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Advancing Biomedical Science, Education and Health Care Volume 3, Issue 3 May/June 2007 New endowment honors a spirited St.@ Louis ‘symbol of Yale’ MedicineThe family of William R. Orthwein Jr. ising new faculty (later to become McDonnell Douglas,Yale aircraft industry, particularly in the and the William R. Orthwein Jr. and members recruited now part of the Boeing Company), realm of computer-aided design and Laura Rand Orthwein Foundation, at the medical where he would enjoy a 45-year manufacturing. a St. Louis, Mo.-based philanthropic school. career. According to his daughter, Although Orthwein is dealing organization, have made a combined Orthwein, a 1938 Nettie O. Dodge, of Wheatland, Wyo., with complications of a stroke he suf- $2.5 million gift to the School of Medi- graduate of Yale Orthwein began in the personnel fered in 2003, he gathered in February cine to endow a new Yale Scholar in College, did a brief division of the company and eventu- with family and friends to celebrate Ophthalmology and Visual Sciences. stint after gradu- ally headed that unit. He later became his 90th birthday. Stephen Jones, j.d., The Yale Scholars program, a William Orthwein ation as a sales- the first president and chairman of a 1970 graduate of Yale College and recent initiative of Dean Robert J. man for the General American Life McDonnell Douglas Automation trustee of the Orthwein Foundation Alpern, m.d., provides four years of Insurance Company, but soon moved Company, or McAuto, which pio- who attended the celebration, consid- research funding to the most prom- to McDonnell Aircraft Corporation neered systems integration in the Orthwein, page 7 Gene defect plays ‘What else would you do with money?’ role in early-onset Betty and John Anlyan Yale’s wartime help have made a lasting heart disease mark on the School of Yale scientists led by cardiologist Arya inspires gifts from most Medicine. generous alumnus, wife Mani, m.d., have identified a rare “Yale gave me my defect in a single gene associated with start,” he says. “It gave early heart disease and metabolic Each day, a bustling community of all three of us our syndrome, a cluster of risk factors 6,000 faculty, students and staff tend start.” that includes high levels of harmful to the business of the School of Medi- In gratitude for ldl cholesterol and triglycerides, low cine—teaching the art and science the aid Yale provided hdl, or “good,” cholesterol, hyper- of medicine, studying, taking care of to John and his broth- tension and diabetes. patients and conducting research in ers at a difficult time “The belief is that coronary artery one of the world’s leading academic in their lives, John disease and most other diseases are centers. and Betty Anlyan caused by mutations in several genes. But to spend an hour with John made arrangements Each gene, in combination with Anlyan, m.d., a retired thoracic and in 1990 to leave their environmental factors, exerts a small oncologic surgeon and member of estate to the School of effect, so it is very difficult to identify the medical school’s Class of 1945, is Medicine, setting in them in the general population,” says to glimpse a more intimate time in motion the largest- Mani, assistant professor of medicine. the education of young doctors, an ever alumnus gift to “But if we find families in which some era when the first-year class had 46 the medical school. members have an extreme form of the students and the school’s complement Once fully realized, disease, such as very early onset, while of tenured professors was only a few the Anlyans’ pledge other family members are unaffected, dozen. “It was just a beautiful experi- could yield more than they are optimal for genetic research.” ence,” Anlyan says during a phone $50 million. Thanks As reported in the March 2 issue call from San Rafael, Calif., where he to their desire to see of the journal Science, on a research lives with his wife of 60 years, Betty William, who graduated with the their philanthropy in action at Yale, trip to his native Iran, Mani discov- Anlyan. Yale College Class of 1945w and the they have transferred millions of dol- ered one such extreme case: a man Born in Egypt to Armenian medical school’s Class of 1949, went lars to the school already. In addition, with high blood pressure, high cho- parents, Anlyan came to Yale as an on to become the chancellor of Duke at Betty Anlyan’s request, their estate lesterol and diabetes who had suffered undergraduate in 1939, as World War University Medical Center. Frederick, will endow a professorship in the a heart attack at age 48. Although the II loomed on the horizon. Dur- a 1951 alumnus of Yale College, also humanities at Yale. man had been treated with coronary ing the war years, Anlyan’s family’s entered medicine and is now a retired John Anlyan would have finished artery bypass surgery, atherosclerotic overseas assets were frozen, so he and pathologist living on Long Island. medical school a year earlier had he plaque continued to build up in his his younger brothers, William and John, who graduated from Yale Col- not contracted tuberculosis at the grafted heart arteries and in his ca- Frederick, relied on Yale for finan- lege in 1942, will return to New Haven start of his first year. The disease rotid arteries, and he eventually died cial support during their education. in June for his 65th college reunion. of a stroke. Anlyan, page 6 Gene, page 6

Non-Profit Org. Inside this issue Medicine@Yale U. S. Postage Lifelines RNA has its day 300 George St., Suite 773 PAID Elizabeth Bradley’s prescription Two Yale researchers receive New Haven, CT 06511 New Haven, CT for better hospital management, p. 2 Ellison Foundation awards, p. 5 www.medicineatyale.org Permit No. 526 Life begins at 40 A life in science For Connecticut Mental Health Center, Nephrology society honors the best is yet to come, p. 3 a 50-year career, p. 8 From mouse to man Also New immunobiology program Advances, pp. 3, 5; Out & About, p. 4; will target human disease, p. 5 Grants and Contracts, p. 7

Want to find out more about medicine at Yale? E-mail us at [email protected] or phone (203) 785-5824. cyan mag yelo black 3975 MAC Tumor virus expert will direct research at Cancer Center Daniel C. DiMaio, m.d., ph.d., the Waldemar Von Zedtwitz Professor and vice chair of genetics and profes- sor of therapeutic radiology, has been named scientific director of Yale From Ethiopia to your local Cancer Center (ycc). In this new role, emergency department, Elizabeth Bradley’s hard- DiMaio will broadly oversee all basic nosed research is promoting science research at the ycc. improved hospital care and As director of the ycc’s Molecular management. Virology Program since 1993, DiMaio has guided collaborations among 17 independent but interactive laborato- ries with a common interest in cancer. His own laboratory is focused on papillomaviruses, an important cause of catheterization lab. The group human cancers, par- Making hospitals better identified six best practice strate- ticularly in women. gies, published in the New England DiMaio’s research For management expert, and procedures, but Bradley says Journal of Medicine in 2006, which group has explored the key to good health care there was no equivalent scrutiny have formed the basis for a national how these viruses of organizational changes made by alliance of more than 800 hospitals is all in the details control cell growth hospital managers. “I was eager to devoted to improving outcomes for Daniel DiMaio and proliferation, As a teenager in New Britain, Conn., step back from what I was doing heart attack patients. revealing potential new drug targets Elizabeth H. Bradley, ph.d., volun- and apply the same rigorous meth- There are large differences for cancer, and is using the viruses as teered at the local hospital, but odology to evaluate management among hospitals in severity-adjusted novel research tools to manipulate the she had little interest in being a practices as those used to evaluate mortality rates after heart attack, behavior of normal cells. physician. “The adults I knew were medical care,” she says. and the two researchers now plan After graduating summa cum in manufacturing as engineers or After obtaining her ph.d. in to determine which organizational laude from Yale College in 1974, management,” says Bradley. “To public health from Yale in 1996, strategies are linked to reduced DiMaio earned his m.d. and ph.d. me, the interesting part of a hospi- Bradley embarked on just the kind mortality. degrees from the Johns Hopkins Uni- tal was how it was organized and of management systems research Bradley is also using her man- versity School of Medicine. managed—and how much it was she felt was lacking. She has since agement skills in Ethiopia, where In announcing DiMaio’s appoint- not like a regular business.” published many research articles government officials requested help ment, ycc Director and Professor Now a professor of public health on the organizational and other in improving hospital care. With a of Dermatology Richard L. Edelson, at the School of Medicine, director factors involved in translating our team of 23 Yale-Clinton Foundation m.d., said, “Dan brings a wide range of its Health Management Program best health care knowledge into Fellows in International Healthcare of experience to this senior leadership and co-director of the Robert Wood the best possible systems of care Management, she has developed a role, which is critical to ycc’s efforts Johnson Clinical Scholars Program, for real-world patients. Bradley has strategy to implement fundamental to successfully expand our research Bradley is still drawn to the orga- worked in the areas elements of good hospital manage- initiatives. In addition to his own nizational aspects of health care. “I Lifelines of hospital care, ment, including triage systems, internationally recognized scientific guess I’ve never changed,” she says. Elizabeth long-term care, and inventory management, practices to accomplishments, he has shaped our After receiving her undergradu- hospice care; since reduce hospital-acquired infections, Molecular Virology Program into one ate degree at Harvard University, Bradley 1996 she has col- and quality improvement methods. which serves as a superb example of Bradley went on to earn an m.b.a. laborated with the Although her work in Ethio- first-rate interactive science.” in health administration at the Uni- John D. Thompson Hospice Institute pia might seem far removed from versity of Chicago Graduate School for Education, Training and Research, streamlining heart attack patients’ of Business. She then completed an Inc., in Branford, Conn. @ trips to the catheterization lab, MedicinePeter Farley, ManagingYale Editor administrative fellowship at Massa- Recently, Bradley was part of a Bradley says the goal in both cases is Contributors: Amy Chow, John Curtis, chusetts General Hospital in Boston, team led by Harlan M. Krumholz, encouraging hospitals to adopt best Michael Fitzsousa, Renee Gaudette, Jennifer Kaylin, where she stayed on as an adminis- m.d., the Harold H. Hines Jr. Pro- practices. Jill Max, Pat McCaffrey, Kara Nyberg, Richard Peterson, trator for several years. fessor of Medicine, that enlisted Both projects also include an Jane Halbing Stitelman, Jacqueline Weaver. “As a hospital administrator at researchers from the School of evaluation component, ensuring Photographs and Illustrations: American Society of Mass General, I helped make lots of Medicine, the School of Nursing, that these practices are supported Nephrology, John Curtis, Terry Dagradi, Nettie Dodge, Amy Etra, ©Images.com/CORBIS, Martin Klimek, changes—in staffing levels, work Yale-New Haven Hospital and by objective evidence. Michael Marsland, Margaret Sasaki, Susan Woodall. flow, admissions practices,” Bradley several other institutions to devise “We want to learn what dis- Design: Peter W. Johnson, Maura Gianakos/Yale RIS says, “but we never had the time to ways to shorten “door-to-balloon tinguishes the hospitals that get evaluate whether the changes were time,” the critical period between the best results,” Bradley says, but Medicine@Yale is published six times each year by the Office of Institutional Planning and Communications, making a difference.” Physicians a heart attack patient’s arrival at a she won’t settle for assumptions or Yale School of Medicine, 300 George St., Suite 773, conduct randomized trials to assess hospital and the completion of an anecdotes. “We need the evidence to New Haven, CT 06511. the safety and effectiveness of drugs angioplasty procedure in a cardiac back it up.” Telephone: (203) 785-5824 Fax: (203) 785-4327 E-mail: [email protected] Website: medicineatyale.org Student-run auction for New Haven charities has a banner year Copyright ©2007 by Yale School of Medicine. All rights reserved. The annual student-run Hunger Recipients of this year’s funds are If you have a change of address or do not wish and Homelessness Auction, held last the Community Health Care Van; to receive future issues of Medicine@Yale, November, raised more than $36,000 haven Free Clinic; Community please write to us at the above address for seven community agencies in Soup Kitchen; Domestic Violence or via e-mail at [email protected]. New Haven, the most ever raised by Services of Greater New Haven; Im- Postal permit held by Yale University, the auction and an increase of $5,000 manuel Baptist Shelter; Leeway Inc.; 155 Whitney Avenue, New Haven, CT 06520 over the previous year. Loaves and Fishes; and the St. Thomas Yale School of Medicine Robert J. Alpern, m.d., Dean This year’s auctioneer was Wade More Catholic Chapel and Center at Ensign Professor of Medicine Brubacher, father of first-year medical Yale University. Jancy L. Houck student Jake Brubacher. State Attor- As in past years, the fundrais- Associate Vice President for Development ney General Richard Blumenthal, ing began with a silent auction from and Director of Medical Development (203) 436-8560 j.d., made a guest appearance to auc- November 13 to 16, followed by a live Mary Hu tion his own donation—lunch and a auction in the Harkness Ballroom on Director of Institutional Planning and Communications Eager bidders at the silent auction. personal tour of the State Capitol. November 16. Michael Fitzsousa, Director of Communications  www.medicineatyale.org cyan mag yelo black 3975 MAC Forty years of research, teaching and healing Advances Health and science news from Yale Psychiatry Chair A bold experiment Benjamin “Steve” in mental health care Bunney (seated) and Deputy Chair reaches a new milestone John Krystal have witnessed the many When Yale psychiatrist Frederick C. successes of the Connecticut Mental “Fritz” Redlich, m.d., met with newly Health Center. Bun- elected Governor Abraham A. Ribicoff ney will retire this in 1955 to discuss how services for year after 38 years Connecticut’s mentally ill might be on the Yale faculty, including 20 years as For better health, improved, he came prepared, accord- department chair. ing to Benjamin S. Bunney, m.d., can the soft drinks the Charles B.G. Murphy Professor The annual U.S. production of of Psychiatry. Redlich, who served as soft drinks exceeds 600 8-ounce psychiatry chair from 1950 to 1967, brought together within one building mine systems; and clinical researcher servings per person. These bubbly had given a great deal of thought were really revolutionary,” Bunney Malcolm B. Bowers Jr., m.d., studied beverages have become a fixture of to public policy issues surrounding says. “The cmhc has an entire floor the dopamine system in patients with our culture despite numerous stud- mental health, much of which he later where one side is basic laboratories schizophrenia. This work lent support ies correlating soft drink consump- crystallized in Social Class and Mental tion with health problems. and the other is an inpatient research to the emerging concept that some Illness, a classic 1958 book he wrote ward for biological psychiatry. This of the brain’s dopamine systems are Kelly D. Brownell, ph.d., profes- with Yale sociologist August B. Hol- sor of psychology and epidemiol- brought basic scientists and clinical hyperactive in schizophrenia, which lingshead, ogy and director of Yale’s Rudd ph.d. investigators together long before the ultimately led to a new generation Center for Food Policy and Obesity, When Redlich appealed to Ribi- term ‘translational research’ was ever of antipsychotic medications with recently led a thorough analysis of coff for more services for Connecticut invented. At the cmhc, basic re- greater efficacy and fewer side effects. 88 previous reports on the health citizens with psychiatric disorders, searchers learned about clinical prob- Another important early research effects of drinking soda. particularly the poor, Ribicoff shot lems and clinical researchers learned accomplishment at the cmhc, the In the March issue of the back, “Well, Fritz, what is Yale going the vocabulary of the basic scientists, discovery of clonidine as the first American Journal of Public Health, to do about mental health?” In reply, which made communication possible non-opiate treatment for opiate Brownell’s group reports that soda Redlich described the innovative de- between these two groups. This in dependence, vividly illustrated the increases caloric intake and body partment he had built in his first five weight, decreases intake of calcium turn spawned all kinds of collabora- power of Redlich’s integrated model years as Yale’s Psychiatry chair. Based tions, including hypothesis-driven of psychiatry. and other nutrients and raises the on a graduate-school model, the risk of type 2 diabetes. clinical research.” In work with animals, Aghajanian basic and clinical research done by its Moreover, the additional Beginning in the early 1970s, and D. Eugene Redmond, m.d., now calories associated with soft drink faculty members formed the founda- cmhc scientists led by George K. professor of psychiatry and neuro- consumption add up to more than tion for all of its teaching and patient Aghajanian, m.d., made the first surgery, found that inhibiting the those in the drinks themselves, care. Redlich argued that a mental electrophysiological recordings in the noradrenaline system with clonidine suggesting that drinking soda health center adhering to the same brain regions that make use of the decreased the symptoms of opiate may increase hunger or decrease philosophy would provide the best, neurotransmitters noradrenaline and withdrawal, making rapid and rela- a sense of fullness. most scientifically sound psychiatric serotonin. By studying the function- tively painless withdrawal possible for treatment to Connecticut’s citizens. ing of these neurotransmitters, these addicted individuals. When cancer is Over the next four years the De- scientists laid the groundwork for Building on this research, Mark partment of Psychiatry and the state drug treatments for opiate depen- S. Gold, m.d., now Distinguished a family affair of Connecticut hammered out a joint dence, depression, anxiety disor- Professor of Psychiatry at the Univer- In life’s genetic lottery, we often partnership that proposed a wholly ders and attention deficit disorder. sity of Florida, Professor of Psychiatry inherit unfavorable characteristics. new approach to mental health care: Meanwhile, basic scientist Bunney Thomas R. Kosten, m.d., and Herbert Some, like mom’s wiry hair, are a community-based center in which made similar recordings in brain D. Kleber, m.d., now professor of innocuous, but certain defective psychiatric treatment, training and regions that use the neurotransmitter psychiatry at Columbia University, genes can slowly wreak biologi- research would be brought together dopamine; Robert H. Roth Jr., ph.d., found that patients being treated at cal damage over time. In two such under one roof. studied the biochemistry of dopa- genes, brca1 and brca2, mutations In the summer of 1966, with the CMHC, page 4 predispose their carriers to devel- opening of the Connecticut Mental oping cancers, especially breast Health Center (cmhc), Redlich’s and ovarian cancers. vision became a reality. The 65,000- To determine how prevalent The rewards of life on the front lines square-foot facility featured space for and risky brca mutations are, Har- Jane Halbing Stitelman, editor of Yale stressors, which can be countered by day patient and outpatient services, 22 vey A. Risch, m.d., ph.d., professor Psychiatry, the Yale Psychiatry Bulletin strengths and supports. Our under- beds for inpatients, an additional 22 of epidemiology, and colleagues and the cmhc newsletter CenterPages, standing of the causes of mental in Ontario, Canada, asked ovar- beds for clinical research, an emergen- wrote the following essay to commem- illness is still evolving, and our treat- cy unit, a 140-seat auditorium, class- ian cancer patients to report the orate the cmhc’s 40th anniversary. ments continue to evolve as well. incidence of cancers among their rooms and a library. Redlich served as The life of this place is on the first-degree relatives. The patients the cmhc’s first director; the research After we read over cmhc’s Annual front line of a struggle with a terrible were tested for brca1/2 mutations, facilities were later named in honor of Reports from the past 40 years, we illness, played off against the possibil- which were correlated with the Governor Ribicoff. family histories. felt like we’d eaten 40 boxes of Rye ity of health, comfort and normal life. Today, the cmhc still stands as Krisp. There’s nothing like reducing an It’s a struggle that occurs with each In the December 6 issue of a model for research-based mental the Journal of the National Cancer institution to a four-page bureaucratic interaction that attempts to fine-tune health training and patient care. Institute, the team estimates that report to drain the life out of a place. reality, ability and acceptance. How do brca1/2 mutations lurk in 1 of Under the direction of Professor of This was a particular problem for me, you keep score? Ann Joy, our director every 99 individuals (1.01 percent) Psychiatry Selby C. Jacobs, m.d., the because I wrote most of them. of psychosocial rehabilitation services, in the general population—a much center complements its scientific and The reports told of our annual once said that Professor of Psychiatry higher frequency than previously educational roles with inpatient and caseload of 5,000 patients and initia- Michael Hoge had explained, “For thought—and that carriers are outpatient psychiatric services for tives that organized and reorganized some of the people we treat, just 4.6 to 102 times more likely than over 7,000 New Haven-area residents people and programs to accommodate being able to sit with other people for noncarriers to develop ovarian, each year. As part of the “Yale Tomor- a burgeoning caseload and limited 15 minutes is a success. Small steps are testicular, pancreatic and female row” capital campaign, the medical and male breast cancers. resources. The line that captured it big gains.” Happily, there are also those school has launched a special fund- best, perhaps, was “We are doing more for whom success has meant much “Families with appreciable raising drive to expand and improve histories of any cancers, not just and more with less and less.” more, including joining the ranks of upon ’s facilities. breast and ovary and not just cmhc If I had it to do over again, I’d write caregivers. “The ideas that research would cancers in females, should think about the day-to-day life of the place. cmhc’s vitality is where the care- about mutation screening because define care and training, and that all I’d start by reminding the reader that givers of all kinds—physicians, nurses, methods of prevention are becom- parties—psychotherapists, psycho- mental illness is a wide and subtle psychologists, social workers, mental analysts, social psychologists and ing available,” Risch says. confluence of factors, of genes and , page 6 biological psychiatrists—would be Rewards

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Out & about

1 2 3 September 29: The 40th anniversary gala of the connecticut mental health center (cmhc), a treatment, research and teaching partnership of the medical school and the State of Connecticut (see related story, p. 3), featured dinner and dancing at the New Haven 4 March 17: alumni of the school of medicine’s physician asso- Lawn Club. 1. The keynote speaker for the event ciate program and their guests joined , m.m.sc., pa-c, was television personality Jane Pauley, author of Skywriting: A Life Out Mary Warner assistant dean and director of the program, for a relaxed evening get-together of the Blue, a memoir of her struggle with bipolar disorder. 2. From left: in Hanover, N.H. Hanover-area alumni regaled Warner with stories of their cmhc Chief Operating Officer and gala emcee Robert Cole, m.h.s.a.; Susan days in New Haven and beyond. Warner hopes to expand the program’s Woodall, executive director of the cmhc Foundation; and Tomàs Reyes Jr., alumni outreach program by meeting with as many graduates as possible the cmhc’s manager of communications and public information. 3. Clock- within the next year. Clockwise from lower left: , pa-c ’93; wise from left: Sheila Allen Bell, director of the Housing Authority of New Gayle Spelman , pa-c ’77; , pa-c ’76 (behind Kathy De Rham); Haven; John DeStefano Jr., mayor of the city of New Haven; Audrey Tyson; Kathy De Rham John Bond , pa-c ’80; , pa-c ’73; , pa-c and Barbara Lamb, director of cultural affairs for the city of New Haven. Cary Stratford Jack Cassidy Alice (Hofmann) Mello ’99; , pa-c ’99; Warner; and . 4. From left: Candace Buchanan and Katura Bryant. Tim Mello Abbott De Rham

March 6: A ceremony in honor of connecticut state senator April 9: the family of sydney hoff and friends visited the medical toni harp was held in the Historical Library of the School of Medicine’s school’s Center for Neuroscience and Regeneration Research to present checks Harvey Cushing/John Hay Whitney Medical Library. In Washington, D.C., in totalling $50,000 to Stephen G. Waxman, m.d., ph.d., chair and Bridget February, the American Medical Association (ama) presented Harp with its Marie Flaherty Professor of Neurology, to support his research on the molecu- Dr. Nathan Davis Award for Outstanding Government Service. The award, lar basis of erythromelalgia (em), a rare, incurable neurological disorder that named for the founder of the ama, is the highest honor the association causes burning pain in the hands, feet and other extremities. Eleven-year-old confers on public officials. Harp was recognized for her advocacy of commu- Sydney Hoff of Briarcliff Manor, N.Y., was recently diagnosed with the disor- nity health centers, pediatric dental care, expanded access to health care and der; her mother, Sharon Hoff, and friends raised the funds with appeals to regulating medical insurance premiums and co-payments for the economi- their families and the wider community. Front, from left: Sharon Hoff, Alex cally disadvantaged. From left: Michael M. Deren, m.d., chair of the board Martucci, Sydney Hoff, Marty Hoff, Drew Shaulson. Back, from left: Waxman of trustees of the Connecticut State Medical Society (csms); Gary J. Price, and Karen Shaulson. m.d., immediate past president and councilor-at-large of the csms; Toni N. Harp (D-New Haven); and Dean and Ensign Professor of Medicine Robert J. Alpern, m.d.

CMHC from page 3

the cmhc for opiate abuse recovered The unusual productivity of the tween a university and a government agrees. “A lot of the policy questions even more rapidly if given an opiate cmhc’s translational approach con- agency, say the psychiatry depart- that we deal with are pretty compli- blocker along with clonidine. tinued into the 1990s, as Eric J. Nes- ment’s state partners at the Connecti- cated, and they affect thousands of John H. Krystal, m.d., who was tler, m.d., ph.d., now the Lou and cut Department of Mental Health and people’s lives. In a university setting, a student at the School of Medicine Ellen McGinley Distinguished Chair Addiction Services (dmhas). tenured faculty have a rather long at the time, was greatly impressed by in Psychiatric Research at UT-South- According to Thomas A. Kirk Jr., view of things, but the median term the cmhc’s pioneering research on western Medical Center in Dallas, led ph.d., dmhas commissioner, “The of office of a commissioner of mental clonidine. groundbreaking studies on the neu- fact that this partnership has been health in the United States is about “This research was a landmark in robiological basis of drug addiction. sustained so long is really a statement 21 months,” Dailey says. “There’s a psychiatry,” says Krystal, the Rob- Today, Ronald S. Duman, ph.d., the about the shared commitment to lot of pressure on commissioners to ert McNeil Jr. Professor of Clinical Elizabeth House and Jameson Mears clinical services, research and teach- act quickly, and often the evidence Pharmacology and an expert on post- Professor of Psychiatry, is one of the ing. The National Alliance on Mental and data available to a commissioner traumatic stress disorder. “It may have leading proponents of the neurogenic Illness recently reviewed the mental in making a key policy decision are been the first time a clinical condition theory of antidepressant drug action, health systems of each of the states not very good because of that pres- was understood at the cellular level, one of the most significant advances and assigned grades. Connecticut sure. But when you have a university leading to the development of a novel in the understanding of mood disor- was one of the top two states in the partner that is bringing research that’s treatment based on scientific prin- ders in decades (see related story, p. 5). nation, and I think our relationship been used in developing evidence- ciples. It exemplifies the Yale tradition This record of achievement is all with cmhc was clearly a contributor based practices into the policymaking of translating basic science insights the more remarkable given the orga- to our high grade.” dmhas Deputy process, you have a much stronger into treatment advances.” nizational and cultural differences be- Commissioner Wayne Dailey, ph.d., basis for making those decisions.”  www.medicineatyale.org cyan mag yelo black 3975 MAC

Advances Building new bridges from lab to patient Health and science news from Yale Over the past two decades, researchers the Department of Immunobiology provides special incentives to compa- in the School of Medicine’s immu- for the Section of hti in January. nies developing compounds to treat Growing out nobiology group have led the way in “To make translation work, you rare diseases. unlocking the secrets of the immune need a way to connect physicians and Herold and his work represent of depression system. Richard A. Flavell, ph.d., basic scientists, and that is best done “the best kind of bridge,” says Carolyn For decades, people suffering chair of the newly designated Depart- by people with both interests who are W. Slayman, ph.d., Sterling Profes- from mood disorders have found ment of Immunobiology pioneered willing to work in the middle,” says sor of Genetics and deputy dean for relief with antidepressants, but the use of genetically engineered mice Pober. “That’s what hti is going to academic and scientific affairs at the biological basis for the action to study the fundamental principles provide.” the School of Medicine. “He brings of these highly of organization and regulation of im- The work of the program’s first together a track record for excellent prescribed medi- mune responses. Using mice to mimic recruit, Kevan Herold, m.d., is a basic research with a new treatment cations remains human diseases, researchers found model of trans- for an important human disease.” unclear. One theory, evidence of immune system involve- lational research. Slayman adds that Herold’s work based on landmark studies by Ronald S. ment in many maladies, including While at Columbia links immunobiology with another Duman, ph.d., the cancer and heart disease. University, Herold, strong Yale academic unit, the inter- Elizabeth House But there are enough differences now professor of nal medicine/endocrinology group and Jameson Mears between the immune systems of mice immunobiology led by diabetes researcher Robert Professor of Psy- and humans that Flavell and his col- and medicine at the S. Sherwin, m.d., the c.n.h. Long chiatry, proposes that these drugs leagues hit a wall when it came time School of Medicine, Professor of Medicine. exert their effects by stimulating to test their theories in people with Jordan Pober advanced the most The hti initiative comes at an neuronal growth factors; these diseases. Frustrated by the barriers to promising new treatment for type 1 opportune time for translational proteins generate new nerve cells moving laboratory findings into the diabetes in children. The disease starts research at Yale. In October, the in certain brain areas that lead to clinic, Flavell devised a plan to bridge when the immune system mistakenly newly formed Yale Center for Clinical changes in mood and behavior. the chasm between mouse and man. attacks insulin-producing islet cells in Investigation received a five-year, $57 With Jennifer Warner-Schmidt, ph.d., a former graduate student His solution, embedding clinical the pancreas. As the cells die, insulin million Clinical and Translational now at Rockefeller University, researchers in the Department of Im- production declines, and children Science Award from the National Duman has identified vascular munobiology, resulted in the medical become dependent on multiple daily Institutes of Health, funding that will endothelial growth factor, or vegf, school’s newly launched program in injections of insulin. help provide the infrastructure hti as one such protein. Human and Translational Immunol- First in mice, and then in human investigators need to conduct research In the March 13 issue of the ogy (hti), which will eventually in- clinical trials, Herold and Jeffrey A. and to train a new generation of clini- Proceedings of the National Acad- clude six new faculty members whose Bluestone, ph.d., of the University cal immunologists. emy of Sciences, the team reports research spans both basic and human of California, San Francisco, and By removing roadblocks to that vegf is produced in the brain’s experimentation. The program will their research teams have shown that clinical research, Flavell, Pober and hippocampal region following also reach out to clinical researchers administering antibodies designed to their hti colleagues hope to see Yale administration of various antide- in a variety of medical departments inhibit a particular immune response discoveries turned into treatments pressants. Higher vegf levels led to increased cell division and positive with an interest in immunology. in children with early symptoms of for a wide range of diseases, from behavioral responses in well- The new program will be headed type 1 diabetes delays, and may even diabetes and cancer to heart disease established rat models of depres- by Jordan S. Pober, m.d., ph.d., the prevent, the full-fledged development and stroke. sion. Conversely, blocking vegf founder and former director of Yale’s of the disease. The antibody formula- “For 18 years, immunobiology has action inhibited these effects. highly successful interdepartmental tion, further refined by MacroGenics been focused on studying the basic These findings point to the translational research program in of Rockville, Md., under the name mechanisms of immunology and vegf pathway as a possible target Vascular Biology and Transplantation. mga301, is currently in advanced- applying that to disease, but almost in the development of new and Pober, whose own research has eluci- phase clinical trials for Food and all our focus has been on mice,” better antidepressant drugs. dated the role of the immune system Drug Administration (fda) approval. Flavell explains. “So the new program in vascular disease and organ trans- The fda recently named mga301 an is the same thing, really, just now in A closer look at plantation, became the vice-chair of “orphan drug,” a designation that humans.” bacterial insurgents American troops in Iraq are bat- Two Yale RNA experts receive Ellison awards tling on yet another front, one as ancient as war itself, yet as modern The Ellison Medical Foundation in human lung cancers, a finding that as the post-penicillin era. Over (emf) has named two Yale scientists has led him to propose that many 240 wounded soldiers have been Senior Scholars in Aging, an award cancers may be caused by dysfunctions afflicted with bloodstream infec- that recognizes creative and produc- in mirna regulation over the lifespan. tions of the antibiotic-resistant tive research into processes that affect Slack joined the Yale faculty in bacterium Acinetobacter bau- mannii. Left unchecked, this bacte- lifespan and age-related diseases and 2000 after doctoral work in molecular rium causes urinary tract infec- disabilities. biology at Tufts University School of tions, pneumonia, meningitis, Frank J. Slack, ph.d., associate Medicine and postdoctoral training at Frank Slack Sandra Wolin sepsis and even death. professor of molecular, cellular and Stanford University School of Medi- Using dna sequencing tech- developmental biology, and Sandra L. cine and at Harvard. He is a member hopes to identify genes involved in nology from 454 Life Sciences, a Wolin, m.d., ph.d., professor of cell of Yale Cancer Center. detecting and degrading damaged Branford, Conn., biotech company, biology and of molecular biophysics Wolin studies how rna molecules rnas and to determine how they may Michael Snyder, ph.d., the Lewis B. and biochemistry, will each receive fold into intricate shapes inside the contribute to aging and neurodegen- Cullman Professor of Molecular, $150,000 per year for four years to cell and how a protein known as Ro eration. Cellular and Developmental Biol- support their research. binds rnas that have been misfolded. Wolin joined the medical school ogy, and colleagues analyzed the Slack studies the role of micro- She and her research team have faculty in 1991. She received her m.d. bacterium’s entire genome. In the March 1 issue of Genes rnas, or mirnas, short strands of shown that rna binding by Ro helps and her ph.d. degree in molecular and Development, Snyder’s group genetic material that act as “switches,” cells survive damage from ultraviolet biophysics and biochemistry from revealed that a surprising 17 orchestrating development and ag- radiation. Yale, and completed her postdoctoral percent of A. baumannii’s genetic ing by activating or shutting down They also found that mice training at the University of Cali- material originated in other patterns of gene expression over lacking Ro develop an autoimmune fornia, San Francisco. She is also a microorganisms. Over half of these time. In research on the microscopic disease that resembles lupus, indicat- member of the Yale Cancer Center. “alien islands” contain genes that roundworm C. elegans, Slack and his ing that the normal function of Ro The Bethesda, Md.-based emf are critical to the bacterium’s abil- colleagues have elucidated how two could be important for preventing was created by Lawrence J. Ellison, ity to harm humans. mirnas known as lin-4 and let-7 autoimmunity. founder and chief executive officer of The study shows that the ensure that organs emerge at their Damaged small rnas have been software giant Oracle Corporation, organism has gained a tactical ad- proper time during the worm’s devel- detected in the brains of aging ani- and Joshua Lederberg, ph.d., who vantage by incorporating foreign dna. Understanding these evolu- opment. Slack has also shown that the mals and patients with neurodegen- received his doctoral degree at Yale tionary adaptations will bolster mirna let-7, which he discovered as erative diseases such as Alzheimer’s and went on to share the 1958 Nobel the antibiotic armamentarium. a postdoctoral associate at Harvard and Parkinson’s. With the help of the Prize in Physiology or Medicine for Medical School, is poorly expressed Senior Scholar in Aging award, Wolin his studies of genetic recombination.  Medicine@Yale May/June 2007 cyan mag yelo black 3975 MAC

Anlyan from page 1

stranded him in a sanitarium near After medical school, Anlyan The 457,000- New Haven—playing poker, as he completed a surgical internship and square-foot Anlyan recalls, with his fellow patients and residency at the University of Chicago Center for Medical Research and waiting to be liberated from his con- Clinics, then spent two years at Ohio Education, Yale’s finement. His recollection of medical State as a resident in thoracic sur- largest building, school in the early 1940s is a parade gery and graduate student in enzyme provides state-of- of larger-than-life professors whose chemistry. In 1949, then-surgery Chief the-art facilities for bench science, personalities, one gets the sense, were Gustaf Lindskog, m.d., invited him education and mag- matched at times by that of their stu- back to Yale as an instructor at a salary netic resonance dent. He recalls Harry Zimmerman, of $5,000 a year. (“You could hardly imaging studies. m.d., the eminent neuropathologist live on that,” Anlyan says, “but we and friend of Albert Einstein, as a had fun.”) After two years he moved lively teacher who would go on to to New York, spending the next three become the first dean of the Einstein years as a Damon Runyon Fellow School of Medicine. at the Sloan-Kettering Institute and Anlyan and his classmates were Memorial Hospital. also impressed by Milton C. Win- In 1957, with John having complet- badly needed facilities for anatomy noticed Anlyan’s brush strokes get- ternitz, m.d., another professor of ed his clinical training and his Navy and histology instruction and includ- ting broader and his colors brighter. pathology who had transformed the service, he and Betty set off across the ed an extensive vivarium, a state-of- Perhaps in explanation, Anlyan says medical school during his deanship country in a Mercury sedan in search the-art magnetic resonance research macular degeneration has limited his from 1920 to 1935. of a suitable place to settle and launch center and a new auditorium. sight in recent years. Anlyan remembers him as “a little his surgical practice. As he tells it, “I Lawrence J. Rizzolo, ph.d., an But the place Yale occupies in short guy who was just like dynamite. couldn’t stop coughing in L.A.; San associate professor of surgery who Anlyan’s memories and sentiments He made the medical school.” Stu- Diego was boring. But the minute we teaches anatomy in the Anlyan Cen- is undimmed. John has long been dents called him “Winter” when he hit the Golden Gate, we said, ‘This is ter, says that when the Anlyans toured involved in alumni and develop- wasn’t listening, and a high-spirited it.’” San Francisco became their home. the new building in 2005, John looked ment activities, serving on the Yale Anlyan used the same moniker one During John’s long surgical career down the long third-floor hallway Development Board and the last Yale morning when passing Winternitz in specializing in cancer treatment, he and joked, “This is too stark. I want to capital campaign, which raised $1.7 the hall. and Betty invested in California real give the students something to laugh billion for the university from 1992 to “I said, ‘Good morning, Winter,’” estate; their bequest of the return at.” An avid painter, he provided pho- 1997. The Anlyans are deeply involved he recalls, his companions falling from those investments would eventu- tographic reproductions of his favor- in Yale’s current capital campaign, the silent. There was a moment’s pause, ally fuel the growth of the medical ites among the oils he had created to $3 billion “Yale Tomorrow” fundrais- and then “he put his arm around school through the construction of Yale’s Office of Development, which ing effort. me and said, ‘Call me Milt. It’s more Yale’s largest building, the 457,000- had them framed and displayed them Yale made a lasting impression on informal.’” The tension dissolved in a square-foot Anlyan Center for Medi- along the corridor. Soon after, Rizzolo John Anlyan, and his and Betty’s lega- burst of laughter. cal Research and Education, which says, canvases started arriving— cy has changed the shape of the medi- Richard Breck, m.d., a retired opened in 2003. followed by more canvases. Now, the cal school in a lasting way. But Anlyan, geriatrician in Wallingford, Conn., The Robert Venturi design, which third-floor hallway of the Anlyan the most generous alumnus in the and classmate of Anlyan, remembers combines a north and a south build- Center’s north building is lined with school’s history, is self-effacing when Anlyan as a popular student and life ing across a central atrium, signifi- dozens of brightly colored canvases he explains his and his wife’s gifts to of the party. “He was well known for cantly increased the space available at depicting San Francisco scenes, land- the School of Medicine. “We don’t his ability to tell stories and jokes,” the medical school for bench science scapes, flowers and a few portraits. have any children,” he says. “What else Breck recalls. and translational research, provided Rizzolo says that since 2003 he has would you do with money?”

Gene from page 1

When Mani looked at the medi- bolic syndrome and early cad, Mani in certain malignant of Wnt-related genes will reveal that cal records of 58 of this man’s blood obtained blood samples from affected tumors. defects in the pathway are involved in relatives, he found that 28 had been and unaffected family members and The family stud- more common forms of cardiovascu- diagnosed with early cad—be- returned to the School of Medicine to ied by Mani exhibits lar disease. fore the age of 50 in men and 55 in complete genomic analyses. Working an extreme case of “The main finding is the role of women—and that 23 of those 28 died in collaboration with Richard P. Lif- heart disease and Wnt signaling in the development at young ages; family members with- ton, m.d., ph.d., chair and Sterling associated metabolic of metabolic syndrome and cad,” out cad died much older. Test results Professor of Genetics, Mani eventually risk factors, and the Mani says. “That is where science has from the 13 available family members zeroed in on a mutation that affected Arya Mani mutation he identi- to focus now to understand the basic with early cad showed that nearly all family members had in a gene on fied is quite rare. However, genes with molecular mechanism of the disease.” of them had high ldl cholesterol and chromosome 12 known as lrp6. similar functions to lrp6 and the Lifton agrees. “We expect that triglyceride levels, high blood pressure One change in an amino acid in Wnt pathway itself have been highly studies of the Wnt signaling pathway and diabetes, meeting National Insti- the lrp6 gene altered the activity of conserved over evolutionary time in in patients with early cad and meta- tutes of Health criteria for metabolic the protein it encodes, which acts in species as diverse as frogs and hu- bolic syndrome will provide new in- syndrome. the Wnt (pronounced “wint”) signal- mans. This suggests that the pathway sight into the basic biology of disease With evidence of a strong genetic ing pathway, a network of proteins has basic physiological importance, causation and allow new approaches component in this family’s meta- involved in normal development and and Mani believes that further study to disease prevention,” he says.

Rewards from page 3 and every clinician who tried to keep give life to the phrase “a network sors, who are often the first responders health workers, occupational and a released prisoner out of trouble. of services.” The very nature of our to crises of all kinds. The place would rehab therapists—champion their This is the time to thank everyone work requires the highest degree of close without you. patients in countless ways. who has taught us to understand collaboration. cmhc exists because of everyone This is a time to acknowledge the nuances of human spirit and It is a time to acknowledge who comes to work each day—or every clinician who has called around behavior. the cmhc environment itself: our night—to meet whatever surprising the state to find a bed; every doctor We thank our researchers for their able public safety department, our developments his or her shift may who has weighed the benefits and work on the complicated pathways to switchboard operators, our computer hold. The remarkable thing about costs of medications for his or her the causes and treatment of mental and records staff, and the myriad cmhc is that regardless of the think- patient; every case manager or peer illness and addictions, as well as of people—carpenters, electricians, ing, the funding or the treatments advocate who has worried where those who prepare the endless grants, housekeeping and building crews— available, for 40 years we have been someone’s next meal or coat would and who keep the labs and clinics who keep the place clean and safe, here to help steer a difficult, some- come from. We acknowledge every running smoothly. We thank the many warm and even welcoming. And there times heartbreaking, often hopeful clinician who hoped a shelter could agencies of the Community Services is the true front line of our work: the process. overlook this one last outburst; Network of Greater New Haven that secretaries and administrative supervi- Hardly a box of Rye Krisp at all.

 www.medicineatyale.org cyan mag yelo black MAC Grants and contracts awarded to Yale School of Medicine September/October 2006

Federal

Maria Teresa Baquero, Department of the ifiers of Child Depression, 4.5 years, $1,858,595 Bay Pines Foundation, Release of mif Protein Diagnostics, llc, Broad Spectrum Therapeutic Army, Microtubule-Associated Protein Expres- Trace Kershaw, nih, hiv/std Risk Among Complexes in Vivo: Response to Inflammation, Human Antibodies for Dengue Virus Infections, 1 sion and Predicting Taxane Response, 3 years, Young Expectant Fathers: Relationship Attach- 11 months, $13,272 • David Calderwood, U.S.- year, $77,122; L2 Diagnostics, llc, Antivirals $96,120 • Clifford Bogue, nih, Hex—A ment and Transition, 4.5 years, $2,537,672 Israel Binational Science Foundation, Cytoplas- Targeting Flavivirus Envelope Proteins, 1 year, Homeobox Gene Essential for Liver Development, Michael Krauthammer, nih, Text Mining as a mic Regulation of lfa-1 Assemblies Underlying $153,384 • Kitt Petersen, Novartis Pharmaceuti- 2 years, $432,300 • Lloyd Cantley, nih, Stem Translational Tool in Biomedicine, 3 years, Lymphocyte Adhesion Transmigration and cals, Regulation of Muscle pdh Flux in Different Cells in Organ Maintenance and Repair, 1 year, $439,857 • Daeyeol Lee, nih, Cortical Mecha- Immune Cell Recognition: The Talin Link, 4 Populations, 9 months, $202,010 • Marc $12,000 • Thomas Carpenter, nih, Center of nisms of Sequence Learning, 7 months, $303,729 years, $71,564 • Michael Carrithers, National Potenza, University of Maryland at Baltimore, Research Translation Program (cort), 5 years, Chiang-Shan Li, nih, Imaging Inhibitory Multiple Sclerosis Society, T Lymphocyte Sur- Genetic Contributions to Adolescent hiv Risk $8,213,600 • Kathleen Carroll, nih, Computer- Control in Cocaine Dependence, 1 year, $208,800 veillance and the Neuroprotective Barriers in Behavior, 1 year, $28,655 • Joseph Santos- Based Training for Cognitive Behavioral Haifan Lin, nih, Regulation of Germline Stem Health and Disease, 3 years, $415,719 • Owen Sacchi, Stanford University, New Technologies Therapy, 3.5 years, $1,407,143 • Junjie Chen, Cell Division in Drosophila, 1 year, $94,875 Chan, Juvenile Diabetes Research Foundation for Investigation of the Hair Cell Afferent Fiber nih, Study of the Role of dna Damage Brett Lindenbach, nih, Hepatocellular Carci- International, Role of gaba in Modulation of Synapse, 1 year, $74,587 • Gerald Shadel, Ameri- Reponses in Tumorigenesis and Senescence, 4.5 noma: Targeting hvc Replication, 3.5 years, Counterregulatory Responses to Hypoglycemia, 3 can Federation for Aging Research, Mouse years, $1,265,587; nih, Analysis of brca1 Func- $613,302 • Xiaomei Ma, nih, Myelodysplastic years, $89,308 • Junjie Chen, Susan G. Komen Models of Aging and Age-Related Pathology via tion in dna Repair, 4.5 years, $1,334,551; Syndromes: Previous Exposures, Survival, and Breast Cancer Foundation, Understanding the Mitochondrial dna Transformation, 1 year, Department of Defense, Genomic Instability Quality of Life, 5 years, $698,600 • Robert Tumor Suppression Function of brca1, 1 year, 7 $124,296 • Wei-Xing Shi, National Alliance for and Breast Cancer, 4 years, $825,000 • Yung-Chi Malison, nih, Genetics of Opioid Dependence months, $120,080; Mayo Clinic of Rochester, Research on Schizophrenia and Depression, Cheng, nih, Nucleoside Analogs as Anticancer in a Hmong (Thai) Isolate, 2 years, $553,320 Mayo Clinic Breast Cancer spore, 1 year, Prefrontal Control of DA Neurons in the vta, 2 Compounds, 4.5 years, $1,495,498 • Judy Cho, Irvin Modlin, nih, Molecular Strategies to $178,326 • Paul Cleary, Harvard University, years, $100,000 • Gerald Shulman, Medical nih, Mapping Chromosome 3q Inflammatory Define Carcinoids and Rationalize Surgical National Implementation of Medicines Con- College of Georgia, Coordinating and Bioinfor- Bowel Disease, 3 years, $867,270 • Jimmy Choi, Intervention, 3.5 years, $1,173,350 • Laura Nikla- sumer Assessment of Healthcare Providers and matics Unit for the Mouse Metabolic Phenotyp- nih, Motivation and Learning in Schizophrenia, son, nih, Biological Vascular Grafts, 4 years, 7 Systems, 7 months, $117,978 • Michael ing Center, 5 years, $511,500 • William Sledge, 1 year, $56,199 • Vladimir Coric, National Geo- months, $3,477,864 • Jordan Pober, nih, DiGiovanna, Breast Cancer Research Founda- Eli Lilly and Company, Recovery Guide Treat- spatial-Intelligence Agency, Efficacy of Forensic Chronic dth and ifn-gamma in Human Graft tion, Activated her2 as a Predictor of Thera- ment Program for Recurrent Psychiatric Hospi- Analysis in Detecting Deception During High Arteriosclerosis, 5 years, $11,635,495 peutic Response and as a Target in Novel Combi- talization, 1 year, $99,193 • Stefan Somlo, Stress Situations, 1 year, $119,632 • Kelly Cos- Vazhaikkurichi Rajendran, nih, Role of IK nation Therapies, 1 year, $249,263 • Wawrzyniec Plexxikon, Graft Inhibitors in Polycystic Kidney grove, nih, Brain Imaging of Sex Differences in Channels in Rat Distal Colon, 5 months, $1,614 Dobrucki, Juvenile Diabetes Research Founda- Disease, 1.5 years, $89,542; Icagen, Icagen Tobacco Smokers, 5 years, $893,700 • Joseph Faye Rogers, nih, Altered Helical Structures: tion International, Noninvasive Assessments of Research Agreement, 1 year, $41,214 • Scott Craft, nih, Genetic Analysis of T Cells in Lupus, Repair and Induction of Genomic Instability, 3 Myocardial and Peripheral Therapeutic Angio- Strobel, Howard Hughes Medical Institute, 5 years, $1,818,504 • Alan Dardik, nih, Flow years, $445,161 • Robert Sherwin, nih, Clinical genesis in Animal Models of Type-1 Diabetes Bioprospecting for Natural Products in the Responses to Carotid Angioplasty, 4.5 years, and Translational Science Award TL1, 4.5 years, Mellitus, 3 years, $88,214 • Glen Farr, American World’s Rainforests: An Undergraduate Science $665,550 • Christopher DeFeo, nih, Structure $57,330,994 • Arthur Simen, nih, Epigenetic Cancer Society, Regulation of Na,K-atpase Expedition, 4 years, $1,000,000 • Fattaneh and Function of the Human Copper Transporter, Factors in Stress-Enhanced Acquisition of Function by the Tetraspanin Protein CD81, 3 Tavassoli, Calibrant Biosystems, Breast Cancer 2 years, $66,060 • James Duncan, nih, LV Cocaine Self-Administration, 2 years, $330,083 years, $138,000 • Simmie Foster, United Negro Proteome via Laser-Free Microdissection and Strain Quantification from 4D Echocardiogra- Dennis Spencer, nih, Origin of Extracellular College Fund, An Adaptive Response of the Gemini Technologies, 2 years, $37,196 • Terence phy, 4.5 years, $7,244,829 • Brian Elbel, Agency Glutamate in Human Temporal Lobe Epilepsy, Innate Immune System, 2 years, $52,000 Trow, CoTherix, Educational Grant Agreement, for Health Care Research and Quality, Choice 3.5 years, $2,056,128 • Matthew State, nih, The Gerald Friedland, aids Project Hartford, hiv 1 year, $5,000 • Ping Wang, American Heart Sets and Consumer Selection of Health Plans, 1 Role of slitrk1 in Tourette and Related Disor- Prevention Intervention Research with hiv- Association (Heritage Affiliate), Role of plc- year, $32,400 • Julia Etchin, Department of the ders, 5 years, $2,217,291 • Rebecca Sweet, nih, positive Incarcerated Populations, 2 years, beta3 in the Initiation and Progression of Athero- Army, Molecular Basis for brca2-Mediated Autoimmune Memory Development and Main- $123,048 • Alison Galvani, James S. McDonnell sclerosis, 1.5 years, $70,000 • Dianqing Wu, Uni- dna Repair and Breast Tumor Supression, 3 tenance, 2.5 years, $127,392 • Fred Volkmar, Foundation, Developing and Applying Game versity of Connecticut, Vascular Remodeling: years, $97,200 • Leigh Evans, Agency for Health nih, Autism and Related Disorders: Develop- Theoretic Vaccination Models with Psychological Macrophage/Monocyte Signaling in Vascular Care Research and Quality, Simulation Training ment and Outcome, 5 years, $5,906,778 Data, 6 years, $442,905 • Alexandria Garino, Pathophysiology, 8 months, $148,873; University for Ultrasound Guided Central Venous Catheter Kathleen Wilson, Department of the Army, Physician Assistant Education Association, of Connecticut, Polarity in Networks and Path- Insertion, 2 years, $532,681 • John Forrest, nih, The Roles of nfbd1, 53BP1, and brca1 in the Improving Clinical Anatomy Recall and Spatial ways: The Study of Neutrophil Polarity, 7 Yale Predoctoral Clinical Research Training dna Damage Response, 3 years, $96,746 Reasoning in Physician Assistant Students, 1 months, $70,307 • Zhinan Yin, Amino UP Program, 1 month, $581,683 • Jorge Galán, nih, Dianqing Wu, nih, Wnt Signaling and Bone year, $2,500 • Walter Gilliam, Child Health & Chemical, ahcc Reduces Chemotherapy Side Predoctoral Training Program in Microbial Biology, 3 years, 6 months, $1,521,756; nih, Development Institute of Connecticut, Pre- Effects, 1 year, $19,800 • Yufeng Zhou, U.S.- Pathogenesis, 5 years, $1,061,569 • Joel Gelern- Molecular Function of Chemoattractant-Medi- school Mental Health Climate Scale: A Tool for Israel Binational Science Foundation, Activa- ter, nih, Genetics of Cocaine Dependence, 4 ated Signaling, 3 years, 6 months, $1,776,906 Preschool Mental Health Consultants and Other tion Gating of Potassium Channel Pores: A Uni- years, 7 months, $5,980,328 • Harindarpal Gill, Professionals, 1 year, $50,000 • Bryan Hains, fying Mechanism Controlled by Hydrophobic nih, nbce1 and n1: Crystal Structure Determi- Dana Foundation, Neuroimmune Modulation Interactions, 4 years, $19,205 nation, 2 years, $85,989 • Charles Greer, nih, Non-Federal of Chronic Pain after Spinal Cord Injury, 2 Mechanisms of Aging in the Olfactory System, 5 years, $200,000 • Robert Heimer, Gilead Foun- years, $6,652,339 • Mridu Gulati, National Ali Abu-Alfa, Genzyme, Genzyme–Yale Educa- dation, Evaluating the Effects of Expanded Institute for Occupational Safety and Health, tional Conferences, 7 months, $20,700 • Diana Hours for Syringe Exchange Programs in Con- Longitudinal Study of Respiratory Function in Beardsley, University of Massachusetts, Pre- necticut, 1 year, $25,000; Gilead Foundation, Aluminum Smelter Workers, 3 years, $291,600 vention of the Complications of Bleeding Disor- Pilot Intervention Research: Brief Care-Based Noam Harel, nih, Nogo’s Role in Intracellular ders, 1 year, $23,189 • Henry Binder, Christian hiv Prevention for Newly Diagnosed Men, 1 Trafficking, 4.5 years, $782,316 • George Hen- Medical College Hospital, Comprehensive year, $25,000 • Erica Herzog, Edward Mallinck- inger, nih, Substance Abuse Education for Studies of a New Improved Oral Rehydration rodt, Jr. Foundation, Mechanisms of Bone Medical Students, 2.5 years, $652,532; nih, Clin- Solution for Diarrheal Disease, 1 year, $69,250 Marrow: Epithelial Fusion in the Murine Lung, 3 ical and Basic Neurobiology of Nervous System Hilary Blumberg, National Alliance for years, $210,000 • Amy Justice, University of Diseases, 2 years, $134,362 • Henry Huang, nih, Research on Schizophrenia and Depression, California, San Francisco, Treatments for New pet Radioligand for Serotonin Transporter, Frontal Markers of Vulnerability and Resilience Complex Patients in New Settings, 1 year, 2 years, $714,183 • Karl Insogna, nih, Impact of to Bipolar Disorder, 2 years, $100,000 • James $24,800 • Mark Mamula, L2 Diagnostics, llc, a Protein Supplement on Bone Mass in Older Boyer, Mount Desert Island Biologic Labora- Modified her-2 Tumor Antigens for Vaccination Women, 4 years, $1,876,418 • Sven-Eric Jordt, tory, Development of a Comparative Toxicoge- in Cancer, 11 months, $264,075 • Aaron McGee, nih, trpa1 Channels in Sensory Neurons as nomics Database, 5 years, $22,890 • Michael Burroughs Wellcome Fund, Inhibition of Plas- With support from the National Institutes Targets for Environmental Irritants, 5 years, Bracken, Johns Hopkins University, Genome- ticity in the Adult Central Nervous System by of Health, Matthew State, m.d., ph.d., Harris $2,390,822; nih, Sensory Neural Mechanisms of Wide Association Studies of Asthma in Popula- Nogo-66 Receptor Signaling, 5 years, $500,000 Associate Professor of Child Psychiatry in Pulmonary Agent and Vesicant Toxicity, 4.5 tions of African Descent, 3 years, $188,881 Haiying Meng, International Dyslexia Associa- the Child Study Center, is studying the role years, $2,446,733 • Amy Justice, nih, Veterans David Brissette, Physician Assistant Education tion, A Deletion in Intron 2 of dcdc2 Gene of a gene known as slitrk1 (bright blue Aging Cohort Study, 5 years, $13,928,272 • Joan Association, Physician Assistants as Medicine Regulates Protein Expression in Developmental areas at left of photo) in Tourette’s syn- Kaufman, nih, Genetic and Environment Mod- Hospitalists, 1 year, $4,972 • Richard Bucala, Dyslexics, 1 year, $10,000 • Yorgo Modis, L2 drome and related disorders.

Orthwein from page 1

ers Orthwein a “surrogate father” and Jones, an attorney in the St. the city, including St. Luke’s Hospital, Though he has enjoyed good often refers to him as “Uncle Bill.” Louis-based firm of Armstrong the Saint Louis Symphony Orchestra, vision throughout his life, Orthwein “He is one of the guys who, when I Teasdale llp, says that Orthwein has the Saint Louis Zoo, the Saint Louis had a personal encounter with visual was faced with a particularly vexing been the most prominent figure in the Science Center and the Missouri science in 1993, when his ophthal- question, I would ask ‘What would my St. Louis community of Yale alumni, a Botanical Garden. “His involvement mologist reported on his anisocoria, father do?’ and then ‘What would Bill “symbol of Yale” for as long as he can in the Yale community and in the St. or uneven pupil size, and its possible Orthwein do?’ ” Jones says. “It’s a role remember, and that he has given over Louis community more generally, in relation to the dispersion of pig- that he has always played, and will 100 years of combined service to cul- terms of his time, his talent and his ment from his iris, in the Journal of always play in my life.” tural and charitable organizations in treasure, is remarkable.” Glaucoma.  Medicine@Yale May/June 2007 cyan mag yelo black MAC Honoring fifty years of far-reaching scientific influence Physiologist caps Gerhard Giebisch ology, says that Giebisch is driven by (left) and his an insatiable curiosity and love of an illustrious career longtime friend beauty in both his scientific and per- and collaborator with nephrology award Peter Aronson at the sonal life, citing his annual mountain- American Society of eering trips to the Alps—including In recognition of his 50 years of Nephrology’s annual one undertaken last fall at age 80—his meeting in Novem- fluency in several languages and his research, teaching and leadership ber 2006. in the field of nephrology, Gerhard exhaustive knowledge of classical H. Giebisch, m.d., Sterling Profes- music and opera. sor Emeritus of Cellular and Mo- For Aronson, Giebisch was a lecular Physiology, was awarded the natural choice for the Peters Award, 2006 John P. Peters Award from the chanan Professor of which honors broad contributions to American Society of Nephrology Internal Medicine the field over and above a successful (asn). Giebisch is the first Yale faculty at UT Southwestern research career. “He’s trained many, member to receive the Peters Award, Medical Center in many people who have gone on to named in honor of a well-known Dallas, he is co- open laboratories all over the world. physician-scientist who served as editor of the pre- He’s been a leader in many societies, chief of the Metabolic Section of Yale’s eminent textbook organized many conferences and he’s Department of Medicine from 1922 in nephrology, The edited what has become the major to 1955. Kidney: Physiology textbook in renal physiology,” says Born in Vienna, Austria, Giebisch and Pathophysiology. Aronson. “For the last thirty years, Dr. moved from Cornell University Medi- He has been a Giebisch has been probably the most cal College to Yale in 1968 to chair the research mentor prominent ‘international statesman’ School of Medicine’s Department of nephron, the kidney’s basic structural to over 75 trainees who now work of nephrology.” Cellular and Molecular Physiology. He and functional unit. He also employed as physiologists and nephrologists Dean and Ensign Professor of won the asn’s Homer Smith Award in patch-clamping techniques to record throughout the world. Giebisch was Medicine Robert J. Alpern, m.d., 1971 for his research elucidating how the movement of ions through chan- president of the asn from 1971 to himself a nephrologist and researcher, hormones and diuretic drugs affect nels within the membrane of kidney 1972, and he has served on numerous concurs. the passage of ions such as potassium, cells. Giebisch has endeavored to editorial boards for scientific journals “While Gerhard has been honored sodium and chloride across cell mem- frame these fine-grained details in and on study sections that review throughout his career for his research, branes in the tubules of the kidney, a terms of how they affect kidney func- grant proposals for the National the Peters Award recognizes his con- process that is crucial to maintaining tion in the whole organism. “You can Institutes of Health. He is a member tributions to the broader nephrology chemical balance in the body’s inter- take the system apart to do detailed of The National Academy of Sci- community,” Alpern says. “He has nal environment. analysis,” he has said, “but the art is to ences and has received five honorary directly mentored researchers all over In this work, Giebisch used tech- put it all back together.” doctorates. the world, but in addition Gerhard niques known as micropuncture and Giebisch is the author or co- His colleague and collaborator has been an advisor and supporter for microperfusion to precisely map how author of more than 400 research Peter S. Aronson, m.d., the c.n.h. a multitude of researchers in nephrol- and where potassium is secreted and articles and book chapters. With Don- Long Professor of Medicine and pro- ogy. He is internationally recognized excreted at various points along the ald W. Seldin, m.d., the William Bu- fessor of cellular and molecular physi- for his intellect and generosity.” Scientist wins Wiley Prize for research on protein-folding

Although Arthur L. Horwich, m.d., B. Anfinsen,ph .d., who showed that chain and attempt- approach, his group is seeking to prefers to spend as much of his time folding instructions are encoded in ing once again to elucidate the structure of fibrillar as possible in the lab, he made a the sequence of amino acids that correctly fold it. aggregates formed in one such disease, happy exception on April 6, when he make up proteins, in 1989 Horwich’s This process of so-called amyloid. He is also working traveled to The Rockefeller University lab, in a collaboration with Hartl cycling consumes on a model of amyotrophic lateral in New York City to accept the Wiley and his postdoctoral mentor Walter cellular energy sclerosis, a paralyzing movement Prize in Biomedical Sciences. The Neupert, reported in the journal in the form of disorder, known also as Lou Gehrig’s prize is given by the Wiley Founda- Nature that a specialized mitochon- adenosine tri- disease, which is in some cases caused tion, which was established in 2001 drial protein called Hsp60 acts as a phosphate, or atp, by misfolding of a specific enzyme, by John Wiley & Sons, a 200-year-old protein-folding “machine.” Because of Arthur Horwich which binds to the superoxide dismutase. Work in publisher of scientific, technical and this protein’s helping role, it was soon machine to enable the encapsulation microscopic nematode worms has medical books and online services. dubbed a “chaperonin.” Horwich and step and then hydrolyzes thereafter, shown that misfolding of this par- Horwich, the Eugene Higgins Hartl and their colleagues then went allowing release of polypeptide. ticular protein causes a paralyzing Professor of Genetics and Pediat- on to elucidate the mechanism of “Art’s work has beautifully disorder in them as well. rics and a Howard Hughes Medical action of the machine using the bacte- demonstrated that the notion that Horwich and Hartl have also Institute investigator, was honored rial relative called GroEL. all proteins can fold unassisted is won the 2004 International Award along with Franz-Ulrich Hartl, m.d., Chaperonins are double-ringed simply wrong. In fact, emerging from Canada’s Gairdner Founda- dr.med., of the Max Planck Institute molecules that assist in protein fold- evidence from his lab suggests that tion, which recognizes outstanding of Biochemistry in Germany for their ing by binding unfolded proteins in in the absence of the protein- achievements in biomedical research, significant contributions to under- an open ring and then encapsulat- folding machines he has discovered and the 2006 Stein and Moore Award standing how proteins fold. Scientists ing them under a cooperating “lid” and characterized, cellular life is from The Protein Society. Horwich have long wondered how proteins structure (GroES) where they can fold impossible,” says Richard P. Lifton, was elected to the National Academy make the transformation from chains without sticking to each other. This m.d., ph.d., chair and Sterling Pro- of Sciences in 2003 and was named of amino acids to three-dimensional prevention of aggregation is an im- fessor of Genetics and professor of a fellow of the American Association structures whose specific shape portant function because such aggre- medicine and molecular biophysics for the Advancement of Science determines their function. Over the gates can harm the cell as in a number and biochemistry. “His work has truly last year. last 17 years, Horwich and Hartl’s labs of neurodegenerative diseases. The revolutionized our understanding Horwich has been a member of have helped unravel this mystery. two rings of a chaperonin take turns of the most fundamental aspects of the medical school faculty since 1984, “In some respects it’s a recogni- binding and folding proteins so that cellular physiology.” when he joined as an assistant profes- tion of our field,” says Horwich. as one ring finishes a folding reac- It remains unclear why the sor of genetics. Now, as a full professor “People are beginning to recognize tion, the other takes over with a new chaperone machines are unable to in the same department, he works as that chaperone-type machines are “substrate” polypeptide. prevent a number of neurodegenera- a bi-coastal scientist, splitting his time significant and play a significant role Oftentimes a protein does not fold tive diseases in which protein misfold- between New Haven and the Scripps in the cell.” Horwich and Hartl will properly with one passage into the ing occurs, like Alzheimer’s Disease, Research Institute in La Jolla, Ca. He divide a $25,000 grant, and each gave machine and will be released from it Parkinson’s Disease, Huntington’s holds an a.b. and m.d. from Brown a special lecture at Rockefeller. without having reached folded form; Disease, and mad cow disease, and University and completed his resi- Building on the work of Nobel the machine will then make another these days Horwich has turned his dency and internship in pediatrics at prize-winning biochemist Christian attempt, binding the non-folded attention to such diseases. In one Yale-New Haven Hospital. 8 www.medicineatyale.org