may 2012 volume 8, issue 2 Advancing Biomedical Science, Education, and Health Care

Honoring an RNA pioneer, backing science’s next generation In 2007, Natalia B. Ivanova, ph.d., provides young scientists with sup- deceased), a Yale College alumnus arrived at the School of Medicine port that allows them to focus on and physician-scientist at Harvard with ambitious plans. A rising star in science during their earliest years as Medical School and Massachusetts stem cell biology, she had just left a independent researchers rather than General Hospital for five decades. postdoctoral fellowship at Princeton, scramble for funding. Now McCluskey has created a and her first order of business was to The brainchild of Dean Robert J. second Yale Scholar endowment, hire a team for her Yale laboratory. Alpern m.d., the Yale Scholars Award named for Joan A. Steitz, ph.d., Most medical investigators are provides $250,000 per year for four Sterling Professor of Molecular Bio- funded not from a central budget, years to cover salary and start-up physics and Biochemistry, Howard but through grants from the govern- costs for a promising new faculty shapiro harold Hughes Medical Institute investiga- ment or other institutions. Young member at the School of Medicine. (From left) Joan Steitz has been honored by a tor, and pioneer in the study of rna. scientists are pressed to win sup- “This was a tremendous advan- new Yale Scholar fund endowed by Donald Mc- Steitz has said that she “fell in port from these backers, who tend tage, allowing me to get right to Cluskey, the eighth such fund in the initiative love with rna” as a college student in to favor established researchers. But work on my ideas,” Ivanova says, launched by Dean Robert Alpern in 2005. the early 1960s, and she maintained Ivanova, assistant professor of genet- adding that the promise of sup- was endowed in 2006 by Donald S. that focus through graduate school ics, had a leg up: she was the medical port from the Robert T. McCluskey, McCluskey, m.eng., an alumnus of and postdoctoral training. She joined school’s first recruit to benefit from m.d., Yale Scholar Fund sealed her Yale College and the Faculty of En- the School of Medicine faculty in the Yale Scholars initiative, which decision to come to Yale. That fund gineering, to honor his brother (now 1970, and within // Scholar (page 7)

Office supporting A firm foothold in the genetics of autism student research New study applies advanced genomics in a celebrates 25 years carefully assembled population to yield some Women who of the first solid data in autism genetics Google the phrase “increase Matthew W. State, m.d., ph.d., had never seriously consid- chances of con- ered a career in genetic research until 1995, when he spent a ceiving twins” few months in a child psychiatry ward during his residency are advised to try at the University of California, Los Angeles. There he cared eating yams. Par- for a few children with Prader-Willi syndrome, a rare genet- ents of children ic disorder caused when all or part of a seven-gene stretch John Forrest suffering from of chromosome 15 is missing. Children with Prader-Willi tend a middle ear to be intellectually delayed and prone to compulsive behav- infection might be advised to “wait iors such as skin-picking and uncontrollable eating. and see” before starting antibiotics. glinn “These kids just had one region lost, but it led to a variety c These disparate pieces of advice of psychiatric manifestations,” State recalls. “It made me start evan m both stem from thesis research by thinking, quite naively, about studying rare mutations as a Matthew State led one of three new genomic studies that provide some Yale medical students that was way of understanding disorders that are much more common of the strongest evidence to date on genetic causes of autism. overseen by the Office of Student in the population.” The notion led State, at age 35, to enroll Research, which celebrated its 25th in the graduate program in genetics at Yale, where others to the notoriously diverse autism spectrum disorders. Stud- anniversary in February. were thinking along the same lines. Most famously, faculty ies have found dozens of genetic blips in people with autism, “Not all student theses lead to member Richard P. Lifton, m.d., ph.d., now chair and which is characterized by repetitive behaviors and problems changes in standards of care, but Sterling Professor of Genetics, had discovered a trove of in communication and social interactions, but researchers many of them do,” says John N. For- new genes involved in hypertension by screening families have struggled to sort out which of these gene variants are rest, m.d., who founded the Office with rare, extreme blood pressure disorders. harmful and which benign. of Student Research 25 years ago and In recent years, State, now the Donald J. Cohen Profes- State and several other groups around the country have has remained its director ever since. sor in the Child Study Center, professor of psychiatry and attacked this problem by focusing on an unusual group of During that time the office has genetics, and co-director of the Yale Program on Neuroge- study participants known as the Simons Simplex Collection evolved to become the main funding netics at the School of Medicine, has been employing the lat- (ssc). Assembled and maintained with funding from the source for medical student research, est genomic technologies to take the same general approach New York City-based Simons Foundation, // Autism (page 7) introduced // Student research (page 7)

Non-Profit Org. inside this issue 1 Church St., Suite 300, New Haven, CT 06510-3330 U. S. Postage www.medicineatyale.org 2 Lifelines paid Pietro De Camilli has come full-circle, New Haven, CT from medical student to distinguished Permit No. 526 researcher to translational scientist. 3 New blood The Yale Cardiovacular Research Center amps up its collaborative potential. 5 Shutting down malaria A cross-campus collaboration advances treatment for the deadly disease. also Advances, pp. 3, 5 Out & About, p. 4

@YaleMed f /YaleMed Pediatric Surgery lifelines announces arrival of new section chief

One of the world’s leading In March, researchers in the cell biol- the School of ogy of the synapse, Pietro Medicine and De Camilli has catalogued Yale-New Haven and characterized a host of proteins involved in synaptic Children’s Hos- vesicle trafficking. Vesicles, pital (ynhch) which are crucial to brain announced the function, are spherical sacs appointment of shaped from nerve cell Michael Caty Michael G. Caty, membranes that are loaded with neurotransmitters. m.d., m.m.m., At synapses, vesicles fuse as chief of the Section of Pediatric with the membrane and Surgery and surgeon-in-chief empty their cargo to send at ynhch. a chemical message. Then Caty comes to Yale from the the membrane reshapes to form a new vesicle, and Women and Children’s Hospital of

Pietro De Camilli michael marsland the cycle begins anew. Buffalo, where he was surgeon-in- chief, director of pediatric surgical services, and professor of surgery and pediatrics at the University at Buffalo School of Medicine and Cycle of life Biomedical Sciences. After three decades in carry neurotransmitters to synapses. sphere, which pinches off and migrates “Dr. Caty is a skilled surgeon, There they fuse with the synaptic mem- into the cell. This newly born vesicle researcher, and academician who basic science, a biologist brane and empty their cargo, passing is loaded with a neurotransmitter, brings more than two decades of circles back to medicine on to other cells the chemical messages and the secretory cycle begins anew. experience to his role as our new that allow the brain to function. “These processes are so fundamental pediatric surgeon-in-chief,” said The poet William Carlos Williams exalted De Camilli soon shifted his focus to that what you learn can be applied Robert Udelsman, m.d., m.b.a., the ordinary: “So much depends,” he neurobiology, and in 1978 he joined the to every cell,” says De Camilli, whose chair and William H. Carmalt Pro- wrote, “upon/a red wheel/barrow.” Seen Yale laboratory of Paul Greengard, ph.d., wide-ranging work on every step in this fessor of Surgery, and surgeon-in- from the vantage point of Pietro De who went on to win the Nobel Prize for progression has earned him election chief at Yale-New Haven Hospital. Camilli, m.d., the seemingly unremark- his studies of synaptic transmission. As to the National Academy of Sciences Caty is board certified in able fact that cell membranes can bend a cell biologist, De Camilli’s favored tool and appointment as a Howard Hughes pediatric and general surgery. His into different shapes is likewise invested was the microscope, and he needed time Medical Institute investigator. clinical interests include neonatal with the greatest importance, for life to adjust to Greengard’s biochemistry De Camilli’s career seems itself to surgery, thoracic surgery, intestinal itself—and every thought, emotion, and lab, in which “they studied the nervous be unfolding in a cycle. Mouse strains motility disorders, pediatric surgi- memory—depends upon it. system with a Waring blender,” isolating with defective vesicle trafficking that cal oncology, pediatric laparoscopy, As a child, De Camilli spent each proteins from homogeneous solutions were created in his lab to explore basic and minimally invasive thoracic year’s four-month school vacation in of brain tissue using chromatography. biology turned out to have character- surgery. He earned his b.s. at his mother’s ancestral village by Lake But in a “magic moment” De Camilli istics seen in various human diseases, Boston College and his m.d. at Maggiore, in northern Italy. There he realized that antibodies being developed rekindling De Camilli’s interest in the University of Massachusetts developed the “passion for understand- by his colleagues could be used with concepts he learned in medical school. Medical School. He trained in ing nature” that drew him to biology. light and electron microscopy to localize In 2006 he joined with Stephen M. general surgery at the University Because little rigorous advanced train- subcellular proteins. Before long he had Strittmatter, m.d., ph.d., the Vincent of Michigan, and also completed ing in general biology was available in characterized synapsin, the first synaptic Coates Professor of Neurology and a residency in pediatric surgery at Italy at that time, De Camilli enrolled in vesicle protein to be understood in any professor of neurobiology, to launch Children’s Hospital Boston and medical school. He had little interest in depth, and after launching his own Yale the program in Cellular Neuroscience, Harvard Medical School. Caty is a a career as a physician, but relished the lab, he continued to build an inventory Neurodegeneration, and Repair, which member of the American College chance to be “exposed to one organism, of such proteins. aims to rapidly translate lab discover- of Surgeons and a number of other from molecules to mind.” But De Camilli, now the Eugene ies into new treatments for neurode- professional societies. His early research was in endocri- Higgins Professor of Cell Biology and generative diseases and injuries of the nology, specifically on how hormones professor of neurobiology, gradually brain and spinal cord. are secreted from cells in a process became intrigued with the question “Basic science helps us understand called exocytosis. This manner of secre- of how new vesicles form after neuro- medicine,” he says, “but increasingly,” as genomics inspires experiments tion is ubiquitous in biology, but is par- transmitters are released. In this Editor Peter Farley based directly on human biology and ticularly crucial in the nervous system. process, called endocytosis, intracellular Assistant Editor Charles Gershman disease, “medicine has become a tool In neurons, the membrane is shaped proteins bend the now-flat synaptic Contributors Sonya Collins, Virginia Hughes, Kathy into spherical sacs called vesicles that membrane back into a proper-sized of science.” Katella, Sarah C.P. Williams Design Jennifer Stockwell Medicine@Yale is published five times each year by the Office of Institutional Planning and Specialist in pancreatic cancer lauded for outstanding patient care Communications, Yale School of Medicine, 1 Church St., Suite 300, New Haven, CT 06510-3330 Ronald R. Salem, m.d., Lampman Pro- Robert J. Alpern, at the Royal Postgraduate Medical Telephone: (203) 785-5824 Fax: (203) 785-4327 fessor of Surgery, professor of diagnos- m.d., characterized School at Hammersmith Hospital in E-mail [email protected] tic radiology, and chief of the medical Salem as “absolutely London. He was chief resident and a Website medicineatyale.org school’s Section of Surgical Oncology, dedicated to patient research fellow at the New England Copyright ©2012 by Yale University. All rights reserved. If you have a change of address or do not wish to receive is the recipient of the 2011 David J. Lef- care. . . . He works Deaconess Hospital and the Dana future issues of Medicine@Yale, please write to us at the fell Prize for Clinical Excellence. with extreme com- Farber Cancer Center in Boston. above address or via e-mail at [email protected]. Salem’s accomplishments since passion, and his ex- The annual prize was established Postal permit held by Yale University, his arrival at Yale 22 years ago include traordinary caring in 2008 by David J. Leffell, m.d., 155 Whitney Avenue, New Haven, CT 06520 establishing the Oncologic and General Ronald Salem nature is evident to the David Paige Smith Professor of Surgery group, now one of the busiest all of his patients.” Dermatology, professor of surgery, Robert J. Alpern, m.d. clinical practices in the Department of Colleagues who nominated Salem for and deputy dean for clinical affairs, Dean and Ensign Professor of Medicine Surgery. A specialist in treating pancre- the prize praised “his availability, his and his wife, Cindy, to mark Leffell’s Jancy L. Houck Associate Vice President for Development and atic cancer Salem is an expert in perform- calm disposition during critical mo- 30th Yale College reunion. The award Director of Medical Development (203) 436-8560 ing the Whipple procedure, in which the ments, and above all his counsel.” recognizes a faculty member who Mary Hu head of the pancreas is removed. Salem earned his medical degree exemplifies clinical expertise, skilled Director of Institutional Planning and Communications At an April 9 ceremony, Dean at the University of Rhodesia and teaching, and the highest standards and Ensign Professor of Medicine completed a general surgery residency of care and compassion for patients. Printed on recycled paper ♻

2 www.medicineatyale.org advances Health & Science News Cardiovascular science as social network In bringing cardiovascular researchers together function. The vascular and nervous systems appear to be Human stem cells more closely related than previously thought: “In multicel- play by own rules under one roof, Yale center gathers momentum lular organisms,” Simons explains, “the nervous system and funding, stimulates scientific collaboration evolved first, and the vascular system followed, and it’s be- ginning to look like they used the same set of molecules.” There is strength in numbers, and in unity, as members This connection holds tremendous potential for biomedi- of the Yale Cardiovascular Research Center (ycvrc) cal research, says Simons. “It turns out that the vascula- know. Less than a year after moving into new laboratory ture controls the function of the nervous system, and the space expressly designed to foster collaboration and shared nervous system controls the function of the vasculature. resources, the 16-person team, led by ycvrc Director There’s a huge overlap between neurobiology and vascular istockphoto Michael Simons, m.d., has received Three genes in a constant interplay a $9.5 million five-year Program with one another determine the fate Project Grant (ppg) from the National of embryonic stem cells (escs). The Heart, Lung, and Blood Institute, a genes— Nanog, Oct4, and Sox2—have component of the National Institutes been extensively studied in mice, but of Health. The grant will support little is known about how these genes research on the molecular basis of regulate human stem cells. arteriogenesis—the process by which escs are medically important, new arterial blood vessels are formed— because they can differentiate into any with the aim of developing a new of the myriad cell types that make up framework for drug discovery and tissues. Each gene in the Nanog/Oct4/ other therapeutic advances. Sox2 trio plays a vital part in directing Since his arrival at Yale from cells to commit to one cell fate versus Dartmouth Medical School in 2008, another. Yale Stem Cell Center scientist Simons, a leading researcher on the Natalia Ivanova, ph.d., assistant profes- role of arteriogenesis in cardiovascular sor of genetics, and colleagues mapped diseases, has created a unique scientific out the role of each of these genes in climate at the ycvrc that has attracted human embryonic stem cells (hescs) top scientists he describes as “stars.” In sacco william by selectively inactivating them during turn, the expansion and diversifica- ycvrc Director Michael Simons with (from left) Anne Eichmann, Martin Schwartz, and Karen Hirschi. hesc maintenance and differentiation. tion of ycvrc faculty has opened In the April 6 issue of Cell Stem Cell, Iva- up new research directions and new biology, and we’re trying to build a program that takes nova and her team report that Nanog, avenues of funding. The new ppg is a concrete recogni- advantage of the expertise Yale has in those fields.” Oct4, and Sox2 do not have the same tion of the unusually complementary and interrelated Eichmann has explored the effects of the interac- functions in hescs and mouse cells. research projects happening at the ycvrc, says Simons, tions between nerves and arteries on blood pressure; and There are restrictions on the use the Robert W. Berliner Professor of Medicine, professor another recent recruit, Jean-Léon Thomas, ph.d., m.sc., of hescs in research, but “it is difficult of cell biology, and chief of the Section of Cardiovascular associate professor of neurology, has pursued research on to deduce from the mouse how these Medicine. It reflects an upward spiral in cardiovascular the relationship between vasculature and brain function. cells work in humans,” says Ivanova. research at Yale—research that may lead to new arterio- In 2011, Thomas, Eichmann, and colleagues reported in “Human networks organize themselves genic therapies for illnesses like atherosclerosis, in which the journal Genes & Development that they had identified quite differently.” buildup of cholesterol and fatty materials causes an artery stem cells in the brain that replace damaged nervous tis- wall to thicken, and metabolic syndrome, a combination sue, and that a protein called vascular endothelial growth of medical disorders that can jointly lead to cardiovascu- factor (vegf) receptor 3 acts directly in these stem cells to No turning back lar disease and diabetes. “This would not have happened stimulate the creation of new nerve cells in adults—findings the biological clock three years ago,” he says, “because we would not have that have implications for neurodegenerative diseases such Assisted reproductive technologies had the people.” as Alzheimer’s and Parkinson’s. (arts), such as in vitro fertilization, are Another recent addition to the ycvrc is Karen K. Hirs- so established that pregnancy at any Scientific diversity chi, ph.d., professor of cardiology, who joined the faculty age may seem both reasonable and One of the ycvrc team’s greatest strengths is its scientific in the fall of 2011. Hirschi studies signaling pathways that achievable—views that more and more diversity. For instance, Martin A. Schwartz, ph.d., profes- regulate endothelial cell differentiation, specialization, and women hold, according to a new report sor of medicine and cell biology, is an expert in the way growth during early vascular development. Her lab is also from Yale researchers. The reality is that “fluid shear stress,” the friction of flowing blood against using this basic biological information to direct the fate of despite medical advances, women who the endothelium (cells that line all blood vessels), regu- human pluripotent stem cells (both embryonic and in- wait until their early forties to have chil- lates their behavior. As part of the new ppg, Schwartz’s lab duced), which can become any cell type, specifically toward dren face significant risks of infertility will study how increased flow leads to the growth of new vascular cells. Hirschi’s aim is to understand how to get or complications during pregnancy. The arteries. Recruited to Yale in 2011 from the University of human stem cells to efficiently become vascular endothe- new study urges concerted public and Virginia, Schwartz is one of the newest members of the lial cells, so they can be used to form new blood vessels in professional education to address the ycvrc and the ppg team. regenerative medicine strategies. “alarming” misperceptions of arts. Shear stress, Schwartz explains, is “the critical stimu- Other recent recruits include Daniela C. Tirziu, ph.d., “We’re seeing more and more lus” in the formation of collateral arteries that grow around instructor in medicine, who specializes in cell-to-cell patients upset after failing in having blocked arteries, a kind of natural bypass. Following the communications in the heart; Daniel Greif, m.d., assistant their own biological child after age 43,” occurrence of an arterial blockage, as happens in a heart professor of medicine, who works on pulmonary artery says Pasquale Patrizio, m.d., m.b.e., attack, for example, “some people can make these collateral development and function; Hyung Chun, m.d., assistant professor of obstetrics, gynecology, and arteries pretty efficiently, and some people don’t,” he says. professor of medicine, whose interests // Center (page 6) reproductive sciences and director of The making of these collateral arteries is critical to recovery. the Yale Fertility Center. For more than 10 years, Schwartz has investigated the mech- In an advance online edition of Fer- anisms underlying this phenomenon experimentally, and tility and Sterility, Patrizio’s team writes he has made real progress. “We’re now at the point where A legacy of achievement that among women aged 43 and older we can apply our understanding to the problem of flow- For two centuries, Yale School of Medicine has been a center of employing arts, only about 4 percent dependent artery remodeling” in human patients. important advances in science and medicine. The physicians and eventually give birth, a number 10 times Anne Eichmann, ph.d., m.sc., professor of medicine, scientists of the Yale Cardiovascular Research Center were drawn lower than that for women under 35. was recruited to the Center in 2010 from the Collège de to the School of Medicine because of its superb faculty and The researchers urge that women France. Eichmann studies the factors that determine where outstanding core research facilities. The generosity of individual donors allows us to sustain Yale’s be better informed of these odds, and the cells in blood vessels and lymphatic vessels grow. “We groundbreaking research on the prevention and treatment of heart of the options to cryopreserve their know about the factors that tell endothelial cells how to disease and vascular disease. With independent funds, Yale re- grow, but we’re much less familiar with the cues that tell oocytes while at their “fertility peak searchers are able to harness the power of cutting-edge technology years” (under 35) or use donated them where to grow,” she says. and pursue tomorrow’s most significant health breakthroughs. oocytes, methods that have achieved Among Eichmann’s other areas of interest is neurovas- To learn more about cardiovascular research at the School of high success rates in older women but cular biology—specifically, to understand how the vascular Medicine and ways you can contribute, please contact May Cahill, are lesser-known than other arts. and nervous systems influence each other’s growth and director of principal gifts, at 203-436-8528, or at [email protected].

Medicine@Yale May 2012 3 out & about

January 27, 2012 A reception was held in the medical school’s Historical Library February 24, 2012 More than 70 second-year medical students participated in honoring the appointment of Steven M. Southwick, m.d., as the first Greenberg Pro- the production of this year’s Second-Year Show, entitled “The iPocalypse.” 1. Jessi fessor of Psychiatry, Post-Traumatic Stress Disorder, and Resilience (see related story, Gold playing Margaret J. Bia, m.d., professor of medicine and director of the medi- page 8). The professorship was created in 2010 with a gift from Glenn H. Greenberg, cal school’s Clinical Skills Program. 2. Alex Kula sang and played the guitar in the of the Yale College Class of 1968. (From left) Linda Vester Greenberg; Glenn Green- show’s finale. 3. Kelsey Loeliger and the Class of 2014 sang and danced in the berg; Robert J. Alpern, m.d., dean and Ensign Professor of Medicine; and Southwick, show’s final musical number. 4. Samantha Wang, one of the show’s directors, also professor in the Child Study Center. played an evil management consultant hired by Deputy Dean for Education Richard Belitsky, m.d., the Harold W. Jockers Associate Professor of Medical Education and associate professor of psychiatry, who devises a plan to eliminate the venerable Yale System of medical education. 5. Loeliger (left) and Juliet Fraser (right) in the musical number “Defying Belitsky.”

1 2 terry dagradi

3 February 28, 2012 At a panel discussion called “Personal- 1 ized Medicine: How Far Off?”, sponsored jointly by Yale’s Office of Cooperative Research and the New Haven-based bioscience advocacy group cure (Connecticut United for Research Excellence), medical school faculty and biotech entrepreneurs discussed the status and trajectory of medi- cine in the post-genomic age. 1. Richard P. Lifton, m.d., ph.d., chair and Sterling Professor of Genetics and profes- sor of medicine. 2. Paul R. Pescatello, j.d., ph.d., ceo of cure, moderated the discussion. 3. Thomas J. Lynch, m.d., Richard Sackler and Jonathan Sackler Professor of Medicine, director of Yale Cancer Center, and physician- in-chief of Smilow Cancer Hospital at Yale-New Haven. william sacco (3)

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4 5 john curtis (5)

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April 9, 2012 This year’s David J. Leffell Prize for Clinical Excellence was awarded to Ronald R. Salem, m.d., Lampman Professor of Surgery professor of diagnostic radiology, and chief of the Section of Surgical Oncology (see related story, page 2). Pictured here at a reception in the medical school’s Historical Library are (from left) Salem’s mother-in- law, Blanche Feldman; Salem; Salem’s wife, Sharon Salem; and son, Daniel Salem.

3 4 5 john curtis (5)

March 16, 2012 Each spring, fourth-year students at medical schools across the country eagerly anticipate Match Day, when students receive word of acceptance in residency training programs. At Yale, medical students gathered with friends, family, and faculty members in Harkness Ballroom to await the news. 1. Alisse Hauspurg and a friend share a hug. 2. (From left) Alicia Little, Charisse Orme, and Katherine Uyhazi. 3. Julius Oatts (left) and Lilangi Ediriwickrema. 4. Whitney Sheen. 5. (From left)

Adelina Hung, Fayola Edwards, and Odayme Quesada. shapiro harold

4 www.medicineatyale.org advances Health & Science News Stopping malaria dead in its tracks Just seven minutes Cross-campus collaborators work toward the curbs alcohol abuse elusive goal of effective treatment, eliminating drug resistance and side effects in the bargain

For parasites like those that cause malaria to thrive in the human body, they must produce proteins that drive their growth, reproduction, and nutrition. Existing malaria drugs work by blocking parts of this protein machinery, but the pathogens frequently become resistant to these drugs by istockphoto evolving ways to block the drugs from binding to or passing If someone ends up in a hospital’s through their external membranes. emergency department (ed) with signs Now, Yale researchers have discovered a different ap- of harmful drinking habits, as few as proach that works against malaria parasites and other patho- seven minutes of counseling by a physi- gens by destroying the genetic material that encodes some of cian can motivate them to cut back these pathogens’ most vital proteins. terry dagradi their alcohol consumption, says a new Over the past few years, Sidney Altman, ph.d., Sterling (From left) The School of Medicine’s Choukri Ben Mamoun and Yoann study by Yale researchers. Professor of Molecular, Cellular, and Developmental Biology, Augagneur have joined with Sidney Altman (right) and Donna Wesolowski On average, the nearly 900 patients has developed a technique to destroy specific pieces of a cell’s (second from right) to design a malaria-fighting compound that could messenger rna (mrna) with a compound called a peptide- provide the basis for effective, less toxic treatments, against which the enrolled in the study, published in malaria parasite would be unlikely to develop drug resistance. an advance online edition of Annals morpholino oligomer (pmo) conjugate. He and his colleagues of Emergency Medicine, consumed have shown that pmo conjugates can kill bacteria, includ- around 20 drinks in the week prior to ing E. coli and staph bacteria, by stopping the production of gene for gyrase was blocked, the malaria parasites died. “The visiting the ed. When the researchers proteins the pathogens require to survive. next step is to test new targets and optimize the conjugates,” followed up a year later, that number When the pmo binds its targeted mrna sequence, this says Augagneur. “We can use different conjugates against had decreased to 17 drinks per week for structure is recognized by an enzyme in human red blood the same mrna targets and improve the activity by two- to patients with no interventions and to cells that destroys the mrna, preventing it from being tran- three-fold, and we can also find new targets.” The drugs are 14 for those who received counseling in scribed into proteins in the pathogen. an optimal way to target the malaria parasite, he says, because the hospital. Moreover, the counseled “We think that this technique has general importance and resistance, a problem with many other drugs, is unlikely to patients reported fewer binge drinking has lots of applications,” says Altman, who shared the 1989 develop against the pmos. “In principle, there wouldn’t be resis- episodes than those who received no Nobel Prize in Chemistry for helping to establish that rna can tance because you would need several mutations right next to counseling. Patients in the intervention act as an enzyme as well as a carrier of genetic information. each other in order to stop the conjugate from working.” group were also less likely to drive after For the new work, Altman collaborated with malaria And because you can selectively choose where on a stretch having three or more drinks. expert Choukri Ben Mamoun, ph.d., associate professor of of mRNA the pmo binds, scientists can select sequences that “A short intervention has great internal medicine and microbial pathogenesis, and Ben Ma- don’t resemble any human genes, so the pmo won’t interfere potential to increase the health of the moun’s postdoctoral fellow Yoann Augagneur, ph.d., to test with normal body processes. public,” says Gail D’Onofrio, m.d., m.s., whether the pmo conjugates are effective against Plasmodium “All existing anti-malarial drugs have side effects and professor and chair of the Department falciparum, the parasitic species that causes the most severe some of them are very severe,” says Ben Mamoun. “But, of Emergency Medicine and leader of cases of malaria. As a proof of concept that pmo conjugates although we haven’t done human trials yet, we would predict the new study. could enter P. falciparum cells and cause its mrna to degrade, that these oligomers would be quite safe because of their speci- the team of scientists developed a pmo that binds the mrna ficity and selectivity.” coding for an enzyme known as gyrase, the same type of While Ben Mamoun and Augagneur pursue new ways to sequence that Altman had targeted in other pathogens. use the pmos against malaria parasites, members of Altman’s Is cell phone use risky “There are genes that we know are essential to the parasite lab plan to move on to other types of pathogens. during pregnancy? but we can’t knock them out using classical genetics,” says Ben “There are lots of parasites that affect human cells and we Chatting on a cell phone may become Mamoun. “But using this oligomer, we can block the genes just have to find out which ones are attractive as targets of this the next taboo for pregnant women. and study what happens.” As reported in the April 2 issue of drug,” says Altman. “It’s very easy to redesign our compound A recent study led by Hugh S. Taylor, the Proceedings of the National Academy of Sciences, when the to attack anything we want to look at.” m.d., professor and chief of the Divi- sion of Reproductive Endocrinology and Infertility in the Department of Obstetrics, Gynecology, and Repro- Cross-country walk seeks ‘altruistic’ organ donors ductive Sciences, found that when pregnant mice were exposed to cell Donating part of his liver and a kidney where a ceremony for “Walk of 2012” “Mr. Kiernan is one of our heroes. phone radiation during pregnancy, to two different recipients he had took place under the Donate Life flag He saved two patients’ lives by donat- their offspring were more hyperactive never met was not enough for Harry near the hospital’s entrance. Sukru H. ing one of his kidneys and a part of his and forgetful than usual. Kiernan. The Vietnam veteran and Emre, m.d., professor of surgery and liver,” said Emre, chief of the Section of Taylor and colleagues attached cell firefighter is now taking his efforts to pediatrics and the transplant surgeon Transplantation Surgery and ynhtc phones on active calls—and therefore raise awareness about organ donation— who performed Kiernan’s liver dona- director (donated parts of the liver producing radiation—to the cages of including so-called altruistic donations tion surgery, was on hand to wish grow back in donors and grow to the 33 pregnant mice and left them there like his, in which recipients are not Kiernan well and commend him for proper size in recipients). Emre pointed for the full 17 days of gestation. After related or known to the donor—many his generosity. out that, like Kiernan, many altruistic the birth of the offspring, the scientists steps further by walking across the Emre presented Kiernan with an donors are veterans, firefighters, or tested the memory, hyperactivity, and United States. appreciation plaque from the Yale- policemen. “These individuals were on anxiety of the newborn mice. Those Kiernan’s 3,300-mile journey New Haven Transplantation Center front lines in many life-and-death situ- born to mothers with cell phones on began March 18 in Glastonbury, (ynhtc) on behalf of patients on the ations and they know how to sacrifice their cages scored higher on measures Conn., and he reached Yale-New transplant waiting list for his dedica- for others,” he said. of hyperactivity and lower on tests of Haven Hospital (ynhh) the next day, tion and service. In the U.S., only two percent of memory and anxiety than mice born organ donations from living patients to mothers without the cell phone Sukru Emre (left) and are altruistic donations. With each exposure, the researchers reported in Harry Kiernan kicked step he takes from east to west, Kier- off Kiernan’s “Walk the March 15 issue of the journal Scien- nan, founder of the National Living of 2012” on the Yale- tific Reports. The team also found that New Haven Hospital Organ Donors Foundation, hopes to certain neurons in the prefrontal cortex grounds on March 19. increase the number of organ dona- of the brains of offspring exposed to Kiernan, a Vietnam tions, from both deceased and living radiation had decreased activity, which veteran, firefighter, donors, nationwide. and liver and kidney may explain their behaviors. More After leaving New Haven, Kiernan donor, is walking work is needed, they say, to determine across the U.S. to raise set off for New York City and expects a safe level of cell phone radiation for awareness about organ to arrive in Los Angeles during the first pregnant women. sacco william donation. week of July.

Medicine@Yale May 2012 5 // Center (from page 3) include pulmo- focused on translating laboratory occur because of dysregulated blood cells. The aim of the new technology nary hypertension; Suk-Won Jin, discoveries into practical treatments vessel formation—or [as with diseases —which the scientists hope will be ph.d., and Stefania Nicoli, ph.d., for disease. Now led by William C. like “wet” macular degeneration], tested in human patients within four both assistant professors of medi- Sessa, ph.d., the Alfred Gilman Pro- when there’s an overgrowth of blood years—is to alleviate circulatory prob- cine who use zebrafish as a research fessor of Pharmacology, vbt’s diverse vessels in the eye that inhibits vision.” lems arising from obstructive blood model; John Hwa, m.d., ph.d., asso- and collaborative design served as a In May, the ycvrc and vbt will clots and narrowed blood vessels in ciate professor of medicine; Kathleen model for the ycvrc, and functions convene an international neurovascu- patients with coronary stents. Martin, ph.d., associate professor as its “sister” program. lar symposium in New Haven jointly The four-year $4.5 million grant of medicine; Daniel L. Dries, m.d., vbt members meet with ycvrc with University College London is the first ec grant to fund the work m.p.h., associate professor of medi- scientists in regular joint lab meetings. (ucl) scientists, many of whom of American scientists, Simons says, cine and medical director of the Yale A leading researcher on blood vessel “work on [neurovascular interactions and could not have been possible Center for Advanced Heart Failure; function and vascular disease, Sessa is and] eye disease,” Hirschi says. “We without the existence of the Yale ucl and Yibing Q yang, ph.d., assistant one of the new ppg’s seven investiga- hope to form collaborations so that Collaborative, which was created in professor of medicine and of pathol- tors. The others are Tirziu; Simons; we can do studies for eye disease 2010. “This grant is unique in that ogy. Q yang, like Hirschi, studies Schwartz; Themis Kyriakides, ph.d., [similar to our studies on the neuro- it brings together several biotech stem cells—particularly cardiovascu- associate professor of pathology and vasculature of the brain].” companies and academic institutions lar progenitor cells (cpcs), which are of biomedical engineering; Laura In the area of psychiatry, too, there that have complementary expertise,” capable of making nearly an entire E. Niklason, m.d., ph.d., professor is much overlap. Thomas, for instance, Sinusas says. heart during formation—and is work- of anesthesiology and of biomedical studies the effects of vegf signaling Thanks to advances in genome ing to better understand the biology engineering, a pioneer in tissue engi- on behavior, and is working jointly sequencing technologies, and in of cpcs with the aim of developing neering; and Albert J. Sinusas, m.d., with colleagues in the Department of particular to state-of-the-art genetic and enhancing therapies for disease professor of medicine and of diagnostic Psychiatry to gauge the links between screening capabilities now offered by and injury. radiology, a ycvrc member and an vegf and behavioral outcomes like the Yale Center for Genome Analysis, expert in advanced cardiovascular and depression and anxiety. ycvrc scientists are increasingly able Abundant resources molecular imaging. All seven scientists “The symposium enables every- to rely on genetic analyses of indi- Since Simons’ arrival in 2008, grant are members of vbt. one to share his or her work, get a feel vidual patients in conducting basic funding for cardiovascular research at Yale has nearly tripled, increasing from about $8.5 million to about $24 mil- lion in 2012. This amount includes a five-year $6 million grant from the Paris-based Fondation Leducq under the auspices of its Transatlantic Net- works of Excellence in Cardiovascular and Neurovascular Research pro- gram, awarded in 2010. The School of Medicine, at which the Leducq grant is supporting ycvrc research on the link between arteriogenesis and metabo- lism, is one of just six research institu- tions taking part in this international project, which is built around frequent and close communication. But it’s not simply funding that has enticed leading cardiovascular re- searchers to set up shop at the School robert lisak of Medicine. Another crucial factor is the “unique environment” of the “We see vbt and the ycvrc as a (Above) In the lunch- ycvrc, Simons says, a collegial place single program, because people in- room at the Yale where “everybody has a say. People teract so effectively—at seminars and Cardiovascular Research help each other, and we have several retreats, and at joint lab meetings,” Center (ycvrc), faculty members, postdoctoral fantastic interaction forums.” These Sessa says. “There are common fellows, and graduate include a weekly faculty gathering research interests, and everyone is students can mingle held in a purpose-built lunchroom secure enough with their own work informally. in the center’s suite at 300 George to champion collaborative interac- (Left) Members of the Street (see photo). “If you’re there, tions. Michael Simons’ recruitment ycvrc in the center’s you could be asked to talk off the cuff gave us a partner in cardiology to suite at 300 George Street. The suite’s physi- about what you do,” Simons explains. synergize with.” cal design reflects its

“All our joint funding has come out Other budding ycvrc collabo- terry dagradi collaborative culture. of this faculty lunch.” rations involve the Departments of Cardiovascular medicine is a Neurology, Ophthalmology, and for what everyone else is doing, and research—with the hope that this scientific success story, as research has Psychiatry. Each month, ycvrc identify mutual interests on which we research can then be brought “back led to effective medications to manage scientists convene with colleagues can build joint research programs and to the bedside” as therapy for disease. cholesterol as well as angioplasty and from the Department of Neurology training opportunities,” Hirschi says. Cardiovascular genetics efforts at the stents, which allow doctors to widen at a neurovascular meeting to explore Scientists from Yale and ucl are ycvrc, led by Arya Mani, m.d., associ- narrow or blocked blood vessels. “But the implications of vascular research also collaborating on a project recently ate professor of medicine and of genet- there has never been a medication that in the brain. For instance, Jaime funded by a European Community ics, working together with colleagues changes the nature of disease,” Simons Grutzendler, m.d., associate profes- (ec) grant, administered by the Eu- from ucl and Yale’s Department of says. “All the currently available treat- sor of neurology and of neurobiology, ropean Union. Sinusas, Tarek Fahmy, Genetics, have already resulted in ments—and they’re very good—do not studies the brain’s microvasculature ph.d., associate professor of biomedi- “significant new insights in our under- address the underlying biology of dis- —its smallest blood vessels—and is cal engineering, Simons, and Niklason standing of early atherosclerosis and ease, and they basically palliate. The interested in “vascular dementia,” are working jointly with colleagues at metabolic syndrome,” Simons says. question is: how can you understand or the ways neurovascular defects ucl, with U.K.-based Ark Therapeu- Scientists have traditionally what’s going on?” contribute to cognitive decline in tics, and also with teams of scientists believed that cardiovascular illnesses the elderly. The expertise of ycvrc in Germany and Finland, to design are caused by numerous small chang- Collaboration scientists like Eichmann, Hirschi, and test a new technology designed es in many genes. But “it appears ycvrc members collaborate very and Thomas, who all work in areas to improve healing around implanted now that there are a number of genes closely with other groups at the medi- related to neuroscience, is something vascular stents. The technology in which a single mutation will give cal school. One notable relationship is Grutzendler is now able to tap into. involves using magnetized biodegrad- you a significant phenotype,” Simons that between the ycvrc and the Vas- Ophthalmology is closely linked to able stents, which will attract stem says—which increases the odds that cular Biology and Therapeutics (vbt) neurovascular research, says Hirschi, cells that have been loaded with iron scientists can identify the gene vari- Program. Formed in 2000, vbt was because “the retina is a neural tissue. particles; and, additionally, stents in ants that cause a particular disease, the medical school’s first interdepart- Several of us in the ycvrc are inter- which viral vectors have been embed- understand that disease’s biology, mental research program explicitly ested in ophthalmological disorders that ded, to promote the adhesion of stem and find new therapies.

6 www.medicineatyale.org // Scholar (from page 1) five years she had “Dean Alpern envisioned an envi- “A Yale Scholar Award allows a has passed to Andrew Goodman, discovered “initiator regions,” sites in ronment where new faculty members new scientist to gain traction on a ph.d., assistant professor of microbial messenger rna (mrna) strands that are free to work on their best ideas,” research idea even if it is not a con- pathogenesis, who studies microbial mark where the cell’s protein-making says McCluskey, whose new gift brings ventional one,” Alpern says. “A Yale communities in the human gut. machinery begins translating mrna the total number of Yale Scholar funds Scholar has the latitude to take novel “I am deeply grateful to Mr. into proteins. In a classic paper pub- to eight. “I am happy to name this new approaches, to adopt new techniques McCluskey for his generous sup- lished five years later, Steitz showed fund in honor of Joan Steitz, a scientist or to work at the intersection of port,” Alpern says. “Natalia Ivanova that rna-protein complexes in the who exemplifies the power of original disciplines where it is harder to find and Andrew Goodman are at the cell nucleus called snrnps are critical thinking.” To sustain the funds, gifts grants. By year five the researcher start of a long line of distinguished to “splicing,” by which non-coding like McCluskey’s two $2.5 million should be well positioned to attract McCluskey Scholars, and by Sep- sequences are excised from pre- donations establishing Yale Scholar his or her own funding.” tember we will announce our first mrna to form mrna. In the decades Funds are matched by a commitment Today, Ivanova continues her Steitz Scholar. This remarkable since, rna biology has exploded, from Yale University—evidence of work at the Yale Stem Cell Center legacy will shape the School and the and Steitz continues to explore rna’s the program’s importance to recruit- (see “Advances,” page 3), and her discoveries we can make here for diverse and powerful roles in the cell. ing and jump-starting research. position as a McCluskey Scholar generations to come.”

// Student research (from page 1) a fifth of medical school. Today, the office says is a testament to the faculty- leaders, including Nobel laureates. year of medical school for research, funds students during periods of student pairs and the volume and Hardean Achneck, m.d. ’05, now expanded Student Research Day—an research throughout medical school, quality of publications and national assistant professor of surgery at Duke annual event at which students present typically during the summer between presentations arising from Yale medi- University School of Medicine, credits their work in posters and oral presenta- the first and second years, but often cal students’ research. The budget for his fifth year at Yale with teaching him tions to peers and faculty—and “created extending to a fifth year. Each year the Office of Student Research now to think like a researcher.“The general ideal faculty-student pairs,” Forrest more than 200 students receive fund- exceeds $2.5 million per year. principles that have helped me in my says. Those student-faculty matches ing from Forrest’s office, mostly via an Under Forrest’s leadership, Student research career basically started with allowed students like Obinwanne nih Training Grant that has been con- Research Day has been transformed research at Yale,” says Achneck, who Ugwonali, m.d. ’99, to find the link tinuously renewed for 25 years. Also into an eagerly anticipated annual still considers his faculty advisor, John between yams and twin births through providing funding are Yale’s Clinical event. “In the 60s and 70s,” he says, Elefteriades, m.d., professor and chief research in Nigeria, and Khoonyen and Translational Science Award from “there was a modest student research of cardiothoracic surgery, a mentor. Tay, m.d. ’06, to explore the options the nih, the Howard Hughes Medical afternoon where the prize-winning “It’s often a lifelong friendship for treating a middle ear infection in Institute, the Sarnoff Cardiovascular thesis was presented.” Today, the event that’s formed between the mentor and children. Research Foundation, the Doris Duke (held this year on May 8) includes a the student with publications, presen- At its founding, the Office of Charitable Foundation and donations poster session with about 90 post- tations, and all the like that follow,” Student Research had limited fund- to Yale from individuals. A recent re- ers, oral presentations by authors of Forrest says. “It is that faculty-student ing, and could only support student application for the nih training grant the highest-rated theses, and the Farr pair that deserves the emphasis and research during the first summer earned a perfect score, which Forrest Lecture, which has featured scientific the celebration.”

// Autism (from page 1) the ssc includes pathways,” State says. And, he adds, seem to do any harm, how do we the rest of the participants in the blood samples and extensive medical those specific networks will make the know which ones in the autism group ssc, and based on the mutation rate information from 2,700 families in best targets for new treatments. are important? “Sorting out the stuff reported in the Nature papers, they which one child has been diagnosed The ssc was launched in 2008 to that’s damaging from the stuff that’s estimate they will find at least 25 genes with autism. The families are recruited help solve a puzzle. “We knew that not is extremely difficult,” State says. solidly linked to autism in the ssc from 13 clinics across the country, each children with autism don’t usually get “One of the major preoccupations of alone. What’s still unclear, however, using the same precise measures to married and don’t have children, and the paper was finding an unbiased is how much of the broader popula- confirm autism diagnoses. Researchers yet the rate of autism isn’t decreasing,” way of doing that.” tion of children with autism may also collect blood samples from not only the says Gerald D. Fischbach, m.d., scien- The researchers reasoned that a carry glitches in these genes—or how children with autism, but from parents tific director of the Simons Founda- gene was more likely to be meaning- many of these genes will also figure and unaffected siblings. The term tion’s Autism Research Initiative. “So ful if it carried new mutations in more into other psychiatric disorders, such “simplex” in the ssc’s name refers to where is it coming from?” than one unrelated child with autism. as schizophrenia, bipolar disorder, and the fact that the collection includes One leading hypothesis was that They also placed special focus on obsessive-compulsive disorder. only families with a single child with some portion of autism cases are mutations that are highly damaging There’s also the more mysterious autism and at least one unaffected caused by spontaneous—so-called to protein production. Once those issue of environmental and develop- child, making it easier to draw precise de novo—genetic variations, rather criteria were plugged into the proper mental contributions to developmen- genetic comparisons between affected than those inherited from parents. statistical analyses, from over 238 fam- tal disorders. And all three Nature and unaffected family members. A 2007 Science paper reported that ilies studied the researchers ended up papers shed light on a factor that’s In a much-publicized study pub- 10 percent of individuals with autism with just one gene, called scn2a, that been much talked-about: paternal age. lished April 4 in Nature, State’s team carry de novo copy number variations is strongly associated with autism. The data show that as the age of the screened about 10 percent of ssc par- (cnvs), stretches of dna that are Another group of researchers, led father increases, so does the number of ticipants. But rather than sequencing either deleted or duplicated, compared by Evan Eichler, ph.d., of the Uni- spontaneous mutations carried by his the entire genome of each participant, with just 1 percent of controls. Last versity of Washington, did a similar child, which makes sense since sperm which is for now prohibitively expen- year, State’s team and an independent search in a separate group of 677 ssc tend to acquire more genetic muta- sive, the researchers focused on the group screened the ssc samples for de participants. When State’s group tions as a man ages. “It’s a very strong “exome,” those portions of the genome novo cnvs and confirmed that these applied their statistical approach to correlation—there’s no question,” that code for proteins. By applying variations crop up more often in chil- the combined data from both stud- State says. Still, a father’s age probably this technique to the ssc’s unique dren with autism than in controls. ies, three genes made the cut: scn2a, plays a minor role in overall autism population, the research fingered three But cnvs are large, sometimes KATNAL2 and CHD8. risk. The average age of men when genes that almost certainly contribute encompassing thousands of base pairs “Each one of these genes is a they fathered children with autism to autism, and about a dozen others of dna and dozens of genes, making whopper,” Fischbach says. “Because of was only 1.1 years higher than when that are strong contenders. Two ac- it difficult to draw conclusions about the design of these experiments, using they fathered unaffected siblings. And companying papers in Nature turned which individual genes are implicated both parents and unaffected siblings, when paternal age was left out of the up yet more candidates. in a disease. The new studies, in con- this is about as sure as one can be analysis, children with autism were As the cost of genome sequenc- trast, read families’ genomes letter-by- about a genetic cause.” These gene still found to carry more mutations ing continues to plummet, State and letter, so researchers can zoom in on candidates have intriguing biological than unaffected siblings. others will screen more and more variants affecting just one letter. roles in brain cells. scn2a, for exam- But State sees a broader lesson to ssc children. Based on previous After screening 928 ssc partici- ple, makes a protein that helps control be learned from this finding. “It shows work and the findings published in pants, State and colleagues found the transmission of electrical impulses that as you get more insight at the Nature, he estimates that the total 125 single-letter de novo mutations in across nerve cell membranes; a hand- molecular level, you can begin to un- number of autism-linked genes will the children with autism, compared ful of people with epilepsy or intel- derstand what mechanisms might be hit 500 or more—a greater cause for with 87 such mutations in unaffected lectual disability have been reported to behind some of these environmental optimism than it might seem. “Even siblings. That’s a statistically signifi- carry glitches in the gene. influences,” he says. “As you move for- though there are many, many regions cant difference, but also highlights a State, Eichler, and Michael Wigler, ward in clarifying the genetics, you’re in the genome involved, I believe they basic problem: Since healthy people ph.d., of the Cold Spring Harbor also going to clarify the environmental will converge on a small number of carry so many mutations that don’t Laboratory are working on sequencing factors, and vice versa.”

Medicine@Yale May 2012 7 Expert on the effects of post-traumatic stress Biostatistician, substance abuse researcher named the inaugural Greenberg Professor is appointed Susan Dwight Bliss Professor

Steven M. Southwick, m.d., a widely psychiatry at Yale Heping Zhang, ph.d., a specialist in which is funded recognized expert on the psychological School of Medicine. research on substance use, statisti- by the National and neurobiological effects of extreme He currently serves cal methods in genetic studies of Institute of Mental psychological trauma, has been named as an adjunct pro- substance use, and research training Health, and he the inaugural Greenberg Professor fessor at Mt. Sinai in mental health epidemiology, has is a fellow of the of Psychiatry, Post-Traumatic Stress School of Medicine been appointed as the Susan Dwight American Statisti- Disorder, and Resilience. and medical direc- Bliss Professor of Biostatistics in the cal Association and Southwick, also professor in the tor of the Clinical School of Public Health. of the Institute of Child Study Center, has published Steven Southwick Neurosciences Zhang has developed statistical Heping Zhang Mathematical Sta- extensively on the phenomenology and Division of the National Center for methods and software to analyze tistics. Zhang was named the 2008 neurobiology of post-traumatic stress Posttraumatic Stress Disorder. data related to a broad range of Myrto Lefokopoulou Distinguished disorder (ptsd), the longitudinal Southwick has earned numerous health outcomes including preg- Lecturer by the Harvard School of course of trauma-related psychologi- awards in recognition of his clinical nancy outcome, mental health, and Public Health and a Medallion Lec- cal symptoms, memory for traumatic and research accomplishments and his substance use. He has published turer by the Institute of Mathemati- events, treatment of ptsd, and on teaching. These include selection by over 180 research articles. cal Statistics. neurobiological and psychological fac- Yale’s Psychiatry Residents’ Associa- In 2005, Zhang founded the Yale Zhang has also received a first tors associated with resilience to stress. tion as Outstanding Psychiatry Faculty Collaborative Center for Statistics Award from the National Institute of He has worked with a range of stress- Teacher, an honor he has received three in Science (C2S2) to foster collabo- Child Health and Human Develop- sensitive and stress-resilient individu- times; the Stephen Fleck Award for a ration on statistical methods and ment and an Independent Scientist als, including combat veterans with Yale faculty clinician; and the Con- technologies, particularly for under- Award from the National Institute on ptsd, civilian children and adults with necticut Psychiatric Society’s Roger standing the etiology of pregnancy Drug Abuse. ptsd, stress-resilient prisoners of war, Coleman Memorial Award. outcomes and to evaluate treatment In 2009, Zhang, who received his and active Special Forces soldiers. The professorship was created effectiveness for infertility. In only a doctorate from Stanford University. A 1974 graduate of Yale College, with a gift from Glenn H. Greenberg, few years, his center has emerged as was a Chang-Jiang Scholar with Southwick earned his m.d. at George of the Yale College Class of ’68, to a major national resource for repro- the Chinese Ministry of Education. Washington University. He com- enhance understanding and advance ductive sciences. In 2011, he received the Royan pleted his internship at the Johns treatment of psychological trauma, He directs a training program International Award on Reproduc- Hopkins Hospital and a residency in ptsd, and resilience. for pre- and postdoctoral students, tive Health.

Biostatistician who focuses on genetics and Environmental health scientist with a focus molecular biology named Hiscock Professor on cancer risks is designated Bliss Professor

Hongyu Zhao, ph.d., a biostatistician protein-protein Tongzhang Zheng, d.sc., has been examined the rela- whose work is focused on developing interaction network named the Susan Dwight Bliss Profes- tionship between mathematical, statistical, computa- inference, dna sor of Environmental Health Sciences circadian rhythm tional, and visualization tools needed copy number analy- in the School of Public Health. Zheng disruption and to address scientific problems in mo- sis, and pathway- studies environmental pollution and the risk of female lecular biology and genetics, has been based analysis. human health, particularly in cancer breast cancer, and appointed the Ira V. Hiscock Profes- Zhao’s accom- epidemiology and etiology related to found evidence that sor of Biostatistics in the School of plishments and environmental hormone disruptors, exposure to a higher Public Health. Hongyu Zhao professional service genetic susceptibility, and the interac- Tongzhang Zheng level of light at night Zhao, also professor of genet- have been recognized with many tion of genes and the environment. increases risk of the disease. ics and of statistics, is a leader in distinguished honors, including election Zheng’s research emphasizes the Zheng has worked with numer- statistical genetics, computational as a fellow of the American Statistical role of organochlorine compounds— ous Chinese government officials and biology, genetic epidemiology, and Association, the Institute of Mathemati- such as polychlorinated biphenyls scientists to develop educational and human genetics, and has developed cal Statistics, and the American Associa- (pcbs), dichlorodiphenyltrichloroeth- research programs in China that have novel statistical methods and showed tion for the Advancement of Science. ane (ddt), and other pesticides—in benefited Yale faculty and students. how they can be applied to the study Zhao is editor or associate editor of the etiology of several major cancers He helped develop three major cohort of many diseases, including cancer, many statistical and biological journals, in the United States, including breast, studies and a case-control study of liver obesity, hypertension, mental retar- and is a past recipient of the Mortimer non-Hodgkin’s lymphoma, Hodg- cancer in China. dation, hiv/aids, substance depen- Spiegelman Award, given by the kin’s disease, multiple myeloma, and He is also the co-scientific director dence, and immunological disorders. American Public Health Association testicular cancer. of two summer programs that train He has also contributed to to a top statistician in public health Zheng has shown that immuno- epidemiologists and biostatisticians genomic and proteomic analysis under the age of 40. suppression due to increasing exposure worldwide. In 1992 he was chosen as through the development of power- He received his b.s. from Peking to ultraviolet radiation and hair dye Teacher of the Year by students at the ful statistical methods for pathway University in Beijing, China, and use may be partly responsible for a School of Public Health. reconstructions using different types his doctorate from the University of worldwide increase in non-Hodgkin’s Zheng received his doctorate from of genomic data, network analysis, California-Berkeley. lymphoma. In addition, he has Harvard University.

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