Advancing Biomedical Science, Education and Health Care Volume 5, Issue 5 November/December 2009 Smilow Cancer Hospital, a ‘great achievement,’ welcomes patients New $467 million facility of triumph for Yale University, the hundreds of faculty, staff, and do- School of Medicine, and ynhh. nors, and featured a performance by built with gift from alumnus “It is a day of hope,” said Yale Pres- the Trinity Boys Choir and a lineup offers patient-centered care ident Richard C. Levin. “It is a day of of speakers including Connecticut inspiration, a day that we’ve all waited Governor M. Jodi Rell; Levin; medi- Gray skies overhead could not dampen for for many years, and it will allow cal school Dean Robert J. Alpern, the celebratory mood on the grounds this hospital and this medical school m.d.; Marna P. Borgstrom, m.p.h., of Yale-New Haven Hospital (ynhh) to take their places among the leaders ceo and president of ynhh; Bonnie on the afternoon of October 21, where in the world in the care and treatment Kaplan Tymniak, a lymphoma survi-

robert a. lisak a dedication ceremony marked the of cancer.” The ceremony, held in an vor; and the hospital’s namesake and Joel Smilow addresses attendees of the grand opening of Smilow Cancer Hos- outdoor plaza at the foot of the new major donor, Joel E. Smilow. hospital’s opening day celebration. pital at Yale New Haven—a moment 14-story building, was attended by Hospital, page 7 Brothers follow The tiniest scale yields the biggest prize parents’ example Nobel Prize is awarded to help fight cancer for atomic-level studies of It would be an understatement to say cell structure basic to life that philanthropy runs in the family of Richard S. Sackler, m.d., and A telephone ringing before daybreak his brother, Jonathan Sackler. The is unlikely to appear on anyone’s list names of their parents, Richard and of favorite sounds, but for Thomas Beverly Sackler, adorn cultural and A. Steitz, ph.d., it may now rank scientific centers around the world, with the sweetest music. from the Sackler Galleries at the In the early morning hours of Royal Academy of Arts in London, October 7, Steitz, Sterling Profes- to the famed Sackler Wing of New sor of Molecular Biochemistry and York’s Metropolitan Museum, to the Biophysics, learned in a call from just-launched Raymond and Beverly Sweden that he would share the Sackler Institute for Biological, Physi- 2009 Nobel Prize in Chemistry for cal, and Engineering Sciences at Yale his seminal research on the struc- (see related story, page 4). ture of the ribosome, a cell organelle So it’s only fitting that both that is vital to protein synthesis and Richard Sackler and his wife, Beth,

to the action of many antibiotics. christopher capozziello/getty images and Jonathan Sackler and his wife, Later that day, at a press confer- A beaming Thomas Steitz gave a press conference on the afternoon of the announce- Mary Corson, each head charitable ence packed with media repre- ment of his Nobel Prize in Chemistry. Sacklers, page 5 sentatives and well-wishers in the President’s Room of Yale’s Woolsey over and it turned out to be from of the ribosome as determined by Hall, a reporter asked Steitz where Stockholm. Very exciting.” X-ray crystallography. he was when he heard the news. Some of Steitz’s apparent calm The ribosome is an asym- “I was in bed,” a cheerful Steitz may have been due to the fact that metrical structure consisting of a deadpanned, to laughter from the his name has been frequently includ- large and small subunit. In the two crowd. “It was 5:30 a.m., maybe a ed on informal short lists of potential Science articles, hailed as “landmark little bit before that. The telephone Nobelists ever since 2000, when he publications” in an accompanying rang and Joan [Joan A. Steitz, and a team including longtime Yale commentary, Steitz and colleagues ph.d., Thomas Steitz’s wife, also collaborator Peter B. Moore, ph.d., described and depicted the struc- Sterling Professor of Molecular Bio- Sterling Professor of Chemistry, pub- ture of the large, protein-synthe-

chemistry and Biophysics] answered lished a pair of papers in the journal sizing portion of the ribosome in linda naclerio it and said, ‘It’s for you.’ So I went Science on the structure and function Nobel, page 7 Jonathan and Richard Sackler

Non-Profit Org. U. S. Postage Inside this issue 300 George St., Suite 773 PAID Lifelines New Haven, CT 06511 New Haven, CT Pulmonologist and lung cancer expert Lynn Tanoue returns to her Permit No. 526 www.medicineatyale.org musical roots while managing a busy clinical practice, p. 2 Finding light amid darkness The Yale community comes together not merely to mourn, but to celebrate, the life of doctoral student Annie Le, p. 3 Shortening the path from discovery to treatment The Yale Center for Clinical Investigation is training the next generation of translational and clinical medicine, p. 5 Also Advances, pp. 3, 5; Out & About, p. 4; Grants and Contracts, p. 6

Online: Yale Netcasts Additional audio content for many articles in Medicine@Yale is available on iTunesU, or by pointing your Web browser to medicineatyale.org. School of Medicine remembers a student of ‘joy and warmth’ “It’s been a really wonder- In September, friends, ful experience for us. This has been kind of my family, classmates, baby,” says Lynn Tanoue, and teachers gath- professor of medicine and ered in Yale’s Battell violinist, of the Yale Medi- Chapel to remember cal Symphony Orchestra. Begun with a simple and honor Natasha e-mail, the orchestra now Collins, a member of has weekly rehearsals, and the medical school’s has played three concerts Natasha Collins Class of 2012 who died to packed houses in the medical school’s Harkness of leukemia on August 12 at the age of Auditorium. 26. With words, music, and singing, those present recalled a young woman of sensitivity, honesty, compassion, joy, and warmth. julie brown “It was one of my favorite moments of each day—walking in, sitting next to her, and seeing her smile,” said class- If you rent timpani . . . mate Whitney Sheen, as she recalled attending lectures with Collins, who A busy, award-winning They came—and the Yale Medi- first-rate pulmonary clinicians and played violin in the Yale Medical Sym- clinician finds her way cal Symphony Orchestra was born. building clinical programs. Under phony Orchestra. back to the music she loves Ta­n­oue hired Adrian Slywotzky, a doc- their leadership, the number of Yale About five years ago, Collins was toral student at Yale School of Music, clinicans in pulmonary medicine has diagnosed with acute myelogenous Lynn T. Tanoue, m.d., studied the violin to conduct. She scheduled weekly increased from three to 16, and the leukemia and had been in remission through childhood, high school, and rehearsals, selected medical artwork Winchester Chest Clinic at Yale-New after chemotherapy and a cord blood college. She played as a student at the for promotional posters, and rented Haven Hospital (ynhh) now offers transplant. When the cancer returned School of Medicine in the late 1970s, timpani. “We’ve given state-of-the-art specialty care in every Lifelines in February, her classmates launched alongside undergraduates in the Yale three concerts at Hark- aspect of chest medicine. an international search for a bone mar- Symphony Orchestra and in a New Lynn ness,” Tanoue says, The daughter of an accomplished row donor, but the effort was compli- Haven community orchestra. and each time the surgeon and a graduate of the same Tanoue cated because Collins was biracial, and But Tanoue’s free time was soon auditorium has been Honolulu high school that produced an exact match was elusive. scarce. “I know a lot of people who packed. “There clearly is a musical aol founder Steve Case and President At an August meeting held to in- studied an instrument all the way soul to the medical center that was Barack Obama, Tanoue, now interim form the medical school community of through college,” says Tanoue, profes- waiting to be discovered.” section chief, directs the Winchester the circumstances of Collins’s passing, sor of medicine. “But then you go to Tanoue’s musical homecoming Chest Clinic and co-directs, with lung Associate Professor of Medicine Mark medical school, and your instrument is reminiscent of her return to the cancer expert Frank C. Detterbeck, D. Siegel, m.d., who oversaw Collins’s winds up in the closet.” School of Medicine in 1991. After she m.d., professor of surgery, the Thoracic care in her final days, said, “The leu- After a chance encounter with an received her medical degree, Tanoue Oncology Program (top) at Yale Cancer kemia got to the point where her only old friend, Tanoue has now returned remained at Yale for a residency in Center. The top, which has burgeoned chance for survival was to go with a to her musical roots. At a wedding internal medicine and a fellowship as a successful multidisciplinary transplant with a slight mismatch.” Af- in 2007 Tanoue spoke to Lisa M. in pulmonary and critical care. But program, is participating in transla- ter the transplant Collins developed a Wong, m.d., a pediatrician, violin- after completing her fellowship in tional research efforts at the medical severe form of a liver syndrome, which ist, and president of the Longwood 1989, she found herself looking for a school, most notably with David L. led to multiple organ failure. Symphony Orchestra, a group of new home, and she worked for two Rimm, m.d., ph.d., professor of pathol- “What a great doctor she would musically minded physicians and years in private practice in the New ogy, to better predict lung cancer out- have been,” said Nancy R. Angoff, medical students in the Boston area. Haven community. “It was probably comes using molecular technologies. m.p.h., m.d., associate dean for student Speaking with Wong inspired Tanoue the best thing I ever did, to leave for And yet Tanoue, winner of the affairs. “What better doctors we can to approach Thomas P. Duffy, m.d., a little while,” she says. “I learned an 2009 David J. Leffell Prize for Clinical each be because of her. She will shine director of Yale’s Program for Humani- enormous amount very quickly.” Excellence, somehow still has time on in us and make us better people and ties in Medicine, about building an Tanoue’s departure from Yale for music. Known as modest when better doctors.” orchestra at the School of Medicine. coincided with the appointment of discussing her career achievements, Duffy, professor of medicine, asthma researcher Jack A. Elias, m.d. she describes the orchestra’s crea­ secured funding, and Tanoue sent a (now chair of the Department of tion with a sort of surprised delight. school-wide e-mail advertising an open Internal Medicine) as section chief of But to colleagues who watched her Peter Farley, Managing Editor sight-reading in Harkness Auditorium. pulmonary and critical care medicine. build the clinical arm of pulmonary Charles Gershman, Assistant Editor “I got back hundreds of responses— Tanoue returned to Yale in 1991 to medicine at Yale, and to others who Contributors: John Curtis, Michael Fitzsousa, Michael Greenwood, Jane Hadjimichael, ‘Great idea. Sign me up. Here’s what I work with Elias on complementing know her determination, the story is Bill Hathaway, Daniel Jones, Suzanne Taylor Muzzin, play,’ ” recalls a beaming Tanoue. Yale’s world-class research by hiring not, in the end, such a surprise. Karen Peart, Richard Peterson Design: Jennifer Stockwell Medicine@Yale is published five times each year by the Expert on severe mental illness is new director of mental health center Office of Institutional Planning and Communications, Yale School of Medicine, 300 George St., Michael J. Sernyak, m.d., professor of The cmhc, an urban community After graduating Suite 773, New Haven, CT 06511. Telephone: (203) 785-5824 Fax: (203) 785-4327 psychiatry, has been appointed direc- mental health center that provides from Amherst Col- E-mail: [email protected] tor of the Connecticut Mental Health outpatient psychiatric services for over lege with a b.a. in Website: medicineatyale.org Center (cmhc), a partnership be- 7,000 New Haven–area residents each physics and astrono- Copyright ©2009 by Yale School of Medicine. All rights reserved. tween Yale and the state of Connecti- year, is housed with the Abraham Ribi- my in 1983, Sernyak If you have a change of address or do not wish to receive cut’s Department of Mental Health coff Research Facilities, laboratories obtained his m.d. future issues of Medicine@Yale, please write to us at the above address or via e-mail at [email protected]. and Addiction Services (dmhas) that that have furthered our understand- at Jefferson Medical Postal permit held by Yale University, was established in 1966. ing and treatment of mental illnesses College.He com- 155 Whitney Avenue, New Haven, CT 06520 Michael Sernyak Sernyak, who specializes in the including schizophrenia, depression, pleted an internship Yale School of Medicine treatment issues of the severely men- and drug and alcohol addiction. at Greenwich Hospital, and a residency Robert J. Alpern, m.d., Dean Ensign Professor of Medicine tally ill, was nominated to the direc- Sernyak, a nationally recognized in psychiatry at Yale in 1987. He then Jancy L. Houck torship by Yale University following a health services researcher, has stud- served as unit chief of the Psychosis Associate Vice President for Development and Director of Medical Development national search, and was appointed by ied how antipsychotic medications Studies Unit at cmhc for five years. (203) 436-8560 Thomas A. Kirk Jr., ph.d., who retired may contribute to the development of In 1996, Sernyak joined the staff at Mary Hu as dmhas commissioner in June. diabetes in psychiatric patients, and has the VA Connecticut Healthcare System Director of Institutional Planning and Communications Michael Fitzsousa Sernyak succeeds Selby C. Jacobs, examined issues involving the deliv- (vachs) in West Haven, Conn., and Director of Communications m.d., who is retiring at the end of the ery of medical care to patients with in 2001 he was appointed chief of the ♻ Printed on recycled paper academic year. schizophrenia. Psychiatry Service at vachs. 2 www.medicineatyale.org Advances Yale mourns loss of a bright young light Health and science news from Yale enzymes that regulate cell signaling, with emphasis on the An idealistic and dedicated woman, role these enzymes may play in human disease. graduate student Annie Le planned Le, who had dreamed of a career at the National Institutes of Health after her graduate training, was exploring how to devote her life to medical research metabolic stresses influence an enzyme believed to be in- volved in controlling mitochondrial function in muscle cells, On October 12, a memorial service that mixed prayer, possibly leading to metabolic disease. remembrances, and music was held at Yale’s Battell Chapel “Annie came to Yale with high expectations and was truly for doctoral student Annie Marie Le, 24, whose body was excited about the bright prospects of a career in research,” found on September 13 in the School of Medicine’s Amistad Bennett said. “She showed that she was more than ready to franziska bleichert Street Research Building, where she had been conducting do what was expected of her.” Bennett characterized Le as “a experiments. Le’s death was ruled a homicide, and a labora- dreamer with clear visions and plans, who knew that she had Images help scientists tory technician has been charged with her murder. Le, page 4 think outside the box In remarks to the assembled mourners, Yale President Cell structures known as box C/D Richard C. Levin said, “Yale remains a close community. guide ribonucleoproteins (rnps) When tragedy strikes we all feel it intensely. The fabric (Below) In September, students, faculty, and help to maintain the integrity of of the whole here is very tightly knit; when one thread is staff gathered on Yale’s Cross Campus for a candlelight vigil in memory of pharmacol- ribosomes, which synthesize pro- pulled the afghan unravels. We are, by nature, not isolated ogy graduate student Annie Le (left), whose teins in all forms of life on Earth from each other, but interconnected.” Levin called Le “a murder in a medical school research building (see related story, page 1). model student for the Yale of the 21st century . . . And it is in shook the Yale community and the nation. A team in the lab of Susan J. our hearts that Annie’s spirit will live.” Baserga, m.d., ph.d., used electron During the service, solo piano and microscopy to discern the struc- violin performances punctuated prayers ture of the box C/D rnp in Metha- and remarks by Levin; Yale’s University nocaldococcus jannaschii, a hardy microbe found in Antarctic ice and Chaplain and Roman Catholic Chaplain; in boiling vents on the ocean floor. Jon Butler, ph.d., dean of Yale’s Graduate Conventional models have School of Arts and Sciences; and several proposed that box C/D rnps are of Le’s personal acquaintances. composed of one rna molecule Le, of Placerville, Calif., came to and pairs of core proteins. But Yale in 2007 as a graduate student in the as reported in the September 11 Combined Program in the Biological edition of Science, first author and Biomedical Sciences after earning Franziska Bleichert, m.d., and the her undergraduate degree in cell and Yale group found that the M. jan- developmental biology at the University naschii box C/D rnp was instead of Rochester. made up of two rnas and four copies of each of the three core At Yale, she worked in the laboratory proteins (see image above). of her advisor, Anton M. Bennett, ph.d., “It looks like a Wheat Thin with associate professor of pharmacology, feet,” says Baserga, professor of whose research focuses on a family of michael marsland molecular biophysics and biochemis- try. “When you can discern structure, you can often figure out function.” Advocate for women’s health research is honored Giving a gut punch to In an October 29 ceremony held at range of areas in women’s health. In Marna P. Borgstrom, m.b.a., CEO of Parkinson’s disease the Hartford Marriott Downtown, a recent line of research under the Yale-New Haven Hospital. Obesity is a well-known risk factor Carolyn M. Mazure, ph.d., director umbrella of the Women and Trauma The Connecticut Women’s Hall of in diabetes, heart disease, and of Women’s Health Research at Yale core, WHRY scientists are conducting Fame, founded in 1993, showcases the cancer. Now, scientists are finding (WHRY), was inducted into the Con- one of the first studies of how women outstanding contributions of Connecti- links between obesity and neu- necticut Women’s Hall of Fame. veterans returning from combat zones cut women to their communities, their rodegenerative diseases such as Mazure, professor of psychiatry and in Iraq and Afghanistan readjust to state, and the nation. Parkinson’s disease (PD) as well. psychology and associate dean for fac- civilian life. Prior inductees affiliated with PD is caused when dopamine- ulty affairs, was honored for her work in The WHRY’s Pilot Project Program the School of Medicine include Joan producing nerve cells die off in a part of the brain that governs founding WHRY, for her wide-ranging provides Yale scientists with “seed” A. Steitz, Ph.D., Sterling Professor of movement. In the November 11 influence on biomedical research and funding that allows them to generate Molecular Biophysics and Biochem- issue of The Journal of Neuro- health care, and for her own research the data they need to obtain external istry, and the late Patricia Goldman- science, a team led by Tamas L. on gender-specific aspects of depres- grants from the National Institutes of Rakic, Ph.D. Horvath, d.v.m., ph.d., chair and sion which has shown, for example, Health. All told, over $4 million in such Steitz, discoverer of small nuclear professor in the section of com- that stress is a more potent pathway to grants have allowed Yale researchers to ribonucleoproteins, intracellular parative medicine, and also pro- depression for women than for men. obtain more than $40 million in exter- complexes that play a key role in the fessor of obstetrics, gynecology, Mazure founded WHRY in 1998 nal funding to extend their research. splicing of pre-messenger rna, the and reproductive sciences and with the support of The Patrick and Also honored at the October event earliest product of dna transcription, of neurobiology, conclude that Catherine Weldon Donaghue Medical were Connecticut’s three women hos- was inducted into the Connecticut ghrelin, a hormone produced by Research Foundation based on the pital presidents and CEOs, including Women’s Hall of Fame in 2008. the stomach, can protect these neurons from death, and that premise that understanding gender Goldman-Rakic, obesity-related declines in ghrelin differences is vitally important to the who died in 2003, was a may raise the risk of PD. health of both women and men. pre-eminent investiga- Dopamine cells in mice The WHRY program, which is tor of the workings of lacking ghrelin that were exposed dedicated to exploring the wide range the prefrontal cortex, to a cell-killing toxin died off in of conditions that are more prevalent in seat of all higher-level substantially greater numbers women, or for which the causes, treat- cognitive functions than in normal mice; administra- ment, or prevention have gender-spe- in the brain. She was tion of ghrelin reversed this effect. cific differences, has grown to become inducted to the Con- “Because this hormone origi- a national model for initiating and necticut Women’s Hall nates from the stomach, it is fostering interdisiplinary research on of Fame posthumously circulating normally in the body,” Horvath says, “so it could easily be women’s health and gender differences, in 2008. used to boost resistance to Parkin- and for disseminating findings with real-world benefits to the community. Carolyn Mazure is one son’s or it could be used to slow of three inductees into the development of the disease.” The program is now constructed the Connecticut Women’s

around research “cores” devoted to a courtesy ofwhry Hall of Fame in 2009. Medicine@Yale November/December 2009 3 Out & about August 25: The 99 members of the September 21: Latvian President Valdis Zatlers, m.d. (left), an orthopaedic Class of 2013 set Harkness Audi- surgeon who trained as a fellow at Yale in 1990–91, met with Dean and Ensign torium alight with nervous excite- Professor of Medicine Robert J. Alpern, m.d., at the School of Medicine during ment at this year’s WHITE COAT a wide-ranging six-day trip to the United States. Zatlers spoke to Yale students CEREMONy, in which new students in political science and international relations and to residents in orthopaedics. receive physician’s jackets, formally Zatlers received his fellowship training under the auspices of the Keggi Ortho- marking their entrance into the paedic Foundation (kof), an organization founded and led by Kistaps J. Keggi, medical profession. 1. Justin M. m.d., clinical professor of orthopaedics and rehabilitation. Founded in 1988, kof Steinberg, m.b.a., ’13 with his wife, has brought more than 250 health and education professionals from the former Kimberly E. Steinberg, and daughter, Soviet republics and Vietnam to the United States for education. Marjorie. 2. Brooks Van Udelsman ’13 with his parents, Robert Udels- 1 man, m.d., m.b.a., m.s.b., chair and William H. Carmalt Professor of Surgery and chief of surgery at Yale-New Haven Hospital (ynhh), and Nikki J. Holbrook, ph.d., adjunct professor of medicine. 3. A white coat is readied for its new owner by Thomas J. Lynch Jr., m.d., director of Yale Cancer Center and physician- in-chief at ynhh’s Smilow Cancer Hospital, who delivered this year’s keynote speech. 4. Laura Huang ’13 wears her new white coat alongside her mother, Lin-Lan Tang, m.d. (left) and sister, Stephanie Huang. 2 terry dagradi

3 4 terry dagradi (4) harold shapiro

October 16: An inaugural symposium at the Raymond and Beverly Sackler Institute for Biological, Physical, and Engineering Sci- ences was held at Yale’s West Campus. The day-long event, which featured talks by internationally renowned scientists from diverse fields, celebrated both the gift by the Sacklers that helped establish the institute and the arrival of the

michael marsland first class of graduate students in the Integrated Graduate Program in Physical October 8: Leaders of Yale and University College London (ucl) and their asso- and Engineering Biology. (From left) Martin Chalfie, ph.d., chair and William ciated hospitals were joined by former British Prime Minister Tony Blair (right) R. Kenan Jr. Professor of Biological Sciences at Columbia University, who shared to sign an agreement creating the yale–ucl collaborative on biomedi- the 2008 Nobel Prize in Chemistry for the discovery and development of green cine, a new partnership in biomedical research and clinical care. (From left) fluorescent protein; Peter Salovey, ph.d., Yale University provost, Chris Argyris David Fish, m.d., professor of epilepsy and clinical neurophysiology at ucl and Professor of Psychology, and professor of epidemiology and public health; managing director, ucl Partners; Malcolm Grant, cbe, l.l.d., president and Beverly Sackler; Raymond R. Sackler, m.d.; and Lynne J. Regan, ph.d., professor provost of ucl; Yale President Richard C. Levin; and Yale-New Haven Hospital of molecular biophysics and biochemistry and of chemistry, and director of the ceo Marna P. Borgstrom, m.p.h. Blair, founder of the Tony Blair Faith Founda- new Sackler Institute, which is dedicated to promoting research that bridges the tion, is teaching a “Faith and Globalization” seminar at Yale for the second year. gaps between traditional scientific fields.

Le from page 3 to work hard to achieve those dreams,” A eulogy composed by Le’s family she brought to us all. Annie Marie Le 2038, New Haven, Conn., 06521-2038. and noted that she never complained. read, in part, “Annie was loved by will be profoundly missed.” Donations may also be made in Annie’s “Instead, she asked, ‘How can I help?’ everyone who knew her and special to Le is survived by Widawsky; her memory to the “I Have a Dream” Foun- And she always did.” Le’s research is all those who came in contact with her. father and his wife, Mr. and Mrs. dation, 330 Seventh Avenue, 20th Floor, slated to be published in a paper that She was a kind-hearted human being Hoang Le; her mother, Vivian Van Le; New York, N.Y., 10001, and online at she co-authored, Bennett said. “We who was devoted to her family and her brother, Chris Tri Le; her half- https://secure.virtualatlantic.com/ihad/ dedicate this paper in her memory.” friends, always sacrificing her time to siblings, Martin Le and Emmie Le; her ssl/donation.aspx. Le was born in San Jose, Calif., help others. Her laughter was infec- guardian parents, Mr. and Mrs. Robert During Le’s funeral in El Dorado and spent most of her childhood in tious and her goodness was ingenuous. Linh Nguyen and their three children, Hills, Calif., in late September, her Placerville. She graduated from Union . . . She was a considerate daughter, a Dan, Ryan, and Sean Khiem; her mother read a poem in Vietnamese, Mine High School in 2003, at the top of thoughtful sister, a generous niece, a grandmother, Thang Thi Vu, as well as translated into English by Le’s brother her class of 362. As a college student at spirited cousin, a loving granddaugh- several aunts, uncles, and cousins. Chris, that included these lines: “I sang Rochester, she met her fiancé, Jonathan ter, and a gracious friend. We will Memorial donations may be lullabies by your side this week, like I Widawsky, now a graduate student in always remember her beautiful smile, directed to the Annie Le Fellowship, did when you were a baby, wishing you physics at Columbia University. her fun-loving spirit, and the joy that Yale Office of Development, P.O. Box a peaceful sleep.” 4 www.medicineatyale.org Advances Clinical research: the next generation Health and science news from Yale Translational medicine initiative sees educational success stories as it hits the three-year mark

In 2006, former National Institutes of Health (nih) Director

courtesy of pasko rakic Elias Zerhouni, m.d., launched the Clinical and Translational Science Awards (ctsa) program, part of his ambitious “Road- Neurons shouldn’t map” initiative aimed at speeding the translation of biomedical always stick together laboratory discoveries to the bedsides of patients in need. Much of the impetus for the ctsa program came from a The cerebral cortex is organized into widespread appreciation that the challenges of clinical and contiguous cellular columns—the translational research had become so daunting that an entire sort of ordering a dozen pencils generation of physicians and scientists were shying away from takes on if tightly wrapped with a rubber band. These columns form careers in these fields. In addition to standard medical and during embryonic development, scientific training, today’s clinical and translational research- when neurons shimmy up spoke-like ers often need special expertise in biostatistics, genetics, and radial glial cells until they reach their computation, as well as knowledge of the strict regulations proper location in the cortex. governing biomedical research with human subjects. To be However, some neurons in truly successful, investigators must work comfortably in an each column shift away from the emerging scientific culture based on interdisciplinary teams of glial spoke to form interconnec- physicians, scientists, and nurses. To reverse the alarming de- robert a. lisak tions with neurons in neighboring cline in the numbers of clinical and translational researchers, As Co-Director for Education in the Yale Center for Clinical Investi- columns, ensuring a proper neu- the ctsa program included a “Scholars” component, which gation, physician–scientist Judy Cho, m.d., an expert on the treat- ronal “blend” to perform specific provides support for education for the young scientists who ment and genetic bases of inflammatory bowel disease, serves as a functions. Scientists believe that mentor to junior faculty members who aspire to careers in clinical disturbances in this process may will make up the next generation of investigators. and translational research. cause psychiatric disorders. In a happy coincidence, a strategic plan commissioned by In the September 24 issue of Dean Robert J. Alpern, m.d., completed in 2004, had targeted In addition, the ycci Scholars are eligible to receive a Nature, a group led by Pasko Rakic, clinical and translational research as a priority for the School new Master of Health Science Research degree through a m.d., ph.d., the Dorys McConnell of Medicine, which led to the creation of the Yale Center for special ycci program offering courses in epidemiology, bio- Duberg Professor of Neurobiology, Clinical Investigation (ycci). With educational, clinical, and statistics, informatics, practical and ethical issues in clinical reports that in mice lacking genes community-based components, the ycci’s structure mapped and translational research, and topics in human investiga- for the receptor EphA, neurons perfectly onto the goals Zerhouni hoped to accomplish with tion and grant writing. formed tight, even single-file the ctsa, and the School of Medicine was named a recipient “The important thing isn’t the degree, it’s the training,” columns, while overexpression of in the program’s first crop of grants—a $57.3 million award says Eugene D. Shapiro, m.d., professor of pediatrics and of EphA caused too much lateral drift that remains the largest grant ever received by Yale in its 300- epidemiology and public health, who, along with Cho, is co- (green in image). In normal mice, appropriate numbers of neurons year history. director for education at ycci. “The new master’s program drifted to neighboring columns to “When ycci was established, I viewed the commitment to fills a need by providing training for young investigators in perform their assigned duties. train the next generation as perhaps our most important goal, areas that are critical for successfully conducting clinical and “This so-far unrecognized and we’re now beginning to reap the fruit of our efforts to ed- translational research.” mechanism . . . seems to be essen- ucate young clinician-researchers,” says c.n.h. Long Professor Barbara Alving, m.d., director of the nih’s National Cen- tial for the proper intermixing of Medicine Robert S. Sherwin, m.d., ycci director and an ter for Research Resources, the agency that oversees the ctsa of neuronal types in the cortical internationally recognized diabetes researcher. Over the past program, says that educational opportunities that encourage columns,” the authors write. three years, Sherwin says, over 30 junior faculty holding m.d.s physicians and scientists to venture beyond their comfort or ph.d.s have received support through the ctsa as ycci zones are invaluable. “The training that investigators receive Scholars, and the program has given them the wherewithal through the ctsa Scholars program enhances their ability Can an old antibody to seek out and obtain about $42 million in research grants to work in interdisciplinary teams,” says Alving, “providing learn a new trick? of their own. These ycci Scholars have published more than increased opportunities for collaboration and broader research 113 papers (with an additional 31 in press), given conference perspectives.” According to Shapiro, these benefits are crucial Antibody-based drugs, which harness and enhance the power presentations, and collaborated with colleagues both nation- to advancing medicine. “We’re trying to give these folks ad- of the immune system, have been ally and internationally. ditional skills that will lead to success for them, and lead to useful in treating many diseases. “The ctsa has provided crucial support to a broad group of success for humanity as a whole by providing new discover- However, most are expensive, people,” says Judy H. Cho, m.d., associate professor of medicine ies and better ways to deliver medical care,” he says. “Our have unacceptable side effects, or and ycci’s co-director for education. “We have m.d.s without educational programs give people more tools, but I think they cannot be orally administered. much research experience, and ph.d.s with a lot of research also inspire people.” In papers published on the experience who do not have adequate experience or exposure to Yale Netcast Web on October 19 and November clinical research issues to gather data for grant funding.” “Tailoring Research to Promote Better Health” 4 by the Journal of the American Chemical Society, David A. Spiegel, from page 1 ph.d., m.d., assistant professor of Sacklers chemistry, and colleagues describe foundations of their own—the Richard most appreciative of this most recent is terrific,” says Sackler, who credits a new strategy employing small and Beth Sackler Foundation and the gift, which will honor and support all Edelson with laying a solid foundation molecules that direct antibodies Bouncer Foundation. future Yale Cancer Center directors.” for the hiring of the current ycc direc- to kill prostate cancer cells or cells In keeping with their family’s long- Richard Sackler, co-chairman tor, Thomas J. Lynch Jr., m.d., whom infected with the hiv virus. The molecules built by the standing generosity to Yale, the broth- of Stamford, Conn.-based Purdue Sackler calls a “world leader with a Spiegel team are “bifunctional”— ers’ respective foundations have now Pharma and adjunct professor of clear vision.” they have been designed to lock joined forces to donate a $3 million genetics at Rockefeller University, says, For Jonathan Sackler’s part, his onto diseased cells and also onto endowment establishing the Richard “My father raised Jon and me to believe “deep interest in science and tech- anti-dnp, an otherwise passive Sackler and Jonathan Sackler Profes- that philanthropy is an important part nology and in education,” led the antibody that is naturally present sorship, expressly intended to be held of how we should fill our days.” He Stamford-based Bouncer Foundation in many people and can be easily by those appointed as director of Yale explains that the new gift was inspired (named, he says, for a beloved family and safely induced in others. Cancer Center (ycc). by his years of association with Rich- dog) to help establish the professor- “Instead of trying to kill the “The Sackler family has a rich ard L. Edelson, m.d., the Aaron B. and ship. “This is the first significant pathogens directly, these mol- tradition of philanthropy, having Marguerite Lerner Professor of Der- gift that my brother and I have made ecules manipulate our immune provided significant support at Yale,” matology, who served as ycc director together,” says Richard Sackler, who system to do something it wouldn’t ordinarily do,” says says Dean Robert J. Alpern, m.d. for five years until this past spring says it took little prompting on his part Spiegel. “This is an entirely new “They are actively involved in medical and, among other achievements, to convince Jonathan to endow the approach to treating these two school programs, with Richard serv- oversaw approval of the newly opened professorship. “When I described the diseases.” ing on Yale Cancer Center’s Advisory Smilow Cancer Hospital (see related gift to him, he very quickly said, ‘This Board and the Dean’s Council. I am story, page 1). “What he accomplished is something we can do—so let’s do it.’” Medicine@Yale November/December 2009 5 Expression in the Chronic Unpredictable Stress (cus) Measurement of Negative Reinforcement in Adolescent Grants and contracts awarded Model of Depression, 1 year, $59,430 • Marie Egan, Alcohol Use/Abuse, 1 year, $12,979 • Thomas Cystic Fibrosis Foundation, Yale–Cystic Fibrosis McMahon, State of Connecticut Judicial Depart- Therapeutics Development Center, 1 year, $64,800 ment, Juvenile Justice Urban Cities Pilot, 6 months, to Yale School of Medicine Liana Fraenkel, Arthritis Foundation, Improving $119,526 • Asht Mishra, Epilepsy Foundation of Patient Willingness to Accept Escalation of Therapy in America, Neuroimaging Biomarkers and Prevention January–April 2009 RA, 2 years, $194,986 • Alison Galvani, Howard of Spike Wave Epileptogenesis, 1 year, $45,000 Hughes Medical Institute, Workshop on Mathemat- Deepak Narayan, Plastic Surgery Education Foun- ical Modeling of Infectious Disease Epidemiology and dation, Spitzoid Nevi Versus Melanoma by Cellular Federal Control, Durban, South Africa, 1 year, $30,000; Gp100, Nedd9, and Gab2, 1 year, $5,000 • Elaine Nadia Ameen, nih, Functional Relevance of cftr domized Controlled Trial to Reduce Pneumonia in World Health Organization, Integrated Tsetse Fly O’Keefe, Association of Schools of Public Health, Trafficking in Vivo to Intestinal Disease, 4 years, Nursing Home Residents, 5 years, $6,603,979 Ecology and Genetics for Improved hat Control, An Introduction to Public Health Careers for Middle $1,406,752 • Choukri Ben Mamoun, U.S. Army Mladen-Roko Rasin, nih, Molecular Control 1 year, $20,000 • Antonio Giraldez, Muscular and High School Students, 9 months, $30,000 Medical Research Acquisition Activity, Two New of Corticospinal System Formation by Intermediate Dystrophy Association, The Role of Micrornas in Alexander Panda, Preeclampsia Foundation, tlr Plant-Like Pathways Link Hemoglobin Degradation Targets, 2 years, $180,496 • Matthew Roberts, Muscle Development and Muscular Dystrophy, 3 years, Expression and Function of Peripheral Blood Immune to Lipid Biogenesis in Falciparum Malaria, 1 year, nih, Structural Insights of Postsynaptic Scaffolds and $401,300 • Michael Girardi, Skin Cancer Founda- Cells in Preeclampsia, 1 year, $25,000 • Lynne $228,167 • Zubin Bhagwagar, nih, A pet Study Signaling Complexes, 2 years, $82,148 • John Rose, tion, Investigating the Immunogenomic Landscape Regan, Joan’s Legacy, Development of a Novel Class of 5-HT1B Receptor Binding as a Novel Biomarker nih, Novel Vaccines for Broad Protection against of Cutaneous T-Cell Lymphoma, 1 year, $10,000 of Therapeutics for Small Cell and Non-Small Cell for Cocaine, 1 year, $212,250 • Linda Bockenstedt, Avian Influenza, 4 years, $1,655,000 • William Daniel Goldstein, American Heart Association, Lung Cancer, 2 years, $100,000 • David Rimm, Nat’l Research Fund for Tick-Borne Diseases, Inc., Sessa, nih, Endothelial nos by Protein–Protein Nat’l Center, The Interplay of Aging, Viral Immunity Ensemble Discovery Corporation, Proposal for Real-Time Imaging of Vector-Borne Borrelia burg- Interactions, 5 years, $2,431,955 • Erik Shapiro, and Atherosclerosis, 5 years, $500,000 • Jonathan Collaboration on egfr/erbb Dimer Detection in dorferi Infection in Mice, 1 year, $60,000 • Marcus nih, Magnetic Resonance Imaging of Neurogenesis, Grauer, Stryker Spine, Biochemical Comparison Human Breast Cancer and Correlation with Drug Bosenberg, nih, The Role of Beta-Catenin Signal- 2 years, $398,235 • Robert Sherwin, nih, of Uniaxial Screws and Monoaxial Screws, 1 year, Resistance, 1 year, $76,262; Susan G. Komen Breast ing in Malignant Melanoma, 1 year, $469,373 Enhancing Clinical Investigation by Improved Clini- $26,685 • Elena Grigorenko, Florida State Univer- Cancer Foundation, In Situ Detection of Cancer Martina Brueckner, nih, Cilia in Cardiac Mor- cal Research Management, 5 years, $136,160 sity, Research Supplement to Promote Diversity in to Predict Non-Nodal Metastasis in Breast Cancer, phogenesis, 5 years, $2,052,375 • David Calder- Warren Shlomchik, nih, Leukemia Stem Cells Health-Related Research, 1 year, $66,129 • Erol 3 years, $600,000 • Scott Rivkees, United Cere- wood, nih, Integrin–Filamin Interactions in Migra- Essential Targets for gvl and Mediators of gvl- Gulcicek, Columbia University, Yale Proteomics bral Palsy Research and Education Foundation, tion and Signaling, 4 years, $1,356,968 • Lloyd Resistance, 5 years, $1,438,520 • Rajita Sinha, nih, Core for Biodefense, 5 years, $659,008 • Michelle Prevention of Cerebral Palsy with Sulfonylurea Ago- Cantley, nih, hgf Signaling in Kidney Repair, Chronic Alcohol and Brain Stress Circuit Response, Hampson, Dana Foundation, Brain and Immuno- nists, 2 years, $100,000 • John Rose, Columbia 4 years, $1,514,326 • Kelly Cosgrove, nih, gab- 5 years, $2,606,037; Brookhaven Nat’l Laboratory, Imaging, 3 years, $199,482 • Keith Hawkins, University, Development of Novel Vaccines for High aergic Mechanisms of Comorbid Alcohol and Nicotine The Prefrontal Cortex in Salience and Control in Hartford Hospital, Adolescent Maturation of Brain Priority Pathogens, 5 years, $1,861,875 • David Sil- Dependence, 5 years, $2,504,378 • Peter Cresswell, Cocaine Addiction: phfmri Study, 4 years, Network Integration for Executive Control Abilities, verman, American Heart Association, Nat’l Center, nih, Molecular Aspects of Human CDld Functions, $136,188 • Dieter Söll, nih, Studies on Transfer 6 months, $33,893 • Kristina Herbert, Damon Noninvasive Assessment of Regional Changes in Perfu- 5 years, $1,628,186 • Alan Dardik, nih, Molecular rna, 4 years, $6,091,595 • David Stern, nih, Runyon Cancer Research Foundation, Regulation sion during Hypovolemia and lbnp, 1 year, $22,000 Regulation of Vein Graft Adaptation, 5 years, Signaling by Neuregulins and ErbB4 in Breast and Mechanism of pri-mirna processing by Drosha Albert Sinusas, Massachusetts General Hospital, $2,399,015 • Nihal deLanerolle, nih, Efficacy Cancer, 5 years, $1,758,407 • Carlos Stocco, nih, and dgcr8, 3 years, $140,000 • Zhiwei Hu, Absolute Quantification of Myocardial Blood Flow of Erythropoietin (epo) and epo Analogues in the Molecular Pathways Controlling Ovarian Gene Breast Cancer Alliance, Inc., Targeting the Tumor Using Rb-82 pet, 6 months, $22,432 • Lawrence Treatment of Epilepsy, 2 years, $398,235 • Deepak Expression, 5 months, $320,243 • Vinita Takiar, Blood Vessels for Photodynamic Therapy of Chemore- Solomon, CT Hospice, Inc., Hospice Palliative D’Souza, nih, Imaging Nicotinic Acetylcholine nih, Exploiting ampk to Slow Polycystic Kidney sistant Breast Cancer, 1 year, $100,000 • John Medicine Fellowship, 5 months, $100,000 • Chris- Receptors in Schizophrenia, 3 years, $873,711 Disease, 1 year, $45,972 • Peter Tattersall, nih, Huang, Allergan Sales, Inc., 2008 Horizon Grants topher Spock, Plastic Surgery Education Founda- Richard Flavell, nih, The Role of Bcl-Rambo in Molecular Genetics of Parvoviral dna Replication, Program, 1 year, $50,000 • Peter Jatlow, Univer- tion, Micro rna and Classification of Hemangiomas, Thymic Involution, 5 years, $2,068,750 • Joel Gel- 5 years, $2,597,026 • Flora Vaccarino, nih, Mor- sity of Connecticut Health Center, Maternal Genet- 1 year, $10,000 • Matthew State, University of ernter, nih, Genetics of Alcohol Dependence in phogenesis and Function of the Cerebral Cortex, ics: Cigarette Smoking and Infant Birth Rate, Illinois, pet Evaluation: Tourette Syndrome, 1 year, American Populations, 5 years, $3,018,367 • David 5 years, $2,042,428 • Joanne Weidhaas, nih, 10 months, $9,000 • Jing Jin, American Founda- $165,132 • Stephen Strittmatter, Cure Alzheimer’s Glahn, nih, Genetics of Brain Structure and Func- Let-7 Micrornas in Lung Cancer: Altering Growth tion for aids Research (amfAR), Cellular Factors Fund, Specificity and Mechanism of AB-Oligomer tion, 2.5 years, $989,343; nih, Influence of Psychosis and Radioresistance, 5 years, $1,707,161 • Marney Required for hiv Cell-to-Cell Transmission, 3 years, Action through Prion Protein, 1 year, $100,000; Dr. on Brain–Behavior Endophenotypes for Bipolar Dis- White, nih, Placebo-Controlled rct of Bupropion $375,000 • Richard Kibbey, American Diabetes Ralph and Marian Falk Med. Res. Trust, Axonal order, 4 years, $2,092,560; nih, Genetics of Brain for Binge Eating, 2 years, $152,400 • Dianqing Wu, Association, Inc., Characterization of Phoshpoenoyl- Regeneration Therapy for Spinal Cord Injury, 3 years, Structure and Function—Genome Wide Association, nih, Wnt Signaling, 5 years, $1,595,961 • Ying pyruvate Carboxykinase-2 as a Mitochondrial gtp, $1,119,000 • Babak Tahvildari, Robert Leet and 5 years, $3,595,574 • Danielle Guez, nih, facs: Xia, nih, A New Strategy for Protection from Cere- 3 years, $298,350 • Harriet Kluger, American Clara Guthrie Patterson Trust, Functional Organi- A Novel Method to Study Neurons Altered during bral Ischemia, 5 years, $2,068,750 Cancer Society, Inc., Developing an Assay to Predict zation and Connectivity during Active Cortical Cocaine Sensitization, 3 years, $117,508 • Shangqin Sorafenib Response in Renal Cell Carcinoma, 4 years, Network, 2 years, $92,000 • William Tamborlane, Guo, nih, Microrna Regulation of Stem Cell Self- Non-Federal $900,000 • Priti Kumar, Hanyang University, Donaghue Medical Research Foundation, Chang- Renewal, 5 years, $756,409 • Sairy Hernandez, Vikki Abrahams, Alliance for Lupus Research, Korea, Human T Cell Specific rnai-Based Nano- ing Life-Styles for Better Health: A Model Program nih, T B Cell Helpers in Immunity and Autoimmu- Effect of Antiphospholipid Antibodies on Trophoblast Medicine for aids, 4 years, $1,114,875 • Gregory for Community Health, 4 years, $926,586 • Diana nity: Development, Maintenance and Migration, Function in Pregnancy, 16 months, $73,284 • Ali Larkin, American Foundation for Suicide Preven- Vesely, Arthritis Foundation, Langerhans Cell 3 years, $100,428 • Mark Hochstrasser, nih, Abu-Alfa, Genzyme Corporation, Genzyme Educa- tion, Suicide Clusters across the Globe: Geospatial Induction of T Regulatory Cells and Lyme Arthritis, Degradation of Short-Lived Regulatory Proteins in tional Conference, 1 year, $5,475; Abbott Laborato- Trends from America, Ireland, and New Zealand, 2 years, $100,000 • Jun Yu, American Heart Asso- Yeast, 5 years, $1,807,996 • Elizabeth Jonas, nih, ries Inc., Medical Education Lecture Series, 9 months, 2 years, $99,988 • Csaba Leranth, Passport Foun- ciation, Nat’l Center, The Role of Nogo-B on Vascu- Mitochondrial Ion Channels in Hypoxic Neurons, $12,000 • Eitan Akirav, Juvenile Diabetes dation, Negative Effects of Bisphenol A on the Brain, lar Remodeling and Atherogenesis, 4 years, $308,000 5 years, $2,148,484 • Mark Kidd, nih, Mecha- Research Foundation Int’l, Glucose and the Islet 2 years, $20,000 • William Lin, American Skin James Yue, Stryker Spine, Retrospective Review of nisms of Abnormal Enterochromaffin Cell Secretion Vasculature: Key Players in Beta Cell Proliferation, Association, Investigating the Immunogenomic Land- Anterior Cervical Decompression and Fusion vs. Lami- of Serotonin in Crohn’s Disease, 4 years, $1,331,861 2 years, $91,772 • Robert Beech, California Bipolar scape of Cutaneous T-cell Lymphoma, 1 year, $7,000 noplasty vs. Laminectomy for the Treatment of Cervi- Ami Klin, nih, Perception of Social and Physical Foundation, Predicting Response using Expression Z. Ping Lin, Wendy Will Case Cancer Fund, Inc., cal Myelopathy and Myeloradiculopathy, 11 months, Contingencies in Infants with asd, 5 years, Differences in Clinical Treatment of Bipolar Disorder Role of Ribonucleotide Reductase in Cell Cycle Check- $44,109 • Hitten Zaveri, American Epilepsy $2,068,750 • Patty Lee, nih, Innate Immune (predict-BD), 1 year, $49,891 • Choukri Ben points and dna Damage Repair, 1 year, $30,000 Society, Fourth International Workshop on Seizure Mechanisms in Emphysema, 4 years, $2,068,750 Mamoun, Burroughs Wellcome Fund, Function Thomas Lynch, American Cancer Society, Inc., Prediction, 1 year, $10,000 • Edward Zigler, Smith Elias Lolis, nih, Regulation of cxcr4 by Cognate and Regulation of Host and Parasite Nutrient Trans- Yale Cancer Center acs Institutional Research Grant, Richardson Foundation, Inc., Edward Zigler Center and Non-Cognate Ligands, 5 years, $2,049,100 porters during Malaria Infection, 2.5 years, $250,000 3 years, $420,000 • Mark Mamula, Alliance for in Clinical Development and Social Policy, 2 years, Chao Ma, nih, Antigen-Specific Immune Mecha- Thomas Biederer, Dana Foundation, Molecular Lupus Research, Antigen Trafficking between apcs $300,000 • Howard Zonana, University of Mas- nisms of Neuronal Hyperexcitability and Chronic Mechanisms Underlying the Structural Plasticity of as Therapeutic Target for Lupus, 2 years, $494,598 sachusetts, An Observational Descriptive Study of Pain, 2 years, $398,235 • Arya Mani, nih, The Central Synapses, 3 years, $200,000 • Elizabeth Linda Mayes, University of Maryland, Behavioral irb Practices, 16 months, $24,000 Genetics and Pathophysiology of Impaired Wnt Sig- Bradley, William J. Clinton Foundation, Ethiopia naling in Metabolic Syndrome, 4 years, $1,655,000 Hospital Management, 1 year, $141,813; South Essex Graeme Mason, nih, Role of Acetate in Heavy Partnership nhs Foundation Trust, sept Leader- Drinking, 2 years, $455,125; nih, gaba Effects of ship Workshop, 6 months, $54,000 • Judy Cho, Nicotine in Men and Women, 5 years, $1,856,250 Crohn’s & Colitis Foundation of America Inc., Almost a century ago, John W. Sterling, of the Yale Christian Matranga, nih, Investigating the Role Mapping Rare Variants and Expression Quantitative College Class of 1864 (right), ably demonstrated the of rna Helicases in rnai and Innate Immunity, Trait Loci Contributing to Crohn’s Disease Pathogens, 3 years, $148,134 • Ruslan Medzhitov, nih, Toll 3 years, $386,100 • Lynn Cooley, Muscular Dys- ability of one person to shape an institution. Sterling Pathway and Control of Adaptive Immune Responses, trophy Association, Genetic Analysis of Muscle Func- made a bequest to Yale that funded a building boom 5 years, $2,105,573 • Thomas Murray, nih, The tion and Muscle Disease at the Single-Cell Level, in the 1920s and 1930s that literally defined the Regulation of Pseudomonas aeruginosa Surface 3 years, $320,000 • Joseph Craft, Lupus Founda- campus, raising many of the university’s signature Colonization, 3 years, $395,685 • Alexander Neu- tion of America, Mechanisms of Autoantibody Pro- structures. The Sterling bequest extended to faculty meister, nih, Serotonin 1B Receptor Imaging in duction in Lupus, 1 year, $66,000 • Michael ptsd with and without Comorbid Depression, Crowley, Bial Foundation, When Rejection Hurts: and students as well: to this day, the 36 Sterling Pro- 2 years, $354,772 • Mona Nolde, nih, The Role of Probing the Neural Basis of Childhood Social Exclu- fessorships are the highest honor bestowed on Yale’s Mammalian piwi Proteins and pirnas in Hemato- sion with a Dense-array eeg, 20 months, $16,461 faculty—including Thomas Steitz, recipient of the poiesis and Leukemia, 3 years, $153,822 • Chirag Enrique De La Cruz, American Heart Association, 2009 Nobel Prize for Chemistry, whose achievements Parikh, nih, Identifying Acute Tubular Necrosis in Nat’l Center, Mechanics of Cooperative Cofilin–Actin yale manuscripts & archives are chronicled in this issue of Medicine@Yale. Cirrhosis Patients with Renal Dysfunction, 2 years, Filament Interactions and Severing, 5 years, $455,125 • Christopher Pittenger, nih, Targeting $500,000 • Linda Degutis, State of Connecticut, Creating new endowed professorships is one of the medical school’s highest Glutamate in ocd: A Placebo-Controlled, Double- Yale Center for Public Health Preparedness Training priorities. At no point in history has medical research made advances at the Blind Augmentation Trial of Glutamate-Modulating and Technical Assistance, 10 months, $111,000 pace seen in the last 10 years, and this progress will pale by comparison to Agent Riluzole in Treatment-Resistant ocd, 3 years, Michael DiGiovanna, Breast Cancer Alliance, Inc., what we are poised to accomplish in the years ahead. Providing steady, secure $636,750 • Marc Potenza, nih, International Co-Targeting igf-I Receptor and her2 in Breast support for the scientific pursuits of our very best faculty members is one way Society for Research on Impulsivity Scientific Meeting, Cancer, 1 year, $100,000; Connecticut Breast 1 year, $39,627 • Jennifer Prah Ruger, nih, Eco- Health Initiative, Inc., Combination Targeting of to sustain our rapid progress in understanding and treating illness. nomic Evaluation of Drug Abuse Treatment and hiv igf-I Receptor and her2 in Breast Cancer, 1 year, A $3 million gift will create an endowed professorship in your name or a Prevention Services for Pregnant Women, 4 years, $33,000 • Ronald Duman, Repligen Corporation, loved one’s name. Please consider a donation today. $2,702,314 • Vincent Quagliarello, nih, A Ran- Influence of Uridine on Behavior and Trophic Factor 6 www.medicineatyale.org Nobel from page 1

Haloarcua marismortui, an evolution- angstroms—for comparison, this sheet Ramakrishnan, who was a post- arily ancient, single-celled, “extremo- of paper is about 1 million angstroms doctoral associate in Moore’s Yale lab phile” organism that thrives in the thick), the Steitz lab conclusively 30 years ago (“It’s good to see one’s highly salty, oxygen-poor depths of showed that the ribosome was not an ‘children’ doing well,” said Moore) the Dead Sea. Extremophiles have rna framework that made it possible went on to solve the structure of the played an important role in the recent for protein enzymes to catalyze the small subunit of the ribosome in an- history of structural biology (see relat- chemical reactions involved in synthe- other extremophile, Thermus thermoph- ed story, page 3) because their proteins sizing other proteins, but the opposite: ilus, a bacterial denizen of super-hot are unusually stable in the laboratory in the ribosome, proteins provide a deep-sea vents. and relatively easy to crystallize for stabilizing scaffold for a dense mass of Along with Moore and William L. X-ray analysis. rna helices that catalyze these reac- Jorgensen, ph.d., Sterling Professor Since structures as basic to life tions themselves (see image at right). of Chemistry, Steitz is a co-founder of

as the ribosome have been highly In addition to settling these Rib-X Pharmaceuticals, Inc., a New courtesy of thomas steitz conserved over the course of evolution, structural questions, the Science papers Haven–based drug discovery compa- In this image from one of the classic Science the insights that Steitz and colleagues provided intriguing evidence in support ny that is applying knowledge of ribo- articles published in 2000 by Thomas Steitz gained in their studies of H. marismor- of the “rna world” hypothesis, which some structure to the creation of new, and colleagues, the large subunit of the ribosome is seen to be primarily composed tui have broad ramifications. In a no- proposes that life forms dependent on more effective classes of antibiotics. of rna helices (gray), interspersed with table example, many widely prescribed rna as both an information-carrier and At the October press conference, stabilizing protein backbones (gold). antibiotics work by binding to the enzyme were abundant before the rise of Steitz made a plea for the support of ribosomes of infectious bacteria and dna and protein-based organisms. basic science, pointing out designing was doable in principle but we did not disrupting their function, and knowl- Steitz shares the Nobel Prize antibiotics was “the furthest thing know if we would ever get there.” But edge of ribosome structure is now equally with Ada E. Yonath, ph.d., of from our minds” when his team first when he saw a detailed image of the leading to better strategies to combat the Weizmann Institute of Science in decided to crack the secrets of ribo- ribosome for the first time, he added, drug-resistant bacterial strains. Israel, who pioneered the crystallization somal structure. it was “the most exhilarating moment By providing the first detailed 3-D of the H. marismortui ribosome, and Recalling the daunting technical I have experienced in science.” reconstructions of the ribosome (Steitz Venkatraman Ramakrishnan, ph.d., of challenges that faced him and his col- and colleagues imaged the H. maris- the mrc Laboratory of Molecular Biol- leagues, he said, “It seemed a little like Yale Netcast mortui ribosome at a resolution of 2.4 ogy in Cambridge, United Kingdom. climbing Mount Everest. We knew it “Mapping the Ribosome”

Hospital from page 1

“Yale University, Yale School of With his wife, Joan, Smilow, a recently, helped to implement a $120 Medicine, and Yale-New Haven Hos- member of the Yale College Class of million gift from his class, the largest pital together have a long tradition of 1954 and the former ceo, chairman, in Yale’s history. Smilow received the excellence in cancer care,” Alpern said. and president of Playtex, has given Yale Medal, the university’s highest “The first chemotherapy was given generously to his alma mater for de- honor, in 1993. by Yale physicians in 1942 at what cades. In the fall of 2007, Smilow gave Smilow Cancer Hospital has was then called New Haven Hospital, a transformational gift that allowed been under construction since 2006. ushering in the age in which we could construction of the long-planned can- When it is fully complete in April treat and cure patients. There’s a new cer hospital to move ahead. 2010, the new facility will bring all of park place photographers, inc. age coming with much better treat- “The one question that people the inpatient and outpatient cancer George Posener, of Orange, Conn., was pres- ments, and we now have the Smilow have asked me the most in the last services at Yale into one building, ent at the Smilow Cancer Hospital’s opening. Posener, who celebrates his 98th birthday Cancer Hospital, and for that we are couple of years is, would I have done and it is expected to become the most this December, recently made a gift to the incredibly grateful to Joan and Joel it if I had known what was going to comprehensive cancer care facility in new hospital, having previously established Smilow, and to many other donors. happen in the country in the fol- New England. endowments at the School of Medicine We’ll be able to do state-of-the-art lowing two years?” Smilow said in The hospital was designed with an that support stem cell research and training research, and we will be educating, in his remarks at the grand opening. explicit commitment to personalized of fellows in the Department of Surgery’s Section of Trauma and Surgical Critical Care this hospital, the next generation of “I long ago learned that paper assets cancer care. A multi­-specialty team of and in the Department of Internal Medicine’s clinicians and researchers.” were not nearly as important as real physicians and nurses is mobilized to Section of Hematology. Borgstrom’s remarks opened the assets that either you would person- treat each patient, and the teams are afternoon’s proceedings. “Like most ally enjoy, or that would benefit other housed together in suites, dedicated Lynch sees the opening of the great achievements,” she said, “this people. The answer is yes.” to different forms of cancer, that hospital as just one of several develop- point represents the intersection of The Smilows’ philanthropy has facilitate collaboration among the ments advancing cancer treatment and ideas and people. More than six years endowed six coaching positions in various disciplines involved in cancer research at Yale. In the short term, the ago, we knew that we had to increase Yale athletics and enabled the renova- treatment. new hospital offers multidisciplinary Yale-New Haven Hospital’s patient tion of the old Lapham Field House, These interdisciplinary teams will team care and a much greater avail- care capacity. It took a lot of time, now called Smilow Field Center. have easy access to conference rooms ability of clinical trials to patients. and it took a lot of hard work on the Smilow also stewarded the major where they can view diagnostic- But in the long term, coupled part of many people to make this idea gifts component of Yale’s capital quality images on large screens and with the opening of the new Cancer a reality.” campaign in the 1990s and, more interact with local colleagues or, using Biology Institute at Yale’s West Cam- telemedicine technology, with experts pus, Lynch says, the Smilow Cancer at distant sites. Hospital will raise ynhh into the top “The opportunity for expanded echelon of the nation’s cancer research patient services and improved multi­ and care facilities. disciplinary team care in Smilow “Yale’s always done wonderful basic Cancer Hospital will have profound science, and it’s always had wonder- implications for cancer patients,” fully compassionate doctors. But it’s said Professor of Medicine Thomas never put the whole package together J. Lynch Jr., m.d., director of Yale for cancer,” Lynch says. The opening of Cancer Center and physician-in-chief the new hospital and the development at the new hospital. “Each patient will of West Campus are “giving Yale the receive their cancer care from a team ability to put together a truly compre- of specialized physicians who are ex- hensive program in cancer. The medi- perienced in treating their particular cal school and the hospital have come type of cancer. The new facility will together in an unprecedented way to make these interactions seamless for say that cancer really matters here— our patients.” cancer is something that we’re going to robert a. lisak With 500,000 square feet of space, use the resources of one of the world’s (From left) Robert Alpern; Richard Levin; Joel and Joan Smilow; Marna Borgstrom; Joseph the hospital, which cost an estimated great universities to fight.” R. Crespo, chair of the Yale-New Haven Hospital (ynhh) Board of Trustees; Thomas Lynch; $467 million, boasts a rooftop garden Bishop Theodore L. Brooks Sr. of Beulah Heights First Pentecostal Church, a ynhh trustee; with trees and fountains, and a lobby Bonnie Kaplan Tymniak; and New Haven Mayor John DeStefano took part in the Smilow Yale Netcast Cancer Hospital ribbon-cutting. with saltwater aquariums. “More Clinical Trials Needed” Medicine@Yale November/December 2009 7 Expert on visual development is first ZieglerP rofessor Michael C. Crair, Ph.D., who studies general question the Vision Core Facility, overseeing the Investigator Award. He has been the development, structure, and function of how the brain is molecular and cellular biology equip- named an Alfred P. Sloan Foundation of the visual system, has been named the wired up during de- ment, microscopes, and other technolo- Research Fellow, a John Merck Fund inaugural William Ziegler III Associate velopment, research gies used in vision research at Yale. He Scholar, and the March of Dimes Foun- Professor of Vision Research. in Crair’s lab has also serves as director of graduate studies dation’s Basil O’Connor Fellow. Crair, a faculty member in the advanced for the Department of Neurobiology. The new professorship was cre- Department of Neurobiology, uses a understanding Crair received his ph.d. in physics ated by the family of the late William broad range of experimental tech- of how genetic from the University of California, Berke- Ziegler III, of Darien, Conn., a long- Michael Crair niques, including in vitro and in instructions and ley, and completed postdoctoral studies time member of the Yale Eye Center vivo electrophysiology and optical sensory experience interact during in neuroscience at Kyoto University in Advisory Board. imaging, to explore how genes and brain development. Japan, and at the University of Califor- Ziegler, who died in 2008, was the environment guide the develop- Crair joined the School of Medi- nia, San Francisco. an avid sailor and environmentalist. ment of sensory maps in the brain, cine faculty in 2007 as associate profes- He has received numerous honors He was chair and ceo of American especially those that underlie vision. sor of neurobiology and of ophthalmol- for his work, including a NARSAD– Maize-Products Company and later of In addition to shedding light on the ogy and visual science. He is director of Sidney R. Baer Jr. Foundation Young Swisher International Inc.

Neurology chair, MS researcher Nixdorff-German Professor is named Gilbert Glaser Professor neurosurgeon and geneticist David A. Hafler,M.D. , chair and chief scientists from the University of Cam- Murat Günel, m.d., recently named Günel received his medical degree of neurology at Yale School of Medi- bridge and the University of California, the Nixdorff-German Professor of from Istanbul School of Medicine, in cine (YSM) and Yale-New Haven Hos- San Francisco. The group led an initia- Neurosurgery, combines a neurosurgi- Turkey, and completed his residency in pital (YNHH), has been named the first tive to explore the genetic basis of MS, cal practice with research in the genet- neurosurgery at ynhh in 1998. That Gilbert H. Glaser, culminating in the first whole genome ics of neurovascular same year, he joined the Yale faculty as M.D., Professor. scan identifying MS-associated genes, disease. His main an assistant professor of neurosurgery. Hafler, a leader work published in 2008 in The New clinical interest is the Since 2001, he has been chief of the Sec- in the effort to England Journal of Medicine. treatment of intra- tion of Neurovascular Surgery. better understand The new professorship honors cranial aneurysms Among other organizations, Günel the molecular basis Gilbert H. Glaser, M.D., professor (icas), weaknesses is a member of the American Associa- of multiple scle- emeritus of neurology and chair of in the brain’s blood tion of Neurological Surgeons (aans), rosis (MS), joined the medical school’s Department of vessels that can the Congress of Neurological Surgeons David Hafler the faculty of the Neurology from 1971 to 1986. Murat Günel balloon, putting (cns), and the Academy of Neurologi- School of Medicine Glaser, who was the department’s pressure on brain cal Surgeons. He is currently serving a this September. An authority on the founding chair, is widely acknowl- tissue, or rupture, causing hemorrhagic term as president of the Joint Cerebro- mechanisms of autoimmunity and edged as one of the founders of the stroke. He is chief of the Section of vascular Section of the aans/cns. inflammatory diseases of the central field as a distinct medical specialty. His Neurovascular Surgery at Yale-New The Nixdorff-German Professor- nervous system, he was previously work in neurology and neuroscience as Haven Hospital (ynhh). ship was established in 1974 with a director of molecular immunology in both an investigator and a teacher ad- Günel, also professor of neurobiol- bequest from Elizabeth S. Nixdorff in the neurology department at Harvard vanced both disciplines nationally and ogy and of genetics, is co-director of memory of her late husband, Charles Medical School, where he was the internationally. In particular, Glaser’s the Yale Program on Neurogenetics. Edward Nixdorff, and “in recognition Jack, Sadie, and David Breakstone research on epilepsy, which included In his research, he has explored the of the many contributions to medicine” Professor of Neurology (Neurosci- one of the first identifications of a spe- genetic risk factors for neurovascular of William J. German, m.d. German’s ence) and a neurologist at Brigham cific location of epileptic discharges in disease, including icas and cerebral neurosurgical career at the School of and Women’s Hospital. the brain, has helped to improve both cavernous malformations, a less serious Medicine spanned four decades. He Hafler has been a major force surgical and non-surgical treatments vascular irregularity in the brain. retired as professor of surgery and chief in defining the causes of multiple of the disorder. Yale’s epilepsy program In a paper in Nature Genetics in of the Section of Neurosurgery in 1968. sclerosis. He was among the first to under Glaser’s leadership was one of December 2008, Günel and colleagues In a 1981 obituary of German apply the technique of T-cell cloning the nation’s first and has evolved into reported variations in three genetic published in the Journal of Neurosurgery to human disease, identifying the one of the most active and advanced in regions associated with a greater risk of and written by the late Yale neurosur- targets of activated immune cells in the world. ica and proposed a likely causative role geons William F. Collins, m.d., and patients with MS. Glaser received the W. G. Lennox for two specific genes. The study popu- Lycurgus M. Davey, m.d., German More recently, Hafler became an Award from the American Epilepsy lation has since grown to 15,000 people, was remembered as “an unpretentious, associate member of the Broad Institute Society in 1963, and served as presi- and Günel says that more detailed kind, dignified, expert in his profes- at Harvard and MIT, and founded dent of the American Academy of genetic data on aneurysm risk should sion, and, perhaps most of all, a friend an international collaboration with Neurology from 1973 through 1975. soon emerge from his research. to everyone who knew him.”

Harris Professor probes development of social cognition in autism Kevin Pelphrey, ph.d., the newly des- disorders. By com- at Duke University. He remains a core Boyd McCandless Award for a distin- ignated Harris Family Associate Pro- paring the typical faculty member at Duke University’s guished early career theoretical contri- fessor of Child Psychiatry in the Child development of Brain Imaging and Analysis Center. bution in Developmental Psychology. Study Center, focuses his research on social cognition with Pelphrey is a frequent scientific He is a member of the nih’s Child the brain mechanisms underlying the its development in collaborator with colleagues in Yale’s Psychopathology and Developmen- development of different aspects of asd using magnetic Department of Psychology, and is a tal Disabilities Study Section, and a social cognition. resonance imag- member of the Interdepartmental Neu- reviewing editor of Frontiers in Neuro- Pelphrey’s interests include the ing, eye-tracking, roscience Program and the Cognitive science and a member of the editorial Kevin Pelphrey development of social perception, the and virtual-reality Science Program. boards of Autism Research and the perception and regulation of emotion, techniques, members of the Pelphrey Pelphrey’s honors include a Scientist Journal of Autism and Developmental and the development of theory of laboratory are working to uncover the Career Development Award from the Disorders. mind, a crucial cognitive capacity de- building blocks of complex, multi- National Institutes of Health (nih), In addition, Pelphrey serves as a fined as the ability to make inferences faceted, social cognitive abilities. a John Merck Scholars Award in the reviewer for over twenty other scientific about others’ mental states. Pelphrey completed his doctor- Biology of Developmental Disabilities journals. He is a member of the Society Scientists believe that some of these ate in psychology at the University of in Children, the A. Richard Newton for Personality and Social Psychology, capacities appear to be impaired in chil- North Carolina, Chapel Hill, in 2001. Breakthrough Research Award from the International Society for Autism dren with autism spectrum disorders Subsequently, he held a postdoctoral the Microsoft Corporation, and the Research, and the Society for Neurosci- (asd) and other neurodevelopmental fellowship in cognitive neuroscience American Psychological Association’s ence, among other organizations. 8 www.medicineatyale.org