A Passionate Venture Gives Back to Yale Henry Mccance Applauds the “Can-Do by Aiding Students Alum’S $2.5 Million Gift Spirit” of the Yale Scholars Initiative

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Advancing Biomedical Science, Education and Health Care Volume 3, Issue 2 March/April 2007 New PET center will aid drug development@ Medicinemay continue to deteriorate while which contributed $5 million to helpYale State-of-the-art scans their doctors seek the best treatment. establish it and provides $2 million unveil biological processes Researchers at Yale’s new Positron annually to support pet imaging in the living human body Emission Tomography (pet) Center studies of mutual research interest to hope to bring light into this dark- Pfizer and Yale. Although molecular medicine has ness and speed the development of The center’s faculty also hopes to made striking advances in recent new medications by developing novel build additional alliances with other years, for many diseases physicians imaging tools that reveal otherwise companies, but the majority of the are still stumbling in the dark, able hidden molecular abnormalities. research conducted at the center is to glean clues to a therapy’s effective- The development of the cen- anticipated to be supported by fed- The PET center’s senior faculty are Direc- ness only by studying changes in ter was made possible, in part, by eral research grants. tor James Frost (second from right), Henry symptoms. In many cases, patients Pfizer, the pharmaceutical company, PET, page 6 Huang (left) and Co-Directors Yu-Shin Ding (seated ) and Richard Carson. A ‘country doctor’ A passionate venture gives back to Yale Henry McCance applauds the “can-do by aiding students Alum’s $2.5 million gift spirit” of the Yale Scholars initiative. to Yale Scholars program When the late John E. Borowy, m.d., spurs study of Alzheimer’s enrolled in the School of Medicine incumbent legacy of a corporate gi- in 1946 after serving in World War II, Henry F. McCance, m.b.a., has a ant,” says McCance, a 1964 alumnus of he had few financial resources to fall special knack for spotting talent and Yale College. “They haven’t been told back on. According helping young people to realize their it can’t be done, so they go do it. The to Borowy’s nephew, aspirations. Over the course of a idea of supporting the best up-and- Louis “Skip” De- 40-year career at Greylock Partners, coming research talent under the Yale Beradinis, his uncle’s a venture capital firm in Waltham, Scholars program embodies that sort working-class par- Mass., McCance and his partners of entrepreneurial can-do spirit.” ents were elderly and have shepherded almost 300 software Robert J. Alpern, m.d., dean and infirm, and Borowy companies from idea to reality, a track relied on the GI Bill Ensign Professor of Medicine, says, “I John Borowy record that earned him the National am delighted that Henry has cho- and income from Venture Capital Association’s Lifetime sen to support our efforts to find a odd jobs to make his way through Achievement Award in 2004. treatment for Alzheimer’s, and I am medical school. When a family member was diag- especially excited that he will do this Borowy, a revered “country doc- nosed with early Alzheimer’s disease and appealing ring. McCance got on through the Yale Scholars program, tor” in his hometown of Stamford, seven years ago, McCance decided to board enthusiastically with a $2.5 which focuses support on young Conn., for 45 years, recalled his days apply the skills he had honed during million gift endowing the Henry F. investigators.” as a member of the School of Medi- his four decades at Greylock into a McCance Yale Scholar, an honor that Yale ties are strong in McCance’s cine’s Class of 1950 with affection and plan of attack on the disease, which will be bestowed every four years on family. His father, Thomas McCance, gratitude, says DeBeradinis. Borowy, has stubbornly resisted effective diag- a new faculty member in the medical a member of Yale’s Class of 1925, was who died in February 2006, had no nosis. In 2005, McCance co-founded school’s program in Cellular Neuro- a partner at Brown Brothers Harri- children. He left virtually his entire the Cure Alzheimer’s Fund (caf), science, Neurodegeneration and man and Co. in New York City, and estate to the medical school to endow which explicitly adopted a venture Repair. Yale University will match his brother, Thomas McCance Jr., a $2.4 million scholarship fund, a capital approach to fund research McCance’s gift to create a $5 million graduated from the university in 1955. legacy that will benefit deserving “with the highest probability of slow- total endowment, and McCance has Henry says that his father’s example medical students for years to come. ing, stopping or reversing Alzheimer’s contributed an additional $250,000 in inspired him to study economics at “I am so grateful to John Borowy disease by 2016.” current-use funds to ensure that the Yale. “I grew up with it at the kitchen and his nephew, Louis DeBeradinis,” So when McCance first heard first McCance Yale Scholar recruit will table, and then continued at Yale.” says Robert J. Alpern, m.d., dean of about the School of Medicine’s Yale receive support immediately. McCance went on to earn a the School of Medicine. “Dr. Borowy’s Scholars initiative, which provides “Startups are often founded by master’s degree at Harvard Business appreciation for his Yale education support to outstanding young faculty and take their vision from a young, School and then worked for two years and the commitment of his estate to members as they embark on research talented person who really ‘doesn’t for the Department of Defense during scholarships for our students was an careers, the concept had a familiar know any better’ than to take on the McCance, page 8 Borowy, page 6

Non-Profit Org. Inside this issue Medicine@Yale U. S. Postage Lifelines Science in the city 300 George St., Suite 773 PAID Oncologist Kenneth Miller goes Partnership with local high school New Haven, CT 06511 New Haven, CT the extra mile, p. 2 celebrates 10th birthday, p. 5 www.medicineatyale.org Permit No. 526 A step ahead Cause for celebration Pioneering immunology group Yale scientist is honored by is officially a department, p. 3 lupus foundation, p. 8 Topping the charts Also Yale research makes Science’s Advances, pp. 3, 5; Out & About, p. 4; list of 2006 breakthroughs, p. 5 Grants, p. 7; Awards & Honors, p. 8

Want to find out more about medicine at Yale? E-mail us at [email protected] or phone (203) 785-5824. cyan mag yelo black 1605 MAC Cell-signaling expert will lead vascular biology William C. Sessa, ph.d., an expert on blood vessel function in health and disease, has been named director of the medical school’s Program in Vascular Biology and Transplantation A weekly radio show is (vbt). Sessa, vice chair and professor just one of the many of pharmacology, has served as deputy ways in which Kenneth director of vbt since 2005. Miller reaches out to Founded in 2000, vbt was the cancer patients and their families. Miller School of Medicine’s first interdepart- also writes books on mental research program explicitly cancer for a lay audi- focused on translating laboratory ence, and he leads a discoveries into practical treatments regular forum where Yale Cancer Center staff for disease. The 35 members of the can provide support for program, drawn one another. from numerous basic science and clinical departments, A commitment to compassion study the role of vascular biology in years. Miller took a position at ycc “There is a spectrum of things Oncologist grapples with the heart disease and in 2005. that happen to people who have personal impact of cancer peripheral vascular With support from the Kenneth been through the cancer experi- William Sessa diseases, cancer and on families and caregivers B. Schwartz Center, Miller has insti- ence,” Miller says, “and we’re trying stroke. Faculty also search for ways tuted a regular forum in which ycc to address some of these issues in a Throughout his 18 years as an to improve outcomes in organ-trans- doctors, nurses and social workers meaningful way.” Miller is also in the oncologist, Kenneth D. Miller, m.d., plant patients. discuss the difficult emotional and process of building a palliative care has always tried to go above and Sessa studies the signals sent by social issues that can arise when team at Yale to ensure that people beyond what many consider to be various proteins and by the gas nitric caring for patients who are severely receive the same level of medical adequate care for patients and their oxide in endothelial cells that form a ill. Although the sessions focus on attention at the end of life as they families. But it wasn’t until his wife thin lining inside blood vessels. When the caregivers’ feelings, their ulti- do while they are undergoing treat- was diagnosed with acute leukemia these signals are disrupted, vascular mate aim is to provide more com- ment. “We’re all going to reach the in 1999 that he gained a personal disease can result. passionate care to patients. end of life,” he says. “Everyone we understanding of what it is like to As director, he succeeds Jordan Miller’s parents lost many treat should be offered the best that live with cancer. That experience S. Pober, m.d., ph.d., the vbt friends to cancer as they aged, but we can give in terms of holistic and prompted him to reflect on how program’s founder and professor today patients are compassionate care.” patients are cared for not just during of pathology, immunobiology and Lifelines surviving longer, Along with Edward Chu, m.d., treatment but afterward, and it has dermatology. Pober will now head the sometimes with professor of medicine and ycc culminated in his work as the first Kenneth medical school’s program in Human acute disease, creat- deputy director (see related story director of supportive oncology ser- Translational Immunology. Miller ing a new demand below), Miller co-hosts the weekly vices at Yale Cancer Center (ycc). “vbt is lucky to have Bill Sessa, an for strategies to address psycho- Healthline show on wtic-am radio Miller, assistant professor of outstanding vascular biologist who is social as well as medical issues. in Hartford. He frequently gives lec- medicine, traces his interest in deeply committed to the application In October 2006, as part of Yale’s tures to spread his message about oncology to his childhood in Hart- of basic research to real clinical prob- effort to offer patients a broader how caregivers can contribute to ford, when he accompanied his lems,” says Pober. “I expect him to lead range of care, Miller helped open the patients’ quality of life, and he is father to the medical appointments the program in new directions and Connecticut Challenge Adult Sur- distilling his insights into a book, of a number of friends who had toward ever greater achievements.” cancer. After graduating from Tufts vivorship Clinic, where he serves as tentatively entitled Walking in Our University School of Medicine, Miller medical director. Patients’ Shoes: The Role of Empathy returned to Connecticut for his resi- The clinic, named for an annual in Medicine. Another book, Choices in bicycle ride in Fairfield, Conn., that Breast Cancer, is now in press. dency at Yale-New Haven Hospital @ and then completed two fellow- benefits survivorship programs at Miller says that caring for his MedicinePeter Farley, ManagingYale Editor patients, developing programs to ships, one in hematology at the ycc, helps patients who have Contributors: Amy Chow, Rebecca Deusser, Jill Max, National Institutes of Health and finished treatment to reflect on the help improve the quality of life for Karen Peart, Jacqueline Weaver, Marc Wortman experience and begin to rebuild cancer survivors, and working on Photographs and Illustrations: American Association another in medical oncology at the for the Advancement of Science, Hal Blumenfeld, end-of-life issues are all pieces of the Johns Hopkins Oncology Center. their lives. John Curtis, Terry Dagradi, Louis DeBeradinis, He practiced medical oncology Another of the clinic’s programs same puzzle: how to provide com- ©Images.com/CORBIS, Yong Woo Jung, Robert Lisak, assists cancer survivors who are still passionate care to cancer patients at Mark Ostow, Margaret Sasaki, William Simpson, in the community, and then went on Hannah Fairfield Wallander every stage of their illness. “It all fits to work for Connecticut Hospice as undergoing treatment and are expe- Design: Peter W. Johnson, Maura Gianakos/Yale RIS riencing complications. together as a package.” associate medical director for two Medicine@Yale is published six times each year by the Office of Institutional Planning and Communications, Yale School of Medicine, 300 George St., Suite 773, New Haven, CT 06511. Telephone: (203) 785-5824 Medical oncologist is appointed deputy director of Cancer Center Fax: (203) 785-4327 E-mail: [email protected] Yale Cancer Center Yale in 1996 from the National Cancer and enters a new phase of expansion Website: medicineatyale.org

(ycc) is expand- Institute, where he was a tenured with the opening of our new clinical Copyright ©2007 by Yale School of Medicine. ing, and so is the senior clinical investigator. He is facility in 2009,” said ycc Director All rights reserved. role of Edward Chu, internationally known for his research Richard L. Edelson, m.d. If you have a change of address or do not wish m.d. Chu has been on tumor resistance to chemotherapy Chu moves into his new posi- to receive future issues of Medicine@Yale, appointed deputy di- and on new compounds for colorectal tion in the footsteps of José Costa, please write to us at the above address rector of ycc, where cancer. m.d., who helped lead the center for or via e-mail at [email protected]. he will also continue Over the last two years, Chu has 10 years, developing research pro- Postal permit held by Yale University, Edward Chu to direct the center’s recruited 11 clinical investigators from grams and guiding ycc through two 155 Whitney Avenue, New Haven, CT 06520 clinical research initiatives and serve around the country as part of his comprehensive grant submissions to Yale School of Medicine Robert J. Alpern, m.d., Dean as chief of medical oncology. plan to transform Yale into a center of the National Cancer Institute. Costa, Ensign Professor of Medicine Chu, professor of medicine and translational research. professor of pathology and medicine, Mary Hu pharmacology, graduated from Brown “Ed’s experience and dedication remains an active member of the Director of Institutional Planning and Communications University with undergraduate, mas- will be a tremendous asset as Yale Cancer Center and vice chair of the Michael Fitzsousa, Director of Communications ter’s and medical degrees. He came to Cancer Center continues to grow Department of Pathology.

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Advances Immunology comes of age at medical school Health and science news from Yale Top-ranked, influential In this image, made by postdoc- toral associate Yong Woo Jung, research group now a ph.d., in the laboratory of Susan Kaech, ph.d., assistant professor full-fledged department of immunobiology, CD8 T cells (green) are responding to viral Ever since Edward Jenner first pre- infection in the spleen. B cells are vented smallpox infection by injecting seen in red. Breathing easier an English boy with cowpox virus in the 1790s, scientists have worked Understanding the immune about lung injury? to conquer infectious diseases by response is also crucial to untan- gling how it goes awry in autoim- Patients with heart or lung prob- understanding and strengthening mune diseases. Peter Cresswell, lems, including premature babies, the immune response. Yet as recently are given supplemental oxygen. as three decades ago, the most basic the adaptive system with the necessary ph.d., professor of immunobiology, But this intervention is sometimes principles of modern immunology advance intelligence to do its job. dermatology and cell biology, studies too much of a good thing, because eluded researchers, who were scat- “It was like saying there are only how proteins get broken down and prolonged high concentrations of tered across university departments, four planets in the solar system and then “displayed” by antigen-present- oxygen can cause hyperoxic acute working largely in isolation. then one day somebody comes along ing cells that allow T cells to recognize lung injury, or hali, in which the At the School of Medicine all that and says, no, there are eight,” says them. lungs’ capillaries become leaky. began to change in 1988. The adminis- David G. Schatz, ph.d., professor of Schatz is focusing on two proteins The protein angiopoietin-2 tration decided to continue the work immunobiology. he discovered that are involved in (Ang2) destabilizes blood vessels, of the late Richard Gershon, m.d., According to the National Library antibody production and without so Jack A. Elias, m.d., the Waldemar of Medicine, nearly 6,000 scientific ar- which there would be no adaptive Von Zedtwitz Professor and chair who had established an immunology ticles on toll-like receptors have been immune response. of internal medicine, led a study to division within the pathology see whether Ang2 might contrib- department, by recruiting Richard A. published in the wake of Janeway and Sankar Ghosh, ph.d., profes- ute to hali. Flavell, ph.d., to create the Section of Medzhitov’s seminal article, but this is sor of immunobiology, molecular In the November 5, 2006 issue Immunobiology, one of the first just one of many important contribu- biophysics and biochemistry and of Nature Medicine, Elias’s team freestanding groups in the country tions that have emanated from the molecular, cellular and developmental reported high Ang2 levels and devoted to teaching and research in department. biology, has concentrated on a pro- greater cell death in fluids and immunology. Flavell has focused on genetics by tein called NF-κB that allows toll-like lung tissue taken from mice, adult Almost 20 years later, Flavell, now examining how different genes con- receptors to send signals. NF-κB is humans and premature infants af- Sterling Professor of Immunobiol- tribute to the decision-making pro- involved in every kind of inflamma- ter exposure to high oxygen levels. ogy, continues to lead the School of cess that gives rise to two important tory process, from the redness that But mice treated with rna that immune cells known as Th1 and Th2 results when a splinter penetrates the suppressed Ang2 expression had Medicine’s immunologists, but in cells, which regulate the type of im- skin to cancer. far less damage, and mice bred to January his Section of Immunobiol- lack Ang2 lived significantly longer ogy became a full-fledged academic mune response generated by the body. The explosive growth of knowl- than their counterparts, raising department. What started out in 1988 Flavell’s lab has identified molecules edge from the Department of the possibility that drugs de- as a handful of scientists has grown to involved in activating and differentiat- Immunobiology’s basic research over signed to curb Ang2 could protect include 13 world-renowned research- ing T cells that could be useful for the last two decades has led to an patients against hali. ers, including four investigators of the treating hiv and cancer. increasing awareness that the clinical Vineet Bhandari, m.b.b.s., m.d., highly competitive Howard Hughes T cells are also an area of inter- relevance of immunobiology goes far d.m., assistant professor of Medical Institute and two members est for Kim Bottomly, ph.d., Yale’s beyond protection against disease. pediatrics and first author, says of two of the world’s most presti- deputy provost for science, technology Immune mechanisms may lie at the that the study was true bench-to- gious scientific societies: the National and faculty development and profes- root of numerous chronic diseases, bedside research. “All the work sor of immunobiology, dermatology including cancer, coronary artery was initially done on mice ... and Academy of Sciences (nas) and the and molecular, cellular and develop- disease and Alzheimer’s disease. The then we showed its clinical United Kingdom’s Royal Society. “We relevance in human patients with strategized about it and planned very mental biology. Bottomly’s lab has department remains in the scientific acute lung injury.” carefully what we wanted to build, shown that the immune response to vanguard with the recently launched and that’s what we built,” says Flavell. allergens, such as those that provoke Human and Translational Immunol- Yale’s newly christened Depart- asthma, stems from their similarities ogy program, which will work on Changes in Medicare ment of Immunobiology was named to microbes that jump-start the im- applying lessons learned in the lab to help prevent cancers the best in its field in the United mune system. human beings. States in a Chronicle of Higher Educa- When Medicare coverage expand- tion survey published in January. In ed to include screening for colon 2006, department members had over cancer, early diagnosis and treat- $18 million in combined federal Immunobiology chair named to Institute of Medicine ment also increased, according and non-federal research funding; to a report by School of Medicine Richard A. Flavell, ph.d., chair of the and retroviral tech- between 1999 and 2006 the faculty researchers in the December 20, new Department of Immunobiology at nology to elucidate collectively published more than 70 2006, issue of JAMA: The Journal of Yale and an internationally recognized the function of these scientific articles in the top science the American Medical Association. scientist, was named to the Institute of genes and their Medicare reimbursement journals Science, Nature and Cell. Medicine (iom) in October. target sequences. rules first changed in 1998 to A prime example of the depart- The iom was established in 1970 A Howard cover screening colonoscopies for ment’s far-reaching influence is the by the National Academy of Sci- Hughes Medical patients at risk for colon cancer. In discovery of the so-called toll-like ences and is recognized as a national Institute investigator, 2001 coverage was expanded to receptors of the innate immune Richard Flavell resource for independent, scientifically Flavell also studies include all Medicare recipients. system in the 1990s. At that time, A team led by Cary P. Gross, informed analyses and recommen- the mechanisms of programmed most immunology researchers were m.d., associate professor of medi- dations on issues related to human cell death using mice lacking death- focused on the adaptive immune cine, found that colonoscopies health. Those elected to the institute effector molecules, and he investigates system, which quickly creates cus- have increased by 600 percent have made significant contribu- the molecular and cellular bases of tom-made B and T cells that target since the first Medicare change. tions to the advancement of medical autoimmune disease. specific bacterial or viral invaders. But The percentage of patients diag- science, health care and public health, “Richard’s research is outstanding, nosed at an early stage increased the late Charles A. Janeway Jr., m.d., and election is considered one of the clearly placing him among the best from 22.5 percent to 25.5 percent wondered how the adaptive immune highest honors in the health sciences. immunologists in the world,” says since 1998; after 2001, that per- system is able to act so precisely every Flavell, the Sterling Professor of Dean Robert J. Alpern, m.d., Ensign Pro- centage rose to 26.3. time the body is invaded by an infec- Immunobiology, studies the molecular fessor of Medicine. “This is combined “These data strongly support tious microbe. basis of T-cell differentiation in the with a talent for leadership that has initiatives to increase access to and In a scientific tour de force pub- use of screening colonoscopy, yet immune system. His research team allowed him to cultivate an immu- lished in 1997 in the journal Nature, more work needs to be done, as has used genomic approaches to nology program that is unsurpassed Janeway and Ruslan M. Medzhitov, many eligible patients still are not identify the genes that are selectively anywhere. His wisdom and experience ph.d., professor of immunobiology, receiving appropriate screening for expressed in T-cell lineages, and has should prove valuable to the Institute showed that toll-like receptors, a com- colorectal cancer,” Gross says. used gene targeting, transgenic mice, of Medicine.” ponent of the innate system, provide

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Out & about

4 1 2 October 12: wtnh 1 meteorologist “Dr. Mel” Goldstein celebrated his 10th year as a cancer survivor with friends and colleagues at the wonder of it all, a reception and concert held at the New Haven 3 4 Lawn Club. The event helped double the Dr. November 18: The Commons at Yale’s Woolsey Hall was the setting for the Mel Goldstein Multiple third annual discovery to cure gala, which raised over $345,000 to 2 Myeloma Research Fund support research on early detection of and new treatments for ovarian, cervi- at Yale Cancer Center cal and uterine cancers. Peter E. Schwartz, m.d., the John Slade Ely Professor (ycc), pushing the fund of Obstetrics, Gynecology and Reproductive Sciences, was honored with the above $200,000. Gold- announcement of an endowment established in his name by friends, col- stein established the leagues, patients and family. 1. (From left) Kenneth Schwartz and Michelle fund in 1999, three years Fantaci; Andrew Schwartz and Kelly Arnett, ph.d., Peter Schwartz and Arlene after being diagnosed Schwartz; Anne and Bruce Schwartz. 2. José Costa, m.d., professor of pathol- with multiple myeloma. ogy and medicine and vice chair of the Department of Pathology, (left) with 1. (From left) Richard L. Connecticut Attorney General Richard Blumenthal. 3. (From left) Honor- Edelson, m.d., profes- ary Discovery to Cure Chair Rosanne Malouf, Donna Malouf, and Thomas J. sor of dermatology and Rutherford, ph.d., m.d., associate professor of obstetrics, gynecology and director of ycc, with reproductive sciences. 4. (From left) Richard L. Edelson, m.d., professor of der- 3 Goldstein. 2. An avid jazz matology and director of Yale Cancer Center; Ruth Edelson; Discovery to Cure fan and pianist, Goldstein performed “The Circle,” a song he composed for Chair Debra Levin and Marshall Levin. the occasion, accompanied by the John Pizzarelli and John Oddo Quartet featuring the Legends of Jazz. 3. (From right) Ron Shaw, president and chief executive officer of the Pilot Pen Corporation of America, and wtnh anchor Jocelyn Maminta presented Goldstein with a signed photograph, Sunrise on the Sound, donated by photographer Harold Shapiro. 4. Congress- woman Rosa L. DeLauro (D-Conn.) was in attendance.

December 12: 1. The Yale Cancer Center (ycc) hosted Christian McEvoy, cofounder of coast to coast: a run for survivorship, when he arrived in New Haven on a five-month, 3,500-mile run across the country to raise awareness and 1 2 funds for cancer survivors. 2. McEvoy (center in white shirt) joined Richard L. Edelson, m.d., director of ycc (on McEvoy’s left) and Kenneth D. Miller, m.d., director of the Connecticut Chal- lenge Adult Survivorship Clinic (on 1 McEvoy’s right), along with ycc staff and cancer survivors before the group took a ceremonial 1.5 mile run through the city. 3 Jan 25: At the New Haven Lawn Club, Robert J. Alpern, m.d., dean and Ensign Professor of Medicine, hosted a luncheon for retired and emeritus faculty who reside in the New Haven area. 1. Arthur Ebbert Jr., m.d., professor emeritus of medicine 4 and former deputy dean of the medical school (left), with Wayne O. Southwick, m.d., former chair and professor emeritus of orthopaedics and rehabilitation. 2. (From left) Arthur B. DuBois, m.d., professor emeritus of epidemiology, Brenda Ritchie, G. Eric Schonewald, development officer for the medical school, and J. Murdoch Ritchie, ph.d., professor emeritus of pharmacology. 3. (From left) Jack R. Cooper, ph.d., professor emeritus of pharmacology, David Seligson, m.d., sc.d., professor emeritus of laboratory medicine, Charles M. Radding, m.d., professor emeritus of genetics, Robert E. Handschumacher, ph.d., professor emeritus of pharmacology and Peter Lengyel, ph.d., professor emeritus and senior research scientist in molecular biophysics and biochemistry. 4. Robert H. 2 Gifford, m.d., professor emeritus of medicine and former deputy dean for education.

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Advances Yale research makes Science’s ‘top 10’ list Health and science news from Yale Faculty, alumnus research “Discovery of the association of is founder cfh and amd changed the direction and chair- cited by premier journal as of macular degeneration research,” man of the “breakthroughs” of 2006 Hoh says, adding that one of the most board of 454 rewarding aspects of her work has Life Sciences, The research of two School of Medi- been the collaboration it has sparked a Branford, cine researchers and a Yale alumnus— with other scientists. Conn., work on the genetics of a devastating Haifan Lin, ph.d., professor of company Inclined by genes eye disorder, the capacity of stem cells cell biology and director of the Yale that created toward nicotine to make identical copies of themselves Stem Cell Center, was one of four technology and the decoding of the Neanderthal scientists whose laboratories were for the rapid Nearly 5 million people die pre- listed as contributing to break- sequencing of maturely each year from diseases genome—has been recognized by the related to smoking. Yet the World journal Science as among the top 10 throughs in the understanding of genomes. (The sequencer Rothberg’s Health Organization estimates scientific breakthroughs of 2006. small rna molecules known as Piwi- company developed played a role in that more than a billion people The journal cited two genomic interacting rnas, or pirnas. Lin’s lab the discovery of pirnas; two of the smoke, a testament to tobacco’s studies of age-related macular de- first discoveredpiwi /argonaute genes, labs in Science’s top 10 list used the addictive nature. generation (amd) led by Josephine which are essential for the self- technology, and stem cell expert Lin is Growing evidence indicates J. Hoh, ph.d., associate professor of renewal of stem cells, in 1998. But it currently using it in his work.) that some of the tendency for epidemiology and of ophthalmology was not understood what roles these Rothberg and his collaborators in nicotine dependence is inherited. and visual science, along with several genes play in stem cell division until Germany and Croatia took the No. 2 Using dna from smokers in Afri- other amd studies, as represent- last year, when Lin’s group showed slot on Science’s list for successfully can-American and European-Amer- ing significant progress against the that Piwi/Argonaute proteins bind analyzing 1 million base pairs in dna ican families, Joel Gelernter, m.d., to pirnas. taken from a 38,000-year-old Nean- professor of psychiatry, genetics disease, the most common cause of and neurobiology, and colleagues blindness in people over the age of 50. “Despite their tiny size, Piwi- derthal fossil. recently linked several genetic amd attacks the central area of the interacting rnas probably have Neanderthals are the extinct regions to nicotine dependence. retina known as the macula, resulting important functions,” notes Lin, who hominid group most closely related to Many of these regions had in progressive loss of vision. describes them as “tiny, but mighty.” contemporary humans and believed already been targeted by other In 2005, Hoh and colleagues Now that Lin has discovered that to have diverged from modern hu- researchers, but in a new finding compared the dna of patients with pirnas help cells to differentiate mans about half a million years ago. reported in the January issue of amd to those who didn’t have the into many different cell types, he is The dna analysis has revealed that Biological Psychiatry, the Gelern- disease in order to home in on genetic trying to find out how they control the difference between the modern ter team has shown that a region differences between the two groups. gene activity inside the cell. This work human and the Neanderthal genome of chromosome 5 that contains The team eventually linked a variant may have important implications for is just one base pair in 2,000. several genes is strongly associ- the understanding of infertility and According to Rothberg, the ated to nicotine dependence in the of a gene on chromosome 1 known African-Americans in the study. as cfh with the milder “dry” form of cancer; because of their tiny size, the 454 Life Sciences team is poised to “These data add to the grow- amd. Last year a group led by Hoh molecules could also be more easily sequence the entire Neanderthal ing evidence for specific locations went on to identify a single change in used as therapeutic molecules. genome within two years. for genes that influence risk for a gene on chromosome 10 that leads Yale alumnus Jonathan Rothberg, “For the first time,” he says, nicotine dependence,” says Gel- to a significantly increased risk of ph.d., also appeared on the top “Neanderthal gives us a handle on ernter, who now hopes to zero in developing the more aggressive “wet” 10 list. Rothberg, who received his understanding human intellect, one on the specific gene or genes that form of the disease. doctorate from the university in 1991, of the great mysteries left in science.” influence nicotine dependence.

Missing molecule High school partnership celebrates 10 years

puts neurons off track It’s a common sight on any medical Medical student Terri During fetal development, differ- school campus: students being asked Huynh (right) teaches to identify and explain the func- Career High students ent types of neurons must journey in the medical school’s to their proper place in the brain’s tion of a muscle on a cadaver they’re anatomy lab. cerebral cortex. A wrong turn working with in the anatomy lab. But along the way may have devastat- on a recent afternoon, the students ing results, including periventricu- in question weren’t enrolled at the diseases. “One of the lar heterotopia (pvh), a congenital School of Medicine, but high school ideas is that these brain malformation that can cause students participating in the Anatomy kids will become epilepsy, mental retardation and Teaching Program, one of several ways community ambassa- deficits in learning and memory. pvh is associated with muta- in which the medical school collabo- dors for health,” says tions in a gene known as Filamin- rates with Hill Regional Career High Stewart. A, but little has been known School, a New Haven magnet school understand cell structure, the Depart- Thanks to the scholar initiative about how these mutations cause just a stone’s throw from campus. ment of Epidemiology and Public (Science Collaborative for Hands-On neurons to go astray. Research led Career High attracts students Health donated a research-quality Learning and Research), a three- by Pasko Rakic, m.d., ph.d., profes- from the New Haven area who hope electron microscope to their school. week summer residential science sor and chair of neurobiology and to work in health care, business or The medical school assisted Career program for students entering grades director of Yale’s Kavli Institute for computer technology. Though the High in equipping its science labs, 10 through 12, Career High students Neuroscience, has now implicated medical school’s partnership with the and students in the high school’s have had a chance to become more mekk4, an intracellular signal- high school began informally in 1993 Advanced Biology class come to the fully immersed in all Yale has to offer. ing molecule that contributes to with the anatomy program, this year School of Medicine twice a month scholar students, who normally proper neuronal migration. In the December 7, 2006, issue marks the 10th anniversary of a more with their teacher, Shirley Neighbors, participate in the program for three of Neuron, Rakic’s team showed formal partnership that has enabled to get help with course material from years, study science at the college that mekk4 regulates levels of Career High’s students to benefit from medical students. level and conduct research under the Filamin-A protein in the develop- a wide range of the expertise and In Career High’s anatomy course, supervision of Yale faculty. ing brains of mice and that mice resources available at Yale. also taught by Neighbors, two classes Neighbors believes that, in addi- engineered to lack mekk4 had The collaboration now has many meet twice each month in the medical tion to her students, medical students impaired neuronal movement and facets. For a medical careers class, for school’s anatomy lab. First- and and society as a whole will see ben- an increased incidence of pvh. example, faculty from the Depart- second-year medical students over- efits from the Yale-Career High part- The findings shed new light on ment of Epidemiology and Public seen by William B. Stewart, ph.d., nership. As she watched second-year pvh and on cortical development, Health visit Career High during the associate professor and chief of the medical student Rebecca Bruccoleri “a dynamic and complex process first semester to speak about career section of anatomy and experimental explain in a recent class how food is that, in humans, occurs during gestation over many months and options; during the second semester, surgery, volunteer as instructors. In converted to energy, she observed, “If is regulated by numerous mol- the high school students complete an small groups, the students explore they can find time to do this as a med ecules,” says Rakic. internship in clinics and laboratories such topics as cardiovascular health, student, you can imagine what kind at Yale. To help Career High students energy metabolism and infectious of doctors they’ll be.” Medicine@Yale March/April 2007 cyan mag yelo black 1605 MAC

PET from page 1

short-lived radioac- its target in the brain in adequate !WINDOWINTOTHEBODY tive isotopes. In an amounts, and how much would gen- adjacent room, radio- erate unacceptable side effects, chemists collect the according to Jorkasky. isotopes and attach Researchers are usually required GAMMA RAYS them to appropriate to give dosages that escalate over a molecules, and the la- period of several months to large POSITRON ELECTRON beled compounds are numbers of patients in order to estab- COLLISION immediately injected lish the safest and most effective dose DETECTORS into patients. Then of a drug. “If we are able to avoid the patients lie within the need to do large-scale clinical stud- pet scanner, a ma- ies like that, we’ll be saving tons of )NPOSITRON EMISSIONTOMOGRAPHY 4HETRACERRAPIDLYDECAYSANDEMITS #OMPUTERSCALCULATETHE chine much like a CT money and time, and, most impor- ORPET ATINYAMOUNTOFARADIOACTIVE POSITRONS WHICHCOLLIDEWITH GAMMARAYS´ORIGIN ANDHENCE scanner that is able to tant, we won’t expose patients need- ATOMHERE CARBON WITHA ELECTRONS CAUSINGBOTHPARTICLES WHEREINSIDETHEBODYTHE MINUTEHALF LIFE ISCHEMICALLY TOBEANNIHILATED0AIRSOFGAMMARAYS RADIOLABELEDSUBSTANCEBOUND image the accumula- lessly to a drug that may not have any ATTACHEDTODRUGMOLECULESOR ARISEFROMTHESECOLLISIONS TRAVELING TOITSMOLECULARTARGET4HESE tion of labeled com- benefit,” says Jorkasky. Frost says that OTHERBIOLOGICALLYACTIVESUBSTANCES OUTOFTHEBODYINOPPOSITEDIRECTIONS DATACANBECONVERTEDINTO 4HERADIOLABELEDCOMPOUNDIS !RINGOFDETECTORSINTHEPETIMAGING COLOR CODEDMAPS4HISIMAGE pounds in specific the center will serve as a core facility INJECTED ANDQUICKLYACCUMULATESAT EQUIPMENTRECORDSTHEARRIVALOF SHOWSTHEBINDINGLEVELSOF regions in the body. for the entire medical school in that PARTICULARCELL SURFACERECEPTORSOR THEPOSITRONSINEACHPAIR CARBON CARFENTANILTOOPIOID Yale’s new center some biomarkers discovered in the OTHERSITESINTHEBODY´SORGANS RECEPTORSINTHEBRAIN WITHAREAS OFHIGHESTCONCENTRATIONINRED boasts one of only 18 course of research projects with Pfizer pet scanners in the or other companies will be available world that can image for faculty research projects. the human brain at a Along with cardiology and oncol- At a January 18 ceremony mark- chemically attached to drug molecules resolution of 2.5 millimeters. ogy, the center’s major areas of focus ing the official opening of the new or other biologically active substances, “The work we do here will build are Alzheimer’s disease, schizophrenia, 22,000-square-foot facility, George such as glucose. When these chemi- the knowledge we need to develop depression, obesity, post-traumatic Mills, m.d., director of the Division cally tagged compounds are injected diagnostic imaging agents coupled to stress disorder and other conditions of Medical Imaging and Radiophar- into a patient’s body they bind to personalized therapy,” says J. James that are difficult to diagnose and treat. maceutical Drug Products at the Food specific organ sites, which can be Frost, m.d., ph.d., m.b.a., professor Frost hopes that the center’s research and Drug Administration’s Center for detected and converted into images by of diagnostic radiology and psychia- will help to identify biomarkers for Drug Evaluation and Research, said the pet scanner (see “A Window into try, chief of nuclear medicine at Yale- subtypes of these diseases, which can that pet is “the essential foundation” the Body,” above). Researchers and cli- New Haven Hospital and director of help determine the best treatment for of the agency’s efforts to streamline nicians use this information to study the new center, located at 801 Howard specific individuals. “Ultimately this the development of new medicines. changes in organ function as a result Avenue in New Haven. Joining Frost will benefit our patients,” Frost says. Also in attendance were Pfizer of disease or in response to treatment as co-directors are lead physicist “That’s the key.” ceo Jeffrey B. Kindler, j.d., Yale and to determine how much of a drug Richard E. Carson, ph.d., professor The fda’s Mills was enthusiastic President Richard C. Levin and senior compound has successfully reached its of diagnostic radiology and biomedi- in his praise for the new center, which leaders from Pfizer and Yale who desired target. pet enables research- cal engineering and lead radiochemist he said is equipped with “one of the played key roles in conceiving the cen- ers to study the safety and efficacy of Yu-Shin Ding, ph.d., professor of most intensely high-resolution scan- ter, including Diane K. Jorkasky, m.d., different drug doses and to identify diagnostic radiology. Completing the ners that’s out there.” In particular, Pfizer’s vice president of worldwide biological markers of disease that can senior faculty team is Henry Huang, Mills lauded the alliance between Yale research operations, Dean Robert J. aid in diagnosis. ph.d., a radiochemist and associate and Pfizer and the strong links be- Alpern, m.d., James A. Brink, m.d., The heart of the new center is a professor of diagnostic radiology. tween preclinical and clinical research, professor and chair of diagnostic radi- cyclotron encased in a lead radiation Pfizer has already used the School animal and human studies, and pet ology, and psychiatry Chair Benjamin shield filled with water; the shield of Medicine’s new pet facilities to imaging and drug development. S. Bunney, m.d. weighs over 100,000 pounds. Within study a small group of patients to de- “I’ve seen the critical pathway, and In pet, minute amounts of radio- a concrete vault the cyclotron ac- termine how much of a new drug for it’s here,” Mills told attendees. “You’ve active material known as tracers are celerates atomic particles to produce depression would be required to reach got it.” Borowy from page 1

unusually thoughtful way for him to school thesis, which described a novel in the form of apple say thanks. Over many years it will method of measuring blood pressure; pies. “He was very car- help many students acquire a Yale the pen-and-ink wiring diagrams ing, very considerate medical education.” and meticulously plotted graphs and concerned for his Born in Stamford in 1921, Borowy on the yellowing pages (see photo) patients, and gave a lot entered the University of Connecticut reveal a technically inclined side of more than just medical in 1938. War was on the horizon, and Borowy that his nephew had never care,” says DeBeradinis. he joined the Army Air Corps Reserve known. “He was never really a handy “He would make house (Left) A page while in college, graduating in 1942 guy when it came to doing anything calls when patients were from John with a b.s. degree and a second around the house,” DeBeradinis, too sick to come to his Borowy’s 1950 lieutenant’s commission. president of National Meter Indus- medical school office, and he did that thesis. (Above) Almost immediately, Borowy was tries in Bedford, N.H., recalls with a right up until he retired Borowy in 1943. deployed to the European Theater, chuckle. “I used to go over to change from practice in 1999.” followed by a stint in the North light bulbs for him.” After retiring, African Campaign. He rose to the But Borowy was “a brilliant, bril- Borowy continued to rank of captain, and eventually was liant man,” DeBeradinis hastens to visit former patients and placed in charge of communications add. An avid amateur historian with volunteered at Stamford on Ascension Island in the South a special interest in military history Hospital and at the VA Atlantic Ocean, then a major way who “could recite dates, times and Connecticut West Haven Healthcare DeBeradinis says that his uncle’s station for coded military messages places of all these events that changed System, where he had been a resident belief in the importance of good doc- sent between Europe, Africa and the history,” Borowy had a library of more for two years in the mid-1950s. toring only grew when his own health United States. The island was also a than 800 books, which DeBeradinis “Everyone knew him as a simple began to fail several years ago and he refueling stop for planes returning has donated to the Ferguson Library and unpretentious but caring, expe- found himself on the other end of the from Europe and Africa, and DeBera- in Stamford. rienced, qualified physician who was stethoscope. dinis says that Borowy’s encounters When Borowy opened his practice respected by his patients” says Frank Of Borowy’s bequest, DeBeradinis with wounded soldiers on the island in 1954 specializing in pulmonary R. Coughlin Jr., m.d., a member of says that it was his uncle’s belief that were instrumental in his decision to medicine, Stamford had a far more the medical school’s Class of 1952 who students with the potential to become attend medical school. rural character than it does today, frequently worked with Borowy in his skilled and caring doctors should When settling Borowy’s estate, and DeBeradinis says that his uncle’s chest surgery practice in Stamford. never be held back by financial need. DeBeradinis was surprised as he practice retained an old-fashioned “The generosity of this gift was a sur- “This was his way of giving back to thumbed through his uncle’s medical flavor—his ledgers show payments prise, and a very pleasant one.” the community.” www.medicineatyale.org cyan mag yelo black 1605 MAC Grants and contracts awarded to Yale School of Medicine July/August 2006

Benzylguanine Prodrugs, 3 years, $880,401 • Federal Alan Sartorelli, nih, Development of Antican- cer 1.2-Bis(sulfonyl)hydrazines, 4 years, Hervé Agaisse, nih, High-Throughput Screen $1,214,240 • Samuel Sathyanesan, nih, for Compounds Affecting Intracellular Pathogen Choroid Plexus and Antidepressants: Genomics Infection, 1 year, $82,500 • Robert Beech, nih, and Proteomics, 2 years, $337,582 • Nenad A Genetic Model for the Role of Neurogenesis in Sestan, Nat’l Alliance for Research on Schizo- Antidepressant Response, 2 years, $379,125 • phrenia and Depression, Characterization of a Andrea Benin, nih, Outpatient s: Using ehr Novel Candidate Gene in Schizophrenia, 2 years, Electronic Data to Improve Health and Health With support from the National Institutes of Health, Hal Blumenfeld, m.d., ph.d., associate $60,000 • Eugene Shapiro, nih, Effectiveness Care, 3 years, $486,000 Zubin Bhagwagar, professor of neurology, neurobiology and neurosurgery, is performing neuroimaging studies • of Vaccines in Clinical Practice, 5 years, $760,280 National Alliance for Research on Schizophre- of epilepsy. This image shows brain areas involved in absence seizures in a 12-year-old girl. Mark Shlomchik, nih, Role of B Cells and DCs nia and Depression, A Proton mrs Study of in Lupus Pathogenesis, 5 years, $2,339,919 • gaba and 5-HT Interactions, 2 years, $60,000 • Warren Shlomchik, nih, Dendritic Cell Daniel Biemesderfer, nih, Megalin Function Duman, Sepracor Inc., Influence of Eszopiclone Acute Kidney Injury in Critically Ill Patients, 3 Subsets and Paths of Maturation in gvhd, 5 in the Normal and Diseased Kidney, 5 years, on Neurogenesis and Cell Proliferation in Adult years, $150,000 • Albert Perrino, Alcoholic years, $2,066,250 • Julie Staley-Gottschalk, $1,694,325 • Hal Blumenfeld, nih, Functional Limbic Brain Structures, 1 year, $80,025 • Beverage Medical Research Foundation, nih, Cognition, Tobacco Smoke and Nicotinic Neuroimaging in Childhood Absence Epilepsy, Richard Flavell, American Diabetes Associa- Heightened Pain Processing in Individuals at Receptor Occupancy, 1.5 years, $336,257 • 3.5 years, $1,889,682 • Arthur Broadus, nih, tion, Inc., Prevention of Type 1 Diabetes by tgf- Risk for Alcoholism, 6 months, $40,000 • Thomas Steitz, nih, Structure of dna and pthrp Function in the Periosteum and Entheses, Beta-Induced Regulatory T Cells, 3 years, Edward Perry, Alcoholic Beverage Medical rna Polymerases and their Functional Com- 2 years, $330,000 • Robert Bruce, nih, Sub- $300,000 • Gerald Friedland, University of Research Foundation, Interactive Psychophar- plexes, 4 years, $1,564,921 • Lisa Suter, nih, The stance Abuse, hiv and hvc Treatments to Natal, Collaborative aids Program of Research macologic Effects of Alcohol and Nicotine in Cost-Effectiveness of mri in Early Rheumatoid Improve Health Outcomes in Drug Users, 5 in South Africa (caprisa), 1 year, $19,282 • Humans, 2 years, $90,000 • George Porter, Arthritis, 5 years, $663,525 • Eugene Swenson, years, $870,852 • Sonia Caprio, nih, Patho- David Geller, American Heart Assoc. (Heritage Charles H. Hood Foundation, Calcium Chan- nih, Liver Injury and Repopulation by Bone physiology of Metabolic Defects of Juvenile Affiliate), Renal and Extrarenal Effects of Aldo- nels Regulate the Formation of the Cardiac Marrow Stem Cells, 5 years, $671,290 • Hemant Obesity, 5 years, $916,605 • Judy Cho, nih, ibd sterone, 3 years, $198,000; Amgen Nephrology Outflow Tract from the Anterior Heart Field, 2 Tagare, nih, Segmentation of Ultrasound Consortium Genetics Research Center, 1 year, Institute, Molecular Mechanisms of Hyperten- years, $150,000 • Nandhini Ramamoorthi, Images, 4 years, $1,556,175 • Cenk Tek, Nat’l $319,573; nih, Genetics Consortium Data sion in the Metabolic Syndrome, 1 year, $58,868 • Arthritis Foundation, Tick Salivary Protein, ibd Alliance for Research on Schizophrenia and Coordinating Center, 1 year, $922,200 Robert Satish Ghatpande, Charles H. Hood Founda- Salp 15 and Control of Lyme Arthritis, 2 years, • Depression, Mental Transformations in Schizo- Constable, nih, Towards an Improved Under- tion, Novel Mechanisms of Embryo Protection: $150,000 • Jill Reiter, Breast Cancer Alliance, phrenia in Relation to Negative Symptoms and standing of bold Signal Changes, 5 years, The Role of Adenosine Action in the Developing Inc., Quantitative Analysis of egfr Variants in Deficit Syndrome, 2 years, $59,992 • Benjamin $1,847,260 Nihal Delanerolle, nih, Proteomic Heart, 2 years, $150,000 • Daniel Goldstein, Breast Cancer, 2 years, $125,000 • Scott Rivkees, • Turk, U.S. Department of the Army, Identifica- Profiles in Human Temporal Lobe Epilepsy, 2 Society of Geriatric Cardiology, Role of Aging in Chemical Diversity Labs, Inc., Identification of tion of Substrates and Inhibitors of the Anthrax years, $408,375 • Caroline Easton, nih, A Vascular Injury, 1 year, $10,000 • Fred Gorelick, Novel acth Antagonists, 1 year, $183,356 Lethal Factor, 1 year, $259,928 • Sandra Wolin, Therapy Approach for sadv, 3 years, $873,000 • Brentwood Biomedical Research Inst., Alcohol Haleh Saadat, Foundation for Anesthesia Edu- nih, Antibodies to Ro Ribonucleoproteins as Erol Fikrig, nih, Immunotherapeutics for and the Exocrine Pancrease ER Stress Responses, cation Research, Implementation and Biomarkers in Sjogren’s Syndrome, 2 years, Treatment of Flavivirus Infection, 5 years, 1 year, $32,600 • Jonathan Grauer, Medtronic, Testing of a Wellness Program Conducted $431,122 $6,982,520 • Durland Fish, U.S. Department of Inc., Modeling the Deleterious Effect of Infection with Anesthesiology Residents at Yale, 2 years, Agriculture, Northeast Regional Tick Control on Posterolateral Lumbar Fusion in a Rabbit $100,000 • Robert Sherwin, American Diabetes Project, 1 year, $208,544 • Terri Fried, nih, Non-Federal Model and Evaluating the Potential Effect of Association, Inc., cns Responses to Hypoglyce- Treatment Goals at the End of Life, 3 years, bmp2 to Overcome this Effect, 1 year, $155,362 • mia in Diabetes, 4 years, $180,000 • Warren $1,272,050 • Frank Giordano, nih, Zinc Finger Jonathan Bogan, W. M. Keck Foundation, Reg- Kalpana Gupta, The Patrick and Catherine Shlomchik, The Leukemia & Lymphoma Proteins to Modify Heart Function, 5 years, ulation of Glucose Transporter Trafficking, 5 Weldon Donaghue Medical Research Founda- Society, Memory T Cells for Immune Reconstitu- $2,066,250 • Charles Greer, nih, Neuron Glial years, $1,000,000 • Titus Boggon, American tion, Cranberry for uti Prevention in Nursing tion Post-Allogenic Stem Cell Transplantion, 5 Interactions, 5 years, $1,575,361 • Ruth Halaban, Society of Hematology, Structure/Function Home Residents, 2 years, $238,710 • Bryan years, $550,000 • Peter Smith, aclam Founda- nih, Yale spore in Skin Cancer, 5 years, Studies of Janus Jinase Family Members, 2 years, Hains, International Association for the Study tion, Mouse Parvovirus: Effects of Immune $11,500,000 • Graeme Hammond, nih, mhc $150,000 • Elizabeth Bradley, John D. Thomp- of Pain, Sodium Channel Blockers and Pain after Status and Pregnancy on Duration and Potential Suppression as a Model for Transplant Tolerance, son Hospice Institute for Education, Training Spinal Cord Injury, 1 year, $5,000 • James Hill Reactivation of Viral Shedding, 1 year, $25,000 • 2 years, $453,750 • Kevan Herold, nih, Phase II and Research, Inc., Improving Care for Patients III, Albert Einstein Healthcare Network, The Julie Sosa, American Geriatrics Society, A Trial of HoKT3y, 4 years, $2,157,201 • Margaret with Irreversible Conditions and Their Families, Impact of Healthy Work Organization on Return Multi-Institutional Randomized Controlled Trial Hostetter, nih, Developmental Adaptation: 1 year, $100,000 • Pia Britto, Russell Sage to Work Outcomes in an Aging Workforce, 3 Measuring the Effects of Surgery on Depression, Child Health Research Center, 4 years, Foundation, Man Ana: An Investigation of years, $190,374 • Selby Jacobs, State of Con- Memory and Concentration Among Elderly $2,106,443 • Jeannette Ickovics, nih, Integrat- Ethnic Identity Formation of Muslim Arab Chil- necticut Department of Mental Health and Patients with Asymptomatic Primary Hyper- ing Prenatal Care to Reduce hiv/stds Among dren in the United States, 2 years, $103,510 • Addiction Services, pcp: Person-Centered Care parathyroidism, 2 years, $150,000 • Matthew Teens: A Translational Study, 5 years, $4,511,882 Herta Chao, American Association for Cancer for Psychosis, 1 year, $432,166 • Sven-Eric Jordt, State, Tourette Syndrome Association, Inc., Mustafa Khokha, nih, Role of Gremlin in Research, The Detection of Pharmacodynamic State of Connecticut Department of Public Investigation of slit and Trk-Like Family 1 Embryonic Development, 1 year, $121,770 • Diane Changes in Circulating Tumor Cells in Response Health, Sensory Irritant Receptors in the Patho- (sltrk1): A New Candidate Gene for Tourette Krause, nih, Epithelial Engraftment of Bone to Chemotherapy Using Novel Robotic Epifluo- genesis of Smoking-Induced Lung Disease, 2 Syndrome, 1 year, $75,000 • Meredith Stowe, Marrow Derived Stem Cells, 3 years, $743,500 • rescent Microscopy Platform, 2 years, $100,000 • years, $299,723 • Anil Karihaloo, American The Patrick and Catherine Weldon Donaghue Daeyeol Lee, nih, Dynamics and Neural Mech- Katarzyna Chawarska, Autism Speaks, Face Heart Assoc. (Heritage Affiliate), Role of vegf Medical Research Foundation, Reducing Isocya- anisms of Decision Making, 1 year, $56,110 • and Gaze Processing in the Second Year of Life: in Renal Ischemic Repair, 3 years, $198,000 • nate Exposure in the CT Autobody Industry, 3 Douglas Leslie, nih, Patterns of Service Use Comparison between asd, DD and Typical Haifan Lin, Stem Cell Research Foundation, years, $91,180 • Lynn Sullivan, Robert Wood and Costs Associated with Autism, 3 years, Infants, 2 years, $119,979; Autism Speaks, Why Translation Regulation of Stem Cell Self- Johnson Foundation, Reducing hiv Sexual Risk $586,800 • Ming Li, nih, tgf-beta 1 Regulation and When Do Children with Autism Develop Renewal, 2 years, $80,575 • Kangmo Lu, Ameri- Behaviors in Patients Receiving Treatment for of Peripheral T Cell Tolerance, 5 years, $691,200 • Difficulties Recognizing Faces?, 2 years, $100,000 can Diabetes Association, Inc., New Risk Factors Opioid Dependence, 3 years, $46,183 • Lisa Annette Molinaro, nih, Statistical Methods for Haijun Chen, American Heart Association, for Diabetic Retinopathy, 1 year, $100,000 • Suter, Arthritis Foundation, Defining Best Prac- Predicting Survival Outcomes from Genomic The Molecular and Structural Basis of Beta- James Macy, aclam Foundation, Strategies for tices for mri in Rheumatoid Arthritis, 2 years, Data, 3 years, $478,269 • Dhasakumar Navarat- Subunits MinK and MiRP1, 4 years, $260,000 • mpv Screening, 1 year, $25,000 • Arya Mani, $150,000 • Ning Tian, Research To Prevent nam, nih, Studies on Hair Cell BK Channels, 5 Lei Chen, Ambulatory Pediatric Association, American Heart Assoc. (Heritage Affiliate), Blindness, Inc., Research to Prevent Blindness years, $1,859,625 • Laura Niklason, nih, Novel Training of Pre-Hospital Personnel in the Use of Mapping a Gene for Premature Coronary Artery Dolly Green Scholar, 1 year, $70,000 • Susumu Cellular Life Span Extension for Tissue Engineer- Laryngeal Mask Airways in Simulated Pediatric Disease, 3 years, $198,000 • Ira Mellman, Tomita, Esther and Joseph Klingenstein Fund, ing, 1 year, $187,977 • Michael Nitabach, nih, Arrest Scenarios, 1 year, $8,000 • Hongbo Chi, Sandler Program for Asthma Research, Den- Inc., Regulation of Excitatory Synaptic Strength Transgenic Tethered Spider Toxins, 4.5 years, Arthritis Foundation, Regulation of Immune dritic Cell Biology and Asthma, 3 years, $750,000 in the Brain, 3 years, $150,000 • Elizabeth $1,815,282 • Peter Novick, nih, Genetics of Response and Systemic Autoimmunity by sip Guillermo Mor, The Johns Hopkins University, Triche, State of Connecticut Department of Secretion in Yeast, 5 years, $2,182,490 • J. Peter Signaling, 2 years, $150,000 • Susan Compton, Multiplex Protein Test for Early Detection of Public Health, Genetics and Smoking in Preg- Olausson, Nat’l Alliance for Research on aclam Foundation, Murine Norovirus Patho- Ovarian Cancer, 1 year, $50,000 • Laura Nikla- nancy, 2 years, $349,893 • Marianne Ulcickas Schizophrenia and Depression, Reinforcement genesis and Transmissibility, 1 year, $24,998 • son, Texas A&M University, Ex Vivo Delinea- Yood, Henry Ford Health System, Oral Antidia- of Neuroprotection for Stress Hormone-Induced R. Todd Constable, The John B. Pierce Labora- tion of Mechanisms of Cerebral Vasospasm, 3 betic and Insulin Use Among Patients with Dia- Hippocampal Damage by fgf Signaling Path- tory Inc., Cognitive and Affective Influences on years, $89,182 • Marcella Nunez Smith, Robert betes, 2 years, $35,000 • Jack Van Hoff, St. Bal- ways, 2 years, $60,000 • Godfrey Pearlson, Central Taste Processing, 5 years, $100,707 • Wood Johnson Foundation, Minority Faculty in drick’s Foundation, St. Baldrick’s Foundation nih, Reward, Impulsivity and Cocaine Addic- Vladimir Coric, Obsessive Compulsive Foun- Academic Medicine: How to Successfully Support Award, 1 year, $25,000 • Joanne Weidhaas, State tion: fmri Studies, 4 years, $1,618,069 • Marina dation, Inc., A Double-Blind, Placebo Controlled Diversity, 1 year, $49,868 • A. David Paltiel, of Connecticut Department of Public Health, Picciotto, nih, Antidepressant Effect of Nico- Trial of N-Acetylcysteine in sri-Resistant ocd, Massachusetts General Hospital, The Cost- Analysis of mirna Mutations in Lung Cancer, 2 tinic Receptor Blockade, 10 months, $1,580,604 • 1 year, $36,600 • Priscilla Dannies, Elsa U. Effectiveness of Preventing hiv Complications, 1 years, $265,050 • Stuart Weinzimer, Juvenile Douglas Rothman, nih, Acquisition of a 7T Pardee Foundation, Enhancing the Ability of year, $22,287 • Chirag Parikh, American Heart Diabetes Research Foundation International, Human MR System for the Development of Ultra Human Growth Hormone to Reduce Tumor Assoc. (Heritage Affiliate), A Pilot Study Investi- Advanced Studies of Closed Loop Glucose High Resolution Whole Brain mrsi and mri, 1 Burden in a Mouse Model of Human Ovarian gating Novel Biomarkers in Cardiac Surgery to Control on Type 1 Diabetes, 2 years, $618,082 • year, $2,000,000 • David Rothstein, nih, Cancer, 1 year, $131,631 • Alan Dardik, Ameri- Detect Acute Kidney Injury, 1 year, $74,931; The Erin Wolff, University of California—San Peripheral Mechanisms of Immunologic Toler- can Vascular Association, Flow Responses to Patrick and Catherine Weldon Donaghue Francisco, Regulation of hoxa 10 by Putative ance, 5 years, $7,039,959 • Gerard Sanacora, Carotid Angioplasty, 1 year, $75,000 • Enrique Medical Research Foundation, Novel Biomark- Co-Factor Spastin, 1 year, $119,450 • Xuchen nih, Studies of Amino Acid Neurotransmitter De La Cruz, American Heart Association, Actin ers to Detect Delayed Graft Function, 3 years, Zhang, American Heart Assoc. (Heritage Affili- Contributions to Depression, 5 years, $634,230 • Filament Cooperativity and Actin Binding $197,144; Satellite Healthcare, Inc., The Diag- ate), Role of HO-1 and stat3 in Oxidant- Alan Sartorelli, nih, Hypoxia-Activated O6- Protein Function, 3 years, $198,000 • Ronald nostic and Prognostic Value of Biomarkers for Induced Lung Injury, 3 years, $198,000

Medicine@Yale March/April 2007 cyan mag yelo black 1605 MAC Scientist is honored by foundation for research on lupus

Immunobiologist unveils Margaret G. Dowd, executive in 1993 and rose through the ranks to director of the S.L.E. Lupus Foun- become professor in 2004. molecular mechanisms dation, celebrates with Mark Shlomchik at the foundation’s He serves on the scientific adviso- of autoimmune disease annual gala. ry board of the S.L.E. Lupus Founda- tion’s Lupus Research Institute and The S.L.E. Lupus Foundation, the As part of this effort, Shlomchik, is co-chair of its Novel Research and nation’s leading organization pro- has focused his recent research on the Peer Review task forces. He is also viding patient services, education so-called toll-like receptors (tlrs) of Associate Director of the Yale-New and funding for lupus research, has the innate immune system (see related Haven Hospital Blood Bank. named Mark J. Shlomchik, m.d., story, page 3). The foundation paid tribute to ph.d., professor of laboratory medi- It had long been suggested that Shlomchik at its annual gala, held last cine and immunobiology, its scientific B cells might become autoreactive December at the Marriott Marquis honoree for the year 2006. by somehow recognizing dna or hotel in New York City, saying that Shlomchik studies the role of B rna in the cells that form the body’s he had brought “invaluable insight, cells, immune system cells produced organs. During the past five years, it encouragement, and direction to the in bone marrow, in systemic lupus was shown that tlr9 and tlr7, both Lupus Research Institute, helping to erythematosus (sle) and other auto- of which are expressed on B cells, are take it to new levels of scientific excel- immune diseases. specific, respectively, fordna and lence.” Normally B cells help to protect rna. The event’s master of ceremonies the body from infectious agents, but reactive B cells are produced. For rea- Following up on this work, was nbc Sports and hbo sportscast- in sle unknown environmental or sons that are not fully understood, the Shlomchik and his colleagues report- er Bob Costas, and entertainment was genetic factors cause these cells to go symptoms of lupus—joint pain, fever, ed in 2006 in the journal Immunity provided by soprano Barbara Cook, awry and to produce antibodies to skin disorders and fatigue, among that lupus-prone mice lacking tlr9 a star of the musical theater for over dna, rna and other proteins found others—wax and wane, occurring in and tlr7 did not generate antibod- 50 years. in every cell in the body. For this rea- intermittent bursts known as “flares.” ies against dna and rna, and that The foundation also honored son lupus affects many of the body’s The most common treatments used lupus-like symptoms in mice lacking James D. Robinson III, m.b.a., own organs, especially the heart, during flares are corticosteroids or tlr7 were far less severe. chairman of the board of Bristol- joints, skin, lungs, blood vessels, liver, other drugs that suppress the immune These findings suggest that Myers Squibb, for his company’s kidneys and nervous system. These system. But these drugs have serious developing drugs that target tlrs development of abatacept (Orencia), “autoreactive” B cells also cause the side effects, including increased sus- could be valuable new treatments a non-steroidal anti-inflammatory immune system’s T cells to target ceptibility to infection, obesity, dia- for lupus and other autoimmune agent. Abatacept has won Food and these organs, leading to further betes, osteoporosis, hypertension and diseases. Drug Administration approval for damage. cataracts, so there is an urgent need to After receiving his m.d. and the treatment of rheumatoid arthritis sle is a chronic condition with a understand the cellular and molecular ph.d. degrees from the University of and is now being tested in a multi- vicious cycle: as the body’s damaged mechanisms that cause flares and to Pennsylvania, Shlomchik joined the center Phase II trial for treating and tissue becomes inflamed, more auto- develop new drugs to prevent them. Yale faculty as an assistant professor preventing lupus flares.

McCance from page 1 Awards & honors the Vietnam War. Venture capital was a new idea then, but McCance moved Miguel Coca- Sankar Ghosh, Anthony Koleske, into the field soon after. “In 1966 it was Prados, ph.d., ph.d., professor ph.d., associ- a nascent industry, and I wanted to get professor of of immunobiol- ate professor away from the 28,000-person office ophthalmology ogy, molecular of molecular and visual sci- biophysics and biophysics and building that the Pentagon represented ences, recently biochemistry, biochemistry and into something very entrepreneurial.” completed a and molecular, neurobiology, has When Greylock began aggressively professorship at cellular and been awarded the investing in software companies in the Pfizer’s Groton developmental $500,000 Estab- 1970s, that industry was out of favor laboratories as the 2006 Yale-Pfizer biology, has received the Ranbaxy lished Investigator Award from the Global Discovery Visiting Profes- Research Award in basic research for American Heart Association. The with investors, but it soon became sor. Now in its third year, the Visit- the year 2005. The award is given by award supports midterm investiga- McCance’s specialty. “Most people ing Professor Program is a 12-week the Ranbaxy Science Foundation, a tors with unusual promise, a record thought that hardware investments sabbatical in which an outstanding non-profit organization established of accomplishments and a demon- were more interesting and exciting,” Yale faculty member consults and by Ranbaxy Laboratories, India’s strated commitment to cardiovas- McCance says. “We took a contrar- conducts research on Pfizer’s campus largest pharmaceutical company. The cular or cerebrovascular science. in southeastern Connecticut. Coca- award was presented in March at the The award will help fund Koleske’s ian view. Now software touches every Prados studies the way in which gene foundation’s 13th annual symposium research into how cells sense differ- part of our lives in business and in the mutations that cause glaucoma alter in New Delhi. Ghosh studies the role ences in their arterial environment home.” the normal function of the cells in of the regulatory protein NF-κB in and respond by redirecting their McCance says he now devotes the eye in which they are expressed. immune responses and disease, and migration. Understanding these cues about 40 percent of his time to his explores the therapeutic potential of may lead to treatments to block the Joshua A. Copel, inhibiting the protein. formation of atherosclerotic plaque. new foundation, sounding a clarion m.d., profes- call about the urgent need to cure sor of obstetrics, Alan E. Kazdin, Glenn C. Mical- Alzheimer’s disease. He sees philan- gynecology and ph.d., the John izio, ph.d., thropic channels like the Yale Scholars reproductive M. Musser Profes- assistant professor initiative and the caf as necessary sciences and sor of Psychology, of chemistry, has pediatrics, was Child Psychiatry been named an Eli in an age of across-the-board cuts in awarded the Dru and at the Insti- Lilly Grantee for National Institutes of Health re- Carlson Award for tute for Social Organic Chem- search funding, and as a remedy for Research in Ultrasound and Genet- and Policy Studies istry. The award disproportionately low funding for ics in February at the 27th annual at Yale, has been includes a two- Alzheimer’s disease in particular. meeting of the Society for Maternal- named president of the American year unrestricted grant of $100,000, Fetal Medicine (smfm). The award Psychological Association, the largest which Micalizio will use to continue “Even though the disease was was established in memory of Dru association of psychologists in the his research on synthesis of complex discovered 100 years ago, there is Carlson, m.d., an smfm member world. Kazdin, who also directs the biologically active organic molecules. remarkably little understanding of the known for her expertise in ultra- Yale Parenting Center and Child He will also participate in the 13th disease or effective therapeutics,” he sound and genetics research who Conduct Clinic, began his leadership biennial Lilly Grantee Symposium says. “Statistics say that two out of five died in 2003. Copel, also vice chair of the 150,000-member organization in March 2008 in Indianapolis. and director of Obstetric-Gynecolog- on January 1 as president-elect and Micalizio’s research focuses on sim- people will have Alzheimer’s by age ical Ultrasound at Yale, is an author- will continue in 2008 as president. plifying the process of molecular 85 if there isn’t a cure. If you compare ity on high-risk pregnancies, prenatal Kazdin is interested in advancing synthesis by developing new ways to the research dollars spent on this diagnosis, fetal surgery, amniocente- psychological science and service on form carbon–carbon bonds between disease to hiv/aids, cancer or heart sis and first trimester screening and a world stage in the areas of diver- molecules. disease, it’s out of synch. We’re not chorionic villus sampling. sity, children and families and social policy. spending enough in this country to cure this disease.” www.medicineatyale.org