabetics of all ages than did daily insu- nearby doctors and provides the phone number and direc- company in New York City. It is available through the Apple lin injections. The study, published on tions to each physician’s office. iTunes Store for $1.99, with proceeds supporting the research June 29 in the online edition of The New “You can only get Lyme disease in certain areas, only by and education mission of the American Lyme Disease Founda- England Journal of Medicine, is the first certain ticks, and only after a tick has remained attached for a tion based in Lyme, Conn. to show consistent results in children.

Building a case against Grad student lauded for malaria mosquito research an Alzheimer’s culprit Allison Carey, m.d., ph.d., who just participated in a scientific symposium Higgins Professor of Molecular, Cellu- In 2009, a team from the lab of Stephen completed her doctoral studies in on May 7 at the fhcrc. lar, and Developmental Biology, identi- M. Strittmatter, m.d., ph.d., reported in Yale’s Interdepartmental Neuroscience Carey, who received her m.d. in fiedA. gambiae odorant receptors that Nature that small amyloid beta (A-β) Program, is a winner of the 2010 Har- 2009 and her ph.d. at Commence- are precisely tuned and highly sensitive molecules— which aggregate to form old M. Weintraub Graduate Student ment this past June, has focused her to components of human body odors, the plaques seen in Alzheimer’s disease Award. The award, sponsored by the research at Yale on odorant receptors which may help them to locate and (AD) patients’ brains—bind to neurons Basic Sciences Division of the Fred in the mosquito Anopheles gambiae, the infect the hundreds of millions of people expressing cellular prion protein (PrPc), Hutchinson Cancer Research Center primary carrier of malaria in sub- afflicted with malaria each year. In this a ubiquitous protein in the normal (fhcrc) in Seattle, Wash., recognizes Saharan Africa. Carey will soon begin research, which formed the basis of her brain. When A-β bound to PrPc, neural outstanding achievement by graduate a postdoctoral fellowship at the Institut ph.d. thesis, Carey recorded over 27,000 processes believed to underlie memory students in the biological sciences. Pasteur in Paris, France. responses to 110 different odors from a formation were compromised, leading Carey is one of 13 graduate stu- In the February 3 issue of Nature, variety of A. gambiae receptors expressed the researchers to hypothesize that PrPc dents in North America to receive Carey and colleagues, including her ad- in the antennae of mutant fruit flies. binding of A-β is a key early player in the award this year. The awardees visor John R. Carlson, ph.d., the Eugene This work “was of epic proportion,” the cognitive decline of AD. Carlson says. “It required an enormous In the May 5 issue of the Journal amount of effort, a high level of skill, of Neuroscience, Strittmatter and and a great deal of creativity. Allison colleagues present more evidence. was also a wonderful colleague.” Studying a mouse model of AD, the A major goal of the Carlson lab is group found that mice bred to lack PrPc to apply knowledge of the molecular showed no impairment in spatial learn- basis of A. gambiae olfaction to reduce ing and memory—even though their the mosquitoes’ attraction to human brains were riddled with A-β plaques. odors or to lure them into traps, strat- Mice expressing PrPc showed marked egies that may slow the transmission memory deficits and died significantly of malaria. earlier than their counterparts. The Weintraub Award, established “Cellular prion protein is the essen- in 2000, honors the late Harold M. tial mediator that leads to Alzheimer’s- Weintraub, ph.d., a founding member like memory dysfunction and reduced of the fhcrc’s Basic Sciences Division survival in these model mice,” says and a leading researcher in develop- Strittmatter, the Vincent Coates Profes- mental biology. Carey is one of two

sor of Neurology and co-director of terry dagradi students in Carlson’s lab to win the the Program in Cellular Neuroscience, Allison Carey has studied the highly sensitive olfactory system of malaria-carrying Anopheles award recently: Elissa Hallem, ph.d., Neurodegeneration, and Repair. mosquitoes, work that may help prevent them from infecting humans or lure them into traps. was an awardee in 2005.

Medicine@Yale July/August 2010 5 Grants and contracts awarded Polycystin-1, 2 years, $92,352 • Wang Min, nih, Non-federal Inhibiting jnk: A New Anti-Inflammatory Strat- Kathleen Akgun, University of Washington, Risk, egy, 2 years, $1,059,124 • Arie Mobley, nih, Severity, and Outcome of Bacterial Pneumonia in to Yale School of Medicine Mechanisms of Embryonic Olfactory Sensory an hiv +/- Veteran Cohort, 10 months, $135,707 Neuron Axon Targeting, 2 years, $101,764 Joel Beckett, American Vascular Association, September/October, 2009 Shelby Montague, nih, Translation of Olfactory Effect of Polyphenols in Olive Oil on Smooth Input into Behavioral Output in the Drosophila Muscle Cell Proliferation, 4 months, $3,000 Federal Larva, 3 years, $93,073 • Walther Mothes, nih, Richard Belitsky, Gilead Foundation, haven Serap Aksoy, nih, Molecular Aspects of Tsetse tions, 2 years, $4,207,355 • Sarah Gray, nih, Targeting hiv Cell-to-Cell Transmission, 4 years, Primary Care Clerkship, 1 year, $75,000 • Michael and Trypanosome Transmission, 5 years, Mechanisms Underlying Leptin’s Attenuation of $2,218,363 • Michael Nathanson, nih, Silvio O. Bloch, Trichotillomania Learning Center, Inc., $2,326,195 • Colleen Barry, nih, Expanding Cocaine-seeking Behavior in Rats, 2 years, $60,732 Conte Digestive Diseases Research Core Center, Double-Blind, Placebo-Controlled Trial of N-Acet- Treatment for Opioid Dependence among the Pri- Cary Gross, Agency for Healthcare Research and 5 years, $6,007,650 • Lynda Odofin, nih, Prev- ylcysteine for Childhood Trichotillomania, 1 year, vately Insured, 4 years, $1,746,305 • Robert Beech, Quality/dhhs, Multimorbidity and Cancer Screen- alence of Community-Acquired mrsa in Live Pigs $20,000 • Donald Botta, CoolSpine, llc., Intra- nih, Progesterone-Induced Gene Expression ing: Achieving Patient Understanding, 2 years, and their Handlers, 2 years, $85,077 • Stepha- ventricular Cooling Catheter, 2 years, $153,659 Changes and Risk of Relapse to Cocaine Use, $299,340 • Murat Günel, nih, Functional Genom- nie O’Malley, nih, Career Support and Mentoring Cynthia Brandt, Massachusetts General Hospital, 2 years, $496,500 • Hilary Blumberg, nih, Bio- ics of the Cavenous Malformation Gene, 5 years, of Interdisciplinary Alcohol Research, 5 years, Rare Cancer Genetics Registry, 2 years, $72,277 markers of Suicide Risk in Adolescents and Young $2,978,125; nih, Molecular Variants that Deter- $1,236,542 • Charisse Orme, nih, Role of tug in Robert Bruce, Liberty Community Service, Inc., Adults: Factors that Contribute to High Risk in mine Genetic Susceptibility to Intracranial Aneu- the Formation of Insulin-Responsive glut4 Vesi- Services in Supportive Housing, 1 year, $130,000 Bipolar Disorder, 2 years, $998,276 • Hal Blu- rysm, 5 years, $3,265,832; nih, Gene Discovery in cles, 3 years, $114,132 • Godfrey Pearlson, nih, Matthew Burg, Columbia University, Compari- menfeld, nih, Preventing Spike-Wave Epilepto- Recessive Structural Brain Disorders through Genetic Architecture of Alcohol Misuse Candidate son of Depression Interventions after Acute genesis: Critical Period and Neuroimaging Bio- Whole-Exome Sequencing, 2 years, $2,906,138 Endophenotypes, 2 years, $996,533 • Margaret Coronary Symptoms, 10 months, $71,443 markers, 2 years, $821,933 • Clifford Bogue, David Hafler, nih, The Role of Rare Variants in Pisani, nih, Feasibility of Measuring Sleep in a Thomas Carpenter, Thrasher Research Fund, nih, Hex: A Homeobox Gene Essential for Liver Multiple Sclerosis Risk, 2 years, $1,917,986 Critical Care Environment, 2 years, $438,880 Assessing Vitamin D Requirements: The Role of Development, 22 months, $824,822 • Martina Kevan Herold, nih, Type 1 Diabetes TrialNet: Clini- Saif Rathore, Agency for Healthcare Research Vitamin D Binding Protein in the Response to Brueckner, nih, Genetic Determinants of Human cal Center at Yale University, 5 years, $2,028,525 and Quality/dhhs, Race and Cardiac Catheteriza- Vitamin D Supplementation in Infants, 3 years, Heterotaxy and Aortic Arch Malformation, Karl Insogna, Department of Agriculture, Mech- tion Use in the Setting of Acute Myocardial Infarc- $417,736 • Peter Charpentier, Hebrew Rehabilita- 6 years, $4,394,539 • Richard Bucala, nih, Innate anisms of Dietary Protein-Induced Changes in tion: Classifications, Associations, and Long-Term tion Center for the Aged, hrc/ifar, 1 year, $8,742 and Adaptive Mechanisms in Arthritis, 5 years, Calcium Absorption Efficiency, 3 years, $499,123 Outcomes, 14 months, $34,800 • Carrie Redlich, Lauren Cohn, Tufts University, The Role of stat3 $1,859,375 • Lloyd Cantley, nih, Cellular Repair of Elizabeth Jonas, nih, Role of Bcl-xL in Synaptic Center for Construction Research and Training, in Allergic Inflammation and Airway Remodeling, Kidney Injury, 21 months, $706,903 • Thomas Plasticity in the Hippocampus, 2 years, $870,314 Assessment and Prevention of Isocyanate Expo- 1 year, $18,215 • Larry Davidson, Illinois Institute Carpenter, nih, Classical and Non-Classical Leonard Kaczmarek, nih, Biochemical Control of sures in the Construction Industry, 1 year, $149,986; of Technology, Adherence And Empowerment: Responses to Vitamin D in Children: The Role of Excitability in Neurons, 2 years, $909,360 niosh/cdc/dhhs, Isocyanate Skin and Air Expo- Service Participation and Meaningful Outcomes, dbp Genotype, 2 years, $999,475 • Judy Cho, Insoo Kang, nih, Studying the Effects of Vitamin sure: Assessment and Control, 4 years, $1,648,387 1 year, $196,796 • Madhav Dhodapkar, Leukemia nih, Beyond Single-Point gwas: Genetics of D on foxp3 and IL-17 Expression in Human CD4+ T Scott Rivkees, nih, Adenosinergic Mechanism and Lymphoma Society, Combination Therapy Crohn’s Disease in Ashkenazi Jews, 22 months, Cells, 2 years, $413,750 • Walter Kernan, nih, of Intrauterine Growth Retardation, 2 years, Targeting Natural Killer T Cells, 3 years, $600,000 $1,001,477 • Hyung Chun, nih, Role of Apelin in Insulin Resistance Intervention after Stroke (iris) $823,948 • James Rothman, nih, “Suspended” Maria Diuk-Wasser, University of Minnesota, the Systemic and Pulmonary Vasculature, 5 years, Trial, 5 years, $24,307,862 • Trace Kershaw, nih, Bilayers: New Technology to Study the Dynamics Eco-epidemiology of Leptospirosis in Latin Ameri- $667,575 • Paul Cleary, cdc/dhhs, Category 1: Randomized Controlled Trial to Enhance Dual Pro- of Membrane Structure and Function, 2 years, cans: Understanding Transmission Dynamics Meeting Community Needs Across the Prevention tection among plhiv in India, 4 years, $1,455,414 $969,272 • Nenad Sestan, nih, Transcriptional in a Community, 1 year, $15,373 • Wawrzyniec Spectrum, 5 years, $5,316,317 • Joan Cook, nih, Ami Klin, nih, Performance Indices of Social Dis- Atlas of Human Brain Development, 2 years, Dobrucki, Society of Nuclear Medicine Education Theory-Driven Mixed-Methods Evaluation of ptsd ability in Toddlers with Autism, 2 years, $993,553 $9,889,558 • Mark Shlomchik, nih, Murine and Research Foundation, Noninvasive Quantita- Treatment Implementation in VA Residential Set- Michael Krauthammer, nih, Advancing Literature Memory B Cell Development and Function, tive Microspect/CT Assessment of Myocardial tings, 2 years, $918,498 • Lynn Cooley, nih, Mining through Processing and Analysis, 3 years, 5 years, $2,833,059 • Michael Simons, nih, Sup- Angiogenesis and Remodeling Post-MI in Diabetic Dynamic and Super-Resolution Imaging of $1,016,452 • Suchitra Krishnan-Sarin, nih, Incen- porting New Faculty Recruitment to Enhance Rats Subjected to Therapy with Bi-Functional Endogenous Proteins in Drosophila Tissues, tive-Based Intervention for Smoking Cessation and Research Resources through Biomedical Research Angiotensin II Receptor Blocker, 1 year, $25,000 2 years, $946,752 • Cindy Crusto, nih, The Prevention in High School, 2 years, $761,988 Core Centers, 2 years, $1,153,026 • Jeffrey Sklar, Donald Engelman, University of Rhode Island, Study of Multiple Social Determinants of Young Chiang-Shan Li, nih, Amygdala Processes nih, The jazf1 Gene and Type 2 Diabetes, 3 years, phlip Nanotechnology Platform for Cancer Children’s Health, 2 years, $1,035,964 • Pietro and Early Habitual Drinking, 2 years, $384,975 $1,076,754 • Mehmet Sofuoglu, nih, Sensitivity to Imaging and Therapy: Nanoscience and Nano- De Camilli, nih, ocrl and the Pathogenesis of Charles Lockwood, nih, Women’s Reproductive Intravenous Nicotine: Genetic Moderators, technology in Biology and Medicine, 2 years, Lowe Syndrome and Dent Disease, 4 years, Health Research Career Development Program, 2 years, $379,824 • Mark Solomon, nih, Pseudo- $215,450 • Jorge Galán, Columbia University, $1,117,760 • Daniel DiMaio, nih, Molecular Basis 5 years, $2,410,115 • Xiaomei Ma, nih, Myelodys- substrate Inhibition of the Anaphase Promoting Type III Secretion Antigen Delivery System Assem- of Viral and Cellular Transformation, 5 years, plastic Syndromes: Patterns of Care and Out- Complex, 2 years, $662,000 • Sandra Springer, bled in Non-Replicating Platform, 5 months, $6,413,248 • Peniel Dimberu, nih, Role of trim comes, 2 years, $417,476 • Robert Malison, nih, nih, Alcohol Pharmacotherapies among Released $155,509 • Mark Gerstein, Brigham and Women’s Protein in Cellular Innate Anti-viral Responses to dbh, D2High and Cocaine Paranoia/Aversion: A hiv+ Prisoners, 5 years, $4,011,217 • Vinod Srihari, Hospital, Analysis of Patterns of Structural Varia- hcv, 2 years, $82,352 • Claudia Dominguez, [11C]phno pet Study, 2 years, $413,520 • Sadie nih, Specialized Treatment Early in Psychosis tion in the 1000 Genomes Data Set, 10 months, nih, Infection and CD8 T Cell Memory: Develop- Marjani, nih, Analyzing Allele-Specific Gene (step): A Community Health Center-Based $170,445 ; Massachusetts Institute of Technol- ment, Maintenance, and Plasticity, 3 years, Expression and Regulation in C. albicans, 2 years, Cost-Effectiveness Study, 2 years, $749,840 ogy, nih modencode dac GO Grant, 1 year, $108,128 • Deepak D’Souza, nih, gaba Deficits $101,764 • Linda Mayes, nih, erp Neurobehavioral Matthew State, nih, Genomic Profiling and $140,000 • Frank Giordano, Williams Syndrome and Vulnerability to Cannabinoid-induced Psy- Assessment of Negative Reinforcement in Adoles- Functional Mutation Analysis in Autism Spec- Association, Williams Syndrome, 2 years, chosis, 2 years, $374,461 • Lynn Fiellin, nih, Reduc- cents, 2 years, $455,125 • Ellena McCarthy, nih, trum Disorders, 2 years, $2,245,837 • Stephen $320,000 • Tina Goldsmith, Organization for ing Heavy Drinking to Optimize hiv/aids Treat- Cellular Dissection of Neuropeptide Signaling in Strittmatter, nih, Yale Cellular Neuroscience, Autism Research, Comprehension of Pretense in ment and Prevention, 5 years, $3,911,127 • Richard the Circadian Neural Network, 3 years, $148,974 Neurodegeneration, and Repair (cnnr) Program, Young Children with Autism: The Development of Flavell, nih, Understanding the Role of amcase in Justin McDonough, nih, A Systems Biology 2 years, $1,524,000 • Matthew Strout, nih, Assessment and Teaching Techniques, 16 months, Asthma, 2 years, $1,000,000 • Ewa Folta- Approach for Investigating Coxiella burnetii Regulation and Dysregulation of Antibody Diver- $2,000 • Elena Grigorenko, King Faisal Univer- Stogniew, nih, Biacore T100 spr for Yale Keck Lab, Infection, 2 years, $97,264 • Sherry McKee, sification, 5 years, $872,100 • Susumu Tomita, sity, Etiological Bases of Giftedness, 3 years, 1 year, $363,515 • Joel Gelernter, nih, Genetics of nih, Dose-Ranging Study of Varenicline on nih, Genome-Wide Screening of Transmembrane $467,620 • Ruth Halaban, Melanoma Research Alcohol Dependence in African-Americans, Human Alcohol Self-Administration Behavior, Subunits of Ion Channels, 2 years, $1,000,000 Alliance, Sequencing of the Melanoma Exome, 5 years, $3,193,349; nih, Genome-wide Associa- 3 years, $1,054,468 • David Merrick, nih, Charac- Federico Vaca, nih, Development and Crash Transcriptions and Epigenome, 3 years, $999,999 tion Study of Cocaine Dependence in Two Popula- terization of the Cleaved Carboxy-Terminal Tail of Injury Risk in Adolescent Latino Males, 3 years, Lyndsay Harris, Breast Cancer Research Founda- $436,867 • Flora Vaccarino, nih, Biological Corre- tion, Biomarker Incubator to Define and Validate lates of Altered Brain Growth in Autism, 2 years, Predictors of Response to Paciltaxel and Trastuz- $1,987,576 ; nih, Cellular and Genetic Correlates imab, 1 year, $199,999 • Robert Heimer, Biomedi- of Increased Head Size in Autism Spectrum Disor- cal Center, St. Petersburg, Russia, International der, 2 years, $491,452; nih, Injury and Recovery in Feasibility Study of Pharmacy-Based hiv Preven- Developing Brain, 5 years, $6,906,861 • Neil tion: St. Petersburg, 9 months, $38,593; Duke Uni- Vasan, nih, Structural Studies of the Exocyst, versity, Drug Policy, Incarceration, Community Re- 4 years, $123,364 • Stuart Weinzimer, nih, Closed- entry, and Race Disparities in hiv/aids, 10 months, Loop Effectiveness and Ambulatory Regimens $391,623; United Nations Population Fund, Devel- (clear), 3 years, $2,189,034 • Robert Weiss, nih, oping an Evaluation Platform for unfpa’s y-peer Targeted sirna Nanotechnology for Intravesical Projects, 9 months, $168,000 • John Hwa, Ameri- Treatment of Urological Diseases, 22 months, can Heart Association, Prostanoid Receptor Phar- $985,031 • Li Wen, nih, Effect of Diet and macogenetics and Environmental Trace Metals, 28 Commensal Bacteria on Diabetes Outcome in months, $240,372 • Karl Insogna, Dairy Manage- nod Mouse, 2 years, $991,054 • Kenneth Wil- ment, Inc., The Impact of Protein Supplement on terry dagradi liams, nih, yale/nida Neuroproteomics Research Bone Mass in Older Men and Women, 2 years, With funding from the National Institutes of Health, Linda Mayes (left) and associate research Center, 5 years, $8,448,566 • Stephanie Young, $109,975 • Megan King, G. Harold and Leila Y. scientist Michael Crowley (right) use dense-array electroencephalography (eeg) to measure subtle nih, Novel Signaling between Striatal Neurons changes in brain function that result from early childhood stress, whether caused by prenatal and Postnatal Neural Progenitors, 2 years, $51,192 exposure to cocaine or broader, more all-encompassing stressors such as poverty and violence. Huiping Zhang, nih, Association and Function of Denotes new grant funding received Crowley’s daughter, Lia, is wearing a net containing dozens of electrodes, which detect the differ- Opioid Receptor Gene Variants to Substance under the American Recovery and ences in electrical potentials across the surface of the brain. Dependence, 3 years, $786,849 Reinvestment Act of 2009 (ARRA).

6 www.medicineatyale.org New fellowships memorialize Annie Le, ‘an exemplary student’ When Annie Marie Le, an idealis- R. Breaker, ph.d., the Henry Ford II tic and ambitious doctoral student Professor of Molecular, Cellular, and in Yale’s Combined Program in the Developmental Biology and Howard Biological and Biomedical Sciences Hughes Medical Institute Investiga- (bbs), lost her life in a homicide last tor, studies large, non-coding rnas September, the Yale community—and that were recently discovered in several the larger world—reacted with grief species of bacteria, which appear to and dismay. be important for helping the bacteria In the wake of Le’s death, members survive extreme stress. of many parts of the Yale community In addition to their academic work, came together to forge a scholarship both fellows are public-spirited. Button fund that would commemorate her participates in the Hill Neighborhood life and exemplary spirit in a lasting Mentoring Program, has served on the way by supporting the work of current Graduate Student Assembly for two graduate students. Soon after, the Yale years, and has sung with the Academia Corporation established the Annie Le Nuts, the graduate school’s all-female harold shapiro

Fellowship to provide assistance to a cappella group. Wallace provides Julie Button and Jason Wallace, doctoral candidates in the Combined Program for Biological and doctoral candidates in the bbs program Spanish-English translation for his Biomedical Sciences, have been named the inaugural Annie Le Fellows for 2010–2011. “whose demonstrated commitment to church and has served as a career men- bettering the world around them and tor for the Boy Scouts of America. about people and treated everyone with connected with mitochondrial func- outstanding record and research exem- “Annie Le was an exemplary stu- respect. It is for these reasons that Yale tion in muscle cells. She planned to plify the qualities represented in the life dent, and someone who was concerned University established this fellowship devote her life to biomedical research, and career of Annie Le.” about the community in which she in her memory.” and had dreamed of having a scien- Two graduate students in the bbs lived. And so we thought that the fel- An initial $100,000 endowment tific career at the National Institutes program—Julie Button, a fifth-year lowship really would emphasize those from the Yale Corporation has been in- of Health. graduate student in microbiology; and two qualities—that is, the capacity creased by additional gifts from friends “One of the many tragic aspects Jason Wallace, a fourth-year gradu- of someone to really be an absolutely and members of the Yale community. about losing Annie was that it was only ate student in molecular, cellular, and outstanding student, who also was In April, the Association of Asian after her death that the Yale commu- developmental biology—have been concerned about the larger world in American Yale Alumni, the Association nity at large learned about her and her named the inaugural Annie Le Fel- which he or she lives. We thought it of Yale Alumni, the Yale Alumni Asso- wonderful qualities,” says John D. Al- lows and will receive funding for the was a really appropriate way to com- ciation of Metropolitan New York, the varo, ph.d., administrative director of 2010–2011 academic year. memorate her life and her time at Yale,” Yale Life Sciences Alumni Association, bbs. “The fellowship in her name now Button, who works in the labora- says Jon Butler, ph.d., the Howard R. and several other groups collaboratively enables us to identify and celebrate tory of Salmonella expert Jorge E. Ga- Lamar Professor of American Studies, organized a benefit concert for the fund other talented and selfless students, lán, ph.d., d.v.m., the Lucille P. Markey History, and Religious Studies. Butler in New York City. some of the hidden gems among the Professor of Microbial Pathogenesis, was dean of Yale’s Graduate School of After earning her undergraduate student body.” studies the roles that “chaperone” Arts and Sciences when Le died, and he degree in cell and developmental biol- The Annie Le Fellowship will be proteins play in the Type III Secretion oversaw the implementation of the new ogy at the University of Rochester, awarded each year by the Graduate System, an appendage used by many fellowship. Le came to Yale for graduate work School of Arts and Sciences, at the Gram-negative bacteria to help them “Annie came to Yale to study and in 2007. Working in the laboratory recommendation of faculty in the infect a host’s cells by moving factors train as a biomedical scientist,” says of her advisor, Anton M. Bennett, biological and biomedical sciences. into those cells that promote the bacte- Elias Lolis, ph.d., associate profes- ph.d., associate professor of pharma- To contribute to the fellowship fund, ria’s survival and replication. Wallace, sor of pharmacology and Le’s former cology, Le was exploring the effects contact Wesley Poling, ph.d., at wesley. a doctoral student in the lab of Ronald doctoral supervisor. “She also cared of metabolic stresses on an enzyme [email protected] or (203) 432-7919.

Mathers Charitable Foundation, Mechanical Barrett’s and Esophageal Adenocarcinoma Con- // Giraldez (from page 3) anemia. Because the Ago2 processing Communication between the Nucleus and the sortium Genetic Susceptibility Study, 1 year, destroying the genes in that mrna. pathway for miR-451 and other mir- Cytoplasm, 3 years, $1,100,000 • Michael Koelle, $20,889 • Alan Sartorelli, National Foundation Since Ago2 has its own slicing activity, nas has been conserved in vertebrate Merck/United Negro College Fund, 2009 uncf for Cancer Research, Approaches to the Therapy the Giraldez team hypothesized that animals over evolutionary time to Merck Undergraduate Science Research Scholar- of Leukemia, 3 years, $151,940 • Margretta Sea- Ago2, rather than Dicer, might process regulate processes as basic to life as ship Award, 1 year, $10,000 • Richard Lifton, shore, Children’s Nat’l Medical Center, Longitu- miR-451, and this supposition proved red blood cell production, Giraldez Columbia University, A gwas for IgA Nephropa- dinal Studies for Urea Cycle Disorders, 6 months, to be correct: in a zebrafish mutant believes that these seeming exceptions thy, the Most Common Form of Glomerulone- $6,594; Children’s Research Institute, Longitudi- with faulty Ago2, levels of miR-451 to the Dicer-based rule may prove to phritis, 10 months, $344,355 • Nils Loewen, nal Studies for Urea Cycle Disorders, 5 years, American Glaucoma Society, Application for $500,000 • Sachin Shah, American Heart Asso- were sharply reduced. Previous studies have much wider implications. Mentoring for Advancement of Physician-Scien- ciation, Variations of Inpatient Spending and had shown that miR-451 is essential “There is an immense, vast sea of tists (maps) Enabling Award Program, 1 year, Patient Outcomes with Acute MI, 6 months, for normal red blood cell production, small rnas out there, and it is difficult $10,000 • Paul Lombroso, Institute for the $11,000 • Robert Sherwin, Columbia University, and the Ago2-mutant zebrafish were to sort out what is junk from what is Study of Aging, Screening for Inhibitors of step, Hydrozyuera (HU) Use in Sickle Cell Disease, 9 found to be anemic (see photo). functional,” says Giraldez. “This discov- 1 year, $138,600 • Charles Lusk, G. Harold and months, $79,087 • Michael Simons, Fondation This observation nicely comple- ery really opens the door to finding new Leila Y. Mathers Charitable Foundation, Con- Leducq, Transatlantic Network on Therapeutic ments another new study by a Cold families of these rnas that influence necting Chromatin to the Lumen: Making Pores Arteriogenesis and Metabolism Modulation, Spring Harbor Laboratory research many forms of biological activity. With in the Nuclear Envelope, 3 years, $1,100,000 5 years, $936,220 • Stephen Strittmatter, team (two members of which also this new ‘molecular scissors,’ we have Steven Marans, NewAlliance Foundation, Inc., Alzheimer’s Association, Neuronal Receptor worked with Giraldez and colleagues another tool to find smallrna s that are Child Development Community Policing Mediating the Disease-Causing Effects of A-Beta on the zebrafish study), who found important to life, that activate genes in Program, 1 year, $5,000 • Richard Marottoli, Oligomers, 3 years, $200,000 • Vinzenz Unger, Research Foundation for Mental Hygiene, Johns Hopkins University, Structural Biology of that mice with compromised Ago2 disease, and may be important in devel- Health and Aging Policy Fellowship, 1 year, Copper Homeostasis, 1 year, $261,490 • Tong also had reduced levels of miR-451 and oping new therapeutics.” $30,000 • Kathleen Martin, Flight Attendant Wang, University of Cincinnati, Apical Chloride/ Expression of hemoglo- Medical Research Institute, Effects of Second- Bicarbonate Exchangers in Small Intestine and bin (brown), a crucial hand Cigarette Smoke Exposure on Adiponectin, Kidney, 10 months, $41,843 • Nadia Ward, component of red blood mtor and Vascular Disease, 22 months, Research Triangle Institute, Yale University gear cells, in a normal zebrafish $216,000 • Eric Meffre, Mount Sinai School of up Partnership Grant, 1 year, $24,000 • Sherman embryo (left) and in a Medicine, Loss of B Cell Tolerance in Primary Weissman, Stanford University, Mapping Tran- mutant embryo lacking Immunodeficiencies, 1 year, $310,645 • Leonard scription Factors Binding Sites in the Mouse the gene for the enzyme Milstone, TransDerm, Inc., Delivery of Biologi- Genome, 6 months, $48,102 • Scott Woods, Argonaute 2 (Ago2; right). cally Active Nucleic Acids to Epidermal Cells, University of California, Los Angeles, Prevention In the absence of Ago2, 2 years, $885,279 • Marc Potenza, University Trial of Family Focused Treatment in Youth at which is part of a novel microrna processing path- of Minnesota, N-Acetyl Cysteine Plus Behavioral Risk for Psychosis, 2 years, $150,597 • Qin Yan, way recently discovered Therapy for Nicotine Dependent Pathological The V Foundation for Cancer Research, Roles of by a Yale-led research Gambling, 1 year, $237,204 • Peter Rabinowitz, Histone Demethylase Retinoblastoma Binding team, mutant fish develop Harvard School of Public Health, Chronic Occu- Protein 2 in Cancer, 2 years, $200,000 • Herbert severe anemia. pational Noise, Stressors, and Susceptibility in Yu, Brigham and Women’s Hospital, Genome- Cardiovascular Illness, 1 year, $22,223 • Harvey Wide Association Study of Endometrial Cancer,

Risch, Fred Hutchinson Cancer Research Center, 1 year, $126,628 courtesy of antonio giraldez

Medicine@Yale July/August 2010 7 A ‘can-do, visionary’ scientist is named graduate school dean Thomas D. Pollard, m.d., Sterling in Basic Medical lends strength to cells and gives them Pollard earned his m.d., cum laude, Professor of Molecular, Cellular, and Science (2006, their shape. Actin filaments generate at Harvard Medical School, where Developmental Biology, has been ap- with James A. force for locomotion in white blood he was later a professor. He joined pointed dean of Yale’s Graduate School Spudich, ph.d., of cells and cancer cells, and form the the Yale faculty as Eugene Higgins of Arts and Sciences, effective July 1. Stanford School of “purse string” that pinches a cell into Professor of Molecular, Cellular, and As an undergraduate at Pomona Medicine); and the two daughter cells during cell divi- Developmental Biology in 2001. College in his native California in the Gairdner Interna- sion, a process that is also important Pollard is a member of the Na- early 1960s, Pollard, also professor of tional Award (2006, in wound healing. tional Academy of Sciences and the Thomas Pollard molecular biophysics and biochemis- with Alan Hall, “Always a scientist at heart,” as Institute of Medicine, and a fellow of try and of cell biology, was eager to ph.d., of Memorial Sloan-Kettering he was described by Yale President the American Academy of Arts and understand how cells move (cell mo- Cancer Center). Richard C. Levin upon his ap- Sciences, the Biophysical Society, tility) and how they divide to form In addition to their importance in pointment, Pollard has nonethe- and the American Association for the daughter cells (cytokinesis), ques- basic biology, motility and cytokine- less gravitated to leadership roles Advancement of Science, for which he tions that have guided his research sis have direct relevance to oncology, throughout his career. He has served now serves on the board of directors. ever since. because these processes drive cancer’s as president of the Salk Institute for Married to his wife, Patty, since For more than three decades of spread and the growth of tumors. Biological Studies, of the Biophysical 1964 (she has been president of the research on these topics, Pollard has Research in Pollard’s laboratory, Society, and of the ascb, which has Yale University Women’s Organiza- won some of the most prestigious which has combined techniques from called him the “personification of [the tion for the past 4 years), Pollard awards in biomedical science, includ- biochemistry, biophysics, cell biology, society’s] can-do, visionary spirit.” passed on a love of science to his chil- ing the E.B. Wilson Medal (2004), and genetics, has focused on actin fil- He was associate editor of the Journal dren, Katie and Dan, both of whom from the American Society for Cell aments—long, thin protein fibers that of Cell Biology for seven years. are computational biologists. In a Biology (ascb); the Lewis S. Rosen- are a basic component of the cytoskel- With bachelor’s degrees in 1992 ascb profile, he said of his fam- stiel Award for Distinguished Work eton, the intracellular framework that chemistry and zoology from Pomona, ily, “We all like to see things work!”

Expert on disability in elderly elected to venerable medical society Thomas M. Gill, m.d., an authority on investigator on the Precipitating Events on studies of the potential benefits of After completing his m.d. at the the epidemiology and prevention of Project (pep), which has revolution- testosterone treatment in symptom- University of Chicago in 1987, Gill came disability among older persons, has been ized our understanding of disability in atic older men and the effectiveness of to Yale as a Robert Wood Johnson elected to the Association of American older persons. Through monthly phone exercise interventions in preventing Clinical Scholar for research training Physicians (aap). interviews and regular home visits, pep disability, and has explored strategies in clinical epidemiology. After a year as The Humana researchers have learned that, contrary to promote independent bathing in a geriatrics fellow, Gill joined the Yale Professor of Ge- to a widely held belief that disability is community-living older people. faculty in 1994. Gill oversees the Yale riatric Medicine irreversible, older people often recover Gill, also director of the Yale Center Research Fellowship in Geriatric Medi- and professor quickly from disabling events. In 2006, for Disability and Disabling Disorders, cine and Clinical Epidemiology, and is of medicine and the National Institute on Aging backed has received many accolades, includ- director of the Pepper Center’s Research epidemiology, Gill pep with a $3.2 million merit award, ing the Paul Beeson Physician Faculty Career Development Core. seeks to understand allowing Gill to continue the 12-year Scholars in Aging Research Award, and Founded in 1885 by seven physi- Thomas Gill the mechanisms study for several more years. the Outstanding Scientific Achieve- cians (including legendary physician underlying physical decline in commu- More recently, Gill, co-director of ment for Clinical Investigation Award Sir William Osler, m.d.) the aap elects nity-living older people and to develop both the Yale Program on Aging and from the American Geriatrics Society, members who make “outstanding con- means of preventing such decline. the Claude D. Pepper Older Americans and the Ewald W. Busse Research tributions to the advancement of science Since 1997, Gill has been principal Independence Center, has embarked Award in the Biomedical Sciences. and medicine.”

// Rothman (from page 1) // Medzhitov (from page 1) specific adaptive immune responses // Greenberg (from page 1) Medicine, and Richard H. Scheller, Sterling Professor of Genetics and by T cells and B cells have had a huge the world’s first major interdisciplin- Ph.D., formerly at Stanford and now the medical school’s deputy dean for impact on our understanding of in- ary research initiative focusing on the executive vice president of Genentech. academic and scientific affairs. “Year fectious diseases and vaccine devel- disorder. Since then, Yale investigators While at the University of Texas after year, important new insights opment,” says Max D. Cooper, m.d., at the VA have remained at the center Southwestern Medical Center, Südhof keep emerging from his lab.” Georgia Research Alliance Eminent of ptsd research and have helped discovered synaptotagmin, a protein in As a doctoral student at Moscow Scholar, professor of pathology and improve the care of returning veterans vesicle membranes that senses intracel- State University, Medzhitov was laboratory medicine at Emory Uni- nationally. lular calcium levels. When a neuron is fascinated by a new theory put forth versity School of Medicine, and nas Son of National Baseball Hall of stimulated, calcium binds to synapto- by the late School of Medicine im- member. “The elucidation of tlrs by Fame member Henry “Hammerin’ tagmin, which prompts the vesicle to munobiologist Charles A. Janeway Ruslan and others has also height- Hank” Greenberg, the legendary release its contents by interacting with Jr., m.d., which held that the innate ened immunologists’ awareness of first-baseman and power hitter for the snare complexes and fusing with the immune system somehow provides the importance of Darwinian evolu- Detroit Tigers during the 1930s and cell membrane. Structural, genetic, and guidance to the slower, but more tionary principles for understanding 40s, Glenn Greenberg has many Yale cell biology studies in Scheller’s lab have fine-tuned responses of the adaptive how the immune system works.” College ties. His stepfather, the late Joe mapped out the interactions of synapto- immune system. Last December, Medzhitov was Lebworth, was a member of the Class tagmin and snares during exocytosis In 1994, Medzhitov came to Yale awarded the Lewis S. Rosenstiel of 1948. His son Greg is a member of with great precision. as a postdoctoral fellow in Janeway’s Award for Distinguished Work in the Class of 1984, and younger son In addition to the neuroscience laboratory, and the two researchers Basic Medical Science. His election to Duncan graduated in 2008. Green- prize, Kavli Prizes in astrophysics and in made the groundbreaking discov- the nas brings the number of current berg’s brother, Steve, is a member of nanoscience are also awarded every two ery that Toll-like receptors (tlrs), Yale faculty who are members to 60. the Class of 1970. years by the nasl. Rothman’s is the a component of the innate system, The nas, a private organization of Greenberg hopes his gift makes second consecutive Kavli Prize in Neu- indeed provide the adaptive system scientists and engineers dedicated to a difference in the understanding of roscience won by a School of Medicine with the necessary information to the furtherance of science and its use ptsd, and he says that our soldiers researcher. In 2008, Pasko Rakic, ph.d., create custom-made B and T cells for the general welfare, was estab- deserve no less. “If you come home Dorys McConnell Duberg Professor of that target specific bacterial or viral lished in 1863 by a Congressional Act and you’re suffering from ptsd— Neurobiology, shared the prize for his invaders. Since then, Toll-like recep- of Incorporation signed by Abraham you’re anxious, you’re depressed, research on the cerebral cortex. tors have become the subject of in- Lincoln. The Academy acts as an you have a hair-trigger temper, you In 2004, the Kavli Foundation, led tense research activity in laboratories official adviser to the federal govern- can’t sleep at night—you’re not very by Norwegian-born entrepreneur and around the world. ment, upon request, in any matter of likely to be a good father, spouse, or philanthropist Fred Kavli, established “Ruslan’s identification of a science or technology. employee. So it’s going to affect the the Kavli Institute for Neuroscience at Toll-like receptor in mammals and rest of your life,” he says. “And all Yale Netcast Yale. Directed by Rakic, it is one of only his studies linking innate immune “Arming the Immune System” because you accepted very low pay to four such institutes nationwide. responses with the triggering of Available on iTunesU or at medicineatyale.org go into a war zone.”

8 www.medicineatyale.org