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Advancing Biomedical Science, Education and Health Care Volume 3, Issue 4 July/August 2007 Acquisition of Bayer site will accelerate@ biomedical research MedicineYale University’s recent purchase “Yale is already in the midst of aYale research programs that we would of the 136-acre Bayer HealthCare boom in the expansion of its science not have had space to develop for a campus in the municipalities of West and medical facilities,” said Levin. decade or more.” Haven and Orange, Conn., offers the “The addition of this ready-made, School of Medicine Dean Robert School of Medicine an unprecedented state-of-the-art research space will J. Alpern, m.d., says plans for how to opportunity to expand and quicken allow that growth to accelerate at an use the space are not finalized, but the the pace of its biomedical research unprecedented level—potentially medical school will be a major partici- programs, school officials say. making it possible for Yale scientists pant. “There are programs we would Yale President Richard C. Levin to develop new discoveries, inven- really like to grow in which growth announced the acquisition, which in- tions and cures years earlier. The has been limited by space,” he says. Yale President Richard Levin (left) and West cludes 550,000 square feet of labora- availability of Bayer’s science labo- However, Alpern also says he Haven Mayor John Picard swapped hats to tory space, on June 13. ratories will enable us to undertake mark the purchase of the Bayer campus. Bayer, page 6

International effort Passing rewrites the book on the torch the human genome When the Human Genome Project A shared life in research wrapped up in 2003, the world got inspires $2.5 million gift its first complete instruction manual on how to build a human. The only to aid young scientists problem? No one knew how to read When Franklin H. Top Jr., m.d., and most of it. his wife, Lois Top, m.n.ed., paid That’s because a visit to the School of Medicine just a tiny fraction of recently, it was a homecoming for the 3 billion letters them both. In the late 1950s, Lois was in the manual form a nursing student at the University of Franklin and Lois Top (left) drew on their own experiences when making a gift to the Yale words that can be Scholars program started by Dean Robert Alpern (right) to help beginning scientists get a Michael Snyder Connecticut and living in a dormi- foothold in their fields. easily interpreted. tory the program maintained then Scientists have long relegated the rest, near Grace-New Haven Hospital (now entering the field, the couple recently should help alleviate some of the for the most part, to the trash heap. Yale-New Haven Hospital), the hospi- made a $2.5 million gift to the School roadblocks.” But the results of a new study tal where she was born. Franklin, her of Medicine to establish the Lois and After Franklin graduated from the published in the June 14 issue of husband-to-be, had earned an under- Franklin Top, Jr. Yale Scholar. The Yale medical school in 1961, he completed Nature reveal that there’s a lot more graduate degree in biochemistry from Scholars program is a recent initiative his internship and residency in pedi- going on in the vast, uncharted re- Yale College and was working toward of Dean Robert J. Alpern, m.d., which atrics at the University of Minnesota, gions of the genome than previously his medical degree at the School of provides four years of research funding where Lois also obtained a master’s supposed, and suggest that so-called Medicine. “I needed a date for the to the most promising new researchers degree in nursing education. “junk dna” may not be junk after Yale-Dartmouth game, so I went over recruited at the medical school. In 1966, Franklin joined the Army, all. Now the challenge is to figure out to the UConn mixer,” Franklin recalls. “To be able to take talent that’s where he spent 22 years doing infec- what all that dna is for. Doing so “And that’s how we met.” already been recognized in a postdoc- tious disease research at the Walter may prove crucial for understanding That meeting marked the begin- toral program and let that person run Reed Army Institute of Research complex human diseases. ning of an eventful life in biomedical with it makes an awful lot of sense,” (wrair), including a three-year stint “It’s sort of like Lewis and Clark,” research that would take the couple Franklin says. “If you want to encour- that he, Lois and their three young says Michael Snyder, ph.d., Lewis from New Haven to Minneapolis to age good people to get into this field, sons spent together in Thailand, B. Cullman Professor of Molecular, Bethesda to Bangkok. Having each this is a good way of doing it.” where Franklin worked at a laboratory Cellular and Developmental Biol- paid their dues at the lab bench, Lois agrees. “It’s really time-con- affiliated with thewrair . ogy and of molecular and the Tops experienced firsthand the suming to pursue a research career, Franklin eventually rose to the biochemistry. “We’re trying to map challenges of beginning a career in and you can use all the help you can rank of colonel and served as direc- out what’s there.” biomedical research. To help smooth get, from ideas to funding to good lab tor and commandant of the wrair. Toward that end, Snyder’s lab the way for young scientists just space to do your work,” she says. “This When the children were all in school, is part of the Encyclopedia of dna Yale Scholar, page 6 Encode, page 6

Non-Profit Org. Inside this issue @ U. S. Postage 300Medicine George St., SuiteYale 773 PAID Lifelines Reversing rickets Yale researchers battle New Haven, CT 06511 New Haven, CT Cardiologist Lawrence Cohen Permit No. 526 on the art of listening, p. 2 against bone disease, p. 5 www.medicineatyale.org New tool in the anti-cancer kit Sweet success Yale lab’s study of Kit protein Insulin expert joins points the way to better drugs, p. 3 National Academy of Sciences, p. 8 A healthy brew Also Chinese herb arrests a Advances, pp. 3, 5; Out & About, p. 4; serious kidney disease, p. 5 Grants and Contracts, p. 7; Awards & Honors, p. 8

Want to find out more about medicine at Yale? E-mail us at [email protected] or phone (203) 785-5824. cyan mag yelo black 2602 MAC

Yale scientist is new president of Wellesley College H. Kim Bottomly, ph.d., former deputy provost for science, technol- ogy and faculty development at Yale and professor of immunobiology and molecular, cellular and developmental As teacher, mentor, physi- biology, was named cian and valued advisor, cardiologist Lawrence Cohen president of Welles- has touched the lives of stu- ley College in May. dents, colleagues, patients Bottomly is a and leaders of the School of Medicine for more than three widely published decades. researcher on im- mune responses to allergens. She has Kim Bottomly served as a member of the Immunobiology Study Section at the National Institutes of Health (nih), was appointed to the Advisory Clinical master, consummate teacher Council of the National Institute of Allergy and Infectious Diseases and For 35 years, students prevent heart disease and reverse its a member of the School of Med- received the prestigious merit award have learned how to listen course.” icine’s Class of 1976. In February, from the nih. from ‘Larry the Heart’ Those tools exist in part thanks Elefteriades and Cohen published Bottomly was instrumental in to Cohen, who was a key player their second book (Cohen’s fourth), spearheading Yale’s faculty diversity A beating heart has its own sonic in studies showing that heart Your Heart: An Owner’s Guide (Pro- initiative, a plan to add 30 new wom- signature, the steady lub-dub of attacks are caused by the rupture metheus Books). en and 30 minority faculty members the chambers opening and closing of a plaque from coronary artery Cohen is “the cardiologists’ over the next seven years. Bottomly’s as blood flows, backs up and flows walls and the clotting that follows. cardiologist. When any of us is ill, deputy provost position, which com- again through the only muscle in the He was also the we go to him,” Elefteriades says. Lifelines bined two roles to meet her personal body that never rests. To the trained principal investiga- “And whenever there’s a difficult or interests—faculty development and ear, these murmurs, whooshes, Lawrence tor at Yale for the complex case that requires excep- science—has not yet been filled. gallops and rubs speak volumes, first three Throm- tional judgment, cardiologists from Cohen Bottomly’s departure adds to a and provide clear information about bolysis in Myocardial all over the region will send their growing roster of women who have heart disease or defects. Infarction (timi) trials, which were patients to him.” moved on from Yale’s Provost’s Office For more than three decades, multicenter studies demonstrating The Brooklyn-bred Cohen came to head other prestigious institutions. teaching the language of heart that clot-busting drugs could limit to Yale in 1958 as an intern, follow- Former Provost Judith Rodin, ph.d., sounds to medical students has been or prevent damage during heart ing college at Harvard and medical left Yale in 1994 to become president the job of Lawrence S. Cohen, m.d., attacks and dramatically increase school at New York University. of the University of Pennsylvania; Ali- the Ebenezer K. Hunt Professor of survival rates. Twelve years later, after stints at son Richard, ph.d., became head of Medicine. Deliberate, concise and Known for his calm, effective Johns Hopkins, Harvard, the National the University of Cambridge in 2003; always impeccably dressed, Cohen is approach to decision-making, Cohen Institutes of Health and the Univer- the following year, Susan Hockfield, the sort of professor whom medical has served as deputy or special sity of Texas, he returned to Yale as ph.d., was named the 16th president students notice enough to honor advisor to medical school deans for chief of cardiology. of the Massachusetts Institute of with a nickname, recalls Jeffrey R. 16 years, overseeing faculty appoint- Cohen has mentored dozens of Technology. Bender, m.d., who served as a resi- ments and promotions, raising influential cardiologists and leaders dent under Cohen in the early 1980s. money for endowed professorships in academic medicine. John M. “He was known as ‘Larry the and promoting the responsible Lasala, m.d., ph.d., director of inter- @ Heart,’ ” recalls Bender, now the conduct of scientific research. Cohen ventional cardiology at Washington MedicinePeter Farley, ManagingYale Editor Robert I. Levy Professor of Preventive recently stepped down from this University in St. Louis, was a fellow Contributors: Amy Chow, Michael Fitzsousa, Renee Cardiology, “and he was the consum- role and will be succeeded by Linda under Cohen in 1989 and 1990. Gaudette, Johannes Hirn, Jennifer Kaylin, Robin Orwant, Karen Peart, Richard Silverman, Zsuzsanna mate teacher.” C. Mayes, m.d., the Arnold Gessell Lasala recalls, “The most amazing Somogyi, Jacqueline Weaver, Sarah Williams. At 74, Cohen still teaches every Professor of Child Development in thing was his ability to synthesize Photographs and Illustrations: American Diabetes Yale medical student how to listen the Child Study Center. However, he great amounts of information into Association, Bayer HealthCare, Terry Dagradi, to the heart; he estimates that he’s is continuing on full-time as a prac- simple and factually correct assess- Arnold Gold, ©Images.com/CORBIS, Michael Marsland, instructed some 3,000 students over ticing and teaching cardiologist. ments. He could say an awful lot Joseph Schlessinger, Harold Shapiro, Elaine Ubiña. the past three decades. When he That’s good news for the with very little.” Design: Peter W. Johnson, thinks back to the early days of his medical school, says John A. Eleft- Cohen has no intention of Maura Gianakos, Bryan Gillespie/Yale RIS academic career, the advancements eriades, m.d., the section chief and putting aside his clinical duties any Medicine@Yale is published six times each year by the in cardiac care fill him with wonder. William W.L. Glenn Professor of time soon. Office of Institutional Planning and Communications, , 300 George St., Suite 773, “The No. 1 difference between then Cardiothoracic Surgery (see story “Being able to make a differ- New Haven, CT 06511. and now,” he says, “is that someone below), who himself learned to ence in patients’ lives” he says, “is a Telephone: (203) 785-5824 practicing today has the tools to listen to the heart from Cohen as privilege.” Fax: (203) 785-4327 E-mail: [email protected] Website: medicineatyale.org

Copyright ©2007 by Yale School of Medicine. Top heart surgeon is named Glenn Professor All rights reserved. Internationally Elefteriades’ research and clinical Glenn professorship was established If you have a change of address or do not wish to receive future issues of Medicine@Yale, known heart practice focus on aortic aneurysms, with generous gifts from family, please write to us at the above address surgeon John A. advanced left ventricular failure and friends and colleagues to honor or via e-mail at [email protected].

Elefteriades, m.d., heart transplantation. He received both Glenn, a former chief of cardiotho- Postal permit held by , professor of surgery, his b.a. and m.d. from Yale and he racic surgery at Yale who was a world- 155 Whitney Avenue, New Haven, CT 06520

has been named the has spent his entire professional career renowned pioneer of cardiovascular Yale School of Medicine William W.L. Glenn in New Haven. Elefteriades joined the surgery. Robert J. Alpern, m.d., Dean Professor of Car- School of Medicine’s faculty in 1983, During his long career, Glenn Ensign Professor of Medicine John Elefteriades diothoracic Surgery. and became full professor in 1993. created early mechanical heart pumps Jancy L. Houck Associate Vice President for Development Elefteriades is chief of the Section of He has repeatedly been included in and developed the first radio fre- and Director of Medical Development Cardiothoracic Surgery at the medical lists of the best heart surgeons in the quency pacemaker. Glenn also was (203) 436-8560 school and program director of the Northeast and in the country. the first surgeon elected president of Mary Hu Director of Institutional Planning and Communications Thoracic Surgery Residency Program Under the leadership of Lawrence the American Heart Association. He Michael Fitzsousa, Director of Communications at Yale-New Haven Medical Center. S. Cohen, m.d. (see story above), the died in 2003.  www.medicineatyale.org cyan mag yelo black 2602 MAC

Advances Finding a new chink in cancer’s armor Health and science news from Yale The crystal structure of the extracellular Close-up view of protein portion of the Kit receptor in its active form. The binding of Kit’s ligand, stem cell factor offers hope for new, highly (magenta), has caused two Kit molecules targeted cancer drugs (blue, green, yellow, orange, pink) to form a paired structure in which some regions In the July 27 issue of Cell, a research (orange, pink) closely interact. team led by Joseph Schlessinger, ph.d., William H. Prusoff Professor Putting a squeeze and chair of , reports solving the atomic-level structures be universal to quite a few of these on Lyme disease for the active and inactive forms of a rtks,” Schlessinger predicts. The Centers for Disease Control protein that has been implicated in Because the targets are in the and Prevention recently reported several types of cancer. The results extracellular portion of the protein, that the incidence of Lyme disease, highlight previously unidentified scientists won’t have to worry about caused by the tick-borne bacterium changes in the protein’s structure getting the drugs inside cells, a major Borrelia burgdorferi, has more than that seem to be crucial for its activa- challenge in drug design. And because doubled in the past 15 years, with tion. Drugs designed to block these the interactions involve relatively most cases concentrated in New changes could represent a novel class small portions of the extracellular do- England. Now, Yale scientists have of therapies with the potential to main, researchers may be able to de- found a loophole in the bacterium’s life cycle that offers a way to stop work against a broad range of cancers. sign more effective drugs, says Mark ticks from ever carrying the dis- “It gives us totally new avenues for A. Lemmon, ph.d., of the University ease, which they pick up as larvae developing drugs for a large group of Sutent, and those that do typically of Pennsylvania School of Medicine. when they suck blood from mice. target proteins that are responsible for develop resistance to the drugs within Lemmon, who wrote a commen- Erol Fikrig, m.d., professor of several cancers,” says Schlessinger. a few years. tary accompanying Schlessinger’s medicine, epidemiology and micro- The study focused on one of 59 With that in mind, Schlessinger report in Cell, explains that previ- bial pathogenesis, and colleagues receptor tyrosine kinases (rtks), a has spent the last 10 years putting ous drug design efforts targeting discovered that B. burgdorferi takes set of related proteins that normally together a detailed atomic-level view the extracellular domains of Kit and advantage of a protein that ticks become active only under particular of the extracellular domain of an rtk Kit-related rtks have sought to block inject into mice when they bite to circumstances to help cells proliferate, called Kit. All that effort has yielded a dimerization, which involves many prevent an immune response and differentiate and survive. Certain mu- picture of the protein at atomic reso- interactions over large portions of the swelling. When the researchers blocked this protein, either by stop- tations in rtks can turn the proteins lution—about a million times smaller protein. But it takes a big molecule— ping ticks from producing it in their on inappropriately, than the thickness of a sheet of paper. an antibody, for example—to disrupt salivary glands, or by coaxing the causing aberrant cell The results suggest that after enough of these interactions to have mice to obstruct it, the B. burgdorf- proliferation that binding to their ligands and forming an impact on dimerization, and that’s eri couldn’t go from mouse to tick. may ultimately lead dimers, Kit molecules change their not ideal. The findings, published in to cancer. Block- shape such that certain portions of “They’re really sledgehammer the inaugural issue of Cell Host ing the activities of the extracellular domain in one Kit drugs, and they’re not particularly & Microbe in July, may eventually rtks has become molecule move close enough to in- good,” says Lemmon. “These are the help curb infections in humans by a major strategy teract with their counterparts on the first kinds of interactions in the extra- targeting the bacterium at this Joseph in anticancer drug other Kit molecule in the dimer. cellular domains for which you could early stage in its lifecycle. “You Schlessinger design, so knowing These interacting regions repre- devise small molecule inhibitors,” could reduce the number of ticks carrying Lyme disease,” says Fikrig. the structures of the proteins can tell sent completely new targets for cancer and that could lead to much better “That’s the long-term goal.” researchers which parts are important drugs. And since Kit is part of a family drugs in the long run. for turning the proteins on and would of rtks with similar extracellular Most importantly, drugs aimed at therefore make good drug targets. domains, the targets represented by these new targets might be effective These mice like to In general, rtks have three major this study probably exist in more than against Gleevec- and Sutent-resistant spend time chilling parts: an intracellular component, a a half dozen other rtks that have cancers, offering hope to many cancer portion embedded in the cell’s mem- been implicated in various cancers. patients who are trying to stay one When breath mints are called brane, and an extracellular domain “It’s a mechanism that is likely to step ahead of the enemy. “cool” on television, it’s truth in ad- that extends to the outside of the cell. vertising, according to a new study by Sven-Eric Jordt, ph.d., assistant Normally, each rtk binds specifi- professor of pharmacology, and cally to an external signaling molecule colleagues from the University of called a ligand via its extracellular do- California at San Francisco and the main. Binding permits two molecules University of Wisconsin. of the rtk to come together, forming The team reports in the July a paired structure known as a dimer. The Campaign for Yale School of Medicine 12 issue of Nature that mouse Once dimerized, pockets within the neurons engineered to lack trpm8, intracellular portions of the rtks “Finding a New Chink in Cancer’s Armor” documents the 10-year effort of an ion channel receptor involved bind to adenosine triphosphate, or Joseph Schlessinger, ph.d., and his colleagues to determine the molecular in detecting the cooling sensa- atp—an energy-storing molecule tion produced by menthol, were structure of a receptor involved in many cancers in order to develop better found inside cells—and use it to profoundly less sensitive to both drugs. Structural biology, cancer, and drug development are top priorities of menthol and cool temperatures. modify themselves in such a way that The Campaign for Yale School of Medicine. The Campaign will provide the In further experiments, when they are active and able to modify and resources to: mice lacking trpm8 were placed assemble other factors inside the cell • recruit and honor superb faculty by endowing professorships and Yale on test surfaces that included cool to promote cell growth. scholars; areas, they were far less likely than Two recently developed and highly • pursue research to advance medicine; normal mice to avoid those spots. successful cancer-fighting drugs, • secure cutting-edge technology for research; However, if these areas were Gleevec and Sutent, work by prevent- move research from bench to bedside; cooled below 15 ºC (59 ºF), trpm8- • ing the intracellular regions of some invest in outstanding patient care; deficient mice avoided them as • rtks from binding atp. Gleevec is • support and nurture medical and graduate students with funds for schol- much as normal mice, suggest- effective against particular stomach ing that temperatures below this arships, fellowships, student research and educational innovation; cancers and leukemias; Sutent also threshold may stimulate pain path- • meet the pressing demand for space by building a new cancer hospital ways that do not rely on trpm8. works against specific stomach can- and additional research laboratories. The importance of trpm8 in de- cers and fights some kidney cancers. Why is this campaign important? Because at no point in history has tecting menthol is well-established, “As we speak,” says Schlessinger, medical research made advances at the rate and pace of the last 10 years, but some researchers disputed its “hundreds of people are being saved and this progress will pale by comparison to what Yale School of Medicine is role in cold detection. For now, it by these two drugs.” poised to accomplish in the years ahead. seems, the issue’s been iced. But Schlessinger, who helped For information about gift opportunities, visit yaletomorrow.yale.edu/ discover Sutent, says there’s still an medicine or contact Jancy Houck, Associate Vice President for Development urgent need for new drugs. Many and Director, Medical Development (203) 436-8560. cancers don’t respond to Gleevec or  Medicine@Yale July/August 2007 cyan mag yelo black 2602 MAC

Out & about

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3 4 April 29: In the annual faculty-student softball game, the April 21: The 8th annual la cassa faculty team fielded by Dean Robert J. Alpern, m.d., “Bob’s Bulldogs,” jumped magica, a black-tie gala to benefit out to an early lead, thanks to (says a highly-placed faculty source) fine field- Yale Cancer Center (ycc), was held at ing, daring base running, and a tremendous home run by Dennis L. Cooper, The Belle Haven Club in Greenwich, m.d., professor of medicine. The lead eventually built up to 10-3, and the Conn. The event raised over $400,000 faculty may have gotten a bit complacent. In the 7th inning, the students to support the creation of a clinical- staged a spirited comeback, but their efforts fell short. The final score was 10- trials unit within the new Yale-New 5 9 in favor of the faculty, in the closest, best-played and most injury-free game Haven Cancer Hospital, which is now in the legendary three-year rivalry between Alpern’s heroic team and Class under construction. of Greenwich chaired the Kathryn Anderson Adams of 2008 Captain Misaki Kiguchi’s youthful challengers. The Dean donates event. Debbie and Louis Chênevert were vice chairs for the evening, which was chances to join the game to bidders at the students’ annual Hunger and hosted by cnn television news anchor and Yale Cancer Center ycc board Homelessness Auction. (Front row, from left): David L. Rimm, m.d., ph.d., member . Corporate chairs for La Cassa Magica included Paula Zahn George associate professor of pathology; Peter M. Glazer, m.d., ph.d., Robert E. , , , , , and E. Crapple Paul K. Kelly Nicholas T. Makes Joseph R. Perella Hal Parmelee Hunter Professor of Therapeutic Radiology; Sam Glazer; Alpern; Cooper; , m.d. Adams and Zahn were honored for their continued Richard S. Sackler Diane Kowalski, m.d., assistant professor of pathology and surgery; James support for ycc with plaques that will be displayed in the new Cancer Hos- S. Duncan, ph.d., professor of diagnostic radiology and biomedical engi- pital. (From left) , m.d., professor of medicine and ycc deputy 1. Edward Chu neering; Maritza Martel, m.d., assistant professor of pathology; and Richard director; Debbie and Louis Chênevert. , , 2. Duke Brodsky Erica Feingold Howard A. Silverman, director of admissions. (Back row, from left): Kelvin C. Lau , . (From left) with Brodsky John Moccia 3. Jeff and Karin Keith Sean and Duffy ’08; Gabriel A. Widi ’08; Saif S. Rathore ’10; Indy M. Wilkinson, ’08; Scott T.O. . , and . (From left) Zahn; Kilbride 4. Lucy Day Carol Crapple Margie Warwick 5. Kennedy ’08; Maulik P. Shah ’08; Karl R. Laskowski ’08; Kiguchi; Reid Sansone; , m.d., professor of dermatology and ycc director; and Richard L. Edelson Susan A. Sansone, registrar, m.d. /ph.d. Program; Mark H.J. McRae ’08; and Adams. Matthew C. McRae ’09.

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May 5: the science of autism at yale brought scientists and clinicians from the medical school’s Child Study Center May 28: At graduation for the class of 2007, Karen S. Morris-Priester, (csc) to the Yale Club of New York City m.d., spoke to a reporter from New Haven’s wtnh News Channel 8. Morris to present the latest research findings and entered the School of Medicine as a 40-year-old grandmother and mother of treatment options for autism. The event 5 five in 2002. The week before graduation, Morris-Priester’s teachers had lured also celebrated the naming of the csc as her to a classroom for “an important graduation meeting.” Instead, Oprah an Autism Center of Excellence by the National Institutes of Health, a highly Winfrey appeared on a video screen to tell Morris-Priester and her assembled competitive and prestigious designation that includes $7.5 million in direct classmates that she would be honored for her achievements on the “Cheers to research funding for the research program headed by autism expert Ami J. You!” segment of the Oprah Winfrey Show. “Oprah was saying my name!” said Klin, ph.d., Irving B. Harris Associate Professor in the Child Study Center. the shocked Morris-Priester as her fellow students cheered. “You don’t expect 1. (From left) Klin with Matthew W. State, m.d., ph.d., Irving B. Harris Oprah to be talking about you!” During her appearance on the program, Associate Professor of Child Psychiatry and associate professor of genetics; Morris-Priester learned that ambi Skincare, a Johnson & Johnson company, csc Director Fred R. Volkmar, m.d., Irving B. Harris Professor of Psychiatry, will pay her medical school debt, and that Johnson & Johnson is establishing Pediatrics, and Psychology; and Robert T. Schultz, ph.d., associate professor a scholarship in her honor to increase the number of minority women in the in the csc and associate professor of diagnostic radiology. 2. Debbie Hili- sciences. Morris-Priester has begun an internship at Lehigh Valley Hospital in brand, chair of the Executive Council of the Child Study Center Associates, Allentown, Pa., to be followed by an anesthesiology residency at Brigham and and . (From left) with Women’s Hospital in Boston. Barbara de Kwiatkowski 3. Judy Higgins William and Barbara Epifanio. 4. Wendy Pillsbury and Christopher Eichmann. 5. Jesse Mojica and Josh Needelman.

 www.medicineatyale.org cyan mag yelo black 2602 MAC Research center aims to make rickets history Advances Health and science news from Yale $5 million grant brings Hearing voices: cutting-edge science to a brain out of sync? bear on age-old disease Some 200 milliseconds before you When we think of rickets, the bone- speak, brain cells in your motor softening disorder that causes short cortex fire in concert, predicting stature and bowing deformations of the sounds you are the legs, we’re likely to imagine that about to produce. the disease is a relic of the distant This electrical discharge instructs past. But rickets is still very much your auditory cortex with us, says Thomas O. Carpenter, to disregard any m.d., professor of pediatrics and a matching signals leading rickets researcher. coming from your ears, which Carpenter first encountered keeps you from being distracted by rickets in the 1970s as a resident at the sound of your own voice. Children’s Hospital at the University But the story may be different of Alabama in Birmingham. Most of for patients with schizophrenia, as the cases he saw were nutritional in Judith Ford, ph d , and collabora- . . origin—a lack of calcium and vitamin Study Coordinator Elizabeth Olear (left) works alongside Thomas Carpenter on two clinical tors suggest in the March issue of D in the diet are the two main causes studies of rickets, part of a new initiative funded by the School of Medicine’s first Center of the American Journal of Psychiatry. Research Translation (cort) grant. The researchers found that brain of rickets and have accounted for a activity synchronized shortly rising incidence of the disease over however, unlike children with dietary growth, and biomedical science is on before the onset of speech, pos- the past 20 years. rickets, xlh patients have normal the cusp of a new understanding of sibly reflecting communication But Carpenter was particularly levels of both calcium and vitamin xlh, Carpenter says. With the help between the motor and sensory intrigued by children with X-linked D. Carpenter, who directs the Yale of a $5,000,000 Centers of Research cortex. However, in patients with hypophosphatemia, or xlh, an inher- Center for X-Linked Hypophospha- Translation (cort) grant, one of four severe auditory hallucinations, ited form of the disease caused by a temia (yc-xlh), says that 30 years awarded nationwide last fall by the this pre-speech synchronization mutation on the X chromosome. ago he found these contradictory lab National Institute of Arthritis and is weaker, and the brain’s reac- As the disease’s name implies, findings “baffling.” Musculoskeletal and Skin Diseases, tion to self-generated speech is these children have very low levels of not dampened: patients who hear However, recent studies have re- he and yc-xlh co-director Karl L. phosphate because they excrete too voices seem less able to recognize vealed a previously unknown system Insogna, m.d., professor of medicine, much of this mineral in their urine; their own. governing mineral balance and bone Rickets, page 7 Next on the authors’ list is to repeat the study for the “inner speech” that accompanies thinking to see whether a lack of syn- Brewing a new treatment for kidney disease chronization may cause patients with schizophrenia to mistakenly Swirled in a cup, tea leaves are said to anti-tumor agent,” explains Crews, ment,” says Crews. “And they say ‘Well, perceive their inner thoughts as offer a glimpse into the future. Now, associate professor of molecular, you know what? We need to make a external voices. Yale researchers have shown that one cellular and developmental biology, tubule’ and they keep growing and kind of Chinese tea may change the chemistry and pharmacology. “Yet they form a cyst.” People with inher- Stem cells show future for patients with polycystic they don’t know how it works. Our ited polycystin mutations usually start kidney disease (pkd), an inherited ge- thinking all along is that we’d love noticing symptoms of kidney disease promise in Parkinson’s netic disorder in which the formation to know how it works so that we can around age 25, Crews says. “Then they The symptoms of Parkinson’s dis- of multiple renal cysts leads to kidney anticipate potential side effects as well go from a kidney that’s twice the size ease (PD)—muscle rigidity, tremor failure. The disease is the most com- as come up with different compounds of normal at diagnosis to kidneys that and a general slowing of move- mon life-threatening genetic disorder that work in the same way.” can be upwards of 2 liters, the size of a ment—have been successfully worldwide, affecting some 12 million To find out, Crews made a radio- big soda pop.” treated in monkeys using human people. There is no cure, and the only active version of triptolide, added it Working with Postdoctoral As- stem cells. effective treatments for pkd-induced to kidney cells and tracked where it sociate Stephanie Leuenroth, ph.d., PD is caused when large num- renal failure are dialysis and kidney went. He found that the compound and Stefan Somlo, m.d., the c.n.h. bers of dopamine-producing cells (DA cells) die off in a brain region transplants. clustered around a protein called Long Professor of Medicine and known as the substantia nigra. A team led by biochemist Craig polycystin-2, a calcium channel found chief of nephrology, and colleagues, In the July 17 issue of Proceed- M. Crews, ph.d., recently showed in kidney cells that is mutated in Crews went on to show that trip- ings of the National Academy of that triptolide, a compound found many cases of pkd. tolide, when it binds to polycystin-2, Sciences, a team headed by D. in the thunder god vine, a medicinal During normal development, stops kidney cysts from growing: in Eugene Redmond Jr., m.d., profes- plant used to make the traditional kidney cells arrange themselves mice engineered to have polycystin-2 sor of psychiatry and neurosurgery, Chinese tea known as lei gong teng, ac- into tubules that course through mutations, triptolide reduced the size reports that human neural stem tivates a cascade of molecular events the organ. When the cells finish this of kidney cysts by 50 percent. Somlo, cells implanted into one side of the that stops kidney cysts from forming. assembly, urine flows through the one of the world’s leading experts on substantia nigra in monkeys with “Triptolide has been looked at, tubules and bends a protein called pkd, was the first scientist to identify severe Parkinsonian symptoms mi- and is still being looked at, as an polycystin-1, which is found on tiny polycystin-2. grated and survived on both sides, where many displayed biochemi- hair-like extensions of Triptolide is now in early clinical cal markers indicating that they the cells. Polycystin-1 trials as a cancer treatment, and the had matured into DA cells. Other then signals a partner researchers hope their pkd findings implanted cells also migrated protein, polycystin-2, will help accelerate clinical tests of to key regions and appeared to to release calcium from triptolide in kidney disease. play a nurturing role, creating a internal stores, which Crews says the new findings protective microenvironment that stops the tubule growth. strengthen his opinion that traditional restored the function of the mon- In people with inherited Chinese remedies hold vast untapped keys’ own surviving DA cells. mutations in either poly- potential for new medicines. Over a four-month period, the cystin gene, this message “Clearly, these mixtures have monkeys treated with stem cells to stop tubule formation some type of effect or they wouldn’t had vastly improved. “Not only are stem cells a potential source of is silenced. have been used for literally millennia,” replacement cells,” says Redmond, “When these cells he says. “The challenge for Western “they also seem to have a whole can’t sense or can’t researchers is to try to identify what variety of effects that normalize respond to urine flow, the active ingredient is. Then, as I did other abnormalities.” they think they are at an with triptolide, we can find out how Biochemist Craig Crews found a powerful medicine for poly- earlier stage in develop- it works.” cystic kidney disease in a traditional Chinese herbal tea.

 Medicine@Yale July/August 2007 cyan mag yelo black MAC

Bayer from page 1

could envision the new campus as a Zdru says that the Bayer campus While Bayer is not planning to va- transplantation. President Levin also place for other parts of the univer- adds both flexibility and immediacy cate all the office buildings and ware- emphasized that the acquisition of the sity to converge with the medical to the planning process. houses until 2008, Alpern says that lab Bayer campus will not affect plans to school. “It would be terrific if we “When you build a project, it’s space is already available and that Yale build more than 2 million square feet could also have faculty from the other usually a five-year process from the programs could begin relocating as of new Yale facilities in New Haven side of campus over there,” he says. initial ideas until the time you can early as the fall. over the next six years, and that the “It could act as a meeting space to actually use the space,” says Zdru. The purchase of the Bayer Health- heart of the campus will remain in bring together different parts of the “These particular laboratories are Care complex is the largest space the city. university.” designed in a flexible, universal man- acquisition in the university’s history, In addition to payment in lieu of George Zdru, director of the Yale ner that should make it very easy to says Alpern, and the purchase comple- taxes (pilot) funds that the state of School of Medicine Capital Program, occupy them without much renova- ments other recent building initiatives Connecticut will provide to the city manages lab and office space at the tion. It’s a good package.” at Yale. of West Haven and town of Orange, medical school. “Up until now, plan- In addition to lab space, the Bayer The 457,000-square-foot Anlyan Yale has agreed to make additional ning has always been constrained by complex includes office buildings and Center for Medical Research and voluntary payments to the munici- lack of space,” he says, “and the plan- warehouses, which may be used as Education, which opened in 2003, is palities proportional to the voluntary ning process was almost like a game storage space for the Yale University Yale’s largest building. The Amistad payments the university now makes to of checkers, requiring the movement Art Gallery and the Peabody Museum Building, which will officially open the city of New Haven. of a lot of people to get to the end- of Natural History. this fall, will house laboratories for Yale will also invest $1 million over point. Now it can become something The financial details of acquiring interdepartmental programs in stem the next three to four years to enhance a little more elegant, allowing us to the 136-acre campus will be disclosed cell biology, human translational im- science education in the Greater New think of planning more holistically.” at the time of closing. munology and vascular biology and Haven area.

Yale Scholar from page 1

Lois joined the Branch serious illness from respiratory syn- Infectious Diseases, a leading textbook appreciate the gains medical science of The National Institutes of Health’s cytial virus, a lung infection common that saw nine editions published has made in our lifetimes,” Franklin National Cancer Institute, where she in early childhood that can be danger- between 1955 and 1981. says. “We’d like to give back the fruits worked as a clinical research nurse on ous to premature infants or children “There have been huge changes of our good experience with the Army some of the earliest studies of gene with heart or lung problems. Since in my lifetime,” Franklin says. “When and with MedImmune to keep that therapy and on treatments for adult then, MedImmune has successfully I was an intern and resident, we were going.” T-cell leukemia/lymphoma. developed FluMist, a flu vaccine in just beginning to influence child- “It has been a pleasure for me to But the most significant chapter nasal-spray form, and Ethyol, which hood leukemia. We were not keep- come to know Frank and Lois Top,” in the Tops’ lives began in 1988, when protects cancer patients’ salivary ing children alive. We were giving says Dean Robert J. Alpern, m.d., Franklin retired from the Army to gland against damage from radiation them a longer duration of reason- Ensign Professor of Medicine. “When become executive vice president of treatments. ably good health, but we always I first met Frank, he told me of his a fledgling biotechnology company In June, MedImmune was ac- lost them. Now 85 percent of those deep gratitude to the School of Medi- called Molecular Vaccines; two years quired by global pharmaceutical giant children are essentially cured. In my cine, and when he and Lois recently later the company changed its name AstraZeneca for $15.6 billion. The own field, infectious diseases, most acquired funds from the sale of Med- to MedImmune. company will retain its name, and cases of childhood meningitis were Immune, they were swift in making The company, based in Maryland, Franklin remains on board as execu- caused by the pneumococcus or a commitment to the Yale Scholars where the Tops now make their home tive vice president of MedImmune Haemophilus influenzae. As a result of program. Frank’s accomplishments in Rockville, went on to make biotech Ventures, which identifies companies good work—basic research and then are a credit to the quality of the medi- history in 1998 when the U.S. Food that may be suitable for MedImmune applied development work—these cal school’s educational program, and and Drug Administration approved partnerships or investments. infections are pretty well eliminated I am also very grateful that Frank has MedImmune’s Synagis, the first Franklin Top inherited his interest from the United States.” agreed to serve on the newly formed monoclonal antibody treatment for in medicine and in infectious disease The Tops believe that such accom- Dean’s Council, providing us with an infectious disease. Synagis is now from his father, Franklin H. Top Sr., plishments will occur at an even more sage advice based on his many experi- the standard treatment to prevent m.d., who edited Communicable and rapid pace in the future. “We both ences over the years.”

Encode from page 1

Elements (encode) project, a mam- genome—aren’t transcribed at all. The surprising by interfering with the expression of moth undertaking of the National Not so, according to results from the results of the genes at distal sites? Human Genome Research Institute encode pilot project. They show encode study Snyder and his collaborators garnered (nhgri; part of the National Insti- that most of the letters in the genomic worldwide at- hope to answer questions like this by tutes of Health) involving a consor- instruction manual wind up being tention after mapping out where all the regulatory tium of 35 groups of researchers at transcribed. This happens, in part, publication regions are and how they work. “To 80 institutions in 11 nations. These because each gene is often transcribed in Nature in me,” he says, “this is really what the June. researchers have spent the last four along with a surprisingly large num- encode project is all about.” years sifting through more than 400 ber of non-protein-coding sequences The next step is for scientists to go million data points to make sense to produce some extraordinarily from looking at just 1 percent of the of just one percent of the human long rna fragments. The results also genome to analyzing the whole thing. genome. That may not sound like indicate that a single gene can be As daunting as that sounds, Elise A. much, but scrutinizing even this small transcribed into many different rna Feingold, ph.d., the program direc- portion of our dna has turned up fragments of varying lengths such that project has identified new regulatory tor for encode at nhgri, believes some surprises. each gene is represented, on average, regions—portions of the genome that there’s good reason to be optimistic. For one thing, the genome hosts a by more than five transcripts that do not encode proteins but instead, “The pilot project was a success,” lot more activity than anyone expect- share overlapping sequences. control when, where and how much says Feingold, who earned one of the ed. For over four decades, the canoni- “That’s a lot more than we genes are expressed. A slew of recent first ph.d. degrees from the School cal view has been that the important thought there would be,” says Snyder, studies have linked complex diseases of Medicine’s Department of Genetics bits of our dna—the readily deci- adding that it’s unclear what all these with variations in npc regions of the (then Human Genetics) in 1986. “It pherable genes making up 1.5 percent extra transcripts are for. human genome that could have regu- shows we can do this.” of the genome—get converted into Even more perplexing is the preva- latory functions. And because cheaper, faster tech- rna via a process called transcrip- lence of rna molecules transcribed In May, for example, two indepen- nologies keep popping up, Feingold tion. rna, in turn, instructs the cell to entirely from gene-free portions of the dent groups linked heart disease with believes it won’t be prohibitively make proteins, the molecular mov- genome. Non-protein-coding (npc) dna variations in npc portions of expensive or time-consuming to do. ers and shakers that do all the heavy rna transcripts were previously chromosome 9, and in April, a diabe- nih has set aside $100 million to fund lifting in the cell. Scientists have long known to exist, but the encode proj- tes-linked variation was found in the the scaled-up project for the next four assumed that, in general, each gene is ect identified many new ones. Again, same npc region, along with six other years. This might not be enough to transcribed into one rna fragment their purpose is unknown. variations found elsewhere in the fully analyze the whole genome, and that the gene-free portions of our As intriguing as these findings are, genome. Might some of these varia- Feingold concedes, but “we’ll get a dna—a whopping 98.5 percent of the Snyder is even more excited that the tions in npc dna promote disease good way there.”  www.medicineatyale.org cyan mag yelo black MAC Foundation supports Yale research “of practical benefit”

Two School of Medicine researchers on driving safety. “This will be the in Connecticut, particularly African- received 2006 Investigator Awards first time that driving impairment Americans. from the Patrick and Catherine during seizures will be directly mea- The foundation launched the Weldon Donaghue Medical Research sured,” says Blumenfeld, who hopes to Donaghue Investigator program in Foundation, a West Hartford, Conn.- design improved treatments to 1998 to support scientists at Connecti- based philanthropic organization preserve consciousness and prevent cut academic institutions whose work devoted to supporting biomedical car accidents among individuals promises “a direct, near-term impact research “of practical benefit to hu- with epilepsy. on improving public health, clinical man life.” Becca Levy, ph.d., associate pro- practice or community health inter- Hal Blumenfeld, m.d., ph.d., fessor of epidemiology and psychol- Hal Blumenfeld Becca Levy ventions.” The program, now in its associate professor of neurology, ogy, studies how psychological factors, final year, provides five-year, $600,000 neurobiology and neurosurgery, will particularly how older individuals ized controlled trial to test whether awards to investigators. apply his award to a study of the ef- perceive aging, affect health in old age. healthy behaviors can be promoted by In announcing the 2006 awards, fects of epileptic seizures on driving. Her research demonstrated for the positive beliefs about aging in older Raymond S. Andrews Jr., co-trustee of While patients with epilepsy operate first time that positive age stereotypes individuals. the Donaghue Foundation with Bank virtual-reality driving simulators, Blu- can improve the physical and cogni- “It is exciting to have the opportu- of America, said, “We are pleased that menfeld will use neuroimaging and tive functioning of older individuals nity to build on our findings and ap- Donaghue can provide the type of electroencephalography to determine and that positive self-perceptions ply them to health promotion,” Levy support to talented researchers that which brain regions are involved in of age are associated with increased says, adding that the interventions will allow them to pursue innovative epileptic seizures and the effects of longevity. With her Investigator she is studying are likely to benefit and important answers to significant seizure-induced loss of consciousness Award, Levy will conduct a random- high-risk groups of older individuals health problems.”

Rickets from page 5

are using this new knowledge to em- closely resembles xlh. Most strik- of orthopaedics and rehabilitation. if successful, Phase 1 clinical trials. In bark on an ambitious, multipronged ingly, the phex protein, fgf23 and Carpenter and Insogna will lead two addition to the research projects, the scientific attack on xlh, the most dmp1 have been found to be most clinical studies: one will determine yc-xlh has co-sponsored a Bone common inherited form of rickets. abundantly expressed in the same what biochemical markers best Seminar Series with the nih-spon- “Over the past 10 years, the science specialized bone cell, the osteocyte. predict the severity of xlh cases; a sored Yale Core Center for Muscu- really opened up and revealed an en- Carpenter believes that phex (an second will focus on the role of para- loskeletal Disorders, and will soon tirely novel mechanism of phosphate enzyme), dmp1 and fgf23 must all thyroid hormone excess in the disease, be launching a pilot and feasibility regulation,” Carpenter says. In 1995, work in the same pathway that is and will apply a specific therapy to program for further work in this the mutated gene that causes xlh involved in xlh. “This is the most correct this complication of xlh. related field. was identified asphex ; this discovery convincing evidence to date,” Carpen- Marie B. Demay, m.d., associate pro- To complement his work on xlh, has allowed scientists to create mouse ter says, “for an intimate connection fessor of medicine at Massachusetts Carpenter continues to study and models of the disease that exhibit a between skeletal biology and systemic General Hospital in Boston, will lead treat nutritional rickets in inner-city pattern of phosphate depletion, bone mineral balance in the body.” a project exploring her recent finding New Haven children with the help of deformation and dental abnormali- The standard treatments for xlh that phosphate regulates cell death in a 3-year, $844,000 grant he received in ties similar to those seen in human are calcium and phosphate supple- cartilage cells. Finally, Joseph Schless- 2005 from the Gerber Foundation. patients. ments, but the levels of these miner- inger, ph.d., the William H. Prusoff “The newly discovered mecha- It was subsequently discovered als must be carefully monitored to Professor and chair of Pharmacology nisms by which our bodies regulate that a protein known as fibroblast avoid serious side-effects. Carpenter (see related story, page 3) will join phosphate are very exciting, and have growth factor 23 (fgf23) plays a says that the cort grant will allow Veraragavan P. Eswarakumar, ph.d., broad implications in human biol- crucial role in autosomal dominant him and his colleagues to advance newly appointed assistant professor ogy,” says Carpenter. “We have learned hypophosphatemic rickets (adhr), a more precise and effective molecular of orthopaedics and rehabilitation, to so much from the patients who have rare inherited form of the disease that therapies. identify and characterize the cell- contended with so many long-term closely resembles xlh. More recently, The three main lines of inquiry surface receptor for fgf23. Based on consequences of xlh that it is only yet another protein, dmp1, has been that comprise the cort are be- the fgf23 studies, members of the fitting that we may soon be able to ap- shown to be central to a third form of ing pursued with the support of a yc-xlh will develop small molecules ply these discoveries to new therapies inherited rickets (autosomal recessive Research Core facility directed by to inhibit activation of the receptor that should significantly improve their hypophosphatemic rickets) that also Caren M. Gundberg, ph.d., professor and test them in preclinical trials, and, quality of life.” Grants and contracts awarded to Yale School of Medicine November/December 2006

Alzheimer’s Disease, 1 year, $90,000 • Anthony Friedland, Institute for Clinical Research Inc., $922,312 • Aliza Leiser, The Ovarian Cancer Federal Van den Pol, nih, Hypocretin Neurons, 4 years, International Network for Strategic Initiatives in Research Fund, Inc., Clinical Implications Walter Boron, nih, Physiology of Electrogenetic $1,447,487 Global hiv Trials, 4.5 years, $513,621 • Bryan of the tlr-4/myd88 Pathway in Epithelial Hains, American Pain Society, Supraspinal Ovarian Cancer, 2 years, $75,000 • Yorgo Na/hco3 Cotransporters, 5 years, $1,900,958 Junjie Chen, nih, Study the Role of Chfr in Modulation of Pain after sci by Microglia, Modis, Roche Organ Transplantation Founda- Tumorigenesis, 4.5 years, $1,427,343 • Wonsun 1 year, $20,000 • Kevan Herold, Juvenile Diabe- tion, The Structural Basis of Innate Immune Han, nih, Regulation of Na,K-atpase Distribu- Non-Federal tes Research Foundation Int’l, Phase II Trial of Sensing and Signaling by Toll-Like Receptors, tion and Function by Arrestin and Spinophilin, Zane Andrews, Foundation for Research hokt3yl, 1 year, $82,537 • Fenghua Hu, Para- 3 years, $242,484 • Mary Schwab-Stone, Leon 2 years, $94,772 • Jonathan Kagan, nih, Cellu- Science & Technology, Molecular and Neuro- lyzed Veterans of America, Mechanisms of Lowenstein Foundation, Inc., Greenwich Needs lar and Molecular Aspects of Toll-Like Receptor anatomical Mechanisms of Ghrelin Signaling in Amino-Nogo Inhibition, 2 years, $100,000 Assessment, 1 year, $25,000 • Patrick Sung, Law- Signal Transduction, 1 year, $89,996 • Chun the Brain: Implications for Obesity, 1 year, Henry Huang, GlaxoSmithKline Research & rence Berkeley Nat’l Laboratories, Modulation Geun Lee, nih, Genetic Factors Controlling $58,464 • Aydin Arici, Serono, Inc. (U.S.A.), Development, Ltd., Evaluation of the pet of the Functionality of Homologous Recombina- 11 11 Effector Function of tgf-Beta in copd and The Role of akt Signaling Pathway in the Ligands [ C]gsk981352 and [ C]phno to tional Repair, 9 months, $120,649 • James Tsai, Fibrosis, 5 years, $2,066,770 • Daeyeol Lee, nih, Pathogenesis of Endometriosis, 2 years, $56,824 Image Dopamine D3 Receptor in Rhesus Synabridge Corporation, Instrument for Glau- Dynamics of Cortical Communication, 1.5 years, Xueying Chen, American Heart Assoc. (Heri- Monkey, 9 months, $210,495; GlaxoSmithKline coma Early Detection and Monitoring, 1.5 years, $262,321 • Michael Nitabach, nih, Calcium tage Affiliate), Computational Screening for Research & Development, Ltd., Development of $102,881 • Carol Weitzman, Robert Wood 11 18 Signaling in Circadian Clock Neurons, 4 months, Dosage-Sensitive Genes Involved in Cardiovascu- [ C]/[ F]afm for First-in-Human Trial of the Johnson Foundation, Identifying and Treating $386,500 • Harvey Risch, nih, Case-Control lar Diseases, 1 year, $18,334 • Robert Constable, Serotonin Transporter Ligand afm, 1 year, Maternal Depression in Underserved, Minority Study of Pancreas Cancer in Shanghai, China, , Inc., A Study to Investigate the Utility of $50,000 • Ivana Kawikova, Nat’l Alliance for Women in a Pediatric Primary Care Setting, 5 years, $3,596,491 • Bing Su, nih, Regulation Magnetic Resonance Endpoints for Defining Autism Research, Is Autoimmunity Involved in 2 years, $202,976 • Sandra Wolin, Ellison Medical and Function of mekk3 in Dendritic Cells, Liver Disease in Subjects with Chronic hcv, Pathogenesis of Autism? 2 years, $120,000 Foundation, Investigating the Role of Oxidative 1 year, $349,191; nih, Molecular Mechanisms of 1 year, $195,568 • Karen Dorsey, St. Luke’s- John Krystal, Nat’l Alliance for Research on rna Damage in Aging, 4 years, $991,688 • Yong mekk3, 1.5 years, $143,759 • Patrick Sung, nih, Roosevelt Institute for Health Sciences, Meta- Schizophrenia and Depression, gabra2 Mod- Xiong, Richard & Susan Smith Family Founda- Molecular Basis of brca2-Mediated dna bolic Effects of Differential Organ Growth Rates, ulation of nmda Receptor Deficit-Related pfc tion, Mechanisms of hiv Suppression by Human Repair and Cancer Avoidance, 5 years, $1,841,689 6 months, $151,411 • Marie Egan, Cystic Fibro- Dysfunction, 1 year, $100,000 • Daeyeol Lee, Antiviral Protein apobec3 and hiv’s Counter- Terrence Town, nih, Blocking tgf-Beta sis Foundation, Cystic Fibrosis Clinical Research University of Rochester, Neural Interactions measures, 2 years, $200,000 Immune Signaling as a Therapeutic Target for Facilitation Awards, 1 year, $64,800 • Gerald Among Multiple Motor Structures, 3.5 years,

 Medicine@Yale July/August 2007 cyan mag yelo black 2602 MAC

Awards & honors Diabetes experts win top scientific honors

Richard P. Lifton, m.d., ph.d., Yale researchers lauded for chair and Sterling research, development of Professor of Genetics and pro- innovative treatments fessor of medicine and molecular Two School of Medicine scientists biophysics and have received high honors for their biochemistry, has received the Alfred Newton Richards contributions to diabetes research Award from the International Society and treatment. Robert S. Sherwin, of Nephrology. This award, the highest m.d., the c.n.h. Long Professor of (Left) At the annual meeting of the American Diabetes Association (ada), scientific honor of the society, cited Medicine and director of the Yale Robert Sherwin receives the Banting Medal from Richard Rubin, the ADA’s Lifton’s pioneering contributions to Center for Clinical Investigation, is immediate past-president for health care and education. (Right) Gerald understanding the molecular and Shulman (center) celebrates his election to the National Academy of Sciences genetic basis for renal and cardiovas- the winner of the 2007 Banting Medal with colleagues Roland Baron (left) and Steven Hebert. cular disease. for Scientific Achievement Award from the American Diabetes Associa- with the award in June at the ada’s uses magnetic resonance spectroscopy Bernard Lytton, tion (ada), the association’s highest annual meeting in Chicago, Larry C. (mrs) to study insulin resistance and m.b.b.s., f.r.c.s., honor for diabetes researchers. Gerald the metabolic roles of the liver and Donald Guthrie Deeb, m.d., the association’s presi- Professor Emeri- I. Shulman, m.d., ph.d., professor of dent, lauded Sherwin for his research muscle in type 2 diabetes. tus of Surgery, is medicine and of cellular and mo- and his prominence in the diabetes mrs is a noninvasive procedure president of the lecular physiology, was elected to the field. “His direct contributions to the based on the same principles as mag- American Asso- National Academy of Sciences (nas), development of insulin pump therapy netic resonance imaging that allows ciation of Genito- one of the highest honors in Ameri- researchers to make precise, repeated urinary Surgeons and the landmark Diabetes Control (aagus). The aagus is a profes- can science and engineering. and Complications Trial have led to chemical profiles of regions of tissue sional association of academic urolo- Sherwin’s recent work has focused major improvements in the care of as small as three cubic centimeters. gists from around the world. Lytton, on how the brain senses blood glucose patients with diabetes and his leader- By comparing profiles made during who joined the faculty of the School levels and activates defenses against ship in this area of research should be a brief time span, it is possible to cal- of Medicine in 1962, performed the hypoglycemia. This is an important culate the rate of metabolism in that first kidney transplant in Connecticut applauded,” said Deeb. in 1967. clinical issue because this critical sys- Sherwin also helped organize region of tissue. tem becomes impaired after intensive and co-direct the seminal work of Recent results published by Shul- Cindy R. Miller, insulin treatment of diabetes, which the Kroc Collaborative Study Group, man’s lab show that altered metabo- m.d., associate limits our capacity to prevent the which showed that long-term studies lism in mitochondria—the “power professor of diag- long-term complications of the dis- plants” of cells—in muscle may be nostic radiology of the role of glucose in diabetes com- and co-section ease. These studies are the outgrowth plications are possible. responsible for insulin resistance. This chief of pediatric of pioneering work by Sherwin and Sherwin has served as president work may one day lead to the identi- imaging, received Professor of Pediatrics William V. of the ada, Chairman of the Medical fication of genes that make individu- the Jack O. Haller Tamborlane, m.d., on a portable Science Advisory Board of the Juve- als more prone to diabetes, as well as Award for Excel- pump that continuously delivers treatments for insulin resistance. lence in Teaching from the Society for nile Diabetes Research Foundation Pediatric Radiology at the society’s insulin to treat diabetes. In addition, and as a member of the Food and Shulman also investigates the ben- annual meeting in April. Miller, whose Sherwin’s laboratory has developed a Drug Administration’s Endocrino- efits of exercise in managing diabetes, research interests include the rela- mouse model of type 1 diabetes that logic and Metabolic Drugs Advisory using mrs and other noninvasive tionship between imaging findings shares features of the human immune Committee. He has published over techniques to measure fat metabolism and clinical outcomes in premature system; using this model, Sherwin and and fatigue during aerobic exercise. infants, was honored for her commit- 300 articles in peer-reviewed journals. ment to mentoring medical students, colleagues have identified a new target For his work as a clinical scientist, Shulman has received numerous residents and fellows in pediatrics and of the autoimmune response that Sherwin received the Novartis Award awards for his research, including radiology. could lead to a vaccine to prevent type for Long-Standing Achievement in an Outstanding Investigator Award 1 diabetes. Diabetes. He is the recipient of two from the American Federation for Clarence T. The Banting Medal is named for Clinical Research, the Outstanding Sasaki, m.d., merit Awards from the National Charles W. Ohse Sir Frederick G. Banting, m.d., a Institute of Diabetes and Digestive Scientific Achievement Award and a Professor of Canadian physician and scientist who and Kidney Diseases. Distinguished Clinical Scientist Award Surgery and chief shared the 1923 Nobel Prize in physi- Shulman, a Howard Hughes from the ada. Shulman was elected of otolaryngology, ology or medicine as a co-discoverer Medical Institute investigator, is a to the nas’s Institute of Medicine in is the president of insulin. In presenting Sherwin December 2005. of the American preeminent diabetes researcher who Broncho- Esophagological Association (abea). abea is a society of physicians who Obstetrics/gynecology chair is honored as leader and writer convene each spring to present origi- nal research in otolaryngology. Sasaki, who received his m.d. from the It was an eventful spring for Charles obstetrics, gynecol- numerous administrative committees School of Medicine in 1966 and now J. Lockwood, m.d., the Anita O’Keefe ogy and reproduc- for the School of Medicine, Yale-New specializes in head and neck surgeries, Young Professor of Women’s Health tive sciences, who Haven Hospital and Yale University, began his term in April. and chair of the Department of Ob- will serve as pro- including the Dean’s Advisory Board, stetrics, Gynecology and Reproductive gram director for the the Comprehensive Cancer Center Warren D. Shlom- chik, m.d., asso- Sciences. Lockwood was named presi- meeting. Lockwood Steering Committee, the Executive ciate professor dent of the Society for Gynecological previously served as Committee of the Hospital Medical of medicine and Investigation (sgi) at their annual secretary treasurer Board and the Provost’s Budget Com- immunobiology, meeting in March, and he received Charles Lockwood for the society. mittee. He has been a regular member has received a his second Jesse H. Neal National Lockwood received his writ- and recently served as acting chair Clinical Scientist Award in Trans- Business Journalism Award from ing award from abm for his recent of the U.S. Food and Drug Adminis- lational Research American Business Media (abm) for editorials in Contemporary OB/GYN, tration’s Reproductive Health Drugs by the Burroughs Wellcome Fund. opinion pieces he has written as edi- including articles on how the Internet Advisory Committee. The $750,000 award supports physi- tor-in-chief of Contemporary OB/GYN has affected obstetrics and gynecology Lockwood’s laboratory research, cian-scientists who are dedicated to magazine. practices, the politics of emergency supported by three nih grants, mentoring trainees and to transla- tional research, the two-way transfer With approximately 1,200 basic contraception and the effectiveness of focuses on the molecular mechanisms between laboratory research and scientists and clinical researchers as prenatal care in at-risk populations. of menstruation, contraceptive-as- patient treatment. Shlomchik studies members, the sgi is the world’s lead- Since Lockwood became chair sociated uterine bleeding, preterm immune system responses to alloge- ing scientific organization in repro- of Yale’s Department of Obstetrics, deliveries and the pathogenesis of neic hematopoietic stem cells, such ductive sciences and obstetrics and Gynecology and Reproductive Sci- many adverse pregnancy outcomes. In as those used in bone-marrow trans- plants for leukemia. gynecology. As president, Lockwood ences in 2002, the department has addition, he maintains a busy faculty will preside over the 2008 annual doubled both its National Institutes practice in high-risk obstetrics. He has meeting in San Diego along with his of Health (nih) grant dollars and its been cited annually as a “Best Doctor” School of Medicine colleague Hugh clinical revenue. In addition to his du- by New York magazine and the Castle S. Taylor, m.d., associate professor of ties as chair, Lockwood also serves on and Connolly Survey since 1995. 8 www.medicineatyale.org