November/December 2012 volume 8, issue 5 Advancing Biomedical Science, Education, and Health Care

Yale-New Haven and Saint Raphael are “healthier Levin leaves indelible mark on Yale medicine together.” In 2004, when Yale President Rich- working with him, I could join a > Page 3 ard Levin was hoping to recruit Rob- school that was already great and make ert J. Alpern, m.d., as the 16th dean it even greater. He had a vision for the of the School of Medicine, he told school and recognized that it would Alpern during a visit to New Haven require substantial investment that he that the medical school was excel- was willing to commit to.” lent, but should be better, and that he Levin, who has announced that was prepared to make the investment he plans to retire from the presidency with the right person to make it as next June after a 20-year tenure, made great as it should be. good on that commitment, fully in- Alpern had no plans to leave his tegrating the School of Medicine into Newly appointed position as dean of UT Southwestern his vision of Yale’s role in the world in Ob/Gyn chair has Medical School in Dallas, Texas, an the 21st century. institution where he had been on the In his inaugural address in 1993, michael marsland deep roots at Yale During President Richard Levin’s 20-year faculty for 17 years. Levin had emphasized the impor- At the beginning But over the course of many tance of university-based scientifi c tenure, biomedical science has fl ourished at Yale, with unprecedented increases in funding, of October, Hugh e-mails and conversations, Alpern research, and throughout his tenure research space, faculty hires, and the launch of S. Taylor, m.d., recalls, “Rick convinced me that he has pursued a vision // Levin (page 6) novel interdisciplinary institutes. took up his new posts as chair of the Department of Obstetrics, Neuroscientist joins Institute of Medicine Gynecology, Hugh Taylor and Reproduc- Expert on neurobiology of addiction elected to neurobiology and pharmacology, of her work on the molecu- tive Sciences at lar underpinnings of tobacco and alcohol abuse, depression, the School of Medicine and chief branch of National Academies charged with and eating behaviors. “But the overall philosophy—that you of Obstetrics and Gynecology at providing advice on health to policymakers can say something meaningful about molecules in the brain Yale–New Haven Hospital (ynhh). that can inform how we think about the molecular basis With plans that include new cross- “We’re never going to understand all the molecules neces- of behavior—that’s something that’s approachable, and it’s disciplinary clinical programs and sary for an entire behavior,” says Marina Picciotto, ph.d., the worth doing.” translational research, Taylor aims Charles B.G. Murphy Professor of Psychiatry and professor of The molecules that have attracted most of Picciotto’s to further strengthen an already interest are nicotinic acetylcholine receptors (nAChRs), pro- highly regarded department. teins embedded in nerve cell membranes that are activated “I’m inheriting a department by the neurotransmitter acetylcholine, but also respond to with a fabulous reputation and chemicals like nicotine. In addition to a fundamental in- legacy,” Taylor says, noting that volvement in tobacco addiction, nAChRs have been impli- Yale’s past achievements in Ob/Gyn cated in Alzheimer’s disease and in the dysfunctional sensory include major advances in fetal heart processing seen in schizophrenia. monitoring, obstetric ultrasound, Her scientifi c achievements and their relevance to human and in vitro fertilization (ivf). “I’m health received major recognition this October with her very fortunate to have taken on the election to the Institute of Medicine (iom), the arm of the role of chair in a department that National Academies that provides science-based advice on has trained more leaders in the fi eld medicine and health to policymakers, professionals, and the than any other Ob/Gyn department public at large. in the country.” “Marina has made important strides in the area of nico- As a former resident and fel- tine addiction research, and her contributions to our under- low at Yale, Taylor is himself one standing of the many roles played by nicotinic acetylcholine such leader. Colleagues spotted michael marsland receptors have been seminal,” says Robert J. Alpern, m.d., his promise early. Dean Robert J. Marina Picciotto is one of 70 American scientists elected in 2012 to the In- dean and Ensign Professor of Medicine. “She’s a world-class Alpern, m.d., recalls a conversa- stitute of Medicine (iom), “one of the highest honors in the fi elds of health scientist, and I couldn’t be prouder of her election to the Insti- tion some years ago with Charles and medicine [recognizing] individuals who have demonstrated outstand- tute of Medicine.” Lockwood, m.d., Taylor’s prede- ing professional achievement and commitment to service” according to the iom website. Part of the National Academies, the iom’s mission is “to pro- Picciotto began studying nAChRs as a postdoctoral fellow cessor as chair, now dean of the vide unbiased and authoritative advice to decision makers and the public.” in the lab of Jean-Pierre Changeux, ph.d., at // IOM (page 6) College of Medicine // Taylor (page 7)

Non-Profit Org. inside this issue U. S. Postage 1 Church St., Suite 300, New Haven, CT 06510-3330 2 Lifelines www.medicineatyale.org paid Joan Steitz, celebrated researcher, New Haven, CT forceful advocate for women in science. Permit No. 526 3 The body out of balance New study of inflammatory bowel disorder reveals roots in defense against bacteria. 5 Giving the heart a hand New procedure helps those with weakened hearts get through challenging surgery. also Advances, pp. 3, 5 Out & About, p. 4

@YaleMed f /YaleMed lifelines Medical school alumnus awarded a Nobel Prize Brian K. Kobilka, m.d., a 1981 graduate of the As lauded for her advocacy for women scientists as for medical school her own research, Joan Steitz and professor of has been a leader among molecular and women faculty at the School cellular physiol- of Medicine and contributed ogy and of medi- to the infl uential National Academy of Sciences report Brian Kobilka cine at Stanford “Beyond Bias and Barriers,” University School on the status of women in of Medicine, has won the 2012 Nobel science and engineering. She Prize in Chemistry. He shares the recently won the Vanderbilt prize with Robert J. Lefkowitz, Prize in Biomedical Science for her “stellar record of re- m.d., of Duke University Medical search accomplishments and Center, for their work on sensors . . . her mentorship of women lodged in the cell membrane known in science.” as G-protein-coupled receptors (gpcrs). Joan Steitz terry dagradi Kobilka and Lefkowitz’s work has contributed greatly to our un- derstanding of the ways cells sense and respond to their environment— “But you’re a woman . . . ” about half of all medications achieve their effects through gpcrs. Breaking down barriers, But the summer before she was to University, one of the “big, burning At Duke in 1968, Lefkowitz start, Steitz worked in the cell biology questions” in molecular biology was began using radioactively labeled sidestepping bias to build lab of Joseph G. Gall, ph.d., at the Uni- how the cell’s protein-making machin- hormones to identify their receptors, a bright career in science versity of Minnesota (a Yale alumnus, ery determines where on a strand of and soon unveiled the β-adrenergic Gall would later join Yale’s faculty), messenger rna (mrna) to begin trans- receptor, which binds adrenaline at Lining a shelf in the office of Joan A. and “got so excited about it that I lating its message into proteins. the cell surface and sets off a bio- Steitz, ph.d., is a row of champagne decided I wanted to continue doing The lab’s other postdocs, all men, chemical cascade inside the cell. bottles, each label signed in a rite of research and discovering how things shied away from this problem because In the 1980s, Kobilka joined passage by graduate students when work. I didn’t care if I was ever in a the probability of obtaining an answer, Lefkowitz’s lab as a postdoctoral fel- they completed their doctoral work in position that the men would be in.” especially in two years’ time, was low. Together, Kobilka and Lefkow- Steitz’s lab, almost all of whom moved In 1963, Steitz entered Harvard’s slim. “I’m never going to have a job itz isolated the gene that codes for on to faculty positions or careers in graduate program in biochemistry and anyhow,” Steitz recalls thinking, so she the β-adrenergic receptor. After industry. It may seem unremarkable molecular biology graduate program, took it on. She soon had the answer, noticing the gene’s similarity to a to today’s students that the bottles the sole woman in a class of 10. She which she published in a now-classic light-sensitive receptor in the retina, added from recent years are signed by recalls that when she approached 1969 paper in the journal Nature. they found that both were members roughly equal numbers of women and a scientist about doing her thesis Steitz did “get a job”—at the of a large family of receptors, now men, but Steitz knows that the labels research in his lab, which did similar School of Medicine in 1970, where recognized as gpcrs, that play a carrying women’s signatures mark just work to that she did in Minnesota, she has since accumulated a long list role in a variety of vital functions the beginning of a challenging road. “he said, ‘But you’re a woman, you’ll of accomplishments. Notable among from seeing to digestion to memory. “There weren’t any women doing get married, you’ll have kids, and what them was her 1979 discovery of snrnps In 2011, Kobilka’s team captured this sort of thing when I was being good will all this education be then?’” (“snurps”), rna–protein complexes an image of the β-adrenergic recep- educated,” says Steitz, Sterling Pro- So Steitz got her “second choice,” crucial to the proper splicing of mrna. tor at the moment that it is activated fessor of Molecular Biophysics and as the first female graduate student Steitz, a Howard Hughes Medical and sends a signal into the cell. In Biochemistry and one of the world’s in the lab of James D. Watson, ph.d., Institute investigator since 1986, announcing the prize, the Nobel foremost authorities on rna biology. who had just shared the Nobel Prize as acknowledges that she had “good committee declared, “This image is In the early 1960s, when she received co-discoverer of the structure of dna. timing”: the women’s movement of a molecular masterpiece–the result her undergraduate degree in chemis- Though Watson was known to fancy the 1970s brought women into many of decades of research.” try women in science almost always “cute girls,” she says, when it came to fields that had been dominated by worked as research associates, not science “he judged people purely on men. But she also credits molecular faculty members, she says, so she the basis of what they could contrib- biology’s embrace of “open, adven- planned to attend Harvard Medical ute, regardless of gender.” turesome, trailblazing” people in her School after college—to become a phy- When Steitz moved on, to a post- success. “rna,” she says, “has been a Editor Peter Farley sician instead of a scientist. doctoral position at Cambridge very good field for women.” Associate Editor Charles Gershman Contributors Jenny Blair, Natalie Villacorta, Sarah C.P. Williams, Marc Wortman Design Jennifer Stockwell Recent graduate’s documentary fi lm garners top award at fi lm fest Medicine@Yale is published five times each year by the Office of Institutional Planning and Michael Otremba, m.d., a 2012 “In all my prior research, I had never Communications, Yale School of Medicine, 1 Church St., Suite 300, New Haven, CT 06510-3330 graduate of the School of Medicine encountered the phenomenon of clinics Telephone: (203) 785-5824 Fax: (203) 785-4327 and now a postdoctoral fellow in the being turned into debtors’ prisons. My E-mail [email protected] Department of Surgery, has won the hope is that the fi lm will be used to Website medicineatyale.org award for best documentary feature advocate for health care reform in all Copyright ©2012 by Yale University. All rights reserved. in the New York Los Angeles Interna- communities where patients are unable If you have a change of address or do not wish to receive future issues of Medicine@Yale, please write to us at the tional Film Festival. to access basic health services.” above address or via e-mail at [email protected]. Otremba’s fi lm, Twero“ : The Road Otremba devoted his fi fth year of Postal permit held by Yale University, to Health,” explores the practice of medical school to the project, which 155 Whitney Avenue, New Haven, CT 06520

many Ugandan doctors detaining combines his interests in human rights terry dagradi patients who are unable to pay their and visual arts. He worked under the Michael Otremba, at work on his docu- Robert J. Alpern, m.d. Dean and Ensign Professor of Medicine bills. Twero means “right to health” in mentorship of Gretchen K. Berland, mentary fi lm Twero (right), was advised by Jancy L. Houck Luo, one of the languages spoken in m.d., associate professor of medicine physician-fi lmmaker Gretchen Berland (left). Associate Vice President for Development and Uganda. The Ugandan government’s and recipient of a MacArthur “genius” Networked Digital Library of Theses Director of Medical Development (203) 436-8560 Mary Hu promise of free medical services to all grant for her own documentary work. and Dissertations consortium, which Director of Institutional Planning and Communications Ugandans “has been very diffi cult to In August, Otremba’s fi lm promotes the creation and distribution translate into reality,” Otremba says. was honored by the international of “electronic” thesis projects. Printed on recycled paper ♻

2 www.medicineatyale.org advances Health & Science News With acquisition, hospital broadens reach Blood bounces back With Hospital of Saint Raphael acquisition, and non-profit companies. In March 2011, hsr and ynhh signed a letter of intent to explore integration, followed by a from chemotherapy Yale-New Haven Hospital becomes the fifth definitive agreement in September, in which ynhh agreed to largest hospital in the United States purchase hsr’s assets, to invest in hsr buildings and tech- nology, and to honor hsr’s Catholic heritage at that campus. On September 11, in a historic ceremony, officials from Yale- The Sister Anne Virginie Grimes Health Center, Saint New Haven Hospital (ynhh) and the Hospital of Saint Raphael’s 125-bed skilled nursing and short-term rehabilita- Raphael (hsr) signed final documents. Hours later, at 12:01 tion facility, is also being acquired as part of the transaction. a.m. the next day, the two hospitals officially became a single Both hospitals worked for the past year to minimize 1,519-bed institution with two main campuses. job losses by keeping vacant positions open and managing

istockphoto.com “We are delighted that with all of the Healthy blood cells take a beating dur- necessary approvals and due diligence be- ing chemotherapy. New work by Yale hind us, we can begin the important work researchers suggests a strategy to help of integrating these two great hospitals,” repair the damage. said Marna P. Borgstrom, m.p.h., ceo of A team led by Jun Lu, ph.d., as- ynhh and president and ceo of Yale- sistant professor of genetics, scanned a New Haven Health System. “We believe library of molecules known as that as one unified hospital, we’ll be able micrornas (mirnas) to see if any to enhance access to high-quality health affected the recovery of bone marrow care resources in a more cost-effective cells injured by the cancer drug 5-fluoro- manner. This integration will be critical uracil. One, called miR-150, stood out: to meeting the extraordinary health care cells that had extra miR-150 recovered challenges that lie ahead.” slowly, and cells that completely lacked The integration will allow ynhh to miR-150 recovered the fastest. provide the region with more coordinated mirnas are short stretches of care, to reduce redundancy of clinical genetic material that bind to messen- services and financial investments, and to ger rna (mrna), blocking the cell from become more efficient. It also gives ynhh making protein coded in that mrna. Lu 511 much-needed beds and provides finan- robert lisak and colleagues discovered that miR-150 cial stability for the hsr campus. Marna Borgstrom, ceo of Yale-New Haven Hospital, and Christopher binds to the mrna for a gene called While volume at most Connecticut hospitals has been O’Connor, president and ceo of the Hospital of Saint Raphael, sign the c-myb, and if the group shut down flat or declining over the past several years, ynhh has seen final agreement to make official the integration between the two historic New Haven-based hospitals. c-myb through other means, they could an increase, resulting in significant capacity constraints; partially replicate the slowed recovery the hsr acquisition will allow ynhh to avoid an estimated attrition. About 3,400 hsr employees are transitioning to seen in cells with high levels of miR-150. $650 million investment in a new patient tower. positions in the Yale-New Haven Health System. Addition- The study, published October 25 in The transaction helps hsr to preserve a deeply rooted ally, 400 members of the hsr medical staff have been newly Cell Reports, is the first to use a mirna legacy as an exceptional care provider and to honor its tradi- credentialed as members of the ynhh medical staff. screen in living mice to study an active tions as a Catholic hospital, while also taking on the future as “The integration has the opportunity to increase quality physiological process, and the first to part of a nationally recognized academic medical center. outcomes and provide better access to the entire continuum implicate a mirna in the recovery of “For the Hospital of Saint Raphael, the integration of care for patients,” said Peter N. Herbert, m.d., chief of staff bone marrow cells after chemotherapy. represents an opportunity to assure financial stability in an and senior vice president of medical affairs at ynhh and uncertain time. Proceeds from the $160 million transaction clinical professor of medicine at the School of Medicine. “Care Before eyes open, will allow the hospital to pay off its debt and will help ad- will be better coordinated as clinical information and data dress its pension liabilities,” said Christopher O’Connor, hsr will be accessible to all patients and providers though a new, brain gets ready to see president and ceo. “We are intent on making this integration state-of-the-art integrated electronic medical record system.” For weeks after birth, a newborn go as smoothly as possible for our patients, our employees, Following the signing of the definitive agreement, there mouse is blind, with eyes that have physicians, and the community. This represents a Connecti- was a months-long approval process that included the Con- yet to open. But to prepare the animal cut solution to a Connecticut challenge.” necticut Attorney General, the Federal Trade Commission to see when its eyes do open, neural To better prepare for the 21st century health care land- and Connecticut Office of Health Care Access. circuits in the brain’s visual system scape, hsr leaders began discussions with potential partners Local and state elected officials, community leaders must begin developing. This same situ- two years ago, including both state and national hospitals and regional businesses were overwhelmingly supportive ation, which is in place before birth in and systems; Catholic and secular hospitals; and for-profit of the integration. humans, is a scientific puzzle, because the proper development of many brain regions involved in vision generally re- quires sensory input through the eyes. New research shows that waves Genomic study of bowel disorders is a global effort of spontaneous neural activity in the In one of the largest studies of its kind and abdominal genomic studies of either cd or uc, retinas of still-closed eyes in mice are ever conducted, an international team pain. Ibd patients creating a large dataset that combined necessary to properly wire up the brain: of scientists has thrown new light typically need life- genetic information from some 34,000 when their eyes finally open, the mice on the genetic basis of inflammatory long treatment with individuals who took part in those are able to see. “If you interfere with bowel disease (Ibd), a group of chronic drugs, and often studies. The results then formed part this activity, the wiring details are all autoimmune digestive disorders affect- need surgery to re- of a second meta-analysis that included wrong,” says Michael C. Crair, ph.d., ing 2.5 million people worldwide. pair tissue damage. data from new genome-wide scans of William Ziegler III Professor of Neurobi- The new study links variations “Up until this more than 41,000 dna samples from ology and professor of ophthalmology in 163 regions of the human genome, Judy Cho point we have been cd or uc patients and healthy com- and visual science. 71 of which are newly discovered, to studying Crohn’s parison subjects collected at 11 centers As reported in the October 11 issue increased risk of contracting ibd. These disease and ulcera­tive colitis sepa- around the world by the International of Nature, Crair’s team simultaneously regions showed a striking overlap with rately,” says Judy H. Cho, m.d., the Ibd Genetics Consortium. recorded the activity of neurons in the those implicated in other autoimmune Henry J. and Joan W. Binder Professor In addition to confirming that 92 eyes and brain of newborn mice. They diseases, and suggest that Ibd results of Gastroenterology (see related story, regions identified in previous studies found that waves of activity in the reti­ from overactive immune defense page 4) and professor of genetics, a confer a significant risk of Cd, Uc, or na were relayed through the brain and systems that evolved to fight off serious lead author of the study, which was both, the study linked 71 additional produced corresponding activity in the bacterial infections. published in the journal Nature on stretches of the genome to Ibd. The visual cortex, where information from In the two most common forms of November 1. “We created this study on Ibd-linked variants largely fall in the retina is processed. This occurred for Ibd, Crohn’s disease (cd) and ulcer- the basis that there seems to be a vast genomic regions that regulate the at least a week of a mouse’s life. ative colitis, (uc) the immune system amount of genetic overlap between the expression of immune-system genes The work sheds light on how similar produces an ongoing inflammatory re- two disorders.” implicated in other autoimmune dis- neural activity in unborn fetuses shapes action in the intestinal tract that injures As a first step, the researchers con- eases, particularly the skin disease pso- the human visual system. the intestinal wall, leading to diarrhea ducted a “meta-analysis” of 15 previous riasis and a joint disorder // IBD (page 8)

Medicine@Yale November/December 2012 3 out & about

September 3 Psychiatry faculty, residents, and their families ran in the 35th annual September 9 As part of its Hope on Wheels program, which supports pediatric can- New Haven Road Race. (From left) Audra Crutchfield, ph.d., local recovery coordina- cer research and treatment programs around the U.S., representatives of Hyundai tor at the VA Connecticut Healthcare System in West Haven, Conn.; Ilan Harpaz- Car Sales donated $250,000 to Yale. 1. Gary Kupfer, m.d., professor of pediatrics and Rotem, ph.d., associate professor of psychiatry; Ismene L. Petrakis, m.d., professor of of pathology and chief of the Section of Pediatric Hematology/Oncology at Smilow psychiatry and chief of psychiatry at the VA; Shana Ross, principal of Vili and Ve Solu- Cancer Hospital at Yale-New Haven (third from left) with Hyundai representatives tions, and her son Micah Ross; Kurt Shaffert, chaplain at the VA; Catherine Zaneski, Jim Sullivan, Dave O’Brien, Craig Salera, Ken Bloech, and Tony Yantosca. 2. (Back, aprn, psychiatric nurse practitioner at the VA; Michael J. Sernyak, m.d., professor of 1 from left) Cynthia N. Sparer, m.p.a., executive direc- psychiatry and ceo of the Connecticut Mental Health Center; Kirsten Wilkins, m.d., tor of Yale-New Haven Children’s Hospital (ynhch); assistant professor of psychiatry; Louis Trevisan, m.d., associate clinical professor of Kupfer; and George Lister, m.d., chair and professor of psychiatry; David Ross, pediatrics and physician-in-chief at ynhch. m.d., ph.d., assistant (Front, from left) Faith Nelson, Andrew Cohen. professor of psychia- 3. Faith Nelson, ready to make a handprint. try; Donna LaPaglia, 2 3 psy.d., assistant professor of psychia- try; Don Slone; Adam Mecca, m.d., ph.d., resident in psychiatry, with his daughter Lily Mecca; and Marcia Mecca, m.d., clinical fellow in geriatric medicine. courtesy of kirsten wilkins (3) shapiro harold

September 8 At the annual Closer to Free bicycle ride, members of the 1 2 School of Medicine and Yale-New Haven Hospital (ynhh) communi- ties came together to raise money for cancer treatment and research at Yale Cancer Center (ycc) and Smilow Cancer Hospital at Yale-New Ha- ven. 1. Thomas J. Lynch Jr., m.d., the Richard Sackler and Jonathan Sackler Professor of Medicine, director of ycc, and physician-in-chief at Smilow Cancer Hospital. 2. Elizabeth Kunz, msw, lcsw, clinical social worker at ynhh. 3. Jeremy Kortmansky (left), m.d., physician at ycc, and Howard S. Hochster, m.d., professor of medicine and associate director for clinical research at ycc, share a triumphant moment. 4. A crowd of cyclists con- venes waves to patients inside Smilow Cancer Hospital.

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4 chris volpe (4)

September 17 The Shaw Prize 1 2 in Life Science and Medicine was awarded to Arthur L. Horwich, m.d., at a reception in Hong Kong. Horwich, Sterling Professor of Genetics and professor of pediat- rics, shares the prize with longtime collaborator Franz-Ulrich Hartl, m.d., dr.med., of the Max Planck In- stitute of Biochemistry in Germany.

Horwich has devoted his career to terry dagradi (2) understanding protein folding, a September 20 A reception was held in the Medical/Historical Library honoring the ap- process that is disrupted in neuro- pointment of Judy H. Cho, m.d., professor of medicine and of genetics, as the inaugural degenerative conditions such as Henry J. and Joan W. Binder Professor of Gastroenterology (see related story, page 3). amyotrophic lateral sclerosis. Leung 1. Cho (second from right) with members of her lab (from left) Ken Hui ’15; Mónica Chun-ying (right), Chief Executive Bowen ’15; Wei Zhang, m.d., ph.d., associate research scientist; biostatistician Kaida Ning, and President of the Executive m.sc.; and Sok Meng Evelyn Ng, research assistant. 2. Henry J. Binder, m.d., professor Council of Hong Kong, presented emeritus and senior research scientist in the Department of Medicine, who established the award to Horwich (left). courtesy of the shaw prize foundation the Binder Professorship earlier this year with his wife, Joan W. Binder.

4 www.medicineatyale.org advances Health & Science News A rare mutation offers wide possibilities Damaging in lupus, Lessons gleaned from a rare blood disease could useful in cancer . . . lead to treatments for more common disorders of the blood, including sickle cell anemia

As they flow through veins and arteries, most red blood cells are plump with water. Channels lining the membrane of each red blood cell help ensure that it has the right balance of salts and liquids, keeping the cells elastic and healthy. It’s a process vital to human biology, but also one simon caulton that’s been hard for researchers to fully explain. A team An antibody generated in lupus can including scientists at the School of Medicine has now weaken or kill tumor cells, offering both uncovered a protein that is key to how blood cells main-

a new type of cancer treatment and an tain their hydration, and which could have implications shapiro harold explanation for the low rates of some for treating sickle cell anemia, the most common inherited In studying the cellular dehydration that occurs in xerocytosis, Jesse Rine- cancers seen in individuals with lupus. blood disorder in the United States. hart (left) and Patrick Gallagher identified mutations in the gene for the In lupus a person’s immune system The discovery came out of a quest to understand a protein piezo1, which may also cause dehydration in sickle cell anemia. goes awry, creating “autoantibodies” much rarer inherited blood disorder called xerocytosis. or shrinkage of the cell. “This is the first example of a human that target normal cellular compo- In this disease, the equilibrium of red blood cells is off: disease connected to the protein,” says Jesse Rinehart, ph.d., nents. One such antibody derived from extra potassium and water seep out of cells as they careen assistant professor of cellular and molecular physiology, who a mouse model of lupus, 3E10, enters against the sides of blood vessels, leaving the cells fragile joined Gallagher to study the protein’s role in xerocytosis. the nuclei of cells, where dna resides. and causing anemia, a shortage of red blood cells. Sickle- Rinehart showed that piezo1 is indeed found in the As reported in the October 24 issue of cell anemia, which affects some 70,000 Americans, is membrane of red blood cells and went on to analyze its Science Translational Medicine, a team characterized by misshapen red blood cells, and a common structure. He hasn’t yet uncovered the effect of the xero- led by Peter M. Glazer, m.d., ph.d., complication, apart from the clumping of the misshapen cytosis-linked mutations on piezo1’s function, but that’s a chair and Robert E. Hunter Pro­fessor of cells, is cell dehydration. “Some of the mechanisms that next step. “The first take away from this is that here is what Therapeutic Radiology and professor of cause the dehydration are known, but we’ve never uncov- causes xerocytosis,” says Gallagher, director of the Yale genetics, was using 3E10 as a vehicle to ered what is that channel at the top of the mountain that Center for Blood Disorders. “But the second is that it looks carry other molecules into cancer cell starts the avalanche going,” says Patrick G. Gallagher, like piezo1 is a very good candidate to be what initiates nuclei, but they noticed that 3E10 alone m.d., professor of pediatrics, genetics, and pathology. dehydration in sickle cell.” was sufficient to make the cells more Gallagher and a team of collaborators thought that if The cause of sickle cell anemia—a mutation in the susceptible to radiation and cancer they could understand dehydration in hereditary xerocyto- oxygen-carrying protein hemoglobin—has been known for drugs. The group found that 3E10 binds sis, it might help explain the similar phenomenon they see decades. Though scientists haven’t established what causes to broken, loose ends of dna, disrupt- in sickle cell patients. So, in a study supported by the Doris the cellular dehydration seen in the disease, many suspect ing normal dna repair mechanisms. Duke Foundation and conducted in collaboration with a that another protein initiates the dehydration process. If Many cancer treatments—includ- team from the University of Manitoba, they analyzed the piezo1 is that long sought-after protein, says Gallagher, ing radiation and some chemothera- genomes of two large, multi-generational families affected drugs targeting piezo1 could treat some of sickle cell’s peutic drugs—aim to damage the dna by xerocytosis. As reported in the August 30, 2012, issue symptoms as well as those of hereditary xerocytosis. of tumor cells, and 3E10 may make such of Blood, in both families they identified mutations in the At an international meeting on red blood cells at Yale treatments work better. In cancers that gene for a protein called piezo1. this winter, investigators from around the world will be already have deficiencies in dna repair, Fortuitously, the piezo1 protein had been characterized sharing their data on piezo1 to help complete the story. 3E10 alone can kill the cells. for the first time in late 2010 as a channel that senses me- “Already, this really validates the idea that studying the rar- chanical force or pressure on a cell’s outer membrane—such est diseases can help us understand biology more broadly,” . . . and lupus holds as the change in pressure that could be caused by swelling says Rinehart. yet another surprise A hypothesis on the molecular under- pinnings of lupus has been turned on Hybrid technique is a new option for arrhythmias its head in a new Yale study. Lupus is Implantable defibrillators are devices they believe were Connecticut’s first characterized by attacks on the dna that can prevent sudden cardiac ablations for VT using a new hybrid and rna of normal cells by the immune death in patients with ventricular technique that takes advantage of system, but researchers have struggled tachycardia (VT), a potentially life- an extracorporeal membrane oxy- to understand the source of the anti- threatening fast heart rhythm that genation (ecmo) machine, which bodies against the genetic material. originates in one of the ventricles of provides temporary support of heart One theory is based on the every- the heart, by delivering a shock to and lung function for patients whose day destruction of neutrophils, the terminate the abnormal rhythm. weak hearts would have otherwise most abundant type of white blood While most patients tolerate these made the ablation procedure ex- cell. When neutrophils undergo a devices very well, the shocks are tremely risky. particular kind of cell death, their dna unpredictable, and for some people, “With ecmo, patients with weak is packaged into a neutrophil extracel- even a few of them can be psychologi- hearts become candidates for VT lular trap (net) and released. Scientists cally devastating. This uncertainty ablation. This is important for those have suspected that an accumulation of may cause tremendous anxiety that who must endure repeated shocks nets could stimulate the formation of limits a patient’s quality of life. from their defibrillators as a result,” antibodies against dna. Doctors often start medical says Bonde, director of Yale’s ecmo

Mark J. Shlomchik, m.d., ph.d., therapy once a shock occurs, but program, who performed the proce- courtesy of joseph akar professor of laboratory medicine this does not always prevent future dures alongside electrophysiologist More patients are eligible for heart arrhythmia and immunobiology, and colleagues shocks. For some of those patients, Joseph G. Akar, m.d., ph.d., associate surgery thanks to a new procedure being used tested this theory by crossing mice that radiofrequency catheter ablation is professor of medicine and director by cardiac surgeon Pramod Bonde (right). cannot form nets with mice prone to needed to eliminate the short circuits of the Cardiac Electrophysiology had been receiving as many as six lupus: if the theory were correct, such causing the abnormal rhythm. Laboratory. “We can maximize their shocks in less than one minute from mice would be less likely to develop However, in patients with weak chances of survival and chances of his defibrillator, and Akar wanted to full-blown lupus. Instead, the mice had hearts, “the ablation procedure itself success with this new technique.” perform a radiofrequency catheter more severe lupus, with a different can be quite taxing,” says Pramod The first patient treated at Yale ablation to pinpoint the source of the pattern of autoantibodies. The results, Bonde, m.d., assistant professor of with the procedure was a man with problem and treat it. published October 24 in Science Transla- surgery. “In fact, there are a lot of a weak heart and so-called “VT The physicians performed what tional Medicine, suggest that neutro- patients who are turned down for storm,” characterized by incessant they say is typically a 4- to 6-hour phils may be important sources of this procedure because of their poor life-threatening heart rhythms that procedure with a team of about 15 immune-system stimulation in lupus, heart function.” To give such patients trigger multiple repetitive defibrilla- people, including surgeons, electro- but that nets could play a protective, an option, in October, Yale physi- tor shocks. The patient, who had al- physiologists, nurses, perfusionists, rather than aggravating, role. cians successfully performed what ready had two open-heart operations, technologists and // Heart (page 6)

Medicine@Yale November/December 2012 5 // IOM (from page 1) the Institut Pasteur Psychiatry and associate director // Heart (from page 5) others—a proce- foundation for the successful hybrid in Paris, France, and she describes these of the School of Medicine’s Medi- dure that patients with weak hearts ablation procedures. beginnings the way many describe cal Scientist Training Program can tolerate with ecmo. “We’ve matured the adult ecmo their fi rst cigarette: “Once I started,” (informally known as the m.d./ Akar was pleased that the ecmo program and are having very good she says, “I was hooked.” ph.d. Program), Picciotto serves support allowed him to take the time outcomes, and these procedures are Picciotto has also done important on the National Advisory Council he needed to perform the ablation an extension of that,” he says. “We studies of nicotine exposure during of the National Institute on Drug procedure carefully. Most important- waited until now to do it because we gestation and adolescence and its Abuse. In 2000 she was awarded ly, he says, ecmo support allowed wanted to make sure the team is con- effects on learning and memory, and the Presidential Early Career him to induce the dangerous heart fi dent and that complex procedures of the neuropeptide galanin, which Award in Science and Engineering rhythm long enough for him to locate such as VT ablation can be supported modulates ACh release and may exert by President Clinton, and in 2007 its source. with ease.” a protective effect against addiction she was honored with the Jacob P. “The VT procedure is potentially Other centers in the country have to drugs of abuse such as cocaine, Waletzky Award by the Society for long and technically complicated,” offered the hybrid procedure, either amphetamines, and opiates. Neuroscience. Akar says. “Many patients have with ecmo or with pumps that take Picciotto received her undergradu- The iom, established in 1970 by such severe underlying heart disease over the function of the heart, but not ate degree in biological sciences from the National Academy of Sciences, is that they would really be unable to the lungs. “This is the fi rst such case Stanford University in 1985, and a a national resource for independent, withstand the stress of this procedure at Yale and to my knowledge in Con- ph.d. in molecular neurobiology in scientifi cally informed analyses and if it was not for the hemodynamic necticut,” Akar says. “I look forward 1992 from The Rockefeller University recommendations on issues related to support provided by the ecmo.” to offering this important therapy as in New York City, where she worked in human health. Those elected to the Bonde says the development of we build our ecmo and VT programs the Laboratory of Molecular and Cel- institute are judged to have made sig- Yale’s adult ecmo program in the to treat challenging cases.” lular Neuroscience under Paul Green- nifi cant contributions to the advance- past year—at fi rst as a temporary The two doctors predict Yale will gard, ph.d. She became a member of ment of medical science, health care, measure for patients with adult respi- treat at least 20 to 30 patients next the Yale faculty in 1995. and public health, and election is ratory distress syndrome, acute heart year with the hybrid procedure, and Also vice chair for basic sci- considered one of the highest honors failures, catheter-lab emergencies more as patients and referring physi- ence research in the Department of in the health sciences. and other serious events—laid the cians learn the procedure is available.

// Levin (from page 1) of preeminence in interest and benefi t people worldwide, investment would go to the School of the leaders in the world in the care and medicine and science at Yale. “Today, “are a powerful form of ‘international Medicine over the coming decade. treatment of cancer.” Alpern credits the scientifi c capability of American currency’ in academia.” That investment funded outstand- Levin, who as Yale President serves on universities is the envy of the world,” In January 2000 Levin announced ing infrastructure for modern bio- the hospital’s board, with fostering an he said in 1993. “We neglect its support the greatest investment in biomedical medical science—new laboratories, core excellent working relationship between at our peril.” science in the university’s 300-plus-year technology facilities, and high-tech the university and medical school and Levin’s unwavering commitment history. The New York Times called his teaching centers—that could have never ynhh. “He has had a huge commit- to medicine and science in the years dedication of $500 million to science have been shoehorned into the medical ment to the hospital’s success and to since is a direct outgrowth of his and engineering “one of the largest school’s existing facilities. the success of its relationship with the often-stated goal of transforming Yale one-time building plans ever” made by In 2003, the medical school opened medical school,” says Alpern. into an institution with global reach, a university. the largest academic building in Yale In June 2007, Levin spearheaded Alpern says. “Rick understood that Less than a month later Levin history, the 457,000-square-foot the purchase of the former Bayer science and medicine,” as fi elds that said that an additional $500 million Anlyan Center for Medical Research Healthcare North American pharma- and Education. Alpern, who became ceutical headquarters in West Haven, dean in 2004, says that the facility is Conn. Now known as West Campus, so crucial that “I can’t imagine what the purchase added 136 acres and more the medical school would look like if it than 1.5 million square feet of space, in- Pulse weren’t here.” cluding many purpose-built biomedical Together with the 120,000-square- research labs. The life of Yale School of Medicine foot Amistad Street Building, which Levin called on the university to opened in 2007, the medical school make West Campus Yale’s home for increased its existing laboratory space innovative biomedical and clinical by half. science programs that cross and chal- In academic medicine, increased lenge disciplinary boundaries and space drives increased quality: con- take risks for the chance at making struction projects enacted under Levin revolutionary advances. made possible a 76 percent boost in “This has transformative poten- medical school faculty, from 1,300 tial, frankly—only some of which we when he took offi ce to 2,300 today. Col- can envision today,” Levin said as the lectively these faculty propelled a nearly planning for West Campus got under four-fold jump in the school’s annual way. “We’ve given our successors an grant funding, from about $140 million opportunity to dream in ways we can’t in 1992 to about $540 million, accord- imagine today.” Hunger and ing to the latest fi gures. Both Alpern and Carolyn W. Slay- Levin’s strong backing for medi- man, ph.d., deputy dean for academic Homelessness cine and science also spurred Yale’s and scientifi c affairs at the School of Auction adoption of critical new technologies Medicine for most of Levin’s presi- and the recruitment of accomplished dency, say that one of Levin’s greatest The Hunger and Homelessness Auction, an annual event held at the School of and visionary scientists. In addition, strengths as an administrator is that he Medicine that raises funds to help alleviate hunger and homelessness in the New many scientists who were offered po- is an “incredible listener.” Haven area, turned 20 this year. sitions at other schools chose to stay But Slayman stresses that Levin’s is The first auction was organized in 1993, when medical student Jeffrey at Yale, appreciating the university’s not a passive form of listening, but one Meyerhardt, m.d. ’97, m.p.h., now associate professor of medicine at Harvard commitment to them. to which he brings the ability to take Medical School, proposed the idea to Robert H. Gifford, m.d., professor emeritus The school’s principal teaching what he hears and “integrate it and fi t it of medicine and associate dean of student affairs at the time. “He and I cooked hospital, Yale-New Haven Hospi- together. He builds a framework in his up the first auction, which was held in Harkness Ballroom,” Gifford recalls. That tal (ynhh), also grew, especially mind, so he’s not just hearing random year, the auction raised about $3,500. In 1994, the proceeds were $7,000. through the 2009 opening of the things and remembering them–he’s Organized by students from the School of Medicine, the Physician Associate 14-story Smilow Cancer Hospital at putting them together in a very logical, Program, and the School of Nursing, the event now typically generates more Yale-New Haven, which united all of connected way.” than $25,000. The auction has grown into a week-long slate of activities, includ- Yale Cancer Center’s myriad clinical By combining these skills, say ing a football game between the first- and second-year classes, panel discussions, services under one roof. Alpern and Slayman, during his tenure performances, and films—all culminating in both silent and live auctions of do- “It is a day of inspiration, a day that Levin developed extremely well- nated items. Past recipients of proceeds from the auction include the Community we’ve all waited for for many years,” informed views on academic medicine Health Care Van, Loaves and Fishes, Domestic Violence Services of Greater New Levin said on Smilow’s opening day. “It that guided his decisions. Haven, and New Haven Home Recovery, and Youth Continuum. will allow this hospital and this medi- But most important, says Alpern, cal school to take their places among “He followed through.”

6 www.medicineatyale.org Project to explore roots of autism in girls NIH awards grant of $15 million for research Stay in touch at Center of Excellence The reasons why autism spectrum disorders (asds) are almost five times with the more common among boys than among girls may soon be revealed, School thanks to a five-year, $15 million National Institutes of Health (nih) grant awarded to the School of Medi- of Medicine cine’s Autism Center of Excellence (ace) research program. Led by principal investigator on Facebook Kevin Pelphrey, ph.d., the Harris Family Associate Professor in the Child Study Center (csc), the Yale

ace award is part of a $100 mil- stan godlewski lion National Institutes of Health Kevin Pelphrey, pictured here with his three children, two of whom have autism spectrum disorders program that will provide funding (asds), is the lead investigator of a five-year, $15 million Yale study that will investigate the causes to nine institutions to investigate the of autism in girls, who are about five times less likely than boys to be diagnosed with an asd. The causes of and treatments for asds. School of Medicine’s Autism Center of Excellence is one of nine institutions participating in the $100 million project, which is funded by the National Institutes of Health. “It is my hope that this award will invigorate research in autism at and will focus on issues as children and adults who Yale and allow us to maintain our genes, brain func- have limited or no speech, possible outstanding history of cutting-edge tion, and behavior links between asds and other genetic work in this field,” says Pelphrey, also throughout child- syndromes, potential treatments, associate professor of psychology and hood and adoles- and the possible reasons why asds director of the Center for Develop- cence. asds are are more common among boys than mental Neuroimaging. complex develop- girls, according to Alice Kau, ph.d., Pelphrey and a collaborative mental disorders of the Intellectual and Developmen- team of researchers from Yale, James McPartland that affect how a tal Disabilities Branch at the Eunice UCLA, Harvard, and the University person behaves, Kennedy Shriver National Institute of of Washington will investigate the interacts with others, communicates, Child Health and Human Develop- poorly understood nature of autism and learns. According to the Centers ment (nichd), one of five institutes in females. Other labs at the School of for Disease Control and Prevention, funding the ace program. Medicine that will participate include asds affect approximately 1 in 88 Other supporters of the ace pro- that of James C. McPartland, ph.d., children in the United States. gram include the National Institute assistant professor in the csc and nih created the ace Program in on Deafness and Other Communica- assistant professor of psychology, and 2007 to launch an intense and coordi- tion Disorders, the National Institute director of the Yale Developmental nated research program that supports of Environmental Health Sciences, Disabilities Clinic. large collaborative efforts to advance the National Institute of Mental The team will study an unprec- broad research goals. The program Health, and the National Institute of edented number of girls with asds expanded this year to examine such Neurological Disorders and Stroke.

// Taylor (from page 1) and vice presi- In addition to seeing patients, on his agenda is improved clinical care dent for Health Sciences at The Ohio Taylor has been continuously funded through collaboration. Already hard State University. “Charly told me that by the National Institutes of Health at work to create a cross-disciplinary someday, when he left or retired, I for over 20 years for his research into incontinence program, Taylor plans would do a national search, and after I endometriosis, adult stem cells, and to organize medical teams for other had looked at candidates all across the reproductive developmental biology, challenging clinical problems. “We’re country, I would appoint Hugh Taylor among other areas. He has also long working with pediatrics and pediatric as the next chair,” Alpern recalls with been a lauded mentor to students, surgery to increase our offerings in a laugh. “And that’s exactly what hap- residents, and faculty. fetal therapy,” he says, “and col- pened. We’re absolutely delighted.” Taylor has deep Yale roots. He laborating in maternal-fetal medicine Alpern says that Taylor is “spectac- graduated from Yale College and the with neonatology, to be more closely ular” and brings a unique constellation University of Connecticut School of aligned on high-risk pregnancies and of talents to the job. “He’s a great clini- Medicine, then completed his residency in the neonatal intensive-care unit.” cian, great teacher, and an outstanding at ynhh in 1992. Pursuing parallel ca- This multispecialty approach, he says, researcher. He’s got it all, in addition reers at bench and bedside at the School is the future of medicine. “Rather than to being an incredibly nice person, and of Medicine, he completed a postdoc- be siloed into departments, we bring he’s quite mature administratively for toral fellowship in molecular biology as all the different areas of expertise that someone who hasn’t been a department well as a fellowship at Yale’s Division might have relevance to a patient’s chair yet.” of Reproductive Endocrinology and disease together under one roof.” That maturity may be owing to Infertility (rei). He has been a Yale Taylor plans to act on ynhh’s Taylor’s national leadership experi- faculty member since then, going on to recent acquisition of the Hospital ence. Among other positions, he is a serve as chief of rei. During his six-year of Saint Raphael (see related story, member of the boards of directors of tenure in that position, Taylor turned page 3) to strengthen the department’s the Society for Gynecologic Investiga- around rei’s fiscal deficit and expanded relationships with community Ob/ tion and of the American Society for its patient volume, range of services, Gyn physicians. He will also recruit Reproductive Medicine, both premier and ivf success rate, positioning rei as new faculty leaders and expand the organizations in the field. He also a national leader in the field. department’s involvement with inter- served for two years as clinical direc- To his new job, Taylor brings a national capacity-building. tor of the Society for Assisted Repro- slew of ambitious goals. He plans to “We’ve got tremendous opportu- ductive Technology, the nation’s most expand the department’s research ef- nities, starting on a fabulous founda- facebook.com/YaleMed important group of ivf professionals, forts in translational medicine, such as tion,” he says. “I hope to be able to and he is editor of the journal Repro- research in cancer genomics that may take the department to even greater ductive Sciences. lead to personalized treatments. Also heights.”

Medicine@Yale November/December 2012 7 Chair of immunobiology honored by the Cancer Research Institute

Richard A. Flavell, ph.d., chair and H. Glimcher, m.d., the Stephen and and retroviral tech- The cri was established in 1953 Sterling Professor of Immunobiol- Suzanne Weiss Dean and provost for nology to elucidate to transform cancer patient care ogy and a Howard Hughes Medical medical affairs at Weill Cornell Medi- the function of these through the discovery and develop- Institute (hhmi) investigator, has cal College, and Kenneth M. Murphy, genes and their ment of safe and effective immune received the 2012 William B. Coley m.d., ph.d., the Eugene Opie First target sequences. system-based strategies to treat and Award for Distinguished Research in Centennial Professor of Pathology A member of the eventually cure all cancers. The Coley Basic Immunology. and Immunology and hhmi inves- Institute of Medi- Award is one of the cri’s highest The award was given by the Can- tigator at Washington University cine (see related honors for those who have made cer Research Institute (cri) jointly School of Medicine in St. Louis. Richard Flavell story, page 1) and seminal contributions to the fields of to a group of three scientists for their Flavell studies the molecular basis National Academy immunology and cancer immuno- work to define the gene transcription of T-cell differentiation. His research of Sciences, he also studies the mecha- therapy. The award was presented at factors that regulate differentiation team has used genomic approaches to nisms of programmed cell death using the cri’s 26th Annual Awards gala of CD4+ T cells, a crucial component identify the genes that are selectively mice lacking death-effector molecules, on October 17 in New York City by of the adaptive immune response. expressed in T-cell lineages, and has and the molecular and cellular bases of James P. Allison, ph.d., director of Flavell shares the award with Laurie used gene targeting, transgenic mice, autoimmune­ disease. the cri Scientific Advisory Council.

Research of two medical school scientists Pediatrician recognized by international body is boosted by NIH Director’s Awards for work on preventing, treating child abuse

Two School of Medicine scientists John M. Leventhal, and helped establish the Society. were honored recently with National m.d., professor of Leventhal delivered the Kempe Lecture Institutes of Health (nih) Director’s pediatrics and in the in September in Istanbul, Turkey, at Awards. Child Study Center, ispcan’s biennial congress. Alan Anticevic, ph.d., associ- has been honored with Leventhal’s clinical and research ate research scientist in psychiatry, the C. Henry Kempe interests center on the evaluation and received the nih Director’s Early Memorial Lecture- treatment of physically abused, sexually Independence Award, and Andrew ship Award from the abused, and neglected children; devel- L. Goodman, ph.d., assistant pro- Alan Anticevic Andrew Goodman International Society John Leventhal opment and behavior; and the primary fessor of microbial pathogenesis, for the Prevention of care of children. Also clinical professor has received the nih Director’s New influence of microbial communities Child Abuse and Neglect (ispcan). of nursing and medical director of the Innovator Award. in the gastrointestinal tract on drug The award is given to an individual Child Abuse Program at Yale-New The Early Independence Award metabolism. who has made “significant contribu- Haven Children’s Hospital, he re- will support Anticevic’s work, which Taking a novel approach that tions to the welfare of children and ceived his m.d. from Tufts University combines neuroimaging, computa- combines microbial ecology, robot- demonstrate[d] teaching experience.” School of Medicine and completed his tional modeling, and pharmacology ics, and pharmacokinetics, Good- The award’s namesake, C. Henry residency and fellowship at Yale-New to better understand the cognitive man seeks to understand why drugs Kempe, published a classic article in Haven Hospital, where he was a Rob- dysfunction seen in schizophrenia, an commonly used to treat ulcerative 1962 called The Battered Child Syndrome, ert Wood Johnson Clinical Scholar. aspect of the illness for which there colitis are ineffective for 35 percent of are no effective treatments. Anticevic, patients despite compelling evidence administrative director of the Na- implicating gut microbes in both tional Institute on Alcohol Abuse and drug activation and inactivation. Alcoholism’s Center for the Transla- The New Innovator awards, tional Neuroscience of Alcoholism, established in 2007, support inves- Charitable gift annuities: is one of only 14 scientists in 2012 tigators who are within 10 years of to receive the Early Independence their terminal degree or clinical resi- A good choice for today’s economy Award, which is designed to provide dency, but who have not yet received junior scientists of exceptional merit a Research Project Grant (R01) or Are you concerned about the personal impact of possible changes in income tax “with the opportunity to conduct equivalent nih grant, to conduct rates, charitable deduction allowances, and estate taxes? Do fluctuations in the independent biomedical or behavioral exceptionally innovative research. financial markets make planning for the future difficult? Creating a charitable research by skipping the conven- They are a part of the nih’s Com- gift annuity (cga) can give you the security of a safe, fixed income now at an at- tional postdoctoral training period.” mon Fund High Risk-High Reward tractive rate, provide you with an immediate tax deduction for a portion of your Anticevic received his doctorate from program, which “provides opportu- gift, and enable you to support Yale School of Medicine in the future. Washington University School of nities for innovative investigators in How it works Medicine in 2011. any area of health research to take 1. You transfer cash or securities to a Yale gift annuity. Goodman’s project, titled risks when the potential impact in 2. Yale pays you, or up to two annuitants you name, a lifetime annuity. “Defining the Contribution of biomedical and behavioral science 3. The remainder passes to the School of Medicine, for the purpose you desig- Interpersonal Microbial Variation is high,” according to nih Director nate, when the contract ends. to Drug Metabolism,” explores the Francis S. Collins, m.d., ph.d. Yale’s gift annuity rates

Age Immediate CGA Deferred 3 years Deferred 5 years // IBD (from page 3) known as ankylosing it can contribute to the inflammation spondylitis. Genes affected by these that leads to Ibd.” 70 4.5% 6% 7% regulatory regions are also involved in Nearly 100 scientists in 15 coun- 75 5.5% 8% 10% the production of immune cells that tries contributed to the new work, 80 7% 11.5% 15% fight infection by mycobacteria, a fam- which “highlights the incredible ily of microbes that cause diseases such power that working together in a as leprosy and tuberculosis. large team can have,” says Cho, direc- Benefits “We see a genetic balancing act tor of Yale’s Inflammatory Bowel • You receive an immediate income tax deduction for a portion of your gift. between defending against bacterial Disease Center in the Department of • Your lifetime annuity is backed by all of Yale’s assets. infection and attacking the body’s own Internal Medicine’s Section of Diges- • Your payments are treated as part ordinary income, part capital gains income, cells,” says Jeffrey C. Barrett, d.phil., tive Diseases. “This would not have and part tax-free income. • You have the satisfaction of making a significant gift that benefits you now, of the Wellcome Trust Sanger Insti- been possible without the thousands and the School of Medicine in the future. tute in Cambridge, England, also a of dna samples from patients with lead author of the study. “Many of these conditions assembled by the In- For more information or a personalized charitable gift annuity illustration, visit the regions we found are involved in ternational ibd Genetics Consortium. www.yale.planyourlegacy.org/GIFTcharitg.php or contact Jancy Houck, associate sending out signals and responses to Collectively, our findings have begun vice president for development and director of medical development, at defend against ‘bad’ bacteria. If these to uncover the biological mechanisms 203 436-8560 or [email protected] responses are over-activated, we found behind this disease.”

8 www.medicineatyale.org