Two on Yale Faculty Elected to Institute of Medicine Genetics Chair

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march/april 2014 volume 10, issue 1 Advancing Biomedical Science, Education, and Health Care

Two on Yale faculty elected to Institute of Medicine Leaders in emotional lab compared the effectiveness of con- the belief that people work have since trasting interventional approaches— have a wide range been applied around intelligence and immunity either presenting the benefits accrued of emotional and the world. join prestigious corps by adopting a healthier behavior or intellectual skills that Medzhitov, a warning of the risks of not adopting can be developed and Howard Hughes Yale University President Peter that behavior. Investigative studies monitored to better Medical Institute Salovey, ph.d., and immunologist by Salovey, the Chris Argyris Profes- guide their think- investigator, has Ruslan M. Medzhitov, ph.d., the sor of Psychology, and professor of ing and actions. His made pioneering David W. Wallace Professor of Epidemiology and Public Health and seminal research on Peter Salovey Ruslan Medzhitov contributions to Immunobiology, have been elected in the School of Management, have the ways that human the understanding to the Institute of Medicine (Iom), been widely used in tailoring edu- moods and emotions affect behavior of innate immunity, which provides one of the most prestigious bodies in cational and public health messages and decision-making, and his lab’s immediate defense against infection. health and medicine. about adopting healthier behaviors to development of methods to study His studies helped elucidate the criti- Salovey’s research has focused on prevent or detect disease. and measure these factors, laid the cal role of toll-like receptors (Tlrs) how effective communication and Along with John D. Mayer, ph.d., groundwork for the establishment of in sensing microbial infections, promotional techniques can persuade of the University of New Hampshire, the Yale Center for Emotional Intel- mechanisms of Tlr signaling, and people to change risky behaviors Salovey was a pioneer in developing ligence. The principles of emotional activation of the inflammatory and relevant to cancer and Hiv/Aids. His the concept of emotional intelligence— intelligence arising from Salovey’s immune response. // IOM (page 8)

In new Yale-AbbVie Genetics chair receives major new prize research partnership, $3 million Breakthrough a ‘true symmetry’ Prize honors geneticist’s With the aim of advancing under- research on hypertension standing of the molecular, cellular, and genetic underpinnings of autoim- Richard P. Lifton, m.d., ph.d., mune and inflammatory diseases, and chair and Sterling Professor of Genet- to find new and better treatments, ics and professor of medicine, was Yale School of Medicine (ysm) has en- among six scientists awarded the tered into a research partnership with Life Sciences Prize by the Break- the global pharmaceutical company through Prize in Life Sciences Foun- AbbVie. The North Chicago, Ill.-based dation on December 12. The prize, AbbVie, formed in 2013 when Abbott which carries an award of $3 million, Laboratories divided into two compa- honors Lifton’s breakthrough work nies, will provide $14.5 million over a in genetics. five-year period to fund research led Lifton, a Howard Hughes Medical by ysm faculty. Institute investigator, uses genetic According to the American Autoim- approaches to identify the genes and mune Related Diseases Association, pathways that contribute to common autoimmunity is the second-leading human diseases, including cancer, cause of chronic disease in the U.S., and cardiovascular, renal, and bone affecting some 50 million individu- disease. The prize recognizes his pio- als. There is also growing recogni- neering work in identifying the ge- tion among scientists that immune- netic and biochemical underpinnings mediated inflammatory processes are of high blood pressure, or hyperten- at the root of a wide array of common sion, which affects more than 1 bil- and deadly disorders, including cancer, lion people worldwide // Prize (page 7) heart disease, and Alzheimer’s disease. Catalyzed by Yale’s preeminence in immunobiology research, the partner- Richard Lifton’s work has demonstrated the fundamental role of salt reabsorption by the ship marks another milestone in the kimberly white/gettykimberly images kidney in the regulation of blood pressure. formation of // Partnership (page 6)

Non-Profit Org. inside this issue U. S. Postage 1 Church St., Suite 300, New Haven, CT 06510-3330 2 Lifelines www.medicineatyale.org paid Having developed critical therapies for New Haven, CT Type 1 diabetes, Robert Sherwin continues Permit No. 526 to advance our knowledge of disease. 3 Innovating while educating The resources of the Teaching and Learning Center support the medical school’s educational mission in new ways. 5 Rewriting the genetic code In altering the genetic instructions of a common bacteria, a group of scientists opens a new door to possibility. also Advances, pp. 3, 5 Out & About, p. 4 @YaleMed f /YaleMed lifelines Widely acclaimed hematologist joins Cancer Center

Yale Cancer Center (ycc) Robert Sherwin’s research and Smilow on Type 1 diabetes has paved Cancer Hospital the way for some of today’s at Yale-New most common therapeutics. Haven have ap- For 26 years, Sherwin served as director of the School of pointed Steven Medicine’s training program D. Gore, m.d., in diabetes and metabolism, Steven Gore an internation- funded by the National Insti- ally known tutes of Health. hematologist, as director of hematologic malignancies at Smilow Cancer Hospital (sch). Gore comes to Yale from The Johns Hopkins University School of Medicine (jhusom), where he was professor of oncology and a faculty

Robert Sherwin shapiro harold member in the Program in Cellular and Molecular Medicine. He came to Yale in November. “Dr. Gore’s national leadership The art and science of diabetes care on clinical trials for patients with A career spent shaping betes lab there. At the nih and after- Sherwin’s research today relies leukemia and meylodysplastic syn- knowledge of diabetes, ward, he came to see that treatments on cutting-edge imaging techniques, dromes and focus on translational for Type 1 diabetes—which affects including functional magnetic reso- research will elevate our hematology and improving lives nearly 3 million Americans today— nance imaging (fmri) and positron- program,” says Madhav V. Dhodap- could be vastly improved. emission tomography (pet), and aims kar, mbbs, the Arthur H. and Isabel When Robert S. Sherwin, m.d., began In 1974 Sherwin joined Yale’s to clarify the neurological bases of Bunker Professor of Medicine, pro- a fellowship in 1972 in the medical Department of Internal Medicine. hypoglycemia and obesity. Working fessor of immunobiology, and chief school’s Department of Internal Medi- Working with Professor of Pediatrics with a diverse group of researchers— of hematology at ycc and sch. cine, his plan was to deepen his knowl- William V. Tamborlane, m.d., he played from psychiatrists to pediatricians— Gore is a member of the Ameri- edge of metabolism and return to a critical role in the development of his research into areas of the brain can Society of Hematology, the New York City’s Mount Sinai Hospital, insulin pump therapy—in which a that control emotion, motivation, and American Society of Clinical Oncol- where he’d completed his residency, to small pump slowly delivers insulin, sta- reward has revealed dramatic differ- ogy, and the American Association establish a diabetes research program. bilizing blood glucose levels. “As late ences between the brain responses of for Cancer Research, among other 42 years later and still at Yale, he as 1980 our treatments kept people lean and obese children. Interdisciplin- organizations. He received his b.s. hasn’t looked back. with Type 1 diabetes alive, but we had ary collaboration of this kind is central from Yale College and his m.d. Now the C.N.H. Long Professor of no real way to monitor what we were to the research being supported by from Yale School of Medicine. He Medicine and chief of the Section of doing or much to offer therapeuti- ycci’s five-year $45.4 million Clinical completed his residency in inter- Endocrinology, Sherwin has been at the cally,” says Sherwin, also director of Translational Science Award—the uni- nal medicine at the University of forefront of research that has funda- the Yale Center for Clinical Investi- versity’s largest nih grant—and is, he Chicago Hospitals and Clinics and mentally improved medicine’s ability to gation (ycci). However, the advent believes, key to the future of medicine. a fellowship in oncology at jhu- address the body’s lack of insulin pro- of continuous infusion, along with Today, Sherwin continues to see som. He has authored more than duction in Type 1 diabetes, an autoim- ancillary advances like the finger prick patients despite a busy research 200 peer-reviewed articles and book mune disease that results in unregulated blood test and the ability to measure schedule and broad administrative chapters on hematologic malignan- levels of blood glucose and, if untreated, glucose over an extended period, dra- duties. The creativity in research and cies and myelodysplastic syndromes. can cause organ damage and death. matically enhanced treatment. the prospect of improving the lives A Bronx-born New Yorker with a In later research, Sherwin defined of many continue to excite him, correction passion for art, Sherwin minored in how the brain senses glucose and he says, while acknowledging that In our last issue, we incorrectly labeled our art history while at Union College. activates defenses against low blood working with patients helps keep Grants and contracts listing “July-August 2012.” We reported grants and contracts After earning his m.d. at Albert Enstein sugar, or hypoglycemia—the major him grounded. from September-October 2012. We regret College of Medicine, he planned to complication of insulin therapy. “There “The creative struggle in research the error. research kidney disease at the National are adaptations in the brain that make is similar to what happens when Institutes of Health (nih), but was glucose-sensing cells more efficient so you’re trying to achieve a vision in art,” instead accidentally offered, and people are less aware of their hypogly- Sherwin says. “The excitement comes

accepted, a research position in a dia- cemia,” he explains. when things reveal themselves.” Senior Editor Charles Gershman Contributors Jenny Blair, Michael Fitzsousa, Dan Hebert, Kathy Katella, Betty Marton, Shane Seger, Sarah C.P. Williams National Cancer Institute renews Yale Cancer Center’s designation Design Jennifer Stockwell Medicine@Yale is published quarterly by the Office of Institutional Planning and Yale Cancer Center (ycc)’s designa- The renewed designation is “a One of 41 com- Communications, Yale School of Medicine, tion as a comprehensive cancer center reflection of the groundbreaking prehensive cancer 1 Church St., Suite 300, New Haven, CT 06510-3330 by the National Cancer Institute (nci) research efforts in our laboratories centers in the Telephone: (203) 785-5824 Fax: (203) 785-4327 [email protected] was recently extended for an addi- and the increasingly fast pace of nation, ycc is the E-mail Website medicineatyale.org tional 5 years following an extensive translating our research findings only designated Copyright ©2014 by Yale University. All rights reserved. grant submission and review process. to improved patient care and treat- center in Connecti- If you have a change of address or do not wish to receive future issues of Medicine@Yale, please write to us at the The award includes $12.2 million in ment options for our patients,” says cut. Among the above address or via e-mail at [email protected]. funding over five years to support Thomas J. Lynch Jr., m.d., director many advantages of Postal permit held by Yale University, ycc’s research programs and shared of Yale Cancer Center and physician- Thomas Lynch receiving care at a 155 Whitney Avenue, New Haven, CT 06520 resources, along with the continuation in-chief at Smilow Cancer Hospital at comprehensive can- of ycc’s comprehensive status, the Yale-New Haven. “Our successes in cer center are access to a large variety Robert J. Alpern, m.d. most prestigious level of designation cancer treatment, research, and edu- of oncologists specializing in specific Dean and Ensign Professor of Medicine Zsuzsanna C. Somogyi from the nci. The designation is given cation over the past five years, and types of cancer, and the close link Interim Director of Medical Development (203) 436-8559 to centers that meet strict criteria those promised to come, will ensure between research and clinical care, Mary Hu Director of Institutional Planning and Communications for patient care, cancer research, clini- Yale Cancer Center is exceeding the which ensures that patients receive cal trials, and community outreach nci’s expectations for comprehensive the most innovative and targeted and education. cancer centers,” Lynch says. treatments available. Printed on recycled paper ♻

2 www.medicineatyale.org advances Medical education is new center’s focus Health & Science News For stem cells, fate Using an array of tools, Teaching and iPads that allow easy access to specially developed digital tools. Using the iPads, “we’re actually integrating these depends on location Learning Center supports pedagogical tools into the curriculum,” says Michael L. Schwartz, innovation at the School of Medicine ph.d., associate dean for curriculum and associate professor of neurobiology, who spearheaded the initiative. Accomplished faculty at medical schools across the United One of the Tlc’s biggest challenges may be assessment States often receive little formal training in pedagogy, and of faculty, students, and the curriculum itself. To meet this academic medicine is known for rewarding research ac- challenge, two experts in the Tlc are devoted to assess- complishments while not always incentivizing excellence in ment. Assistant Professor of Psychiatry John A. Encandela, teaching. At the School of Medicine, however, the teaching Ph.d., associate director for curriculum and educator

istockphoto of medicine is not only benefiting from a Stem cells are widely studied in part new, central home on campus; it is also because they can transform: they can quietly attracting national attention. become heart, liver, and even brain In 2012, the medical school introduced cells. Research on stem cell “fate” has a new means of supporting medical largely focused on the cells’ intrinsic education: the Teaching and Learning properties and genetic patterns. Center (tlc). As the tlc enhances faculty A Yale study implicates a differ- teaching, measures students’ learning, as- ent factor: a cell’s original location sesses the curriculum, and delivers digital in its “niche.” The lab of Valentina educational tools, it is supporting the Greco, ph.d., assistant professor of teaching of medicine at Yale with an array genetics and dermatology and senior of new resources. author, developed a novel form of The tlc is part of the Strategic microscopy to track individual stem Plan for Medical Education, a vision cells in the hair follicles of living mice. for ysm’s future advanced in 2010 by a Monitoring these cells dynamically as group of stakeholders under the leader- a hair grew, first author Panteleimon ship of Deputy Dean for Education Rompolas, ph.d., postdoctoral fellow Richard Belitsky, m.d., the Harold W. in genetics, and colleagues found that Jockers Associate Professor of Medical sacco william cells from the lower part of the follicle Education and associate professor of psychiatry. The Stra- The Teaching and Learning Center (tlc) supports the medical school’s niche tended to end up in the hair tegic Plan called for the school to rebuild its curriculum educational mission with an array of new resources. The tlc’s leadership includes (from left) Anna Reisman, John Encandela, Gary Leydon, Janet structure, while those at the top of “from the ground up” and to elevate the status of teaching. Education has been center-stage at the School of Hafler, Michael Green, Jacqueline Fordiani, Frederick Haeseler (retired), the niche tended to remain stem cells. and Dorothy DeBernardo. When they killed only cells in one Medicine since its founding in 1810, and was the subject of area, other cells moved in and began intense focus when the “Yale System” of medical education, assessment in the tlc, develops methods of weighing fac- behaving like the cells they’d replaced. which prizes students’ independence and their original re- ulty members’ teaching skills and educational scholarship The findings, published online Oc- search, was established in the 1920s. However, the instruc- that can count toward reappointments and promotions. tober 6 in Nature, suggest that stem tor support the Tlc provides is unprecedented. Professor of Medicine Michael L. Green, M.d., M.sc., as cell location has far more influence on Led by Janet Hafler, ed.d., associate dean for educa- associate director for student assessment, faces a particu- cell fate than previously thought. tional scholarship and professor of pediatrics, the Tlc has lar challenge. Schwartz says, “it’s a very complicated task: a team of experts who work together to develop innova- how to create assessments that are useful to the learner, tive assessment strategies, incorporate technology into the but still allow us to validate our programs and graduate An organelle’s role in learning process, and support educators by drawing upon physicians that are appropriately trained. We don’t want to appetite, weight gain and conducting educational scholarship. “Faculty are very integrate things that are the antithesis of the Yale System.” Mitochondria, organelles that serve interested in effective teaching strategies to promote learn- Green’s role is to examine ways assessment can aid the as the powerhouses of living cells, ing,” says Hafler. School of Medicine’s educational mission while preserv- generate and maintain proper energy The new curriculum—set to launch in 2015—will em- ing—and contributing to—the school’s unique spirit of levels in complex organisms. But they phasize small-group student-centered learning. The Tlc independence and collegiality. do more than just generate energy. offers resources to support this format: educators can ask One of the tlc’s functions is to draw on pedagogical A new School of Medicine study the tlc’s experts for confidential feedback on their teach- research. With Hafler’s expert help in accessing and inter- shows that the size and shape of ing styles or request help with course objectives, curricu- preting such scholarship, faculty can make more informed mitochondria in specialized brain lum, slides, or written materials. Tlc experts offer many decisions about how to approach education-related tasks. cells is key to controlling appetite and workshops on teaching strategies, including, for example, The Tlc also guides faculty in conducting // TLC (page 4) weight gain in mice. Analyzing AgRP a workshop on how best to teach clinical reasoning skills; neurons in mice, known to play a role some 100 faculty have taken it. The Center has also offered in appetite, the team found that in a a faculty fellowship for the past four years that covers sub- The future of education fasting state, the neurons had many jects like offering feedback, making talks interesting, and Yale School of Medicine must prepare students to excel in a small mitochondria. When the mice keeping learners engaged. rapidly changing health care landscape. The school’s educational were fed high fat diets, the mitochon- “The Teaching and Learning Center has been a godsend mission requires stable and continuous support to thrive, and dria fused together: they were fewer for clinician-educators like me,” says Dana W. Dunne, you can help in the following ways: in number, but larger. To test whether M.d., assistant professor of medicine, who worked with Endowing the Teaching and Learning Center $10 million Hafler to implement a curriculum in humanistic bedside Leaders in medical education collaborate with faculty to support these changes were integral to how excellence and innovation in teaching. AgRP functioned, the team blocked teaching. “Some of us hadn’t been immersed in adult learning theory, or had any access to education experts. Endowed Professorships $3 million mitochondria from fusing in the AgRP For distinguished faculty members whose scholarship in education neurons of some mice. The mice not If you have an interest in educating faculty, students, or represents the highest standards. only had impaired neuron signaling residents, the Center can help with a framework and the Endowed Programs for Teaching $500,000 to $1 million when they ate, but failed to gain tools to get going.” Providing sustainable faculty development and programmatic support for innovative curriculum development and teaching. weight on a high-fat diet. Some of those tools are digital. Gary B. Leydon, the Endowed Faculty Advisors $500,000 The findings, reported September Tlc’s associate director for technology services, works For faculty who give individualized career and life guidance to 25 in Cell, show a direct link between with faculty to create tailor-made educational apps students throughout their years at Yale. and websites, some of which are used during class time. mitochondria changes and whole- Endowed Educational Technology Fund $250,000 and up body metabolism. “Mitochondra need Leydon developed an interactive pharmacology website Facilitating access to and utilization of cutting-edge technologies. to have ongoing dynamic plasticity that lets students plug in different values to explore how Endowed Clinical Mentor $250,000 in order to support neurons, which the body processes a drug. He has also built websites for For faculty who provide formative personalized feedback and concentrated guidance to students in a clinical environment. are necessary for appetite and for the posting faculty-generated curricular videos supporting a maintenance of life,” said lead author variety of courses and clerkships, and to facilitate faculty Endowed Educational Resource Fund $100,000 and up Enhancing the learning experience by supporting scholarship, curricular Tamas L. Horvath, dvm, ph.d., the development in areas like the teaching of clinical reasoning. innovation, unique training opportunities, and professional development. Jean and David W. Wallace Professor In the fall of 2011, the School of Medicine drew na- For more information about these or other gift opportunities, of Biomedical Research and chair of tional attention by doing away with paper copies of course contact Eric Schonewald at [email protected] or the Section of Comparative Medicine. materials and instead, providing medical students with 203-436-8557 or visit www.medicine.yale.edu/support.

Medicine@Yale March/April 2014 3 out & about September 7 At the annual Closer to Free bicycle September 15 A reception for minority faculty, residents, 1 1 ride, members of the medical school and Yale-New students, and fellows was held at the home of Gary V. Desir, Haven Hospital communities raised more than m.d., professor of medicine and of forestry and environmental $1.2 million for cancer treatment and research at studies, interim chair of the Department of Internal Medicine, Yale Cancer Center and Smilow Cancer Hospital 2 3 and co-chair of the School of Medicine’s Minority Organization at Yale-New Haven. 1. (From left) William Casey for Retention and Expansion (more), whose goal is to attract King, ph.d., executive director of the Yale Center for and support minority faculty members. 1. Nadia A. Ameen, Analytical Sciences at the School of Public Health; mbbs, associate professor of pediatrics and of cellular and 2 Susan T. Mayne, ph.d., 4 molecular physiology (left), and Linda K. Bockenstedt, m.d., the C.-E.A. Winslow Professor Harold W. Jockers Professor of Medicine. 2. James P. Comer, of Epidemiology; and her m.d., Maurice Falk Professor in the Child Study Center (csc), husband, James Mayne. professor of psychiatry, and associate 2. Ken Pelletier, of Onyx dean for student affairs (left), and For- 3 Pharmaceuticals. 3. Sajid rester A. “Woody” Lee, m.d., professor A. Kahn, m.d., assistant of medicine and assistant dean for professor of surgery. multicultural affairs. 3. (From left) 4. Cyclists at the ride’s Carla E. Marin, ph.d., associate research

opening ceremony. chris volpe (4) scientist in the csc; Marin’s partner, Anthony Jones; Giselle Gutiérrez, predoctoral fellow in psychiatry; Hanako Shishido, m.a., atr-bc, predoctoral October 7 After the news broke that the 2013 Nobel Prize in Physi- 1 fellow in psychiatry; and ology or Medicine had been awarded to James E. Rothman, ph.d., Katrina Round- chair and Fergus F. Wallace Professor of Cell Biology and professor field, predoctoral fellow in psychiatry. john curtis (3) of chemistry, a press conference was held in the medical school’s Historical Library. Rothman is one of the world’s foremost experts on membrane trafficking, the means by which proteins and other October 13 Inauguration Ceremonies marked the materials are transported within and between cells. The prize 2 start of Peter Salovey’s tenure as Yale’s 23rd presi- highlights his contributions to the understanding of exocytosis, a dent. Pictured with Salovey are Kimberly M. Goff- form of trafficking in which spherical sacs called vesicles fuse with Crews, j.d., secretary and vice president for student cell membranes to deliver their contents outside the cell. 1. In his life (left), and Margaret H. Marshall, j.d., former chief remarks, Rothman, also director of the Nanobiology Institute on justice of the Supreme Judicial Court of Massachu-

Yale’s West Campus, touched on 3 michael marsland setts and the senior fellow of the Yale Corporation. the challenges posed today by the uncertainty surrounding federal funding of science. 2. Robert J. Alpern, m.d., dean and Ensign 1 2 Professor of Medicine (left), and Yale President Peter Salovey. 3. A crowd

awaits Rothman’s entrance. terry dagradi (3)

October 26 Past Yale recipients of the Homer W. Smith Award, 3 4 5 the American Society of Nephrology’s top honor, gathered at New Haven’s Roia Restau- rant with Stefan Somlo, m.d., the C.N.H. Long terry dagradi

Professor of Medicine, professor of genetics, chief of the Section of Nephrology in the carl kaufman (6) Department of Internal Medicine, and the 2013 recipient of the award. (From left) Somlo; 6 October 27 School of Medicine students and faculty took their talents to Somlo’s wife, Joan O. Cho, assistant clinical professor of medicine; Deborah Lifton; Richard the court at the Faculty-Student Tennis Classic. 1. 52 students and faculty P. Lifton, m.d., ph.d., chair and Sterling Professor of Genetics, professor of medicine, and members participated in the tournament, an annual tradition begun in a Howard Hughes Medical Institute investigator; Marie-Louise Landry, m.d., professor of 2011. 2. Mark Youngblood ’20, a student in the Medical Scientist Training laboratory medicine and of medicine; Peter S. Aronson, m.d., the C.N.H. Long Professor Program (known informally as the m.d./ph.d. Program), delivers a serve. of Medicine and professor of cellular and molecular physiology; Betty Boulpaep; Emile L. 3. (From left) Karel F. Liem Jr., m.d., ph.d., assistant professor of pediatrics; Boulpaep, m.d., professor of cellular and molecular physiology; Gerhard H. Giebisch, m.d., Vikram Jairam, ’15, Sriram Ramanan, postgraduate associate in neurology, and professor emeritus of and senior research scientist in cellular and molecular physiology; Ketan R. Bulsara, m.d., associate professor of neurosurgery. 4. Ysabel Ilagan, Patricia A. Preisig, ph.d., professor of medicine and of cellular and molecular physiology; Yale College ’14. 5. Lance H. Linke, ph.d., associate research scientist in psy- and Robert J. Alpern, m.d., dean and Ensign Professor of Medicine. chiatry. 6. Lee Ying, ’20, a student in the m.d./ph.d. Program, gives it his all.

// TLC (from page 3) their own educa- says Ray Chen ’14, a fourth-year the University of Pennsylvania’s strengths. Belitsky has told students tional research for publication in medical student and former presi- Center for Teaching and Learning that these changes in medical educa- peer-reviewed journals. dent of the interest group, who adds offers resources to instructors across tion are intended to strike a balance The popularity of the Tlc’s that students directly seek out tlc the university. between the School of Medicine’s activities attests to a widespread resources for their own research. But Yale School of Medicine’s collegial, collaborative values and interest at Yale in medical pedagogy. The School of Medicine is not successes with original educational the need to innovate responsibly, The Center’s Medical Education Dis- alone in prioritizing formal pedagog- scholarship and its creative use of keeping apace with the times. And cussion Group draws crowds, as did ical support: other top-tier medical technology are nudging the school in all the interactions with faculty its first annual Medical Education schools have taken similar steps in into the spotlight. In April, the and students, Hafler says, the tlc Day last year. A new medical educa- recent years. For example, the Stan- school will host the Association of harmonizes with the Yale System by tion elective offers students the ford Faculty Development Center American Medical Colleges’ North- emphasizing a supportive approach. chance to work with simulators and for Medical Teachers offers work- east Group on Educational Affairs; “We want the Teaching and Web-based tools to gain advanced shops and consultations to faculty, and Schwartz is frequently ap- Learning Center to be a safe place educational experience. while the Institute for Excellence proached by medical schools curious to explore teaching, make mistakes, When a Medical Education Inter- in Education at the Johns Hopkins about Yale’s use of iPads and video learn how to teach from uncertainty, est Group launched last year, it drew School of Medicine provides faculty technology in the curriculum. and not be judged,” says Hafler. “And in some 300 students and faculty. with educational research support Outside attention aside, the tlc’s we want the same learning environ- “[The tlc] is seen as a great asset,” and training seminars. Similarly, innovations are designed to fit Yale’s ment for the students.”

4 www.medicineatyale.org advances Health & Science News A new first: rewriting the genetic code Triggering the By editing its genome, scientists from Yale, Uag is a stop codon: it tells the translation machinery that the end of a gene has been reached, like a period. But two ‘domino’ of life Harvard, and mit re-engineered a bacteria other codons serve the same function: uaa and UGA. So, to better protect against a virus using precise gene editing techniques that they had previously developed, the scientists changed every occurrence of Imagine that you wanted to remove every instance of the Uag in a strain of Escherichia coli, 321 in all, to Uaa. letter Q from the English language without losing mean- “What’s really powerful about these techniques is that we ingful words spelled with Q , and without adding any new can take these oligonucleotides and insert them with high ef- letters to the alphabet. You’d have to choose an alternate ficiency, and it allows us to simultaneously target many sites letter to take Q’s place—C or K, perhaps—then rewrite across the genome,” Isaacs says.

istockphoto books with the new letter and re-teach The codon replacement worked, but In its first day of development, a people to spell and read using the new that wasn’t the end of the project. The human embryo follows instructions alphabet. Such an undertaking is what a team then introduced a genetic mutation produced by its mother’s nearby cells. team of Yale, Harvard, and mit research- into the protein that normally interprets Afterward, the embryo begins fol- ers have recently completed. Rather than the Uag as a stop codon—called release lowing its own genetic instructions. altering the English language, however, factor 1 (RF1). In a normal cell, deleting Scientists haven’t yet uncovered the they removed a letter from the genetic RF1 would lead to a jumble of misread instructions that cause this transition, alphabet of a bacteria. genes: one protein would run into the but new Yale research offers clues. The re-engineered bacteria didn’t just Farren Isaacs Jesse Rinehart next with no break, since the stop codon In shifting from dependent to contradict classic rules of biology: it also wouldn’t be read between genes. But in self-directing, an embryo must turn was able to better fight off invading viruses that normally the newly engineered E. coli, there were no Uag sequences on three specific genes, the team re- relied on the host’s language to function. to be read. Unlike other strains of bacteria, removing RF1 ported online September 22 in Nature. In all living organisms, genes are made up of long from this strain had no effects. Or, at least, no negative Sequencing the genomes of strings of four nucleotides. Every set of three nucleotides effects: when the altered E. coli was infected with a bacte- zebrafish embryos, the team found in a row—64 different possible combinations—codes for riophage, a type of virus that infects bacteria, the invading that among genes that are turned on one amino acid, the building block of a protein. Each of phage could no longer function. first, Nanog, SoxB1, and Pou5f1 had these so-called codons is translated into its corresponding “When the phage infects the cell, its genes contain stop the highest expression levels. When amino acid through a unique trna molecule. At one end, codons, including Uag stop codons,” Rinehart says. “And it the scientists blocked these genes, the trna binds the three nucleotides; at the other it carries relies on the bacteria’s release factor to read those codons.” the embryos failed to continue devel- the associated amino acid. The team of scientists, which By removing a codon from the bacteria’s entire language, oping. Interestingly, these same three includes the School of Medicine’s Jesse Rinehart, ph.d., the scientists had given the bacteria a new defense against genes have been found to reprogram assistant professor of cellular and molecular physiology, the virus. The research was published October 18 in the adult human cells into stem cells and Farren J. Isaacs, ph.d., assistant professor of molecu- journal Science. resembling those found in an embryo. lar, cellular, and developmental biology, wanted to remove “This is an important advance in understanding the ge- These genetic factors “provide an one of these codons from a strain of bacteria. netic code,” Rinehart says. “But it also shows that we are in entry point to understanding the first “No one had ever entirely removed a codon from a ge- an exciting new reality where we can take the lessons we’ve domino to fall in the creation of life,” netic code,” Rinehart says. “But if we could remove a codon learned from biology, from understanding the genome and says Antonio J. Giraldez, ph.d., associ- and the organism was fine, biologists could start utilizing the proteome, and we can go forward into a more exciting ate professor of genetics and senior that codon for their own engineering purposes.” time where we can engineer new properties into cells.” author of the study. If Qs, for example, were no longer used in words like The advance opens up the door to a new way of adding “quick” and “mosque,” then Q could be assigned a differ- amino acids to proteins—by assigning Uag to a new trna, ent meaning—like a new punctuation mark. For synthetic with a completely novel amino acid on the protein side. Molecule links aging biologists, having an unassigned codon is key to adding The team plans to continue optimizing the techniques and inflammation new amino acids to a protein to give it new properties. and pushing the boundaries of what’s possible in protein Inflammation in the body is most To show that removing a codon was possible, Rinehart, engineering. “We could now introduce entirely new proper- often thought of as a healthy defense Isaacs, and George Church, ph.d., professor of genetics ties into these organisms by assigning this codon to a new against an invading bacteria or virus. at Harvard Medical School, set their sights on the least amino acid,” Isaacs says. “That we were able to change the But inflammation can also occur sepa- common codon: a string of the three nucleotides U-A-G. code, as well as introduce new biological functions, is excit- rately from outright infection, and Rather than code for an amino acid in a protein’s structure, ing and satisfying.” scientists know that as people age, constant low-level inflammation of many organs becomes more common Digital tomosynthesis enhances accuracy of breast cancer detection and is thought to contribute to many chronic diseases. For more than 50 years, radiologists radiologists were A team of scientists led by Vishwa have screened women for breast calling back more Deep Dixit, d.v.m., ph.d., professor of cancer using 2-D mammography, a than 10 percent of comparative medicine and immuno- low-energy X-ray imaging technol- all women. With biology at the School of Medicine, has ogy that aids diagnosis, and also tomosynthesis, that found a new piece of this puzzle: a sometimes leads to false alarms and number has been re- molecule that controls this age- “callbacks” for further screening. duced by 30 percent. related inflammation. The protein, Now, thanks to a new technology, The procedure nlrp3, was already known to be accuracy is improving. In a little more was approved by the linked to unusual types of inflamma- than two years, digital breast tomo- U.S. Food and Drug tion: that associated with obesity and synthesis, or 3-D mammography, is Administration diabetes, for example. significantly reducing callbacks while in 2011 following Dixit’s team reported October picking up more cancers. It’s working trials at Yale-New 1 in Cell Metabolism that removing so well that all eligible patients who Haven Hospital and the nlrp3 protein in mice prevented visit the Yale Breast Center (ybc) four other medi- many physiological changes that for mammography are receiving cal centers. It is the robert lisak typically accompany aging, including tomosynthesis in addition to 2-D first technology to deliver three- Since incorporating the use of digital tomo- changes to the immune system, eyes, mammography. The results, says dimensional images in mammog- synthesis in breast cancer screening, Liane bones, metabolism, and brain cells. Liane E. Philpotts, m.d., professor raphy, allowing radiologists to view Philpotts and colleagues at the Yale Breast Center have seen an increase in accuracy. Mice without nlrp3, they found, had of diagnostic radiology and chief of the breast in detailed 1 mm sections. a longer “healthspan”—the portion of breast imaging for the ybc at Smilow “We can characterize lesions better. Radiology that the technology is most a lifespan free of serious illness. Cancer Hospital at Yale-New Haven, You get a better view of the margins beneficial for patients aged 40 to 50 The study is the first to show have outpaced expectations. [the area at the edge of the tumor], and those with dense tissue, but that that inflammation is causally linked “We’ve seen a 20 percent increase which makes for a better assessment,” it also has significant benefits for to functional decline in aging and in cancer detection rates over 2-D Philpotts says. patients into their 70s. suggests that drugs altering nlrp3 in mammography,” Philpotts says. In 2013 Philpotts and colleagues Says Philpotts, “The bottom line humans may extend healthspans. Before tomosynthesis was used, ybc reported online in the journal is that every patient benefits.”

Medicine@Yale March/April 2014 5 Grants and contracts awarded nih, Hyperglycemia, Thromboxane and Platelet Mechanism by Disorderly Peptides, 4.1 years, Hyperactivity in Diabetes Mellitus, 4 years, $1,505,890 • Arie Mobley, nih, Activity Depen- $1,643,874 • Elizabeth Jonas, nih, Role of Bcl-xL in dent Mechanism of Olfactory System Develop- to Yale School of Medicine Synaptic Plasticity, 1.5 years, $385,300 • Samuel ment, 3 years, $490,675 • Yorgo Modis, nih, The Katz, nih, Cell Death Regulation by Pro-Apoptotic Structural Basis of Nucleic Acid Recognition by July-August 2012 bok During Hematopoiesis, 3 years, $402,055 Toll-Like Receptors, 4 years, $1,238,602 • Marcella Young-Shin Kim, nih, The Roles of Environmental Nunez-Smith, nih, Validating the Patient- Federal Risks and gex in Increasing asd Prevalence, Reported Experiences of Discrimination in Care Morris Bell, nih, Research Training in Functional Use Risk, 5 years, $823,250 • Ralph DiLeone, nih, 4.8 years, $2,737,179 • Martin Kriegel, nih, Role of Tool (PreDict), 4.9 years, $3,228,664 • Kevin Disability Intervention, 5 years, $1,211,422 Exploring the Neural and Molecular Basis for the Gender-Associated Microbiota in Organ-Specific O’Connor, David Hafler, DoD, Commensal Micro- Choukri Ben Mamoun, nih, Function and Inhibi- Effects of Vitamin D on Diet-Induced Obesity, Autoimmunity, 3.9 years, $537,466 • Haifan Lin, organisms Affect Autoimmunity in Multiple Scle- tion of Plasmodium Lipid Decarboxylases, 5 years, 2 years, $384,017 • Clare Flannery, nih, Effect of nih, Toward a Central Question on Epigenetics: rosis, 1 year, $132,037 • Stephanie O’Malley, nih, $2,040,256 • Steven Bernstein, nih, Implementa- Insulin on Estrogen Receptor Alpha Activity in A Major Epigenetic Programming Mechanism Moderators and Predictors of Response to Treat- tion of hit-Enhanced Tobacco Treatment for Hos- Human Endometrial Cells, 4.9 years, $658,350 Guided by pirnas, 3 years, $2,445,532 • Jun Lu, ments for Alcohol Dependence, 2 years, $410,801 pitalized Smokers, 4 years, $3,065,704 • Jonathan Jackie Fretz, nih, Regulation of Podocyte Differ- nih, Novel Bioinformatics Tools for Mammalian Chirag Parikh, nih, Novel Kidney Injury Tools in Bogan, Varman Samuel, nih, Vesicle Transloca- entiation by the Transcription Factor (ebf1), Microrna Target Prediction, 9 months, $281,465 Deceased Organ Donation to Predict Graft tion and the Metabolic Syndrome, 2 years, 1.8 years, $180,000 • Gerald Friedland, Sheela Robert Malison, nih, Clinical Neuroscience Outcome, 3.9 years, $2,769,709 • Sunil Parikh, $490,072 • Jonathan Bogan, nih, Regulation of Shenoi, nih, Implementing Point of Care CD4 Research Training in Psychiatry, 5 years, $1,222,658 nih, Innate Immune Responses in Populations Insulin Sensitivity by tug Acetylation, 1.9 years, Analysis to Decentralize hiv Care in Rural Africa, Thomas Manes, nih, Identification of Human with Differing Susceptibility to Malaria, 1.9 years, $445,678 • Kathleen Carroll, nih, A Stage I Study 2 years, $340,649 • Vamsi Gangaraju, nih, Novel pecam-1 Receptor, 2 years, $83,021 • Praveen $381,807 • Jamy Peng, nih, Epigenetic Regulation of Computer Based Training in cbt for Alcohol Use Role of Piwi/pirna Pathway in Developmental Mannam, nih, mkk3 is a Mediator of Sepsis and of Drosophila Germline Development, 10 months, Disorders, 2 years, $358,209 • Sarwat Chaudhry, Robustness, 1.1 years, $180,000 • Antonio Lung Injury in the Elderly, 2 years, $161,692 • Steve $114,380 • Marina Picciotto, nih, Yale scor Trans- nih, Risk Stratification in Older Persons with Acute Giraldez, nih, Functional Analysis of the Zebrafish Martino, Kimberly Yonkers, nih, Three Strategies lational Center to Develop Gender-Sensitive Treat- Myocardial Infarction: silver-ami, 4.8 years, Genome Through rna-seq and Ribosome Profile, for Implementing Motivational Interviewing on ment for Tobacco Dependence, 4.9 years, $638,571 $11,336,130 • Katarzyna Chawarska, nih, Pivotal 4.7 years, $2,452,353; nih, Molecular Mechanisms Medical Inpatient Units: See One, Do One, Order Christopher Pittenger, nih, Glutamate in ocd: Response Treatment for Infants at Risk for asd: of Microrna Mediated Regulation, 3.8 years, One, 5 years, $3,693,694 • Carolyn Mazure, nih, A Magnetic Resonance Spectroscopy Study, A Pilot Intervention, 1.8 years, $162,900 • Tian Chi, $1,253,302; nih, Development of rna Interference Yale scor Translational Center to Develop Gender- 4.9 years, $1,759,560 • Marc Potenza, nih, Clini- nih, Remodeling-Independent Function of the in Zebrafish, 2.1 years, $444,513 • Daniel Gold- Sensitive Treatment for Tobacco Dependence, cian Scientist Training Program (cstp), 5 years, baf Complex in T Cells and Beyond, 2 years, stein, Timothy Nottoli, nih, Hyaluronan as an 4.9 years, $306,566 • James McGrath, nih, Inves- $2,622,099 • James Rothman, nih, Regulation $444,701 • Daniel Colon-Ramos, nih, Cellular and Innate Ligand that Induces Inflammation after tigations of Mouse Interspecies Hybrids, 1.9 years, of Exocytosis at Neuronal Synapses, 4 years, Molecular Mechanisms that Temporally and Spa- Transplantation, 2 years, $444,701 • Fred $446,511 • Sherry McKee, nih, Yale scor Transla- $2,980,834 • Craig Roy, nih, Genetic Analysis tially Restrict Synaptic Development, 4.9 years, Gorelick, nih, Training Program in Investigative tional Center to Develop Gender-Sensitive Treat- of Legionella Phagosome Trafficking, 5 years, $1,877,535 • Christian Connell, nih, Effects of the Gastroenterology, 5 years, $1,649,153 • Ann ment for Tobacco Dependence, 4.9 years, $2,630,046 • Gary Rudnick, nih, Ion and Biogenic Wraparound Service Model for Maltreated Youth Haberman, nih, Analysis of B Cell Transcriptome $286,522; nih, Yale scor Translational Center to Amine Transport Mechanism, 5 years, $1,650,680 in a System of Care, 1.7 years, $455,634 • Joan Shifts Prior to Lineage Divergence In Vivo, 2 years, Develop Gender-Sensitive Treatment for Tobacco Mehran Sadeghi, nih, Imaging Protease Activa- Cook, dhhs, Advancing the Science of Education, $439,893 • David Hafler, Kevan Herold, nih, Dependence, 4.9 years, $524,505 • Jaimie Meyer, tion in Calcific Aortic Valve Disease, 5 years, Training and Practice in Trauma, 1 year, $49,989 The Role of the Innate Immune System on Treg nih, Evaluating and Improving hiv Outcomes in $2,060,020 • William Sessa, nih, Institutional Kelly Cosgrove, nih, Yale scor Translational Reprogramming in Human Autoimmune Disease, Community-Based Women Who Interface with National Research Service Award, 5 years, Center to Develop Gender-Sensitive Treatment for 5 years, $3,776,077 • Tamas Horvath, nih, the Criminal Justice System, 5 years, $821,147 $1,696,871 • Albert Shaw, nih, Midcareer Award Tobacco Dependence, 4.9 years, $644,116 Hypothalamic AgRP Neurons are Determinants Perry Miller, nih, Biomedical Informatics Research in Translational Immunology of Aging, 5 years, Michael Crowley, nih, Neural Correlated of Nega- of Healthy Lifespan and Higher Brain Training at Yale, 5 years, $4,398,925 • Andrew $836,640 • Robert Sherwin, nih, Yale University tive Reinforcement in Adolescence & Substance Functions, 3 years, $2,445,532 • John Hwa, Miranker, nih, An Orderly Approach to Toxic Clinical and Translational Science Award

// Partnership (from page 1) industry- Allen, Ph.d., director of global external vessels) that target white blood cells The $14.5 million in funding is academia partnerships at Yale. “This research in immunology. “We’re very to particular sites, recently discovered available to School of Medicine faculty is a collaboration between an industry excited because we see it as a new way that pericytes, the cells that support with primary or secondary appoint- leader in the treatment of autoimmune to strengthen our science,” Olson says. endothelium in small blood vessels, ments in the Department of Immuno- diseases and one of the best academic Since the founding of Yale’s also regulate inflammation by restrict- biology. Of the 14 grants awarded, immunology research programs,” says immunobiology program in 1988 it ing the number of white blood cells six will be four-year “full research” Richard A. Flavell, Ph.d., chair and has become a world leader in basic that exit vessels, a finding that could grants of $1 million each, and eight Sterling Professor of Immunobiology immunology research. Among the lead to new drugs to treat inflamma- will be two-year pilot project grants of and a Howard Hughes Medical Insti- key breakthroughs made at Yale was tory diseases. $160,000 each, to support early-stage tute (Hhmi) investigator. “Our shared the 1997 discovery by the late Charles Iwasaki and colleagues have research. Of the annual payments, goal is the development of better treat- A. Janeway Jr., M.d., and Ruslan M. recently developed a novel vaccine $2 million has been allocated toward ments for immunologic diseases.” Medzhitov, Ph.d., David W. Wallace technology that recruits immune cells funding for Hhmi investigators begin- The AbbVie-Yale Collaboration in Professor of Immunobiology and an into vaginal tissue to provide long- ning in the Collaboration’s second year. Immunobiology will be directed by a Hhmi investigator, that components term protection against genital herpes Following an application period, five-member joint steering commit- of the innate immune system called infections. Her group is now exploring grant awards will be determined by tee. Members from Yale are Flavell; toll-like receptors (Tlrs) prompt the ways to adapt this strategy to other members of the joint steering committee. Jordan S. Pober, M.d., Ph.d., Bayer expression of genes that provide the tissues to fight a range of infections, The grants will be awarded in stages, Professor of Translational Medicine, adaptive immune system with the including Hiv and infectious disor- staggered over the Collaboration’s five- professor of dermatology and pathol- necessary advance intelligence to do its ders of the skin, respiratory tract, and year term. In addition, the Collaboration ogy, and director of the Department job. The study of Tlrs is now one of digestive system. enables lab meetings, a retreat, and an of Immunobiology’s Human and the most active and important research AbbVie, in turn, is known not annual joint scientific symposium. Translational Immunology Program; areas in immunobiology. only for its pharmaceutical research The Collaboration has its roots in and Akiko Iwasaki, Ph.d., professor of Flavell’s recent work on metabolic and drug discovery capabilities, but the longstanding relationship that Fla- immunobiology and of molecular, cel- syndrome, a condition associated with for an array of specialized strengths. vell built with Abbott Laboratories in lular, and developmental biology, and the Western high-fat diet, suggests “They’re superb at certain kinds of the 1990s. As part of that relationship, an Hhmi investigator. Members from that interactions between our genes, automation of processes, at chemistry, Flavell helped guide Abbott’s acquisi- AbbVie are Lisa M. Olson, Ph.d., vice our diet, and the microbes that inhabit and at generating biological reagents,” tion of a research facility in Worcester, president of immunology, and Hamish our bodies have an important influence says Flavell, adding that the Collabo- Mass. Now known as the AbbVie Bio- on inflammatory ration will give Yale researchers access research Center, that facility is less than responses and on to proprietary AbbVie molecules a two-hour drive from Yale, a factor the incidence of known as dual-variable domain an- Olson cites as important. “Our proxim- such diseases as tibodies, which combine two targets, ity allows for close interactions between obesity, nonalco- making them valuable experimental AbbVie and Yale scientists, which will holic fatty liver and treatment tools. greatly advance a deep understanding disease, Type 2 “Yale and AbbVie have highly of the biology around potential new diabetes, and complementary skills and interests therapeutics,” Olson says. “People at heart disease. in the field of immunology, and we AbbVie are incredibly motivated to Pober, an look forward to a productive collabo- make new medicine.” authority on ration,” says Carolyn W. Slayman, Says Flavell, “This is a genuinely

william sacco william changes in vas- ph.d., deputy dean for academic and synergistic connection between [insti- Members of the AbbVie-Yale Collaboration in Immunobiology’s steer- cular endothelial scientific affairs, Sterling Professor tutions with] two sets of complemen- ing committee include (from left) Richard Flavell, Lisa Olson, Akiko cells (which form of Genetics, and professor of cellular tary skills, with very common interests. Iwasaki, Jordan Pober, and Hamish Allen. the lining of blood and molecular physiology. It’s a true symmetry.”

6 www.medicineatyale.org Program-KL2, 4 years, $3,122,344; nih, Yale Univer- Medical Research Institute, Mechanisms of Cross-Center Projects, 1 year, $153,993 • Jeffery in Vivo, 3 years, $255,200 • Joseph Schlessinger, sity Clinical and Translational Science Award Synergy between Cigarette Smoke and rsv, Kocsis, National Multiple Sclerosis Society, Trans- Gilead Sciences, Yale-Gilead Collaboration: sirna Program-TL1, 4 years, $1,420,989; nih, Yale Clinical 2 years, $217,000 • Shawn Ferguson, Ellison plantation of opcs into the Demyelinated Spinal Libraries and Their Use for Functional Genomic and Translational Science Award Program-UL1, Medical Foundation, Identification of Mecha- Cord, 4 years, $614,593 • Peter Krause, Immunet- Screen, 2 years, $834,214 • Margretta Seashore, 4 years, $3,182,021; nih, Yale Clinical and Transla- nisms Regulating Lysosome Homeostasis and ics, Inc. (nih), Screening and Confirmatory Tests State of CT Dept of Public Health, State of CT tional Science Award Program-UL1, 4 years, Their Role in Protecting Neurons against Aging, for Human Babesia, 2 years, $34,579 • Harlan Genetics, 5 years, $990,812 • Robert Sherwin, $3,683,748; nih, Yale Clinical and Translational 4 years, $400,000 • Thomas Fernandez, Simons Krumholz, Robert Wood Johnson Foundation, New York University (nih), The Norepinephrine Science Award Program-UL1, 4 years, $25,328,536 Foundation, Genetic Investigations of Motor The rwjf Clinical Scholars Program: 12-14 Cohort Transporter: A Novel Target for Imaging Brown Mark Shlomchik, nih, Role of B Cells and DCs in Stereotypes, 2 years, $249,076 • Liana Fraenkel, Grant, 2 years, $522,915; Robert Wood Johnson Adipose Tissue, 2 years, $326,659 • Mark Lupus Pathogenesis, 1.2 years, $458,855 • Satinder Brigham and Women’s Hospital (nih), Rheumatic Foundation, The rwjf Clinical Scholars Program: Shlomchik, Hoffmann (F) - La Roche, Ltd, Investi- Singh, nih, Structural Studies of Vesicular Mono- Expertise Expanded Access to Improve Commu- 12-14 Core Grant, 2 years, $1,035,239 • Tassos gation of Efficacy and Mechanism of GA101 in amine Transporters, 1.9 years, $432,300 • Peter nity Health: reach:RA, 1 year, $14,250; American Kyriakides, William King, University of Nicosia, Lupus Mice, 1 year, $80,674 • Albert Sinusas, nfl Tattersall, Susan Cotmore, nih, Molecular Basis College of Rheumatology, Improving the Delivery The University of Nicosia-Health Research/Ser- Charities, Non-Invasive Quantitative Imaging of of Parvoviral Target Cell Specificity, 4.8 years, of Care Using a Theory-Based Decision Support vices Training Grant, 2 months, $6,431 • Robert Muscle Growth and Vascularization in College $2,415,877 • Hugh Taylor, nih, Environmental Tool, 2 years, $347,324 • Jose Gomez Villalobos, Leeman, Alcoholic Beverage Medical Research Football Athletes, 1.5 years, $100,000 • Mark Estrogen Induced Epigenetic Alteration of Uterine Flight Attendant Medical Research Institute, Foundation (abmrf), A Brief, Web-Based Alcohol Solomon, American Heart Association, Transcrip- Stem Cells, 4.8 years, $2,058,875 • Agnes Vignery, A 3-Gene Signature in Smoking Exposure and Reduction Intervention for Undergraduates: Initial tion Factors as Substrates of the Anaphase- nih, Osteoclasts Exosomes, 1.8 years, $400,180 Asthma, 3 years, $325,500 • Andrew Goodman, Study, 2 years, $100,000 • Janghoo Lim, Charles Promoting Complex in Budding Yeast, 3 years, Joanne Weidhaas, Frank Slack, nih, Micrornas to Global Probiotics Council, Connecting Interper- H. Hood Foundation, Molecular Pathogenesis $198,000 • Yang Song, American Heart Associa- Understand Cause and Outcome in Breast Cancer, sonal Microbial Variation to Drug Efficacy, 1 year, Studies of Childhood Neurological Disorders: Rett tion (Founders Affiliate), Role of vsmc-Mediated 4.9 years, $1,705,591 • Brian Weiss, nih, Symbiosis $50,000 • Celeste Greer, Pharmaceutical and Angelman Syndromes, 2 years, $150,000 Cytokine Production in Age-Associated Inflamma- and Immunity in the Tsetse Fly, 2 years, $427,199 Research & Manufacturers of America (PhRMA) Jun Lu, Health Research Inc. (nih), Novel tion and Atherosclerosis, 2 years, $45,000 Yawei Zhang, nih, phahs and Thyroid Cancer Risk Foundation, Transcriptional Elongation Blockade Approaches to Mammalian Microrna Target Pre- Jeongmin Song, Columbia University (nih), Role in DoDSR Cohort, 4.7 years, $3,305,686 • Z. Jimmy as a Mechanism of Transcriptional Repression and diction, 1.8 years, $554,466 • Don Nguyen, Inter- of Typhoid Toxin in the Pathogenicity of Salmo- Zhou, nih, Synaptic Function and Organization of Anti-Cancer Activities of Histone Deacetylase national Association for the Study of Lung nella Typhi, 1.1 years, $135,893 • David Stern, the Mammalian Retina, 5 years, $2,059,188 Inhibitors, 2 years, $40,000 • Isaac Hall, Ameri- Cancer, Targeting Lipid Metabolic Pathways in de-biopharm S.A., Combination Screening Debio can Heart Association, Profiling Renal Repair for Metastatic Lung Adenocarcinoma, 2 years, 0932, 1.3 years, $118,318; debiopharm S.A., Combi- Non-federal Outcomes After Kidney Injury in Transplantation, $80,000 • Richard Nowak, University of Miami nation Screening Debio 1143, 1.9 years, $167,288 Renata Batista Brito, Childs (Jane Coffin) Memo- 5 years, $593,000 • Kristin Hoffmann, Dermatol- (dhhs), The Effectiveness of Prednisone for the Tamara Vanderwal, American Psychoanalytic rial Fund, Control of Cortical Inhibition by Nrg1- ogy Foundation, Identifying Prognostic Markets Treatment of Ocular Myasthenia (epitome), Association, Cross-Modal Sensory Processing in ErbB4 Signaling, 3 years, $154,500 • Lauren in Melanoma using Tissue Microarrays and Quan- 1.2 years, $16,256 • Roni Nowarski, Jane Coffin Infants: A Longitudinal Brain Mapping Study, Beslow-Kaye, The Children’s Hospital of Philadel- titative Analysis, 2 years, $30,000 • Theodore Childs Memorial Fund, Role and Mechanisms 1 year, $16,000 • Vamsidhar Velcheti, American phia (nih), Functional Connectivity & Pediatric Holford, Massachusetts General Hospital (nih), of Inflammasome Dysregulation in Colorectal Society of Clinical Oncology, Prognostic and Stroke, 3 years, $307,152; University of Colorado at Lung Cancer Group for nci’s cisnet Program, Tumorigenesis, 3 years, $154,500 • Alexander Predictive Value of Programmed Death-1 Ligands Denver (nih), Investigation of Prognostic Factors 2.2 years, $246,201 • Tamas Horvath, DiaLean Panda, American Federation for Aging Research in Non-Small Cell Lung Cancer, 1 year, $50,000 in Childhood-Onset ais: Role of Stroke Subtype, Ltd., Dln-101 for the Treatment of Parkinson’s (nih), Age Associated Defects in Localization and Merceditas Villanueva, University of Connecti- 1 year, $2,000 • Vineet Bhandari, Cornerstone Disease, 2 years, $131,658 • Evelyn Hsieh, Ameri- Trafficking of Toll-Like Receptor 1, 5 years, cut (nih), art Adherence and Secondary Preven- Therapeutics, Inc., Surfactant-Enhanced Delivery can College of Rheumatology, Osteoporosis $100,000 • Chirag Parikh, Roche Organ Trans- tion of hiv, 1 year, $64,602; University of Massa- of Silencing rna (sirna) in Neonatal Mouse Among hiv-Infected Individuals in China, 2 years, plantation Research Foundation, Impact of chusetts (dhhs), New England aids Education Models of Bronchopulmonary Dysplasia, 5 years, $125,000; University of North Carolina at Chapel Donor Kidney Function and Injury on Kidney and Training Center, 2 years, $372,501 • Emily $15,000 • Alfred Bothwell, The Mary Kay Foun- Hill (nih), Building Research Capacity for Global Transplant Recipient Allograft Function, 2 years, Wang, Foundation for California Community dation, (Formally The Mary Kay Ash Charitable Health, 1 year, $19,687 • Yiyun Huang, New York $156,530 • Sunil Parikh, University of California, Colleges (dhhs), Transitions Clinic Network: Foundation), Modeling Human Immune System University School of Medicine (nih), Cb1 Receptor San Francisco (nih), Antimalarial Pharmacology Linking High-Risk Medicaid Patients from Prison Interaction with Breast Tumors and Treatments pet Imaging Reveals Gender Differences in ptsd, in hiv Co-infected Children and Pregnant Women to Community Health Care, 2 years, $207,303 in Mice, 2 years, $100,000 • Elizabeth Bradley, 2 years, $257,705 • John Hwa, University of Penn- in Uganda, 1.9 years, $168,667 • Farzana Hanbing Wang, American Heart Association, Asghar Rastegar, Linda Arnold, Urania sylvania (nih), Personalization of Therapeutic Pashankar, State of CT Dept of Public Health, Hilary Hanbing Wand aha No. 179941620, Magriples, Ministry of Health, Rwanda, Building Efficacy and Risk, 1.8 years, $516,493 • Natalia State of CT Genetics, 5 years, $502,250 • Daniel 4 months, $3,320 • Stephen Waxman, Nancy Human Resources for Health: Yale University and Ivanova, Mount Sinai School of Medicine (nih), Pelletier, Johns Hopkins University, A Random- Taylor Foundation for Chronic Diseases, Inc., the Ministry of Health of Rwanda, 1.5 years, Expression2Kinases: mrna Profiling Linked to ized Controlled Trial of Vitamin D Supplementa- Nav1.7 and Chronic Pain: Generation of a Model $1,663,080 • Cynthia Brandt, University of Pitts- Multiple Upstream Regulatory Layers, 1.8 years, tion in Multiple Sclerosis, 1.7 years, $27,555 Human Inherited Erythromelalgi (iem) in burgh (nih), The Risk of Types of Heart Failure $24,646 • Min-Jong Kang, Flight Attendant Ismene Petrakis, Ernest Gallo Clinic and Research Rodents, 2 years, $241,959 • Joanne Weidhaas, Among hiv Infected and Uninfected Veterans, Medical Research Institute, Role of nlrx1 in copd Center, Zonisamide and cpt for Veterans with University of Texas M.D. Anderson Cancer 2 years, $231,389 • Clemente Britto-Leon, Cystic Pathogenesis, 3 years, $325,500 • Haben Kefella, ptsd and Comorbid Alcohol Dependence, 2 years, Center - Science Park, Microrna as a Prognostic Fibrosis Foundation, Regulation of splunc1 Howard Hughes Medical Institute, Regulation of $449,719 • Virginia Pitzer, Princeton University, Marker in Cervical Cancer Patients After Chemo- During Airway Inflammation, Infection, and Autophagy in the Retinal Pigment Epithelium, a Evaluation of Candidate Vaccine Technologies radiation: Analysis of Tissues from rtog 90-01 Cystic Fibrosis, 1 year, $68,250 • Richard Bucala, Punitive Target for the Treatment of Age Related Using Computational Models, 1 year, $48,738 and an Institutional Prospective Trial, 2 years, Alliance for Lupus Research, Function of the Poly- Macular Degeneration, 2 years, $39,000 • Kaveh Srikala Raghavan, American Cancer Society, Inc., $30,000 • Brian Weiss, University of Richmond morphic mif Locus in sle, 2 years, $336,385 Khoshnood, Bhutan Foundation, Training the Investigating the Role of Integrins in Organizing (nih), Sodalis Glossinidius Irion Acquisition, Daniel Campbell, Autism Speaks, Improved Early Royal Institute of Health Services Faculty and Stu- the Extracellular Matrix, 3.4 years, $624,076 3 years, $114,787 • Graham Williams, Stacy Detection of Autism Using Novel Statistical Meth- dents in Capacity Building and Curriculum Devel- Farah Rahiem, American Psychiatric Association, Castner, Cure Huntington’s Disease Institute odology, 1.5 years, $102,846 • Richard Carson, opment for New Public Health Programs in apa Minority Fellowship, 8 months, $46,306 • Lis- Foundation (chdi), Evaluation of pde9 Inhibitor ucb Pharma S.A., Novel pet Ligand Selection Bhutan, 11 months, $48,639 • Richard Kibbey, sandra Ramsey, Tourette Syndrome Association, chdi-00396436 and pde4 Inhibitor chdi- Study in nhps (Project 1 Under Research Collabora- American Diabetes Association, Inc., Compart- Inc., Behavioral, Neurochemical and Pharmaco- 00315447 (DG-071) on the Performance of Rhes, tion Agreement), 3 years, $806,844 • Silvia mentalized Phosphoenolpyruvate Metabolism in logical Analysis of hdc-KO Mice, a New Animal 1.2 years, $535,711 • Andrew Xiao, Ellison Medical Corbera, Hartford Hospital (nih), The Social Brain Insulin Secretion, 3 years, $212750; Pfizer Inc., U.S. Model for Tourette Syndrome, 1 month, $36,362 Foundation, Investigating the Role of Epigenetic in Schizophrenia and Autism Spectrum Disorders, Pharmaceuticals Group, Mechanism of Improved Harvey Risch, H. Lee Moffitt Cancer Center and Mechanisms for Genome Integrity Maintenance 5 years, $319,446 • Joseph Craft, Rheumatology Function and Health in Human Islets Treated with Research Inst. (nih), Follow-Up of Ovarian Cancer in Stem Cells during Aging, 4 years, $400,000 Research Foundation (Formally: American the GK Activator PF-04937319, 2 years, $472,711 Genetic Association and Interaction Studies (foci), Mingyi Xie, Leukemia and Lymphoma Society, College of Rheumatology), Novel B Cell Marker Grace Kim, Wilkins (Lawson) Pediatric Endocrine 2 years, $89,057 • Kurt Roberts, Foundation for Microrna Target Identification & Biogenesis in and Therapeutic Target in Rheumatoid Arthritis, Society, Nutrigenetics Study of Fatty Liver Surgical Fellowships, Foundation for Surgical Fel- a T-Cell Leukemia Causative Virus, 3 years, 1 year, $75,000 • Leslie Curry, Commonwealth Disease in Obese Youth, 1 year, $50,000 • Steven lowship 2012-2013, 1 year, $61,000 • Matthew $165,000 • Jie Yao, American Heart Association, Fund, cmwf: staar 100 Survey, 6 months, Kleinstein, Mayo Clinic of Rochester (nih), Devel- Rodeheffer, American Diabetes Association, Inc., Functional and Systematic Analysis of Gene $49,091 • Charles Dela Cruz, Flight Attendant opment of hipc Data Standards to Support Characterization of Brown and Beige Adipogensis Positioning in Muscle Cells, 4 years, $308,000

// Prize (from page 1) and is the most the scientific rationale for worldwide Said Google co-founder Sergey the Institute of Medicine, and a prevalent risk factor for heart attacks, efforts to prevent hypertension and Brin and his wife, biologist and entre- past recipient of the Wiley Prize in heart failure, and stroke. reduce morbidity and mortality by preneur Anne Wojcicki, co-sponsors Biomedical Sciences. Lifton has identified mutations in limiting dietary salt intake, and also of the December 12 awards gala, Founded in 2013 by technology more than 20 genes that cause either for improved therapeutic approaches “Scientists should be celebrated as entrepreneurs, the Breakthrough extreme hypertension or hypoten- to hypertension. heroes, and we are honored to be part Prize in Life Sciences Foundation is sion (low blood pressure) in people. “The importance of Rick Lifton’s of today’s celebration.” a nonprofit corporation dedicated to He pioneered the discovery of hu- work on the genetic basis of hyperten- Lifton earned his m.d. and ph.d. advancing breakthrough research, man disease through the study of sion cannot be overstated. As a scientist in biochemistry at Stanford Uni- celebrating scientists, and generating “outliers,” people and families with and colleague, Rick represents the very versity, and completed a residency excitement about the pursuit of sci- extreme forms of common diseases. best of Yale School of Medicine. We in internal medicine at Boston’s ence as a career. Its founders include His work has demonstrated the are delighted that the foundation has Brigham and Women’s Hospital be- Brin; Wojcicki; Internet entrepreneur fundamental role of salt reabsorp- chosen to recognize his achievements,” fore coming to Yale in 1993. Among Jack Ma; entrepreneur and venture tion by the kidney in the regulation says Robert J. Alpern, m.d., dean and other honors, he is a member of capitalist Yuri Milner; and Facebook of blood pressure, and has provided Ensign Professor of Medicine. the National Academy of Sciences, ceo Mark Zuckerberg.

Medicine@Yale March/April 2014 7 Vilcek Foundation recognizes Yale geneticist’s ‘creative promise’ Awards & Honors

The Vilcek Foundation has named responsible for foreign-born scientists, age 38 or Gary E. Friedlaender, Antonio J. Giraldez, ph.d., associ- the clearance of younger, for exceptional accomplish- m.d., chair and Wayne ate professor of genetics, one of three maternal mrnas, ments early in their career. Each re- O. Southwick Profes- recipients of the 2014 Vilcek Prizes providing insight cipient receives a $35,000 cash award. sor of Orthopaedics for Creative Promise in Biomedical into the mecha- In 2013, Yale’s Richard A. Flavell, and Rehabilitation and Science, awards that recognize sig- nisms of how ph.d., chair and Sterling Professor professor of pathol- nificant contributions to American mrnas regulate of Immunobiology, and Ruslan M. ogy, is the recipient of the 2014 William W. science made by immigrants. gene expression. Medzhitov, ph.d., David W. Wallace Tipton Jr., m.d. Leadership Award from Giraldez, born in Spain, focuses Antonio Giraldez His findings aid Professor of Immunobiology, were the American Academy of Orthopaedic on the ways micrornas (mrnas) our understanding jointly awarded the Vilcek Prize for Surgeons (aaos). The award recognizes and other non-coding rnas shape of the first steps that lead to embryo- Biomedical Science for their long- leadership, mentorship, and significant gene expression during embryonic genesis after fertilization. standing and influential work on the accomplishment in and commitment to development. Working with zebra- The Vilcek Prize for Creative innate immune system, the first line the field of orthopaedic surgery. Fried- fish, he and colleagues recently found Promise in Biomedical Science of defense against infection by bacte- laender has served as chair of the Depart- that the mrna family miR-430 is is awarded annually to three ria and viruses. ment of Orthopaedics and Rehabilitation since 1986. He received the award at the aaos’s annual meeting in March. Yale-Jefferson Award honors couple’s commitment to public service Valentina Greco, ph.d., Two alumni of the School of Medi- The award, presented at the assistant professor of cine received the Yale-Jefferson Public assembly of the Association of Yale genetics and dermatol- Service Award for their commitment Alumni by Vice President Linda ogy, is the 2014 winner to service and social responsibility in Koch Lorimer, j.d., was first given in of the International November. Richard D. Gibbs, m.d. ’86, 2012. It is conferred by Students and Society for Stem Cell and Patricia H. Gibbs, m.d. ’87, were Alumni of Yale (stay) to recognize Research’s Outstand- recognized for founding and sustain- individuals who inspire the Yale coming Young Investigator ing the San Francisco Free Clinic munity through their contributions Award. The award recognizes Greco’s research into the interactions between (sffc), which provides urgent tony fiorini to the greater good. Candidates must stem cells and their niches, including medical care to uninsured people in Yale Jefferson Public Service Award recipients have a demonstrated involvement in the first direct, real-time visualization of San Francisco. (from left) Richard Gibbs, Tricia Gibbs, and a Yale service project or have made stem cell divisions noninvasively in living More than 8,000 patients visit the Kara Scroggins (right) with Vice President substantial use of Yale facilities or Linda Koch Lorimer. mammals. Greco is a past recipient of clinic each year to receive medications services for an outside service project. the Dermatology Foundation’s Research and care at no cost. Since the sffc’s the sffc, and with their help as early The stay awards are the local itera- Career Development Award and the founding 20 years ago, the Gibbses advisors, the Gibbses were instru- tion of the national Jefferson Awards, American Skin Association’s Research have taught, mentored, and inspired mental in developing the haven given since 1972. Scholar Award. She came to Yale in 2009. Yale medical students doing primary Free Clinic, the School of Medicine’s care clinical rotations at the clinic. student-run free clinic in the Fair Video “The Yale-Jefferson Award for Public Service” Becca Levy, ph.d., With the precedents established by Haven section of New Haven. Available at youtube.com/yalecampus associate professor of epidemiology and psychology, was awarded Pioneer in women’s health research is Spungen Bildner Professor the Ewald W. Busse Research Award for Carolyn M. professorship is named in honor of with the broader public through Excellence in Social and Mazure, ph.d., Elisa’s mother and in memory of outreach efforts. Behavioral Sciences by professor of Robert’s mother. Since its founding, whry has the International Association of Geron- psychiatry and Mazure, also associate dean for awarded more than $4.5 million in tology and Geriatrics (iagg). Levy's re- psychology and di- faculty affairs, founded whry in pilot grants to nearly 70 investiga- search explores psychosocial factors that rector of Women’s 1998 as an interdisciplinary research tors, who have obtained more than influence elders' cognitive and physical Health Research at center focused on women’s health and $52 million in external grants to functioning, as well as their longevity. Yale (whry), has gender differences. As director, she further their research. She is the recipient of numerous other been appointed the Carolyn Mazure has steered whry through steady Mazure’s contributions in honors and awards. The Busse Research inaugural Norma growth into a national model, widely women’s health began with her own Award, given once every four years, was Weinberg Spungen and Joan Lebson known for initiating and supporting research in the field of depression. presented at the iagg’s World Congress in Seoul, South Korea, last summer. Bildner Professor of Women’s Health investigations on women’s health and Her current research focuses on the Research at Yale. gender differences and emphasizing interplay of stress, depression, and The professorship is endowed by the translation of discoveries into addictive disorders with an emphasis Two Yale scientists a leadership gift from Elisa Spungen practical health care advances. on gender difference. have been honored Bildner, of the Yale College Class of The other key missions of whry Mazure received her doctorate with National Insti- ’75, and her husband, Robert Bildner, include training new investigators in in clinical psychology from Penn- tutes of Health (nih) of the Yale College Class of ’72, which women’s health, facilitating collabo- sylvania State University in 1980 “High-Risk, High- Reward” Research complements gifts from other donors rations among scientists and institu- and joined the School of Medicine’s Awards. Amy F.T. Arn- and an anonymous foundation. The tions, and sharing health findings faculty in 1982. sten, ph.d., professor of neurobiology and // IOM (from page 1) “Peter and Rus- Science, and of the Shaw Prize in Life psychology, received lan are two very different scientists Science and Medicine for 2011. He is Yale Medicine one of 12 nih Pioneer who represent the spectrum of excel- also a past recipient of the Else Kröner Now on your iPad! Awards. The five-year, lence we have among our Yale faculty,” Fresenius Award and the Lewis S. $2.5 million grant supports Arnsten’s re- said Robert J. Alpern, m.d., dean and Rosenstiel Award for Distinguished Visit yalemedicine.yale.edu/app to download search on the molecu- Ensign Professor of Medicine. “We Work in Basic Medical Research, and lar vulnerabilities for are delighted that once again this has was elected to the National Academy disease in the brain’s been recognized by the Iom.” of Sciences. His role in elucidating highly evolved association cortex. Jason Salovey has been honored with a the workings of the innate immune M. Crawford, ph.d., assistant professor National Science Foundation Presi- system won him the Blavatnik Award of chemistry and microbial pathogen- dential Young Investigator Award, a for Young Scientists in 2007. esis, received the nih Director’s New National Cancer Institute cis Partner The iom is an honorific member- Innovator Award—also a five-year, $2.5 in Research Award, and a Substance ship body that also advises lawmakers, million grant, awarded to early-career Abuse and Mental Health Services health professionals, and the public on scientists pursuing highly promising lines Administration Excellence Award. In health care and health policy. Salovey of inquiry. The grant enables Crawford’s research on gut-dwelling bacteria that 2013 he was elected to the American and Medzhitov are among 70 new play a role in the development of colorec- Academy of Arts and Sciences. members and 10 foreign associates tal cancer. The 2013 “High-Risk, High- Medzhitov was co-recipient of elected to the iom, bringing iom’s Reward” grants total about $123 million the 2013 Vilcek Prize for Biomedical total membership to 1,966. and support more than 78 scientists.

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