Medicine@Ya le

Advancing Biomedical Science, Education and Health Care Volume 1, Issue 2 August/September 2005 New look at how resistant bugs dodge drugs Yale biologists have opened a new Many widely used antibiotics mined the atomic-level structure of front in the war on antibiotic- work by latching onto and inhibiting five common antibiotics when the resistant bacteria by creating the first ribosomes, the protein factories drugs were bound to the ribosomes high-resolution pictures that show present in all cells. Using X-ray crys- of sensitive or resistant bacteria. how some resistant bacterial strains, tallography, Thomas A. Steitz, .., Although the antibiotics used in which threaten to undo years of Sterling Professor of Molecular the study have quite different chemi- progress against infectious disease, Biophysics and Biochemistry and a cal structures, Steitz and Moore thwart commonly used antibiotics. Howard Hughes Medical Institute found that they all bind to the same The new research, published in investigator, and Peter B. Moore, site on the ribosome’s large subunit In the ribosome of a resistant bacterium the April  issue of Cell, provides .., Sterling Professor of and that resistance to all of them is (lower left), a “bulge” (red area at center) scientists with a fresh battle plan for Chemistry and professor of molecular generated by the same change in just keeps the antibiotic erythromycin (upper right) from binding tightly. creating new antimicrobial drugs. biophysics and biochemistry, deter- Ribosome, page 8

YALE PROJECTS FOR GLOBAL HEALTH RECEIVE MAJOR FUNDING Using laser light, team guides flies by remote control Researchers at the School of Medicine Richard Flavell will have created a high-tech puppet show, spearhead a new only their marionettes are alive and approach to vaccine development with a have no strings attached. With the $17 million grant from help of some genetic tweaking, the the Grand Challenges in team got fruit flies to walk, jump and Global Health initiative, fly on command—simply by flashing which is supported by a light at them. the Bill and Melinda Gates Foundation, the Over centuries, to better under- Wellcome Trust and the stand the brain’s normal functions Canadian Institutes of and the roots of disease, scientists Health Research and have devised many methods of managed by the manipulating animal behavior, but Foundation of the National Institutes they have had to rely on invasive tech- of Health. Flies, page 7 Mouse breakthrough will speed vaccines Fund will honor mentor, aid students All progress in biomedicine is made been subjected to over evolutionary on the horns of a dilemma. The Foiling malaria mosquitoes, p. 6 time, not the same set of pathogens This spring, when Applera Corp. of testing of drugs or other therapies that infect humans. And, as its Foster City, Calif., asked members of in humans before they are shown gap in knowledge, and only a small name implies, the immune system its board of directors to suggest likely to be safe and therapeutically fraction of the drugs that enter isn’t a unitary organ like the liver, worthy recipients for gifts from the promising in preclinical studies is clinical testing are eventually but a multifaceted mechanism dis- corporation, Carolyn W. Slayman, prohibited by ethical considera- approved for use in medicine. tributed throughout the body, .., the medical school’s deputy tions. But the tools available for This state of affairs has pre- which is difficult to emulate faith- dean for academic and scientific preclinical work—laboratory sented particular challenges in fully in a petri dish. affairs, suggested a grant that would animals or isolated cells in a dish— immunology research, says Richard “You don’t really want to be do double duty to promote her ideals are no substitute for testing in the A. Flavell, .., chair and Sterling studying mouse cells; you want to in biomedical education. living human body. Professor of Immunobiology. Mice, study human cells, and ultimately Slayman, a director of Applera— Bringing a potential cure from the most commonly used research you study humans, in clinical the parent company of Applied laboratory science to human clini- animal, have immune systems that trials,” says Flavell, who is also a Biosystems, a manufacturer of scien- cal trials often requires an unset- are tailored to deal with the bacte- Howard Hughes Medical Institute tific equipment, and Celera, which tling leap across an unavoidable ria and viruses that the species has Flavell, page 6 played a major role in sequencing the Fund, page 6

Non-Profit Org. Inside this issue Medicine@Yale U. S. Postage Lifelines Strength in numbers P.O.Box  PAID Arthur Horwich, seeking what’s Adding up proteins brings power New Haven, CT  New Haven, CT never been seen, p. 2 to ovarian cancer test, p. 5 www.medicineatyale.org Permit No.  In praise of talented teachers A demand for supplies Faculty are feted at Medical equipment reaches Commencement, p. 2 the needy,p.5 Tracking down autism Also A hunt for childhood disorder’s Advances, pp. 3, 5; Out & About,p.4; first traces, p. 3 Grants, p. 7; Awards, p. 8

Want to find out more about medicine at Yale? E-mail us at [email protected] or phone (203) 785-5824. Notable teachers Form leads receive high honors to function at Commencement At the medical school’s Commence- Solving the puzzles of ment ceremony on Harkness Lawn in protein folding may shed May, the Class of  enjoyed their new light on Alzheimer’s day in the sun, basking in the admira- tion of family and It’s true that biologist Arthur L. friends. But faculty, Horwich, m.d., received last year’s too, were honored for Gairdner International Award for their many contribu- having “revolutionized our under- tions to education. standing about basic cellular func- For the first time, tions,” but to hear him talk, he’s not the Bohmfalk Prize Peter Aronson much different for teaching basic sci- from the twenty- Lifelines ences was awarded to something post- a husband-and- doctoral re- Arthur L. wife team, Marie- searchers who Horwich Arthur Horwich (third from right) in his element—amongst the graduate students, postdoc- Louise Landry, .., staff his lab. toral fellows and research scientists with whom he shares the lab bench. “I just have never matured beyond professor of labora- postdoc,” says Horwich, the Eugene Christian B. Anfinsen, ph.d., who P. Lifton, m.d., ph.d., an hhmi tory medicine, and Higgins Professor of Genetics, profes- showed in the early 1960s that the investigator who is chair and Peter S. Aronson, Marie-Louise Landry sor of pediatrics and a Howard Hughes sequence of amino acids in a nascent Sterling Professor of Genetics at .., the ...Long Medical Institute (hhmi) investigator. protein contains all the information it the medical school. Professor of Medicine and professor “I still work at the bench every day. I needs to fold from a chain into the Colleagues are amazed that, at of cellular and molecular physiology. still like to do my own experiments. I three-dimensional sheets and helices 54, Horwich still enjoys the rigors of The Bohmfalk Prize for teaching like to be able to live with and suffer of a functioning protein. running experiments. “He seems to clinical science went to Michael K. through the problems of understand- But in 1987, Horwich and col- have retained the enthusiasm for O’Brien, .., .., assistant clini- ing how things work side by side with leagues discovered that sometimes science that people who are more my own people, and I always have one proteins need help from other special- senior seem to lose—the day-to-day cal professor of surgery. or two things for myself that I consider ized proteins, aptly known as “chaper- excitement,” says Tony Hunter, ph.d., a Sharon K. Inouye, .., ..., my own laboratory struggle.” onins,” which serve as intracellular cell biologist at the Salk Institute and a professor of medicine, received the In his first-floor lab at the Boyer protein-folding machines. Horwich fellow Gairdner winner who was one Leonard Tow Humanism in Medicine Center for Molecular Medicine, was impressed to discover that these of Horwich’s early mentors. Award, while Catherine Chiles, .., Horwich has helped to solve, bit by bit, molecular chaperones will try up to 20 In his spare time, Horwich enjoys associate clinical professor of psychia- one aspect of what has long been times to properly fold an intractable fly-fishing, tennis and backpacking. try, won the Leah M. Lowenstein known as “the protein-folding protein. In terms of the energy the cell But after a few days on the river or in Prize, for excellence in the promotion problem,” the question of how newly must expend, Horwich notes,“it’s a the mountains, he’s eager to get back of egalitarian medical education. The made proteins transform from long very expensive process,” but misfold- to the Boyer Center. Each day in the first annual Alvin R. Feinstein Award chains of amino acids into three- ing is costly, too: misfolded proteins lab holds out the chance, however for outstanding clinical skills was dimensional structures. This folding are linked to hundreds of devastating small, he says,“to see something that’s . step is essential, because the shapes of disorders, including Alzheimer’s, not been seen before. There’s no sub- awarded to Ronald R. Salem, ., folded proteins determine their func- Parkinson’s and mad cow disease. stitute for it.” associate professor of surgery. tions; for proteins, loosely speaking, “This work is as basic to biology as Robert D. Auerbach, .., lec- anatomy is destiny. understanding the nature of genes turer in obstetrics, gynecology and Lifelines profiles the people who carry out the sci- Horwich’s work has built upon and how genes are expressed and entific, educational and clinical missions of the Yale reproductive sciences, was awarded that of Nobel laureate and biochemist translated into proteins,” says Richard School of Medicine. the Francis Gilman Blake Award for outstanding teaching. Public health students chose Elizabeth H. Bradley, ..., .., associate professor of public health, Student explorations in the world of research for the Award for Excellence in For Doris Duke fellows pursue their own interests. A thesis workers on a sugar plantation in Teaching, the third in her nine-year and classmates, research based on original research has been Tanzania. Helena Hansen, who com- career at Yale. a requirement for graduation since pleted the .. ⁄.. program in event celebrates discovery . Yale is the only medical school May, studied faith-based substance Medicine@Ya le in the United States with this long- abuse treatment in a Pentecostal com- Peter Farley, Managing Editor As he delivered the th annual Farr standing tradition. munity in Puerto Rico. Contributors: Lakshmi Bangalore, Douglas Barnes, John Lecture at Student Research Day in Five prize-winning students gave Eight students won fellowships Curtis, John Dillon, Michael Fitzsousa, Renee Gaudette, May, Arthur L. Horwich, .., oral presentations, and  took part in from the Doris Duke Clinical Andrea Gendrachi, Maureen Grieco, Jane Hadjimichael, Lauragene Lyons, Jill Max, Pat McCaffrey, described his own path to a career in this year’s poster session. Research Fellowship Program for Christopher Pates, Cathy Shufro, Marc Wortman research. He trained as a pediatrician, Among them was second-year Medical Students, a national program Photographs and Illustrations: Aaron Berger, Isabel but the lure of the laboratory ulti- student Mary Dombrowski, who started in the fall of  by the Doris Chenoweth, John Curtis, Terry Dagradi, Jerry Domian, Hannah Fairfield, Peter Moore, Rockefeller Archive mately proved too strong to resist. examined whether transplants of Duke Charitable Foundation (), Center, Harold Shapiro, Hugh Sturrock/The Wellcome Still, he found a balance. “Research olfactory ensheathing cells can regen- with Yale as one of  participating Trust, Elaine Ubina, Paul Webster/House Ear Institute, and the bedside,” he said, “are inextri- erate myelin. She chose the topic universities. The yearlong program S. Mark Williams, Sandra Wolin Design: Tom Strong, Amanda Damour/Strong Cohen cably linked.” Horwich, a geneticist because her father has multiple scle- starts in July with three classroom whose work has shown how proteins rosis. In her experiments with rats she courses before students embark on Medicine@Yale is published six times each year by Yale Lifelines Medicine Publications, P.O. Box , New Haven, CT fold (see above), still consults found that the cells did encourage their own research projects. -. Editorial offices are located at  Church on clinical cases. myelin growth. “It has stimulated my According to John N. Forrest Jr., Street South, Suite , New Haven. “You cannot predict exactly what interest in neurology as a career .., professor of medicine and Telephone: .. Fax: .. E-mail: [email protected] you will be doing in some balance of choice,” she said. director of student research, there Website: medicineatyale.org research and clinical medicine,” said Fourth-year student Hardean must be a clinical element to the If you have a change of address or do not wish to receive Horwich. “Make sure it is a balance E. Achneck found the bright side to Doris Duke-funded projects. future issues of Medicine@Yale, please write to us at that really causes you to have fun.” a devastating disease. Ascending “Someone in the research group P.O. Box , New Haven, CT - Student Research Day is an aortic aneurysms are associated touches the patient,” he said. “It can’t or via e-mail at [email protected]. annual celebration of the Yale System with a decrease in systemic athero- be a mouse model of diabetes.” Postal permit held by Yale University, 155 Whitney Avenue, New Haven, CT  of medical education, established in sclerosis. “If we find out what the Yale received an initial grant of the  by then-Dean Milton C. genes are, we may find the mecha- $, in  from , and its Yale School of Medicine Robert J. Alpern, .., Dean Winternitz, .. nism of this and, eventually, treat participation in the program was Ensign Professor of Medicine The first two years of medical atherosclerosis,” he said. extended this year with an additional Martha E. Schall Mary Hu Associate Vice President Director of Planning school at Yale are absent of grades, Alison H. Norris, an .. ⁄.. $, to carry it forward through for Development and and Communications and students are encouraged to student, studied the  risk for June . Director of Medical Development Michael Fitzsousa, Director of Publications  www.medicineatyale.org Advances A quest to detect earliest signs of autism Health and science news from Yale Child Study Center begins Taking a toll on major effort to track parasitic infections autism markers in infancy

In 1997, a blockbuster article by two Yale A recent issue of the journal Science scientists, the late Charles A. Janeway with the theme “What Don’t We (From left) Ami Jr., m.d., and Ruslan M. Medzhitov, Know?” was organized around  of Klin, Warren ph.d., professor of immunobiology, Jones and kicked off one of the hottest research the most pressing and difficult scien- Katarzyna areas in immunology. tific questions of our time. There, Chawarska have Janeway and Medzhitov alongside the grandiose, perennial set their sights reported that innate puzzlers like “What is the universe on detecting immune system mol- made of?” was a somewhat different, signs of autism as early as ecules called toll-like but no less vexing, sort of question: possible. receptors, or tlrs, give “What causes autism?” early warning of micro- More than  years after autism methods to consistently, accurately away from social engagement, Klin bial or viral invaders to was first identified, it remains among measure behavioral differences as reasoned, it might be possible to the acquired immune the most mysterious and intractable early as possible—a strategy Science provide interventions that steer them system, which marshals the body’s array of defenses against infection. psychological disorders. And the dis- cited as the key to successful interven- in a more normal direction. Scientists have since identified over ability at the heart of autism—pro- tion in autism—is now “one of the Klin’s audacious plan called for a a dozen types of tlrs, which work by found isolation that emerges in early hottest topics in the field.” study on a scale never seen before in detecting distinctive genetic signatures childhood—undermines social bonds In July , the Simons autism research: screening  or proteins found in bacteria and that are basic to human nature. Foundation, a philanthropic organi- infants—including  high-risk sib- viruses but not in the eukaryotic cells For autistic children and their zation headed by the husband-and- lings of older children with autism— that make up our bodies. families, the medical school’s Child wife team of Marilyn Hawrys Simons immediately after birth, every month But some pathogens—such as Study Center (), a landmark facil- and James H. Simons, announced a for the first six months, every three Toxoplasma gondii (above), the parasite ity for the study of child develop- major new initiative to fund autism months until  months of age and that causes toxoplasmosis—are also ment, is both a source of comfort in research, and they asked the ’s every six months after until age . eukaryotes, and a team at Yale and the their day-to-day struggles and a Ami J. Klin, .., Irving B. Harris The ambitious scope of Klin’s National Institutes of Health wondered whether tlrs could recognize them. beacon of hope for future scientific Associate Professor of Child proposal won over the foundation, In the June 10 issue of the journal breakthroughs. Most institutions Psychiatry, to propose a project that which awarded $. million to launch Science, the group reported that tlr11, devoted to autism focus either on would decisively advance the field. the project in the newly constructed discovered at Yale in mice just last year, research or on clinical care, but at the In studies of older children and Simons Laboratory of Social Neuro- detects a protein in T. gondii and trig- , cutting-edge research—in adults using special cameras and soft- science in Infancy. gers a robust immune response. genetics, diagnostic techniques, neu- ware that calculates precisely where a “In our field there are very few The global impact of parasitic roscience and pharmacology—is subject’s gaze is directed at any point things more expensive than a infections such as toxoplasmosis is tightly intertwined with the most in time, Klin and research scientist prospective study of the unfolding of tremendous. Sankar Ghosh, ph.d., pro- effective treatments in the clinic. Warren Jones had shown that autistic socialization in the first two years of fessor of immunobiology and a member Autism is often described as subjects pay far less attention to life,” Klin says. “But the social mind of the research team, says that while it arising “out of nowhere” during the socially relevant information—facial and brain develop at great speed, and is not yet clear whether humans have a functional version of tlr11,“insight second year of life. But according to expressions, for example—than do disruption of this process in autism obtained from these studies should Katarzyna Chawarska, .., assis- normal subjects when viewing human could happen at any stage. Sampling lead to development of novel strategies tant professor and director of the interactions on a screen. Klin sug- a child’s development only once or to combat these infections.” ’s autism screening program, gested that an adaptation of the tech- twice would greatly reduce the power many parents say in retrospect that nique could harmlessly track the eye of our methods.” Emboldened by the they noticed subtle anomalies in their movements of newborns and infants. foundation’s vote of confidence, he New kidney discovery child’s behavior well before full- By pinpointing the time during early says, “we might be able to find vul- may help heart blown symptoms first appeared. development when autistic children’s nerability to autism as early as the Chawarska says that developing patterns of gaze begin to reflect a shift first month of life.” The kidneys filter waste and excess water from the body and keep sodium and other electrolytes in balance, but they also secrete crucial protein hor- Yale visit brings hope to paralyzed veterans mones that regulate heart function and the production of red blood cells. In the highly specialized world of Eight million Americans suffer modern biomedical research, it is all (From left) Stephen from kidney impairment, some 500,000 too easy for scientists to lose them- of whom have end-stage renal disease Waxman describes a selves in the microscopic complexities new microscopy facility (esrd), for which dialysis is a lifesaving of the intracellular world—the genes, at the Center for treatment. Dialysis paired with dietary Neuroscience and restrictions can substitute for the molecules and signaling pathways that are the keys to understanding Regeneration Research, kidney’s filtering and electrolyte- located on the West balancing roles, but even with medica- disease and finding new treatments. Haven campus of the tions that replace important hormones But at least once a year, the scien- VA Connecticut esrd patients are prone to serious, tists at Yale’s Center for Neuroscience Healthcare System, to sometimes fatal, heart problems. and Regeneration Research receive a Delatorro McNeal and Gary V. Desir, m.d., professor of bracing reminder of what’s really at John Bollinger of medicine, and research scientist Paralyzed Veterans stake in their work on spinal-cord of America. Jianchao Xu, m.d., ph.d., suspected that repair when members of Paralyzed there might be additional kidney hor- Veterans of America () roll Neurology. “They have given us a injury, ‘You’re never going to walk mones that promote cardiac health. In through the center’s front door in sense of vision and mission which are again,’” says Bollinger, who was para- May, the scientists announced in The  Journal of Clinical Investigation that their wheelchairs. This year, , felt throughout this building.” lyzed while serving in the Navy. “Now they had discovered a new kidney which has supported the center since John Bollinger, ’s deputy people can actually talk about the protein, renalase, that lowers blood , brought its largest contingent executive director, says there was new cure. We feel very optimistic that pressure and improves heart function. ever, along with a check for $,. excitement in the air during this they’re going to make significant Xu says the discovery “has immedi- “ has been a wonderful year’s visit because the latest scientific advances at this center.” ate implications for therapy.” Desir partner in the battle against spinal- strategies, including stem cell Waxman agrees. “As someone agrees:“We are hopeful that renalase cord injury, but they give us more research, provide the clearest route who chooses words carefully, I didn’t will impact the treatment of chronic than money,” says Stephen G. he’s seen to successful therapies for feel I could use the word ‘cure’  kidney disease and change the way in Waxman, .., .., the center’s spinal-cord injury. years ago. Now I’m saying it’s on the which we treat patients with chest pain director and the Bridget Marie “Every one of us probably heard table. It’s not going to be easy, but it’s and heart attacks.” Flaherty Professor of Molecular a doctor say within hours after our an achievable goal.”

Medicine@Yale August/September 2005  Connecticut’s Out & about $ million stem cell program good news for Yale

In her Yale laboratory in , Diane S. Krause, .., .., surprised the scientific community with her discov- 12 ery that adult stem cells taken from the bone marrow of mice can produce liver, lung, intestine and skin cells. To her dismay, her studies and 1 similar findings have provided ammunition to opponents of embry- onic stem cell research, who have used her results to argue that research with stem cells derived from human embryos is unnecessary. Speaking in 3 January at a hearing of the Connecticut General Assembly, June : THE SURGEON AS Krause told legislators that “[closing] ARTIST, an exhibit of artwork by off this avenue of research based on Yale-affiliated surgeons, was the early promise of adult stem cells placed on display at the Harvey is to play the odds with people’s Cushing/John Hay Whitney lives.” She called upon the legislature Medical Library in conjunction 23 to support both adult and embryonic with the th Annual Spring 4 stem cell research in the state. Reunion of the Yale Surgical In May the General Assembly did April : LA CASSA Society (). 1. Harold Spear, .., and Suzanne Spear. just that as it approved a bill to MAGICA, the sixth 2. Ralph S. Greco, .., with his sculpture “Travertine Torso.” commit $ million to embryonic annual Yale Cancer 3. (From left) James M. Dowaliby II, ..; A. John Anlyan, stem cell research over  years. At a Center () gala, was ..;Greco;Bernard S. Siegel, ..; Paul Barcewicz, ..; ceremony in Farmington a few weeks held at the Country Eiji Yanagisawa, ..; Michael K. O’Brien, .., .. later, with Krause and medical school Club of Fairfield, Conn. 4. Enjoying a snack are Katie and Emily Malison, daughters of Dean Robert J. Alpern, .., looking The event, chaired by Eugenia M. Vining, .., clinical instructor in surgery and  on, Gov. M. Jodi Rell signed the bill Kathryn Anderson 4 board member, and Robert T. Malison, .., associate professor into law. The bill’s passage is expected Adams of Greenwich, of psychiatry. to boost this stem cell research at raised more than $, to support clinical trials at the center. both Yale and the University of Dr. Richard and Beth Sackler were vice-chairs and Louis Connecticut. The legislation estab- Chênevert, Paul Kelly, Nicholas Makes, and Joseph Perella lishes a two-step process in which served as corporate chairs. The Honorable Rudolph W. and experts in both science and ethics Judith S. Giuliani were honorary chairs for the evening, which review requests for funding. was hosted by  anchor and  board member Paula Zahn. Unlike adult stem cells, which 1. (From left) Dean Robert J. Alpern, .., Rudolph Giuliani, have shown a limited ability to  director Richard L. Edelson, .. 2. From left: Adams, develop into other cells, embryonic actress Blythe Danner. 3. Arlene and Mel Goldstein. 4. (From stem cells can generate virtually any left) Zahn, Carol Crapple, Lucy Day. type of cell in the body. Biologists believe they have the potential to help 1 treat diseases such as diabetes and Alzheimer’s and to repair the spine, June : At the second heart and other organs. DISCOVERY TO CURE This field of study has been GALA, Congresswoman limited in the United States by guide- Rosa DeLauro (D-CT) lines established by President Bush was a featured speaker. that restrict federal funding exclu- The event, held under a sively to specific embryonic stem cell 2 festively decorated tent at lines established prior to August , Yale’s Branford College, . Supporters of the research con- 1 netted $, for tend that many of those pre-existing cancer screening for lines have been tainted by cells from April : WOMEN OF women at high risk, the other animals, such as mice, and that VISION AWARDS were training of high school the limited number of lines hampers bestowed by Women’s students for careers in opportunities for study. Health Research at Yale biomedical research, and Krause is spearheading the effort () on renowned fem- 3 the translation of basic to establish a stem cell program at inist author and activist research in gynecological Yale, and is one of more than  sci- Gloria Steinem and oncology into practical 2 3 entists at the university doing stem Roslyn Milstein Meyer, treatments. In one of the cell-related work. Recruitment of a .., co-founder of evening’s highlights, it was senior leader for the Yale program Leadership, Education and announced that two new began this past winter with an inter- Athletics in Partnership endowments in the names national search and will likely be fol- () and New Haven’s of Debra Levin and lowed by the hiring of five to seven annual International 4 Marie Malouf had been new faculty members whose work is Festival of Arts and Ideas, established with funds focused solely on stem cell biology. at a celebration held at the contributed by family and friends. 1. (From left) Rosanne Malouf, Once established, the new 4 5 Omni Hotel. 1. (From left) gala chair, Levin, Marie Malouf. 2. Gala committee members program will likely have investigators Steinem, Meyer, Carolyn Christine and Edward Fleischli, ... 3. Thomas J. Rutherford, performing both adult and embry- Mazure, ..,  director. 2. Linda Koch Lorimer, .., vice .., .., associate professor of obstetrics, gynecology and onic stem cell research, with separate president and secretary of Yale University. 3. Chief Justice reproductive sciences 4. (From left) Peter E. Schwartz, .., John laboratories for any research using Margaret H. Marshall, .., of the Supreme Judicial Court of Slade Ely Professor of Obstetrics, Gynecology and Reproductive embryonic cell lines not approved for Massachusetts. 4. Lt. Gov. Kevin B. Sullivan. 5. William W. Sciences, Arlene Schwartz, DeLauro, Stanley Greenberg, presi- federal funding. Ginsburg, , Community Foundation for Greater New Haven. dent of Greenberg-Quinlan Research.

 www.medicineatyale.org Advances Ovarian cancer test exposes quiet killer Health and science news from Yale For women and their doctors, ovarian cancer is “the disease that whispers,” Greater than the sum of its parts A chink in malignant says Yale’s Gil Mor, .., .., asso- melanoma’s armor? ciate professor of obstetrics, gynecol- In developing a new blood test for ovarian cancer, Yale researchers ogy and reproductive sciences. In tested four different proteins, each of which showed some promise . . . Pathologists have an eagle eye for many cases, this deadly cancer grows POSITIVE CASES ACCURATELY IDENTIFIED silently, or sends out easily misread subtle abnormalities in tissue that may Leptin 48% signal disease, but even the best of signs such as indigestion or bloating. 60% them cannot discern aberrant protein If caught early, the disease has a  Osteopontin patterns within individual cells. percent cure rate, but for most Insulin-like growth factor-II 70% Such patterns are the hallmark of women the first sign of trouble comes Prolactin 89% many diseases, especially cancer, so when they are diagnosed with David L. Rimm, m.d., ph.d., and Robert advanced, largely incurable tumors. . . . but by statistically combining results from all four proteins, the L. Camp, m.d., Trying to hear and heed that first ph.d test reached an accuracy of 95 percent. ., of the whisper, Mor and colleagues have Department of developed a new test for the early All four proteins together 95 % Pathology, de- vised aqua detection of ovarian cancer. Based on Source: Gil Mor. (Automated the levels of four cancer-related pro- Quantitative teins in a sample of blood, the test Analysis), a tech- accurately and sensitively picks out ogy to measure each potential marker new test, it scored positive. “From  nique that combines sophisticated women with early-stage cancers. in blood samples from nearly  high-risk patients screened so far in mathematics and microscopy to reveal The promising advance came women, including newly diagnosed this manner, we’ve had  positives and precisely measure the expression from basic research in Mor’s labora- patients and healthy, age-matched who had all been shown to have of up to five proteins in tissue at once— tory, coupled with the work of Yale- controls. No one protein was found cancer in the pathology lab.” automatically (see photo). New Haven Hospital clinicians in the that could reliably distinguish Despite its potential, the test is In the July 7 issue of Nature, Rimm Discovery to Cure program for between women with and without not ready for prime time:  percent and collaborators reported that with ovarian cancer (see Out & About, cancer, but further analysis revealed a accuracy means that , out of the help of aqua they discovered that mitf, a protein involved in cell survival, page ). The program was initiated set of four protein hormones whose every , women tested would is “amplified”—abnormally copied two years ago to bring researchers combined profiles indicated with  obtain a false-positive result. For many times over—in malignant and clinicians together to accelerate percent accuracy which women had widespread use, the screen needs to melanoma cells. the application of basic research to ovarian cancer. achieve more than  percent accu- In a commentary on the paper, the diagnosis and treatment of The test is now being used exper- racy. Mor hopes to reach that bench- Glenn Merlino, ph.d., a researcher at women’s reproductive cancers. imentally in the Yale Early Detection mark by identifying additional the National Cancer Institute, writes “This detection system, which Program for Ovarian Cancer, where protein markers, and plans are in the that malignant melanoma cells appear could give a tremendous boost to it has delivered promising results works to screen up to , more to depend utterly on mitf amplification early diagnosis of ovarian cancer, under the direction of Thomas J. women in cooperation with the for their survival. The protein “could be started out as absolutely basic Rutherford, .., .., associate National Cancer Institute. a weak link in an otherwise unbreak- science,” says Peter E. Schwartz, .., professor of obstetrics, gynecology So far, Mor’s lab has been a well- able chain,” he notes, leading to new, targeted therapies for a deadly cancer the John Slade Ely Professor of and reproductive sciences, and spring of important clinical prospects that is notoriously difficult to treat. Obstetrics, Gynecology and Repro- Discovery to Cure’s clinical director. in ovarian cancer. A few years ago he ductive Sciences and executive direc- For example, one young high- uncovered phenoxodiol, a new com- tor of the program. “Within the risk patient who had been previously pound that is in Phase II clinical Patient to surgeon: framework of the Discovery to Cure treated for breast cancer elected to testing at Yale under a fast-track des- I hear a symphony initiative, we were able to move the have her ovaries removed because she ignation from the . Now Mor is test quickly into our early detection was concerned about the possibility working on a personalized medicine Operating rooms can be noisy, stressful program.” of ovarian cancer. Although her approach that uses tumor samples places. For decades, doctors and nurses Mor found the four proteins by a ovaries appeared to be normal and from patients and laboratory tests to have turned to recorded music to mask process of elimination, starting with she had no other signs of the disease, select the best course of chemothera- the din and soothe nerves, and anxious  cancer-related candidate marker pathologists who examined the tissue py for each individual woman. patients being prepared for surgery proteins. In collaboration with David after the surgery found a stage A “Whatever Gil can come up with have found solace in favorite melodies. C. Ward, .., then in Yale’s Depart- cancer, “the earliest stage you can rec- in his lab,” Schwartz says, “we are And there appear to be measurable medical benefits to ment of Genetics and now director of ognize,” says Mor. When blood that happy to move quickly into our music in the OR. the Nevada Cancer Center in Las had been drawn from the patient translational laboratory and then on Several studies Vegas, he used protein chip technol- before surgery was examined with the into the clinic.” have found that patients need less anes- thesia when From humble start at Yale, REMEDY thrives music is playing In , after several volunteer mis- hospitals around the United States. and vendors are advertised via e-mail during surgery. But sions to Latin America, anesthesiolo- From Yale alone, the  to  nonprofit humanitarian organ- m.d Zeev N. Kain, ., professor of anesthe- gist William H. Rosenblatt, .., program has donated more than  izations. It has also developed a siology, pediatrics and child psychiatry made an observation that was to have tons of medical supplies to hospitals catalog called the  Atlas, at the School of Medicine, wondered whether this phenomenon was due to far-reaching effects: many of the hos- overseas. “Each of these pieces of consisting of the  supplies most music’s aesthetic qualities or merely its pitals he visited were in dire need of material, whether it be a suture, a often recovered, which will help ability to drown out the racket in the medical supplies, while at Yale-New glove or a sponge, is going to wind up ensure that recipients are getting sup- operating room. Haven Hospital () many of in another part of the world and be plies they need. Kain and colleagues at Yale and the those same supplies were discarded useful,” says Rosenblatt. The program Meanwhile, the collecting, American University of Beirut designed without being used. has also saved the hospital over sorting, packing and shipping of a study in which patients undergoing Thus was born  $, in disposal costs since its surplus medical supplies has largely minor urological surgery who could (Recovered Medical Equipment for inception, at a cost of only about been taken over by students. In , control the dosage of a sedative—they the Developing World), a nonprofit $ per year for disinfecting and  ( at Yale Students had received spinal anesthesia but were committed to recovering surplus bagging the supplies. Association) was started by Jonathan awake—listened through headphones medical supplies and teaching others Today,  trains hospitals S. Cohen, -, a physician associate to either music or white noise gener- ated by a relaxation device. As reported how to do it. to organize their own programs and who is now a surgical resident at The this May in the journal Anesthesia and What started as a local program has helped  hospitals begin recov- Johns Hopkins Hospital. Between last Analgesia, the white noise blocked out at  to collect opened but ery activities. The organization pro- August and January,  volunteers the sounds of the operating room as unused surgical supplies—which have vides teaching packets free of charge, shipped , pounds of supplies effectively as music, but the patients never touched a patient but can’t be and with Yale’s Office of International from the New Haven area to eight who listened to music used significantly reprocessed due to liability con- Health, has developed a notification countries. Information about the less sedative. cerns—has grown into a grass-roots program called -mail, in which program is available on the Web at organization involving hundreds of medical supplies donated by hospitals www.remedyinc.org.

Medicine@Ya le August/September 2005  Fund Finding new perfumes to foil a femme fatale continued from page 1 The female mosquito Challenges initiative was seeking human genome—took advantage of that spreads malaria novel, practical solutions to the the company’s offer by earmarking world’s most massive public health their $, gift to endow a fund might be felled by smell problems. Zwiebel assembled a pro- that will support Yale’s Combined posal to design new repellents and Program in the Biological and With the notable exception of the traps that specifically target Anopheles Biomedical Sciences () and honor West Nile virus, the industrialized and to test them in field settings in the memory of her mentor and thesis world is blessedly free of mosquito- Africa—precisely the sort of “deliver- advisor, Edward L. Tatum, .. borne diseases. But according to the able technology” the initiative was Slayman met Tatum at World Health Organization (), encouraging. Rockefeller University, where she malaria causes over  million acute In the wide-ranging project, earned her doc- illnesses and kills at least a million Zwiebel, the principal investigator, torate under his people each year, mostly children in and Carlson will test hundreds of supervision in the developing countries. The  esti- chemical compounds using fruit flies , just after mates that an African child dies of genetically engineered with Anopheles he won the Nobel malaria every 30 seconds. “We don’t A female of the species Anopheles stephensi, odor receptors to see which elicit the Prize in physiol- think about it much in this country,” the insect that transmits malaria on the most robust response. Colleagues at ogy or medicine says John R. Carlson, .., the Indian subcontinent, seen in flight and full Wageningen University in the for pioneering Eugene Higgins Professor of of blood. Anopheles mosquitoes find their Netherlands will then assess whether work on genetic human hosts by following odors. Molecular, Cellular and Develop- the candidate chemicals actually alter Carolyn Slayman regulation of mental Biology, “but as a world health Anopheles. “After doing all this basic Anopheles behavior. Compounds that metabolism in problem this is just staggering.” research for many years at Yale,” he pass this test will be analyzed again in the cell. “For a very famous man—he Carlson, an expert on the sense says, “I thought we should see specially designed mosquito enclo- was at the height of his career—he of smell in insects, has thought about whether any of it could be useful in sures in Tanzania. Finally, the repel- nonetheless took extraordinary meas- malaria a great deal, and with the addressing real-world problems.” lents and attractants deemed effective ures to work closely with every help of a five- Carlson contacted Laurence J. will be deployed in villages in the student and every postdoc in his lab year, $. million Zwiebel, .., an associate professor Gambia, a nation in West Africa, to group,” recalls Slayman, Sterling grant offered by of biological sciences at Vanderbilt see whether they can reduce the inci- Professor of Genetics and professor of the Grand who studies mosquito olfaction, and dence of malaria. cellular and molecular physiology. Challenges in the two collaborated to identify the This multi-tiered approach was a Tatum did part of the research Global Health genes for Anopheles odor receptors in good fit with the goals of the Grand that led to the Nobel at Yale in the initiative to . Because fruit flies are far easier Challenges initiative, Carlson says. late  with his graduate student Vanderbilt to study in the lab than Anopheles, “They didn’t want just lab research in Joshua Lederberg. The two discerned University, he and Carlson’s lab devised a method to America. They actually wanted to how bacteria exchange and recom- John Carlson a team of scien- place Anopheles receptors in fruit fly develop real, practical solutions to bine genetic material, findings that tists on three con- antennae, and by  Carlson, in these problems, and for that we paved the way for gene sequencing tinents are launching an ambitious collaboration with graduate student needed real expertise in the field and genetic engineering. They shared and innovative plan of attack against Elissa Hallem, had pinpointed an in Africa.” the prize with another Tatum collab- this dreaded disease. antenna protein in the Anopheles Carlson hopes the findings from orator, George W. Beadle, .. In , researchers in Carlson’s female that specifically responds to a the new project will prove useful in Slayman and Ira Mellman, lab identified the genes that encode chemical compound in human sweat. curbing other mosquito-borne ill- .., chair and Sterling Professor of the exquisitely sensitive odor recep- “That was exciting,” Carlson says, nesses, such as yellow fever. “With Cell Biology, were the chief architects tors found in fruit fly antennae—the “because it suggested the possibility insect-borne diseases, the best way to of the  program. Founded in first such genetic mapping of any that we could then identify com- control the disease is often to control , the program has become a cor- insect olfactory system. The mosqui- pounds that either excited or blocked the insect,” he says. “We smell good to nerstone of graduate science educa- toes that spread malaria, females of those receptors, thereby inhibiting the the mosquitoes, so if we can under- tion at Yale, transforming the curricu- the genus Anopheles, use similar ability of the mosquitoes to find us. stand in molecular detail how the lum to reflect the increasingly inter- receptors to find their human hosts, You could sort of jam the system.” insects are attracted to us, we might disciplinary nature of biological and Carlson was eager to apply the The discovery came at an auspi- be able to devise new means of con- science. Knowing Tatum’s dedication techniques he had developed to cious time. In , the Grand trolling them.” to nurturing aspiring scientists, Slayman thought that a fund com- Flavell continued from page 1 memorating him should be linked to the program, and she hopes that the new Edward L. Tatum Fund will investigator. “But most of the studies genetic approaches in the mouse to because mice are normally not sus- support an outstanding  student needed are really invasive, and there- streamline the development of new ceptible to the virus. in the field of genetics. fore cannot safely be performed in vaccines, proposed that his team join But Flavell says that the tech- Ever the scientist, Slayman says people. There are enormous difficul- forces with Manz and with Tarry- nique will have any number of appli- she hopes the Applera gift will be ties making sure that what you do in town, N.Y.-based biotech company cations. “This system, once it’s up and “autocatalytic”—a term from chem- clinical trials is safe and isn’t going to Regeneron Pharmaceuticals to perfect running, could be used to study all istry for the mechanism by which the adversely affect the patient.” a mouse model of human immunity. kinds of things,” he says. “It will be a products of a reaction provide fuel But a remarkable advance in a In late June, Flavell received the big step forward.” for further reactions—and will Swiss laboratory may provide a long- happy news that the Grand Chal- Elizabeth E. Eynon, .., a inspire others to support the  sought bridge between the bench and lenges initiative had offered him a research scientist in Flavell’s lab, says program. The gift already shows signs the bedside for immunologists. In $ million grant to oversee the that the model could make clinical of self-replication: it will benefit from , Markus G. Manz, .., and his project. trials much more efficient. “The  a university policy that matches colleagues at the Institute for “It’s akin to a ‘Manhattan will require people to do just as many endowment gifts to the School of Research in Biomedicine managed to Project,’ to make this work like a true Phase I and Phase II trials as they do Medicine, which will double its create a rudimentary but functional human immune system, so you could now,” she says, “but the likelihood of impact. human immune system in mice by really do experimentation that is pre- failure at those stages would be injecting human umbilical-cord dictive of the human response,” reduced if we can show safety and blood containing stem cells and other Flavell says. “The present system efficacy beforehand.” progenitor cells into a mutant strain doesn’t work exactly like human Flavell and Eynon are gearing up of mice that are born without immunity, but we think we have an to hire a dozen new scientists to begin immune systems of their own. understanding of the deficiencies, and the mouse project in earnest, but the Manz’s paper appeared just as we’re going to make it work.” magnitude of the Grand Challenges the Grand Challenges in Global A mouse model of human grant, the largest foundation grant in Health initiative began accepting immunity would allow scientists to the history of the School of Medicine, grant proposals. Flavell, seeing the test many human vaccines in mice, is only slowly sinking in. vast potential of combining Manz’s including experimental  vaccines, “Our heads are still spinning,” Edward Tatum in his Rockefeller University technique with his own molecular which has heretofore been impossible Flavell says. laboratory in the late 1950s.

 www.medicineatyale.org Grants and contracts awarded to Yale School of Medicine, March/April  Federal George Aghajanian, NIH, Psychotogenic Drug  years, $, • Paul Noble, NIH, Regulation  years, $, • Elias Lolis, Robert Leet and Human Polycystic Diseases,  year, $, Action on Chemically Defined Neurons,  years, of Pulmonary Fibrosis by 3,  years, Clara Guthrie Patterson Trust, Identification of Zhaoxia Sun, Edward Mallinckrodt Jr. $, • Thomas Biederer, NIH, Mechanisms $,, • Lynne Regan, NIH, High- the Allosteric Sites of CXCR4,  year, $, • Foundation, Chemical Suppression of Polycystic of Syncam-Induced Synapse Formation,  years, Throughput Assays for Inhibitors of Protein- Stephen Malawista, G. Harold and Leila Y. Kidney Disease in Zebrafish,  year, $, $,, • Jonathan Bogan, NIH, Proteomic Protein Interactions,  years, $, • Mathers Charitable Foundation, Leukocytes and Flora Vaccarino, Tourette Syndrome Characterization of Insulin Signaling Targets, Jennifer Ruger, NIH, Economic Evaluation of Inflammation,  year, $, • David Morris, Association Inc., Inhibitory Interneurons in the  years, $, • Richard Bungiro, NIH, Addiction Services,  years, $, • Robert Leet and Clara Guthrie Patterson Trust, Cerebral Cortex of Patients with Tourette’s Mucosal Immune Responses in Hookworm Raymond Russell, NIH, Function and Pathogenesis of Fibrotic Lung Disease,  year, Syndrome,  year, $, • Li Wen, Juvenile Infection,  years, $, • Edward Chu, NIH, Regulation of Cardiac Uncoupling Proteins, $, • David Rimm, Breast Cancer Alliance Diabetes Research Foundation International, Molecular Regulation of Translational  years, $,, • Joseph Santos-Sacchi, Inc., Spectral-Spatial Imaging to Detect Tolerance Induction by Insulin Reactive and Regulation,  years, $, • Lauren Cohn, NIH, Membrane Properties of Cells Comprising Premalignancy in Breast Tissue Samples,  year, TGFß Producing T Cells,  years, $, NIH, T Cell Control of Airway Mucus the Outer Hair Cell System,  years, $,, $, • Craig Roy, Health Research Inc., Kevin White, Columbia University, Integrated Production,  years, $,, • Ralph Gerald Shadel, Department of the Army, Coxiella burnetii Type IV Effector Proteins, Approaches to Hox-Regulated  Elements, DiLeone, NIH, Investigating the Role of Leptin Nuclear-Mitochondrial Signals That Control  year, $, • Gerald Shadel, Robert Leet  year, $, • Graham Williams,Astra Signaling in the Ventral Tegmental Area,  years, Oxidative Stress Resistance and Longevity, and Clara Guthrie Patterson Trust, Genetic Zeneca, L.P., Characterization of the $, • Gail D’Onofrio, NIH, Enhancing  years, $, • Albert Shaw, NIH, Top3 Transformation of Mitochondria: Toward Mouse Neurobiological Consequences of Acute Alpha-7 Emergency Room Physician-Performed Alcohol Homologues in Lymphocyte Genome Stability Models and Human Gene Therapy for Treatment in the Nonhuman Primate: Interventions in the Emergency Department, and Aging,  years, $, • Dieter Soll, NIH, Mitochondrial Diseases and Aging,  year, Identification of the Potential for Improving  years, $,, • Durland Fish, Studies on Transfer RNA,  years, $,, • $, • Stefan Somlo, Mizutani Foundation Cognitive Function in Schizophrenia,  year, Department of Agriculture, Eco-Epidemiology Stefan Somlo, NIH, Genetics of Autosomal for Glycoscience, The Role of N-Glycosylation in $, of Emerging Arthropod-Borne Pathogens in the Dominant Polycystic Liver Disease,  years, Northeast,  year, $, • Gerald Friedland, $,, • Carlos Stocco, NIH, Regulation of NIH, New England Program for  Clinical Estradiol Production by Prostaglandin F2alpha, Trial—PROACT,  year, $, • Guadalupe  years, $, • Stephen Strittmatter, NIH, Garcia-Tsao, NIH, Cirrhosis and Its Molecular Determinants of Axonal Regeneration, Complications,  years, $, • Peter Glazer,  years, $,, • Peter Takizawa, NIH, NIH, Cisplatin Damage Response and Cell-to- Mechanism of mRNA Transport by Myo4p, Cell Communication,  years, $,, •  years, $,, • Sandra Wolin, NIH, RNA Ruth Halaban, NIH, Epigenetic Chromatin Quality Control and Environmental Stress, Changes as Melanoma Markers,  years,  years, $,, • Lawrence Young, , $, • Hatim Hassan, NIH, Mechanisms of Regulation of Glucose Transport in the Ischemic Regulation of Anion Exchanger ,  Heart,  years, $,, years, $, • Michael E. Hodsdon, NIH, Structural Basis of Prolactin Receptor Recognition,  years, $,, • Mark Non-Federal Horowitz, NIH, Regulation of Bone Remodeling Richard Bucala, Alliance for Lupus Research, by Megakaryocytes,  years, $,, • Macrophage Migration Inhibitory Factor Themis Kyriakides, NIH, MCP- and Inhibition in Systemic Lupus Erythematosus, Attenuation of the Foreign Body Response,   year, $, • Ronald Duman, Organon years, $,, • Linda Mayes, NIH, Inc., Influence of Organon #2448 and Organon Neurocognitive Development in Children Living #26576 on Neurogenesis in the Adult in Poverty,  years, $,, • David Hippocampus,  year, $, • Marie Egan, McCormick, NIH, Neurotransmitter Actions in Cystic Fibrosis Foundation, The Effects of Neocortex and Thalamus,  years, $,, • Curcumin Treatment on the Function of Delta Laura Ment, NIH, Multicenter Randomized F508 Cystic Fibrosis Transmembrane Indomethacin Intraventricular Hemorrhage Conductance Regulator ,  year,$, • In NIH-funded research reported in Cell in May, Sandra Wolin and Karin Reinisch of the Prevention Trial,  years, $,, • Pramod Alan Garen, Sidney Kimmel Cancer Center, Department of Cell Biology determined how the Ro protein, a major target of the immune Mistry, NIH, Patient-Oriented Research in Targeting Vessels in Tumors,  years, $, • system in patients with autoimmune diseases such as lupus, binds to rna. In normal cell Inherited Metabolic Liver Diseases,  years, Susan Kaech, Edward Mallinckrodt Jr. metabolism, Ro is thought to function in quality control of noncoding rnas, ensuring that 2+ $, • Michael Nathanson, NIH, Ca • Foundation, Identifying the Genes That Regulate misfolded and defective rnas are degraded. These misfolded rnas bind both on the outer Waves in Hepatocytes: Mechanisms and Effects, Formation of Memory CD8 T Cell Precursors, surface of Ro (green and purple strands) and in a hole in the protein (blue strand).

Flies continued from page 1 niques like stimulating nerves and nerve cells that control fruit flies’ dopamine pathologies in humans, muscles with implanted electrodes. escape movements. In rats, these Miesenböck says, adding that before The new Yale study marks the first channels activate cells by opening in these experiments, “very little was time an animal’s behavior has been the presence of adenosine triphos- known about what these neurons do.” shaped by remote control without phate (), but Miesenböck and “It’s a really cool technique,” says such invasive tactics. “We do not have Lima injected the flies with a “caged” Ronald L. Davis, .., a professor of to poke them with electrodes,” says form of  that only functions molecular and cellular biology at Gero A. Miesenböck, .., an associ- when exposed to light. Baylor College of Medicine, citing the ate professor of cell biology at the The tiny flies were placed into an study’s unique strengths as “the medical school, who led the study. arena the size of a dime, where they untethering of the animal, and using The research, which appeared in dawdled until Lima and Miesenböck light as the stimulus.” the April  issue of the journal Cell, flashed laser pulses at them, which The method is also extraordi- prompted a flurry of international “liberated” the caged  and caused narily precise: in one experiment, headlines that made comparisons to the flies to perform characteristic Miesenböck and Lima were able to video games and mind control. It escape responses. The flies behaved place rat ion channels in just two of  , even became fodder for Jay Leno’s on cue up to percent of the time. From the pages of Cell to The Tonight Show’s the cells that make up the fly monologues on The Tonight Show “There was all this hope that it would stage, Gero Miesenböck’s remote-controlled nervous system. And the procedure —twice. work,” Miesenböck says, “but I think flies have created a stir. allows scientists to selectively turn on But jokes aside, Miesenböck says the extent to which it did was a very parts of an intact nervous system. that the research is a new way to learn pleasant surprise.” fruit flies can live for a day or more These parts need not be next to each how nerve cells govern behavior, and Because escape behavior also without their heads, but they remain other, and their locations need not be that it will open new avenues to occurs when a fruit fly detects a shift motionless. However, when equipped known in advance. This creates enor- understanding neurological illnesses. from light to darkness that might with Miesenböck and Lima’s “photo- mous potential for discovering which “Initially, scientists are often passive signal danger—from a descending fly triggers,” the headless flies took flight groups of neurons control which observers,” Miesenböck says. “But at swatter, say—the researchers did the whenever the laser was turned on. aspects of behavior. some point, active control becomes same experiment on a strain of flies In addition to studying the Both Miesenböck and Davis say essential in order to establish causes in which the visual system was engi- escape circuit, Miesenböck and Lima that applying the technique to human and mechanisms.” neered to be insensitive to light, and placed their phototriggers in fruit fly illness is still far off, and for now, Using meticulous genetic tech- they got the same response. In neurons that produce dopamine, a Miesenböck is sticking to fruit flies. niques, Miesenböck and graduate another experiment that hints at the neurotransmitter involved in move- Next he plans to probe the neural student Susana Q. Lima, now a post- technique’s potential for restoring ment that has been implicated in activity around their courtship doctoral fellow at Cold Spring neural function, Miesenböck and Parkinson’s disease and addiction. behavior—essentially, he’ll be playing Harbor Laboratory on Long Island, Lima even got headless flies to When they activated the cells with Cupid. “It’s not just the sex act that inserted rat ion channels, microscopic perform the trick. Because of the light, the flies displayed “quite sur- interests us,” he says, but “it’ll get us pores that admit calcium into cells, in architecture of their nervous system, prising” behaviors reminiscent of on The Tonight Show again, I’m sure.”

Medicine@Ya le August/September 2005  New president of alumni body sees a bright future ahead Frank Lobo, .., has roots that run medical school,” his term July 1. He succeeds Donald Jocelyn S. Malkin, .., was deep at the School of Medicine. He he says. “Our new E. Moore, .., ..., and he says elected vice president of the associa- earned his medical degree here in dean [Robert he’ll pick up where Moore left off. tion. Malkin, a psychiatrist in private , and for many years served as a Alpern] really has “The plans are to carry on with practice in Maryland, has served on faculty member in immunology, demonstrated a the mission of the , which is to the  executive committee and as within the Department of Medicine. great understand- involve the alumni in the affairs of a delegate and member of the board After seven years as an officer and ing not only of the medical school and contribute to of governors of the Association of executive committee member of the what’s so magical its welfare in any way we can,” Lobo Yale Alumni. Christine Walsh, .., Association of Yale Alumni in about Yale, but says. “We have a vigorous expansion serves as secretary until June, . Medicine (), he was elected the Frank Lobo also of the chal- of the missions of research and The  helps shape and lead alumni group’s president in June. lenges that the patient care, as well as a very appro- all the school’s alumni programs, Lobo says that he’s looking school faces. He appears to have a priate sensitivity to the uniqueness of including class reunions each June, forward to his two-year term, in par- very strategic vision about how to our educational mission by our new outreach events around the country ticular because of the strength of the make the appropriate changes.” dean. That will be a very easy and and activities in greater New Haven. school’s current leadership. “This is Lobo, who was the  vice exciting message to bring to the The group will host an outing to the an extremely positive moment for the president for the last two years, began alumni.” Yale-Harvard Game on November .

Ribosome continued from page 1 one of ,-plus  nucleotides Awards & honors that, along with  proteins, make up Henry J. Binder, Alison P.Galvani, Bryan C. Hains, the enormous structure. .., professor of .., assistant .., associate “We found that the resistance medicine and of professor of epi- research scientist in results from a mutation in the  cellular and mo- demiology, has neurology, has been lecular physiology, received a Young awarded a two-year part of the ribosome that puts an has received the Investigators’ Prize Pfizer Scholars extra bump on its surface that pushes Distinguished from the American Grant in Pain the drug a little further away from its Achievement Award Society of Natur- Medicine for his preferred site than it would like to from the American alists for her research on neuro- be,” Moore says. This minor change Gastroenterological research on how pathic pain in Association. The evolutionary forces spinal-cord and causes antibiotics to lose their grip on award recognizes an individual who has shape the engagement between infectious peripheral nerve injury. The award sup- the ribosome. The binding of one made a major contribution to clinical or agents and the immune system of individ- ports the career development of junior drug used in the study, azithromycin, basic research in gastroenterology or in an ual hosts, and on how evolution shapes faculty who are pursuing pain medicine was reduced by a factor of , on allied field. host-parasite interactions. research relevant to human health. ribosomes of resistant bacteria. Bulges of the kind found by Steitz and Moore are so effective at Josephine Hoh, Theodore R. Akiko Iwasaki, protecting bacteria that they have .., associate Holford, .., the .., assistant professor of developed two ways to add them. professor of epi- Susan Dwight Bliss demiology, has Professor of immunobiology, Some, such as those examined in the been selected as a Epidemiology and has been named a new study, mutate their ribosomal  New Scholar Public Health, was  Investigator in , but more commonly they in Aging by the named a fellow of the Pathogenesis of acquire an enzyme that adds the Ellison Medical the American Infectious Disease by the Burroughs bump to unmutated . Foundation. The Statistical four-year, $, Association. Wellcome Fund. Understanding the structural award will allow Holford studies The award will basis of resistance suggests how to Hoh to further her earlier research, which temporal trends in disease maps, models support her research on the interaction beat it: chemists can build new identified at least one important genetic for controlling cancer, and the use of geo- between host and viruses that cause dis- antibiotics one atom at a time, tailor- variant in age-related macular degenera- graphic information systems to assess eases such as genital herpes and respira-  tory influenza infection. ing the chemical shape of the drug to tion ( ), a leading cause of blindness. environmental exposures and disease risk. accommodate that extra bump. Similar approaches have resulted in new drugs to treat  and cancer. Becca Levy, .., Glenn C. Micalizio, Stephanie S. associate professor .., assistant O’Malley, .., “Without detailed structure in the School of professor of chem- professor of psy- information, you do what medicinal Public Health’s istry, has been chiatry and director chemists have done for years—you Division of Chronic named a  of the Division of randomly change the antibiotics in a Disease Epidemi- Beckman Young Substance Abuse kind of blind way, and keep testing ology, has been Investigator. The Research, has won named a fellow in Young Investigator the  Dan them,” Moore says. “Now, we can the Behavioral and Awards are given Anderson Research make guided changes based on the Social Sciences annually by the Award. The award, structure.” section of the Arnold and Mabel sponsored by the Five years ago Steitz and Moore’s Gerontological Society of America (). Beckman Foundation to provide support Butler Center for Research at the lab beat out the competition in a The  is the nation’s oldest scientific to promising young faculty members in Hazelden Foundation, honors a research- organization devoted to research, practice the early stages of academic careers in the er who has advanced scientific under- hotly contested international race to and education in aging. chemical and life sciences. standing of recovery from addiction. solve the high-resolution structure of the bacterial ribosome’s large subunit. They quickly joined with several Yale Lynne J.Regan, Sandra G. Resnick, Raymond Yesner, colleagues to found Rib-X Pharma- .., professor of .., assistant .., professor ceuticals, and the New Haven-based molecular bio- professor of psychi- emeritus and senior startup has been pursuing new antibi- physics and bio- atry and associate research scientist in otic drugs ever since. chemistry and of director of the the School of chemistry, has won Northeast Program Medicine’s According to structural biologist a Guggenheim Evaluation Center Department of Jamie H.D. Cate of the University of Foundation of the Veterans Pathology for more California at Berkeley, the quality of Fellowship for her Health Adminis- than 50 years, has Steitz and Moore’s structures makes research on novel tration, received been awarded the them particularly valuable. “Their anti-cancer the Carol T. Gold Medal by the reagents. The Fellowships support Mowbray Early Career Research Award International Academy of Pathology structures are really gorgeous,” Cates research in all fields of knowledge, under from the U.S. Psychiatric Rehabilita- () for excellence in research and says. “Steitz and Moore see more the freest possible conditions, on the basis tion Association for her research on teaching. Yesner, a longstanding member detail in the ribosome than anyone of distinguished achievement and excep- consumer-run mental health programs of the , is an authority on pathology else can see, and getting those details tional promise. for veterans. of the lung. right is important for drug discovery.”

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