february/march 2018 volume 14, issue 1 Advancing Biomedical Science, Education, and Health Care

New Yale Institute of Global Health to address worldwide issues Health sciences schools take M.D., Ph.D., dean and Anna M.R. the lead on an initiative that Lauder Professor of Public Health, and professor of epidemiology aspires to have global impact (microbial diseases) and of pediat- rics; and of Ann E. Kurth, Ph.D., The Schools of Medicine, Public C.N.M., M.P.H., dean and Linda Health, and Nursing have come to- Koch Lorimer Professor of Nurs- gether to launch the Yale Institute of ing—both of whom bring a wealth of Global Health (YIGH), a university- expertise in global health research— wide effort that will address world- was another driving factor. wide health issues. The initial focus “There are complicated regula- of YIGH will be on research aimed at tory, legal, and logistical challenges improving the health of individuals to doing research in international lo- and populations around the world. cations,” says Robert M. Rohrbaugh, The creation of YIGH reflects M.D., professor of psychiatry and a growing interest by students, director of the Office of International robert a. lisak faculty, and advanced trainees across Medical Student Education at the “Yale has examples of amazing The Yale Institute of Global Health officially came the university in conducting global School of Medicine, where more than work being done in multiple schools into existence in December, with its approval by the Yale Corporation. (Left to right): Deans Robert health research, along with the need 40 faculty members conduct global from which the experience, exper- Alpern of the School of Medicine, Sten Vermund for a centralized resource for faculty health research. “A centralized group tise, and findings can be harnessed of the School of Public Health, and Ann Kurth of the School of Nursing marked the occasion, along to collaborate on these projects. The with this type of expertise is helpful, and further developed within larger- with Robert Rohrbaugh, the School of Medicine’s recent arrivals of Sten H. Vermund, especially for junior faculty.” scale, higher-impact, // YIGH (page 4) faculty lead for the institute. Slayman professorship is established David W. Wallace, 1924-2017, generous Endowment is created to assistant professor and loyal benefactor honor the memory of beloved in the Department of Physiology and David W. Wallace, a former cor- deputy dean and mentor Microbiology. porate attorney, businessman, and After spending her philanthropist who was a longtime The School of Medicine has estab- initial years at Yale supporter of the School of Medicine lished an endowed professorship to as a bench scien- and Yale University, died at home in honor the memory of the late Carolyn tist, she went on Greenwich, Connecticut, on Dec. 24, Walch Slayman, Ph.D., a distin- to assume admin- 2017. He was 93. guished scientist and visionary aca- istrative respon- David Wallace and his wife, Jean demic leader who graced the School of sibilities through McLean Wallace, have donated more Medicine with her inimitable presence which she influ- than $33 million to Yale, about half for almost 50 years. At the time of her enced scores of of which—$16.5 million—was used to death at age 79 in December 2016, students, trainees, endow six professorships at the School Slayman was deputy dean for aca- and colleagues, of Medicine. Their generous gifts place

demic and scientific affairs, Sterling and kept the terry dagradi them among a select group of support- Professor of Genetics, and professor of School of Medicine at the forefront A professorship at the School of Medicine has been ers of the school. endowed in memory of Carolyn Walch Slayman cellular and molecular physiology. in countless areas. She was a trail- (1937-2016), to be occupied by a faculty member “David has a special place of honor “We continue to feel Carolyn’s blazer on many fronts. When named who embodies qualities for which Slayman was because he was such an enthusiastic absence, and her influence will be chair of the Department of Human revered during her nearly 50 years at the school. and committed donor to the medical with us for many years to come,” says Genetics (now Genetics) in 1984, she her appointment as deputy dean she school, says Robert J. Alpern, M.D., Robert J. Alpern, M.D., dean and became the first woman to head a de- said that her job was to be a catalyst, dean and Ensign Professor of Medi- Ensign Professor of Medicine. “I am partment at Yale School of Medicine. bringing people together to foster cine. “David was proud of the fact that delighted that this professorship has In 1995, she became the school’s first active discussion that would guide he had given so many endowed chairs been created to honor her legacy.” deputy dean for academic and scien- the school. By all accounts, she suc- to the medical school, which have en- Slayman joined the School of tific affairs, and the first woman to ceeded admirably in this endeavor. abled us to attract outstanding faculty Medicine faculty in 1967 as an hold a deputy deanship. Shortly after Many sought // Endowment (page 5) and to provide // Benefactor (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 Gary V. Desir, chair of Internal Medicine, New Haven, CT discovered renalase, a protein with impact Permit No. 526 on kidneys, heart, and cancers. 3 Clinical trials innovations Bench scientists and clinicians regularly in- form each other’s work, strenghening Yale Cancer Center’s Phase I Program. 5 With gratitude and hope A patient introduced to Yale after a cancer diagnosis joins her husband in making a generous gift for research. FOLLOW & SHARE twitter.com/YaleMed facebook.com/YaleMed instagram.com/YaleMed lifelines Geirsson is named chief of cardiac surgery section

Gary Desir has served the Arnar Geirsson, School of Medicine with distinction as a researcher, M.D., associ- clinician, educator, and ate professor of administrator. His discovery and further investigation surgery (cardiac of the flavoprotein renalase surgery), has are milestones in the understanding of renal and accepted the cardiovascular function. position of chief of the Section of Arnar Geirsson Cardiac Surgery at the School of Medicine, after serving as interim chief since October 2016. Geirs- son also will serve as co-surgical director of the Heart and Vascular Center (HVC) at Yale New Haven Hospital and medical director of Gary V. Desir the Bridgeport Hospital Cardiac robert a. lisak Surgery program. Since he first joined the faculty of the School of Medicine in 2007, A stalwart in laboratory and clinic his clinical focus has been on mini- mally invasive surgery and valve surgery. He has a busy mitral valve Internal Medicine chair mentors such as Thomas P. Duffy, M.D., was appointed internal medicine chair repair practice done by minimally discovered a protein with professor emeritus of medicine (hema- at the West Haven VA hospital in 2003. tology), persuaded the two to stay. A decade later, he became interim invasive right thoracotomy. Geirsson kidney, heart, cancer roles Desir finished a nephrology fellow- chair of Yale’s Department of Internal performed the first valve-sparing On a spring day in New York, Gary V. ship at Yale in 1987 and joined the faculty Medicine, and then its chair and chief in root replacement at Yale (2008); Desir, M.D. ’80, now chair of Internal as an assistant professor in 1988. At first, 2016. Desir also is board chair for Yale the first hybrid revascularization at Medicine, and Paul B. Beeson Profes- he dedicated himself to research, seeking Medicine, the school’s clinical practice, the West Haven Veterans Affairs sor of Medicine, answered a phone call to better understand ion channel func- where he is working toward making Hospital (2008); the first right tho- from his father back home in Port-au- tion in kidneys and searching for ways to electronic-health-record software less racotomy mitral valve repair at Yale Prince, Haiti. Desir had planned to enjoy advance clinical care. intrusive in physican-patient interac- (2009); and the first robotic heart his first vacation to the United States, Major success came in 2005. “A tions. In addition, he co-founded the operation at Yale (2011). while staying at his cousin’s apart- renal fellow and I were caring for Minority Organization for Retention His research interests include ment in Queens, and return in a couple patients suffering from kidney disease, and Expansion (MORE), with the goal of investigating the biological changes of weeks. “My father said, ‘You prob- and he was lamenting that, in spite of recruiting—and keeping—more minor- ably should stay in the U.S. and go to our best efforts, many of our patients ity faculty and students. and pathways involved in patho- college,’” Desir recalls. “So, I stayed.” ended up dying of cardiovascular- He also has a dual teaching genesis of mitral valve prolapse and Desir’s father, a cardiologist, had related complications,” Desir says. “That appointment with the School of For- thoracic aortic aneurysm. He has trained in Canada and Chicago and was the inspiration for looking into the estry & Environmental Studies, where published various research articles in wanted his children to earn their connection between kidney and heart he co-led a graduate course called both basic and clinical science, and degrees from U.S. schools. So, Desir disease. And that search, which took “Sustainable Development in a Post- serves as an editorial reviewer for applied, and was accepted at New York several years, led us to discovery of Disaster Context,” in collaboration Annals of Thoracic Surgery, Journal of University, where he would major in renalase, a flavoprotein, synthesized in with the Albert Schweitzer Hospital Thoracic and Cardiovascular Surgery, biology. When the time came to follow the kidney and secreted in blood, that in Deschapelles, Haiti, and continues Journal of Heart and Lung Transplan- his father, paternal grandfather, and enhances various cells’ ability to survive. to host visiting Haitian doctors and tation, and Circulation. great grandfather into medicine, he The renalase protein is approximately nurses in an exchange program. Geirsson is an active member considered Johns Hopkins, Cornell, and 3 billion years old, and is encoded by a What at first was going to be a others, but chose Yale because of its single, highly conserved gene.” temporary stay for Desir at Yale has of the Society of Thoracic Surgeons system of medical education, which Desir and his team hypothesized that now turned into four decades, and he and the American Heart Association promotes independent learning. renalase could be used to protect patients says he has never questioned his origi- (AHA), serving on various commit- As a first-year, Desir shared a from kidney injury and heart attacks, nal decision to stay. He and Deborah tees of the AHA. cadaver with a classmate, and soon and minimize cardiac cell damage. More Dyett Desir, M.D. ’80, a rheumatologist decided he wanted to share his life with recently, Desir and others have also found in private practice, have raised four chil- her. He and the then Deborah Dyett that dysregulated renalase signaling dren during 38 years of marriage. And, pursued internal medicine residencies alters the immune response to tumors within the medical school, he is thankful Managing Editor Robert Forman at Yale New Haven Hospital, a decision and can contribute to the development of “to have found collaborators and people Contributors Christopher Gardner, Renee Gaudette, Pamela Hartley, Bill Hathaway, Ziba Kashef, Jill Max, heavily influenced by Samuel O. Thier, certain cancers. His laboratory is develop- at Yale willing to help even though they Kathleen Raven, Abigail Roth, Garrett Sendlewski, M.D., then Yale’s chair of internal medi- ing agents that block renalase signaling were not benefiting from what they Natasha Strydhorst, Ashley P. Taylor, Kendall Teare, cine, who made sure the couple had as first-in-class therapeutic agents for were helping me with. Even when I was and Sarah C.P. Williams Design Jennifer Stockwell similar on-call schedules so they could cancer. Desir holds several renalase- a junior faculty member researching ion Web Coordinator/Proofreader Cheryl Violante enjoy days off together. “Also, at the related patents and is scientific founder of channels, I had people willing to help Medicine@Yale is published four times each year by: time, I wanted to do research in renal two biotech companies. me.” Now, as a senior leader, and by Yale School of Medicine, Office of Communications physiology, and Yale was top-rated in Over time, Desir has taken on added personal example, it is that kind medical 1 Church Street, Suite 300, New Haven, CT 06510-3330 Telephone: (203) 785-5824 Fax: (203) 785-4327 this area,” Desir says. That, along with clinical and administrative roles. He school he is dedicated to maintaining. Email [email protected] Website medicineatyale.org Copyright ©2018 by Yale University. All rights reserved. If you have a change of address or do not wish to receive Garino is appointed director of the Physician Associate Program future issues of Medicine@Yale, please write to us at the above address or via email at [email protected]. Alexandria (Xandi) the PA Program faculty in 2006, explored the non-cognitive factors Postal permit held by Yale University, Garino, Ph.D., PA- and has worked clinically for that explain how students in the 155 Whitney Avenue, New Haven, CT 06520 C, assistant profes- 10 years as a physician assistant at health professions react to, inter- sor of medicine, Yale Cancer Center. pret, and use feedback. Robert J. Alpern, M.D., Dean and has been appointed Garino, who places a high value She graduated from Catho- Ensign Professor of Medicine director of the Yale on the program’s research focus, lic Medical Center’s PA program Charles Turner Associate Vice President for Development and School of Medicine received her Ph.D. in learning sci- in 1999, and earned her M.S. in Director of Medical Development (203) 436-8560 Physician Associate ence in January 2018 from Fordham biostatistics and clinical research Mary Hu Associate Dean for Communications and (PA) Program, after Alexandria Garino University’s Contemporary Learn- design from Columbia University’s Chief Communications Officer serving as interim di- ing and Interdisciplinary Research Mailman School of Public Health rector since July 2016. Garino joined program. Her doctoral work in 2004. Printed on recycled paper ♻

2 www.medicineatyale.org advances Clinical trials take innovative approach Health & Science News Potential new type 2 Frequent consultation between bench and testing [the findings] in rigorous Phase II studies,” says approach identified clinic enhances the effectiveness and impact Bindra. LoRusso says trialists will go a step beyond stan- dard safety-related protocols and send samples obtained of Yale Cancer Center’s Phase I Program from their patients back to the bench scientists, “to try to understand why it’s working or why it’s not working and It is a simple concept: bench investigators who identify in what patients it’s working.” potential cancer therapies, and clinicians who evaluate “You can’t often do that by just looking at the patients,” experimental drugs in patient trials, sitting down together she adds. “You need to take the tumor and the patient to figure out how each can make the others’ work more information and go back into the lab. That’s one of the

shutterstock.com effective. And yet, until just the past few years, the two beauties of having the science and the clinic here.” The protein apelin, previously known to groups often worked separately from one another at many Another development seen as beautiful by those in- improve glucose metabolism, could be- institutions. The thought process at the bench seldom ex- volved is the clinic itself, a dedicated trial facility signifi- come the focus of diabetes treatments, tended to therapeutic practice, and clinical trial physicians cantly funded by Yale New Haven Hospital that opened suggests a new study led by Hyung developed their protocols with limited input from the basic in 2016. “Instead of being a sort of designated corner of J. Chun, M.D., associate professor of scientists who made the initial discoveries. a general medical oncology unit,” says Eder, “it’s now medicine (cardiology). Because of that, Ranjit S. Bindra, M.D., Ph.D., associate a specified place.” LoRusso says the new facility has The study, published in Science professor of therapeutic radiology, says extraordinary lab accelerated the Phase I Program, which served roughly Translational Medicine on September 13, work frequently went unnoticed. “There are so many great 25 patients per year when she came to Yale three years reports apelin’s receptors are located discoveries in journals like Science Translational Medicine, ago, and now is on target to enroll at least 150 patients in specifically on the endothelial cells that Science, and Nature, from many institutions, where the 2018. “I think it’s done wonders,” she says, “There’s noth- line the blood vessels and that apelin clinical implications are so profound, and yet they never ing like working in an extremely pleasant environment. binding of its receptor prevents another made it into the clinic.” Some work, Bindra says, was just It’s a state-of-the-art facility.” protein—endothelial fatty-acid binding not translatable, but in other instances, he says, “they Those comforts matter to patients who struggle to protein 4 (FABP4)—from importing probably also just never had a feasible mechanism to drive follow the strict protocols of a clinical trial, according to fatty acids into the tissues. Excess them into the clinic.” Joseph W. Kim, M.D., assistant professor of medicine fatty-acid accumulation can result in Such a mechanism is now the organizing principle of (medical oncology). Kim designs many of the trials. His insulin resistance and poor glucose me- the Phase I Program at Yale Cancer Center (YCC), one of role also includes explaining both the pros and cons of tabolism—the hallmarks of diabetes. the few academic programs in the country where regular trial participation to his Yale Medicine patients. “These Chun’s team fed mice high-fat contact between bench scientists and clinicians is stan- trials are quite involved with research blood draws and chow, which led them to gain weight dard practice. and develop insulin resistance. Those “There is a special drug development seminar once a mice also produced less apelin. month,” says Joseph Paul Eder, M.D., professor of medi- Injecting those same mice with apelin cine (medical oncology) and clinical leader of the Phase improved their glucose metabolism. I Research Group. “There’s another that’s called clinical Chun believes drugs that activate cancer colloquium, where basic scientists from Science Hill apelin receptors or inhibit FABP4 come talk to us, or we go to them, and say, ‘Here are great might be potential diabetes treat- targets.’ What is special about Yale is that the clinicians ments. Further, since apelin prevents and translational scientists talk almost daily. The clinicians atherosclerosis in mice, such treat- attend the science lectures, we pass each other in the hall, ments could also address diabetes- and I hope that every scientist knows our doors are always associated cardiovascular problems. open and our cell phones are always on.” One project enhanced by these frequent interactions A path toward drug was a paper published in February 2017, whose senior au- thors were Bindra and Peter M. Glazer, M.D., Ph.D., chair synthesis in cells and Robert E. Hunter Professor of Therapeutic Radiology A Yale-led research team has de- and professor of genetics. scribed the structure of pyrrolysyl- Their research, in Science Translational Medicine, dem-

tRNA synthetase (PylRS), a protein onstrated the sensitivity of tumor cells with mutations in robert a. lisak that synthetic biologists rely upon to two metabolism genes, IDH1 and IDH2, to targeted drugs Since their arrivals at Yale within the past six years, Patricia LoRusso (right) and Joseph Paul Eder (center)—shown conferring with Clinical Research Coordinator add new letters to the genetic code. called PARP inhibitors. In the discussion section of the Alexandra Minnella—have overseen a sharp increase in the number of clinical tri- In the past, most biology textbooks manuscript, the authors wrote that their findings could als conducted by the Phase I Program at Yale Cancer Center. Bench investigators and the clinicians who design and conduct early-phase trials interact regularly, have described 20 amino acids—the form “the basis for a possible therapeutic strategy.” They each sharing knowledge with the other that both strengthens the basic science building blocks of all proteins— and could say that confidently because before the paper was and brings new discoveries to patients more quickly and effectively. 20 tRNA synthetases, responsible for even published, Bindra began a series of discussions about matching the amino acids with the how to translate this discovery directly into the clinic with biopsies,” Kim says. “The patients need a lot of attention.” correct genetic molecules. Recently, Patricia M. LoRusso, D.O., director of the early therapeu- While cautioning against false hope, Kim can also describe however, researchers have uncovered tics clinical trials program and associate center director of the encouraging longevity certain patients have enjoyed additional rare amino acids, includ- experimental therapeutics at YCC, who leads the Phase I thanks to recent research advances. “We have patients ing the so-called “22nd amino acid” Program’s Disease Aligned Research Team. from 2014 who remain on treatment without any evi- pyrrolysine, found in bacteria and Bindra recalls, “She raised her hand in a research semi- dence of disease,” he notes. “An average life expectancy of single-celled organisms. nar and said “I’m not impressed with your animal data. patients coming to the Phase I clinic is 3 to 6 months. So, To help advance efforts to inte- You’re showing these curves that are barely separating in a they are well beyond life expectancy. It’s amazing.” grate pyrrolysine into the genomes flank model, you’re not going to be able to convince clini- Kim has adapted other work by Glazer and Bindra for of other types of cells, Dieter Söll, cians to bring this into the clinic.’” Bindra went back to the a current trial to treat patients with advanced prostate Ph.D., Sterling Professor of Molecular lab to “look at the different PARP inhibitors and to find cancer. “We sat down and talked about how hypoxia could Biophysics and Biochemistry, and pro- one that had the biggest difference.” They ended up select- suppress DNA repair,” Bindra says. “He clearly looked at fessor of chemistry, and colleagues ing an FDA-approved PARP inhibitor, olaparib, which the papers and was thinking deeply about it.” Their close determined the three-dimensional demonstrated marked activity in vivo. cooperation mirrors that of many other bench researchers structure of PylRS—the tRNA synthe- That choice is helping patients already. Eder quickly and clinicians at Yale. tase required for pyrrolysine. plugged the findings into an existing protocol designed For Eder, the program puts Yale in a place where it As published October 16 in Nature to thwart cancer cells’ ability to repair their own disease- wants to be. “I don’t think you can find any of the original Chemical Biology, Söll’s team not only promoting DNA. “Yale had set up a clinical trial to be papers on immuno-oncology drugs like ipilimumab and described the structure of a unique reactive to potentially important new information in the nivolumab where Yale investigators were not first or last section of PylRS, but also evolved new area of DNA repair,” says Eder. “Yale investigators took authors on those papers.” variants of the protein using a stan- that basic information and brought it immediately into Now, he says, investigators have the optimal outlet dard lab setup that is both simpler and the clinic. Yale enrolled IDH1/2-mutant patients into the for their work. “It’s not just great scientists at the bench. faster than prior techniques that need study, and already months later we know at least in some It’s not just great docs in the clinic. We can bring these specialized equipment. Söll foresees patients this really works.” two things together and bridge that for a clinical trial that “the exciting prospect of synthesizing LoRusso and Bindra have even more ambitious plans. will benefit [patients] now.” And, he enthusiastically tells new drugs inside living cells.” “Pat and I are writing a series of trials together, really patients, “You can be among the first.”

Medicine@Yale February/March 2018 3 out & about

May 3 Cheryl Henson (front left), Yale College ’84, president of the Jim Henson Foundation founded by her late father, who created the Muppets, helped film a segment for the Yale Early Social Cognition Lab, with puppeteers Lindsey “Z.” Briggs (front, second from left) and Stephanie D’Abruzzo (front right). Katarzyna Chawarska, Ph.D., (center rear), lab director and professor in the Yale Child Study Center, is surrounded by her lab team, which analyzes responses of children with autism to videos of puppets interacting with live actors. courtesy of gary desir

September 9 Gary V. Desir, M.D. ’80, chair of internal medicine and Paul B. Beeson Professor of Medicine, and his wife, Deborah Dyett Desir, M.D. ’80, a rheumatolo- gist, hosted the annual Minority Organization for Retention and Expansion (MORE) reception at their home. Nearly 50 medical school faculty, students, fel- lows, and residents attended the event.

September 28 Harriet M. Kluger, M.D., professor of medicine (medical oncology), and Veronica L.S. Chiang , M.D., professor of neurosurgery and radiation oncol- ogy, presented “The Highlights of courtesy of katarzyna chawarska Brain Metastasis and Melanoma Research,” in Wilton, Connecticut, and thanked friends and donors to October 1 The inaugural First Sunday was held at the home of Darin A. Latimore,

judy sirota rosenthal rosenthal sirota judy the Brain Metastasis Research Fund M.D. (front, center), deputy dean for diversity and inclusion and chief diversity and Melanoma Research Fund for their support. Richard Metz (left) and Stephen officer. More than 45 medical, graduate, and postdoctoral students attended the Connor (right), both melanoma survivors and leaders of the Brain Metastasis Research community-building event, with plans to hold similar gatherings each month. Fund, stand with Kluger (second from left) and Chiang.

October 9 Brothers Srini- vas Seela, M.D., (second from left), and Harinath Sheela, M.D., (right), recently gifted funds to support the Department of Internal Medicine’s Section of Digestive Diseases. This includes research led by James L. Boyer, M.D.

courtesy of darin latimore darin of courtesy (second from right), Ensign

erin shreveerin Professor of Medicine (Digestive Diseases) and emeritus director of the Yale Liver Center, who was the brothers’ mentor when they worked in the section as postdoctoral fellows. Srinivas Seela’s son Rithvik Seela (left) worked last summer in Boyer’s lab.

1. Nov 14–16 The inaugural National Clinician Scholars Program (NCSP) national meeting brought clinician scholars to the Omni Hotel in New Haven to explore themes around “Advancing Health Through Scholar- ship and Action.” 1. From left, schol- ars—and postdoctoral fellows— 2. Raymond Jean, M.D., M.A.; Katie

harold shapiro Piwnica-Worms, M.D.; Kathleen October 6 On National PA Day, New Haven Mayor Toni Harp (center) helped O’Neill, M.D.; Shelli Feder, Ph.D., APRN; celebrate the 50th anniversary of the Physician Assistant (PA) profession with and Paul Joudrey, M.D., M.P.H. Yale leaders. From left, Rita A. Rienzo, M.Sc., PA-C, assistant professor in Yale’s PA 2. (Left to right): Co-directors Sarwat Program; Michael Devanney, MHS, PA-C, current vice president of Connecticut I. Chaudhry, M.D., associate professor harold shapiro (2) harold shapiro Academy of Physician Assistants; Courtney Fankhanel, MM.Sc., PA-C, assistant of medicine (general medicine), and professor in Yale’s PA Program; James Van Rhee, M.S., PA-C, director of Yale’s PA Robin Whittemore, Ph.D., APRN, professor of nursing; as well as Yale’s NCSP direc- Online Program; Alexandria Garino, Ph.D., PA-C, director of the Yale PA Program; tor, Cary P. Gross, M.D., professor of medicine (general medicine) and of epidemiol- David Brissette, MMS, PA-C, assistant professor in Yale’s PA Program. ogy (chronic diseases); made opening remarks.

// YIGH (page 1) sustainable global sciences schools will collaborate with international settings; one challenge faculty who are developing new grant partnerships,” says Vermund. Cur- experts from the Schools of Forestry this trend presents has been student ac- proposals or exploring potential col- rent programs across the univer- & Environmental Studies, Law, and cess to mentors. By bolstering opportu- laborations based on geographic or sity address such areas as infectious Management to expand the institute’s nities for international projects, YIGH topical areas of interest, and seed grants diseases, maternal and childhood interdisciplinary agenda. is expected to develop new mentorship for faculty to pursue new research health, noncommunicable diseases, and It is a sign of increasing demand for capacity to support student research opportunities. health systems and research capacity. what YIGH plans to do that about a at the health professions schools and “We want to harvest all the talent YIGH will build upon this foundation third of each year’s School of Medicine across the university. and the distinct assets we have across to address such global challenges as class travels abroad for an international A search is underway for a faculty the university, to make a deeper impact pandemic preparedness, refugee health, clinical elective. Rohrbaugh notes director and YIGH is already ramp- with our global initiatives,” says Kurth. urbanization, and climate change that many of these students also want ing up its activities. Initiatives include “YIGH will provide a catalyzing center and health. Researchers at the health experience conducting research in a program to provide consultation to for these collaborations.”

4 www.medicineatyale.org advances Gift supports work on a stubborn cancer Health & Science News Major brain impact Non-smoker’s lung cancer, and associated resistant to some of these target drugs while building new arises from few cells gene mutations, are among the priorities for animal models to test new therapies. It’s allowed us to explore new approaches of how to study brain metastases, Yale scientists in both the lab and the clinic and target them in lung cancer research.” The resistance to drugs that Herbst notes has now For a quarter century, Ginny Grunley, her husband Ken caught up with Ginny Grunley. The two good years the Grunley, president and chief executive officer of Grunley afatinib gave her have run their course. So, Herbst and Construction, Inc., and their family have been enthusiastic the Grunleys are teaming up, along with other top cancer philanthropists. Their determination to help others has experts, to determine the next treatment solutions together.

shutterstock.com included Ginny volunteering as a court-appointed special “The thing Roy does is he gives me hope that there’s so Neurons called vasoactive intestinal advocate for disadvantaged children. much coming down the road, that this isn’t by far the last peptide (VIP) cells make up just 1 per- “Writing a check is not enough,” Ginny declares thing to try,” says Grunley. “I just want to make it for my cent of all brain cells, but their as a firm statement of family philosophy. “You need to be daughter’s wedding and my grandson’s bar mitzvah, and disruption in mice causes symptoms involved in the process.” that mimic those of humans with In 2017 the Grunleys became sup- schizophrenia, reports a study by porters of Yale School of Medicine, Jessica A. Cardin, Ph.D., associate with a million-dollar gift to fund lung professor of neuroscience, published cancer research led by Roy S. Herbst, on August 16 in Neuron. M.D., Ph.D., Ensign Professor of Cardin and her team mutated VIP Medicine and professor of pharmacol- cells in young mice, then observed the ogy, associate director for translational consequences in the visual cortex. research at Yale Cancer Center (YCC), VIP cells usually fire when mice start and chief of medical oncology at YCC to walk, but they did not do so in the and Smilow Cancer Hospital. Their mutant mice. The mutant mice also involvement, however, is something had reduced synchrony of neuronal they would not have imagined just a firing and impaired vision. The failure few years ago. Ginny came to learn of neurons to respond to changes in be- about Herbst’s research because she havioral state, of which walking is one had become one of his patients, after example, is characteristic of neurode- being diagnosed with a form of lung velopmental disorders such as autism cancer associated with the EGFR gene and schizophrenia, as are reduced firing mutation—a condition commonly

synchrony and perception problems. known as non-smoker’s lung cancer. courtesy of roy herbst In the mice, all of these symptoms She considers herself lucky that the cancer was discov- Ginny Grunley (left) became a patient of Roy Herbst (center) after being di- emerged by adolescence, the time agnosed with a form of lung cancer associated with the EGFR gene mutation, ered so early—many lung cancers are not—and also that also known as non-smoker’s lung cancer. Grunley and her husband Ken (right) when, in humans, schizophrenia typi- Ellen V. Sigal, Ph.D., founder and chair of the organization have given a million-dollar gift to support Herbst’s research. cally begins. These correspondences Friends of Cancer Research, and the wife of one of Ken between mice with mutated VIP neu- Grunley’s business acquaintances, knows Herbst well be- he knows how important that is to me. He gets it. There are rons and conditions of neurodevelop- cause of his basic and clinical-trials work in the field. Sigal, not enough adjectives to describe Roy. He’s the best.” mental disease suggest to Cardin that whom Ginny now calls “my guardian angel, my best friend, Yale as an institution also impresses Grunley, from VIP neurons may represent a therapeu- my sister,” is well-connected in the cancer community, and Herbst’s lab to the University Art Gallery, which Ken tic target. “she brought Roy in from the very beginning.” and Ginny—an amateur artist—toured with Herbst after The Grunleys flew to New Haven, where Herbst intro- a challenging day of treatment and consultation. “I went Seeing more nuance duced them to his clinical and research teams, including from discussing all these really tough issues to this Katerina Politi, Ph.D., associate professor of pathology. museum full of beauty and history and it was wonder- for a cancer therapy Grunley says Politi, whom she calls “an amazing young ful,” she says with admiration. “Yale has something to A growing number of cancer drugs are woman, so brilliant,” examined her tumor in extraordinary offer everyone, and to feel like you’ve been taken into designed to shut off epidermal growth detail. Based on that analysis, Politi and Herbst recom- their community is just very kind.” A Yale hoodie is now a factor receptor (EGFR), a protein known mended that Grunley switch from her prior medication to frequent part of her wardrobe. to be involved in a wide array of cellular afatinib, a targeted medication that she says kept her can- The Grunleys’ generous philanthropy, in sum, is one processes including proliferation. Now, cer at bay with just minimal side effects for two joy-filled part for Roy Herbst, a physician-scientist they admire; one Yale researchers have answered a long- years. “To be able to see these brilliant minds at work,” part for Yale, an institution that Ginny has come to love; standing question about how EGFR can says Grunley, “you’re just in awe.” Herbst agrees. “My and one part for future patients affected by the EGFR mu- mediate so many diverse processes. proudest achievement is the team I’ve built here at Yale, tation. “I did not know about this form of cancer,” Ginny Scientists already knew that seven and the way they work together,” he says. “They’re com- says. “But now that I do, I want [Herbst and his team] to different growth factors bind to the mitted, and they’re caring, from the lab to the clinic.” understand that I’m not just doing this for a cure for me. I receptor portion of the EGFR protein, As for the Grunleys’ gift, Herbst says, “It has allowed think that they can eventually find a cure for this. Whether each causing two receptor molecules us to expand our sequencing work in lung cancer to look I’m there or not I’m not sure, but I know they can do it, and to come together, turning on the active for new mutations that might result in patients becoming I will never stop supporting it.” portion of the proteins. But researchers had been puzzled by how the binding of each growth factor causes different // Endowment (page 1) her counsel, professor of medicine (medical oncol- of further assistance. The yet-to-be- actions within the cell. benefiting from her wise judgment ogy); and Clifford L. Slayman, Ph.D., named holder of the professorship Mark A. Lemmon, Ph.D., David A. and enthusiastic leadership. emeritus professor of cellular and will be a preeminent scientist at the Sackler Professor of Pharmacology The $3 million endowment to molecular physiology, who was mar- School of Medicine who embodies and co-director of the Cancer Biology create the Carolyn Walch Slay- ried to Slayman for 57 years. the attributes and character Slay- Institute at Yale Cancer Center, and man, Ph.D., Professorship came to Carolyn Slayman was an excep- man displayed in her scientific and colleagues formed crystals of the be thanks to the generosity of Dan tional mentor who was committed administrative roles, is committed to EGFR protein to study its structure Adams, executive chair and head to nurturing the next generation of mentoring young investigators, and is under different conditions. Different of global business development at scientists. In 2012, for example, she supportive of advancement opportu- growth factors, they showed, cause Protein Sciences in Meriden, Con- was instrumental in establishing a nities for women. EGFR’s receptor portions to assemble necticut; Thomas Israel, chair and Junior PI (Principal Investigator) “Carolyn was an outstanding role in slightly different ways, with varia- chief executive officer of Ingleside Retreat—now an annual event— model and a beloved figure,” says tions in the timing and strength of Investors; Richard S. Sackler, M.D., aimed at helping junior investigators Alpern. “She had the rare ability to the association—which the cell ‘reads of Greenwich, Connecticut; Jonathan navigate the complexities of estab- motivate, inspire, and engage indi- out’ as different signals. M. Rothberg, Ph.D. ’91, professor lishing a research program. Early vidual faculty at every level while at The discovery, published online in (adjunct) of genetics and a pioneer career investigators often sought her the same time carrying out a broader Cell on October 12, may lead to drugs of next-generation gene sequencing; advice, which she readily dispensed, vision. This professorship is a fitting that target EGFR in more nuanced Bonnie E. Gould Rothberg, M.D. ’94, and she would periodically check in tribute to the indelible imprint she left ways, rather than simply shutting it off. M.P.H. ’05, Ph.D. ’09, assistant with them to learn if she could be upon the school and its community.”

Medicine@Yale February/March 2018 5 Grants and contracts awarded 2 years, $246,960 • Thomas Durant, College of Connecticut Innovations, Development and Inte- American Pathologists Foundation, Moving Aver- gration of Novel SPECT and PET Quantitative ages and Machine Learning for Reducing Medical Analysis Tools for Sympathetic and Molecular to Yale School of Medicine Error in the Clinical Laboratory, 1 year, $4,960 Nuclear Cardiac Imaging, 3 years, $500,000 Jennifer Dwyer, Thrasher Research Fund, Efficacy Robert Makuch, Boehringer Ingelheim Interna- December 2016–February 2017 of Rapid-Acting NMDA Antagonist for Treatment tional GmbH, CFDA Drug Registration and Regula- of Adolescent Depression, 2 years, $25,000 tory Affairs Course for Boehringer, 3 years, Marie Egan, Jonathan Koff, Cystic Fibrosis Foun- $225,000 • Nikhil Malvankar, Charles H. Hood Federal $2,093,750 • Stephen Strittmatter, NIH, Genome- dation Therapeutics (CFFT), Yale Cystic Fibrosis Foundation, Targeting Bacterial Infections by Alan Anticevic, NIH, Mapping the Longitudinal wide Discovery and Translational Research for Therapeutic Development Center, 1 year, $72,549 Imaging Electrical Interactions Between Host Neurobiology of Early-course Schizophrenia, Neural Repair, 8 years, $8,135,644 • Jane Taylor, Barbara Ehrlich, ILSI Health and Environmental Surface and a Pathogen, 2 years, $150,000 4.8 years, $938,515 • Sviatoslav Bagriantsev, NIH, Decision-making Dysfunction and Chronic Sciences Institute, Optimizing Treatment for Jessica Mariani, Brain & Behavior Research Foun- NIH, Role of Piezo2 and Nav Channels in Rapidly Cocaine, 5 years, $1,653,750 • Rebecca Treger, Breast Cancer Patients, 2 years, $50,000 • Ayman dation (formerly NARSAD), Exploring Trideimen- Adapting Neuronal Mechanoreceptors, 5 years, NIH, Cell-intrinsic Mechanisms of Endogenous El-Guindy, American Cancer Society, Regulation of sional Chromatin Interactions in ASD-derived $1,832,030 • Choukri Ben Mamoun, NIH, Develop- Retroviral Control, 3 years, $105,108 • Alda Tufro, Epstein-Barr Virus Late Gene Expression, 4 years, Brain Organoids, 2 years, $70,000 • Scott Miller, ment of Endochin-like Quinolones for Babesiosis NIH, Molecular Characterization of a Novel Cause $792,000 • Shawn Ferguson, The Bluefield Project University of Utah, Using Numerical Analysis Tools Therapy, 4 years, $2,673,329 • Titus Boggon, NIH, of Human FSGS, 4 years, $2,019,771 • Andrew to Cure Frontotemoporal Dementia, Role of Lyso- to Design and Study Chiral Catalysts, 4 years, Specificity and Regulation in a Protein Kinase Wang, NIH, Regulation of Metabolic Programs for somes in Progranulin-linked Frontotemporal $255,532 • Pramod Mistry, Laboratorio Chamoles, Cascade Affecting the Actin Cytoskeleton, Host Tolerance to Inflammation, 5 years, $783,965 Dementia, 1 year, $170,000 • Sjoerd Finnema, Biomarkers and Genetic Mutations in Gaucher 4 years, $1,306,492 • Susan Busch, NIH, Causes Dan Wu, NIH, Signaling Mechanisms and Func- Brain & Behavior Research Foundation (formerly Disease Population in Argentina, 1 year, $173,713 and Consequences of Out-of-Network Mental tions Related to Patho-physiology of Vascular, NARSAD), PET Measurement of Ketamine- Dennis Moledina, Robert Leet and Clara Guthrie Health Care Use, 1.9 years, $478,706 • John Lung and Blood Systems, 7 years, $6,386,198 induced Changes in Synaptic Density in Patients Patterson Trust, Early Non-invasive Diagnosis of Carlson, NIH, Analysis of a Large Family of Taste with Depression, 2 years, $70,000 • Richard Human Acute Tubulo-Interstitial Nephritis (AIN) Receptors, 5 years, $1,739,466 • Luke Davis, NIH, Non-federal Flavell, Washington University in St. Louis (NIH), with Cytokines Representing T-helper Cell International Research Training on TB and Other Fuad Abujarad, Michigan State University, An Towards True Precision Oncology: Validation of a Pathway, 2 years, $90,000 • Janitza Montalvo- Pulmonary Complications of HIV, 1 year, $271,296 Integrated Model for Personal Assistants Comprehensively Humanized, Autologous Mouse Ortiz, Brain & Behavior Research Foundation (for- Naomi Driesen, NIH, Assessing the Relation- Research and Training (IMPART), 2 years, $106,394 Model, 3 years, $277,428 • John Forrest, Sheela merly NARSAD), Epigenetics of Depression in Early ship between Cortical Oxidative Metabolism Anahita Amiri, Brain & Behavior Research Founda- Shenoi, Doris Duke Charitable Foundation, Inter- Sexually Abused Females, 2 years, $70,000 • Don and Working Memory Deficits Under NMDA tion (formerly NARSAD), High-throughput Quan- national Clinical Research Fellowships for Medical Nguyen, AstraZeneca UK Limited, Therapies for Receptor Blockade, 2 years, $404,250 • Deepak titative Analysis of Enhancer Elements Associated Students, 2.5 years, $462,000 • Patrick Gallagher, Brain Metastasis in Lung Cancer, 3 years, D’Souza, NIH, Characterization of Cannabinoid with ASD, 2 years, $70,000 • Gustavo Angarita- Jackson Laboratory (NIH), Comprehensive $1,726,595 • Linda Niccolai, State of CT Dept. of Induced Acute Persistent Psychosis (CIAPP), Africano, Brain & Behavior Research Foundation Mapping of Long-range Chromatin Interactions in Public Health (DHHS), Connecticut Emerging 2 years, $374,180 • Carlos Fernandez-Hernando, (formerly NARSAD), Vitamin D as a Therapeutic Human and Mouse Genomes, 1 year, $121,709 Infections Program, 5 years, $2,847,156 • Noah NIH, Novel Insights into the Molecular and Cel- Adjunct in the Stimulant Treatment of ADHD: Mark Gerstein, University of Massachusetts Palm, Artizan Biosciences, Exploiting the Host lular Mechanism Regulating Lipid Metabolism A Proof-of-Concept Study of Stimulant-Induced (NIH), EDAC: ENCODE Data Analysis Center, 1 year, Immune Response to Identify and Treat Microbiota- and Atherosclerosis, 7 years, $5,950,413 • Charles Dopamine Release Using [11C]-PHNO PET in $392,000 • Emily Gilmore, University of Southern Driven Inflammatory Diseases, 11 months, Fuchs, NIH, Dietary and Lifestyle Determinants Healthy Humans, 2 years, $70,000 • Nancy California (NIH), The Epilepsy Bioinformatics Study $603,757; Richard & Susan Smith Family Founda- of Colon Cancer Recurrence and Survival, 3 years, Angoff, Arnold P. Gold Foundation for Humanism for Antiepileptogenic Therapy (EpiBioS4Rx), tion, A Universal Genetic Toolkit to Illuminate $1,648,992 • Nicola Hawley, NIH, Development in Medicine, 2017 Leonard Tow Humanism in 4.9 years, $38,800 • Peter Glazer, Marie Egan, W. Host-Microbiota Interactions, 3 years, $300,000 of a Group Prenatal Care Intervention to Address Medicine Award, 10 months, $2,000 • Lynnette Mark Saltzman, PNA Innovations (PNAI), Modi- Abhijit Patel, Alessandro Santin, Honorable Tina Maternal and Child NCD Risk in American Samoa, Averill, Robert Leet and Clara Guthrie Patterson fied PNAs to Develop Gene Editing Therapeutics Brozman Foundation, Early Detection of Ovarian 2 years, $470,679 • Ansel Hillmer, NIH, Multimodal Trust, Connectivity Networks Underlying Ketamine- for Hematopoietic Blood Disorders and Cystic Cancer via Analysis of Genomic Alterations in Neuroimaging of Alcohol Withdrawal: The Role induced Improvements in Suicidal Ideation, 2 years, Fibrosis, 2 years, $3,000,000 • Melissa Grafe, Uni- DNA and RNA from Multiple Sources in Blood, of Glutamate in Neural Reorganization, 5 years, $90,000 • Helene Benveniste, Fondation Leducq, versity of Massachusetts Medical School (NIH), 2 years, $200,000 • Jordan Peccia, University of $894,401 • Tamas Horvath, NIH, Feeding Driven Understanding the Role of the Perivascular Space Rethinking Early Neurosurgery: The Harvey Tulsa, Research to Practice: Translating the Science by POMC Neurons, 4 years, $1,944,525 • Fahmeed in Cerebral Small Vessel Disease, 5 years, $703,330 Cushing Collection, 5 months, $7,689 • David of the Microbiology of the Built Environment Hyder, NIH, MRS Validation of Computational Jonathan Bogan, American Diabetes Association, Hafler, Broad Institute (NIH), A Catalog of Cell Program, 1.5 years, $23,530; University of Tulsa, Metabolic Modeling of Human Brain Function Regulation of Energy Expenditure by Proteolysis of Types and Genomic Elements in Tissues, Organ- Development, Calibration, and Validation of a to Determine Energetic Disruptions Underly- TUG Protein, 1 year, $115,000 • Amanda Brewster, oids and Disease, 4 years, $134,000; Benaroya Simple Tool for Guiding Mold Inspection and ing fMRI-derived Functional Connectivity in Commonwealth Fund, Partnerships and Perfor- Research Institute, Transcriptional Profiling of Fat- Remediation in U.S. Homes, 3 years, $324,876 Degenerative or Psychiatric Disorders, 5 years, mance: The Role of Health Care and Social Service resident Regulatory T Cells in MS, 1 year, $125,556 Rachel Perry, Gerald Shulman, Augusta University $958,512 • Akiko Iwasaki, NIH, Innate Antiviral Networks in Reducing Health Care Utilization and Tamas Horvath, Monash University, The Dorso- (Formerly Georgia Regents University) (NIH), Defense Against Vaginal Transmission of ZIKA Costs, 1.5 years, $296,720; AcademyHealth, medial Hypothalamic Leptin Receptor Expressing Developing a Stable Isotope Tracer Method to Virus, 2 years, $460,625 • Daniel Jane-Wit, NIH, Linking Health Care and Social Services for Older Neurons in the Control of Metabolism, Glucose Measure All Key Hepatic Fluxes in Mice, 8 months, Mechanisms of Non-Canonical NF-kB Activation Adults: Which Strategies Reduce Avoidable Tolerance and Cardiovascular Control, 1 year, $75,000 • Rachel Perry, Augusta University (For- in Transplant Arteriosclerosis, 3 years, $731,879 Utilization and Contain Costs?, 1 year, $10,000 $18,833; Biogen MA, Modulation of AB Pathology merly Georgia Regents University), Development Lucia Jilaveanu, NIH, Inherent Tropism and/or Clemente Britto-Leon, American Thoracic by TREM2, 4 months, $77,834 • Janice Hwang, of a Stable Isotope Tracer Method to Measure all Immune Modulation in Melanoma Brain Metas- Society, SPLUNC1: A Sputum Biomarker of Future American Diabetes Association, Investigating Key Hepatic Flux Rates in Mice, 8 months, $75,000 tasis, 5 years, $1,915,780 • Amy Justice, NIH, 21st Exacerbations in Cystic Fibrosis, 1 year, $40,000 Brain Responses to Hyperglycemia, 3 years, Zorana Pringle, Marc Brackett, Fundacion Mar- International Workshop on HIV and Hepatitis Martina Brueckner, Daniella Teape, American $595,317 • Lucia Jilaveanu, American Cancer celino Botin, Creativity, Emotion, and the Arts, Observational Databases (IWHOD), 11 months, Thoracic Society, Novel PCD Genes in Congenital Society, Inherent Tropism and/or Immune Modula- 1 year, $167,799 • Asghar Rastegar, Brigham and $58,000 • Susan Kaech, NIH, Discovery of Heart Disease, 2 years, $80,000 • Martina tion in Melanoma Brain Metastasis, 1 months, Women’s Hospital (DHHS), Resilient and Respon- NR4A1/2 Ligands Controlling Tissue-resident Brueckner, Cincinnati Children’s Hospital (NIH), $14,650 • Ayana Jordan, University of California, sive Health Systems Initiative, 1 year, $330,518 Memory T (Trm) Cells, 2 years, $460,625 • Samuel Administrative Coordinating Center: Cardiovascu- San Francisco (NIH), Mentoring Early-Career Sci- David Reiss, University of Oregon (NIH), The Early Katz, NIH, Multifactor mRNA Mediated T Cell lar Development and Pediatric Cardiac Genomics entists for Drug Abuse Research Careers, Growth and Development Study Pediatric Cohort, Reprogramming for Systemic Lupus Erythema- Consortia. Steering Committee Chair for the PCG, 10 months, $27,000 • Leonard Kaczmarek, Auti- 6 months, $22,681 • David Rimm, AstraZeneca, tosus, 2 years, $460,625 • Kenneth Kidd, DOJ, 1 year, $40,647; Cincinnati Children’s Hospital fony Therapeutic, Development of Kv3 Channel L.P., Standardization of PD-L1 Assays, 4 months, Enhancing and Sustaining the ALFRED-FROG-kb (NIH), Administrative Coordinating Center: Car- Modulators for Treatment of Tinnitus, 1 year, $406,768 • Matthew Rodeheffer, Monash Univer- Forensic Resource, 2 years, $1,062,736 • Alex diovascular Development and Pediatric Cardiac $159,039 • Kristopher Kahle, Hydrocephalus sity, Identification of Novel Human Adipocyte Pro- Kwan, NIH, Frontal Cortical Neural Dynamics Genomics Consortia- CHD Brain and Genes Proto- Association, Innate Immunity and CSF Production genitor Cell Populations, 1 year, $15,941 • Helena and Chronic Social Stress, 4.8 years, $2,093,750 col, 1 year, $96,866 • Joaquin Camara-Quintana, in Post-hemorrhagic Hydrocephalus, 1 year, Rutherford, Bial Foundation, A Psychophysiologi- Francis Lee, NIH, Bone and Breast Cancer Molecu- DePuy Synthes, AOSpine North America: Complex $50,000 • Benjamin Kelmendi, Brain & Behavior cal Perspective of the Transformative Experience lar Interactions, 4 years, $2,153,394; NIH, Mechano- Cervical Spine Surgery and Complication Manage- Research Foundation (formerly NARSAD), The of Pregnancy, 2 years, $45,484 • Nicholas Ryan, biological Mechanism for Inflammatory Bone Loss, ment, 3 months, $1,518 • Lloyd Cantley, University Effects of MDMA on Functional Connectivity in Harvard University, Decreasing Children’s Expo- 1.2 years, $30,118 • Haifan Lin, NIH, Translational of Southern California, (NIH), (Re)Building a Kidney Posttraumatic Stress Disorder, 2 years, $69,089 sure to Indoor Air Pollution through Modern Cook- Regulation of Embryonic Stem Cell Self-Renewal Partnership Project Program, 2 years, $149,999 Richard Kibbey, Monash University, The Role of stoves: A Proposed Evaluation of India’s Landmark by Pumlio Proteins, 4 years, $1,474,000 • Arya Michael Caplan, GlaxoSmithKline, Proof of Princi- PEPCK-M in Hepatic and Extra-hepatic Glucose Gas-stove Subsidy Program, 1.1 years, $59,323 Mani, NIH, The Identification and Characteriza- ple Experiments to Explore the Potential Applica- Production, 1 year, $3,826 • Anthony Koleske, Emmanuelle Schindler, Heffter Research Institute, tion of Genetic Variants Underlying Cardiovas- bility of Compounds Directed Against BRD4 in the Breast Cancer Alliance, Profiling of Circulating Safety and Efficacy of Psilocybin for the Treatment cular Diseases, 6.9 years, $7,035,000 • David Treatment of Autosomal Dominant Polycystic Tumor Cells to Identify Targets for Adjuvant of Cluster Headache, 3 years, $68,200 • Dongju McCormick, NIH, Cortical Dynamics and Neural/ Kidney Disease, 1 year, $138,816; GlaxoSmithKline, Therapy in Metastatic Triple Negative Breast Seo, Brain & Behavior Research Foundation (for- Behavioral Performance, 8 years, $4,055,354; NIH, Proof of Principle Experiments to Explore the Cancer, 1 year, $100,000 • Priti Kumar, American merly NARSAD), Neurobiology of Stress, Depres- Mechanisms of Rapid Modulation of Auditory Potential Applicability of Gene Therapy Animal Foundation for AIDS Research (amfAR), Targeted sion, and Comorbid Alcohol Abuse, 2 years, Responsiveness, 5 years, $1,779,690 • Wang Min, Study for the Treatment of ADPKD (Autosomal Inactivation of Integrated HIV through Host Cell $70,000; Peter F. McManus Charitable Trust, NIH, CCM3-mediated Exocytosis in Pathogenesis Dominant Polycystic Kidney Disease), 1 year, DNA Repair Pathways, 1 year, $200,000 • Gary Neural Circuits for Stress Resilient Coping and of Cerebral Cavernous Malformation, 4 years, $154,139 • Manavi Chatterjee, Brain & Behavior Kupfer, Hyundai Motor America, Yale Phase 1 Clini- Hazardous Drinking, 1 year, $50,000 • Nikhil Singh, $1,934,049; NIH, Stress Signaling Pathways Linking Research Foundation (formerly NARSAD), Inhibi- cal Trial Program, 1 year, $50,000 • Gary Kupfer, Robert Leet and Clara Guthrie Patterson Trust, Endothelial Injury to Graft Arteriosclerosis, tors of STEP in the Treatment of Fragile X Syn- Peter Glazer, Fanconi Anemia Research Fund, Use Cellular and Molecular Characterization of Human 4 years, $1,675,000 • Christopher Pittenger, NIH, drome, 2 years, $70,000 • Sidi Chen, Breast Cancer of Triplex-forming PNAs as a Strategy for Correc- Acute Kidney Injury, 2 years, $90,000 • Megan Histamine Regulation of the Basal Ganglia and Alliance, Discovering Inhibitory Factors of T Cell tion of the FA Phenotype, 1 year, $112,500 • Alex Smith, Ford Foundation, MOMS Evaluation on the Pathophysiology of Tics, 5 years, $2,056,000 Function in Metastatic Breast Cancer Immuno- Kwan, Simons Foundation, Learning-related Activ- Maternal Depression, 1 year, $250,000 • Derek Aleksander Rebane, NIH, Direct Single-molecule therapy, 1 year, $100,000 • Youngsun Cho, Brain & ity in the Autistic Brain, 1 year, $70,000 • Francis Steinbacher, DePuy Synthes, Craniomaxillofacial/ Observation of Regulated Snare Assembly, 2 years, Behavior Research Foundation (formerly Lee, Musculoskeletal Transplant Foundation, Bio- Orthognathic Research Fellowship, 1.5 years, $56,478 • Lynne Regan, NIH, Designed Proteins to NARSAD), Characterizing Shared Mechanisms of logical Modification of Structural Bone Allografts, $70,000 • Michael Strambler, Spencer Founda- Study and Modulate Cellular Processes, 4 years, Cognitive and Motivational Deficits in Schizophre- 6 months, $100,139 • Rafael Lefkowitz, Associa- tion, Partnering to Support Early Childhood Dual $1,198,993 • David Reiss, NIH, IPA: David Reiss, nia, 2 years, $69,006 • Stephen Collins, Louisville tion of Occupational and Environmental Clinics, Language Learners, 3 years, $399,989 • Toral Surti, 9 months, $76,882 • Matthew Rodeheffer, NIH, Institute, Childlessness in the Church: Exploring Development of Flood Health Hazard Educational Brain & Behavior Research Foundation (formerly Cellular and Molecular Mechanisms of White How Clergy Guide and Support Congregants Resources Addressing Needs of Gulf Coast Com- NARSAD), Sleep-Dependent Learning and Sleep Adipose Tissue Regulation in Development and through Infertility, 1.5 years, $16,342 • Zack munity, 9 months, $25,000; Association of Occu- Spindles in Schizophrenia, 2 years, $70,000 Disease, 4 years, $1,790,651 • Yasmmyn Salinas, Cooper, National Institute for Health Care Man- pational and Environmental Clinics, Development Seyedtaghi Takyar, American Thoracic Society, NIH, Identification of Pleiotropic loci for Asthma agement Foundation, Identifying The Scope for of a Continuing Education Module in Environmen- A Cell-specific Endothelial MicroRNA Adenylation and Obesity, 3 years, $100,108 • Maor Sauler, Shopping and the Limits of Price Transparency, tal Medicine on Possible Flood Related Health Pathway Regulates Th2 Inflammation in Asthma, NIH, MIF and DNA Repair in the Emphysematous 1 year, $18,000 • Kumar Dharmarajan, Robert Leet Concerns in the Gulf Coast, 9 months, $25,000 2 years, $80,000 • Mary Tinetti, Institute for Lung, 5 years, $842,400 • Martin Schwartz, NIH, and Clara Guthrie Patterson Trust, Recovery After Judith Lichtman, American Heart Association Healthcare Improvement, Creating Age-Friendly Endothelial-to-Mesenchyma Transition and Ath- Cardiopulmonary Hospitalization: The REACH (Founders Affiliate), Post-Acute Care Services and Health Systems Prototype, 11 months, $45,628 erosclerosis, 4 years, $3,253,161 • Mitchel Stacy, Study, 2 years, $90,000 • Ronald Duman, Allergan Outcomes Among Elderly Stroke Patients, 2 years, Jeffrey Turner, University of Washington, Seattle NIH, Radiotracer-based Imaging for Quantitative (inclusive of Allergan Sales LLC), Contract # RAP- $154,000 • Janghoo Lim, Kennedy’s Disease Asso- (NIH), Biological Determinants of Peritoneal Dialy- Assessment of Angiosome Perfusion Follow- PH-02, 2 years, $82,230; Allergan (inclusive of ciation, The Role of VCP in the Pathogenesis of sis Outcomes, 1.4 years, $8,983 • Michael Van der ing Lower Extremity Revascularization, 5 years, Allergan Sales LLC), Contract # RAP-PH-03, Kennedy’s Disease, 1 year, $50,000 • Yi-Hwa Liu, Linden, University of Hartford, (Michael Van Der

6 www.medicineatyale.org Yale researcher is a new member Linden) CubeSat Project, 7 months, $1,000 • Sten Behavior Research Foundation (formerly Vermund, FHI 360 (NIH), International Research NARSAD), Cognitive Behavior Therapy to Sustain Training on TB and Other Pulmonary Complica- the Antidepressant Effects of Ketamine: A Ran- of National Academy of Medicine tion of HIV, 10 months, $98,101; Harvard School of domized Controlled Trial, 2 years, $69,804; Robert Public Health (NIH), New Methods for the Design Leet and Clara Guthrie Patterson Trust, Examin- and Evaluation of Large HIV Prevention Interven- ing the Efficacy of Cognitive Behavior Therapy to Arnsten is recognized for National Academy tions, 4 months, $13,988 • Noemi Vila, American Sustain the Antidepressant Effects of Intrave- Heart Association, Functional and Physiological nous Ketamine, 2 years, $90,000 • Kuanlin Wu, work including mechanisms of Medicine,” Arn- Role of ANGPTL4 During Atherosclerosis, 3 years, American Heart Association (Founders Affiliate), sten says. “As my $231,000 • Lisa Walke, University of Colorado PDGF Signaling Regulates Integrin Activation of brain vulnerabilities lab does research Denver, Practice Change Leaders for Aging and Through Arg, 2 years, $51,900 • Yang Yang, Col- Health, 1 year, $5,000 • Shiyi Wang, Cary Gross, leen’s Dream Foundation, Dissecting Mitochon- that is quite dif- Patient-Centered Outcomes Research Institute, drial Function in Ovarian Cancer Cells by Super- Amy F.T. Arnsten, Ph.D., professor of ferent from many Comparative Effectiveness Analyses Among Resolution Microscopy, 1 year, $10,000 • Gihyun neuroscience, psychiatry, and psychol- neuroscientists, it is Conservative Treatment Strategies For Ductal Yoon, Brain & Behavior Research Foundation (for- Carcinoma In Situ, 2.1 years, $438,751 • Stephen merly NARSAD), Intranasal Insulin for Treating ogy, and at the Yale Child Study Cen- particularly moving Waxman, European Commission, Pain-NET, PTSD: A Double-blind, Placebo-controlled Cross- ter, has been elected to the National Amy Arnsten to be recognized by 4 years, $279,705 • Samuel Wilkinson, Brain & over fMRI Study, 2 years, $60,000 Academy of Medicine (NAM), which one’s peers.” recognizes individuals who have dem- Arnsten received her Ph.D. in // Benefactor (page 1) them with the onstrated outstanding professional neuroscience from the University of resources and intellectual freedom to achievements and commitment to California, San Diego, in 1981. She pursue innovative research.” service. NAM membership is widely did postdoctoral research with Susan Wallace understood the financial considered one of the highest honors D. Iversen, Ph.D., at Cambridge Uni- challenges that research entails and the in the fields of health and medicine. versity in the UK, and at Yale with need for philanthropic support to fuel Arnsten’s lab discovered molecu- the late Patricia Goldman-Rakic, scientific discovery. “To have medical lar mechanisms that govern activity Ph.D., Eugene Higgins Professor of progress, you have to feed it money. It’s in the brain’s highest-order circuits Neuroscience. She joined the School the nature of the beast. Running labs, and helped explain why neurons of Medicine faculty in 1986. doing surveys, it’s all expensive,” Wal- (Left to right): Yale benefactors David Wallace are vulnerable to disorders such The National Academy of and Jean McLean Wallace, who endowed six lace said in 2006. “But I think we’re at a School of Medicine professorships, are shown as schizophrenia and Alzheimer’s Medicine, established in 1970 as point in medicine where we’re making with Dean Robert J. Alpern, who says innovative disease. Her research has led to the Institute of Medicine, is an in- leaps and bounds.” research has sprung from their generosity. two treatments now in widespread dependent organization of eminent For Hugh S. Taylor, M.D., chair of clinical use: guanfacine (Intuniv®) professionals from diverse fields the Department of Obstetrics, Gyne- from Yale’s School of Engineering in for treating childhood cognitive including health and medicine; cology & Reproductive Sciences, this 1948, but quickly decided he was more disorders such as attention deficit the natural, social, and behav- includes developing a new test and suited to the law, graduating from hyperactivity disorder (ADHD) ioral sciences; and beyond. It serves therapies for endometriosis, discover- Harvard Law School in 1951. and autism, and prazosin for the alongside the National Academy ing environmental agents that can Reflecting back on a career that treatment of post-traumatic stress of Sciences and the National affect fetal development, understand- included stints at Allegheny Corpora- disorder (PTSD). Academy of Engineering as an ing the effects of cross-gender hor- tion, United Brands (now Chiquita “It is a great honor and a per- adviser to the nation and the inter- mone therapy, and demonstrating the Banana), Piper Aircraft, Bangor-Punta, sonal pleasure to be elected to the national community. benefits of transdermal estrogens on and Todd Shipyards, Wallace put his sexual function in menopausal women. time at Yale above them all, calling it Taylor, who holds the Anita O’Keeffe his greatest achievement. Just prior to Young Professorship, established in his 50th year reunion, Wallace and his honor of a friend of the Wallaces to wife donated $9 million to renovate Yale Cancer Center director led promote women’s health, says, “The Branford College, whose Gothic-style Wallaces’ support enabled me to devote York Street wing is now called Wallace trials for FDA-approved drug time to all aspects of women’s health, Hall. In 2004, he was awarded a Yale not only delivering care to patients but Medal, the highest award presented by The first immunotherapy PD-L1-positive pa- also being an advocate and doing novel the Association of Yale Alumni. “David treatment approved to treat tients had achieved research that I wouldn’t have been able loved Yale from the moment he arrived at least a partial to do otherwise, bringing new under- as an undergraduate,” says Jean Wal- advanced stomach cancer response to the standing of women’s health diseases.” lace. “It was his pleasure and honor to treatment, includ- Lucian V. Del Priore, M.D., Ph.D., be able to support both the university A drug whose clinical testing was led ing several patients chair of the Department of Ophthal- at large and the School of Medicine.” by Charles S. Fuchs, M.D., M.P.H., whose tumors com- mology & Visual Science, who joined Richard Sackler and Jonathan Sack- pletely disappeared. Yale in 2016, says that the Robert R. professorships endowed ler Professor of Medicine (Medi- Charles Fuchs Some of those Young Professorship endowed by by the wallace family cal Oncology) and director of Yale responses lasted for the Wallaces was instrumental in his Jean and David W. Wallace Cancer Center, has become the first what were considered long periods of recruitment, allowing for protected Professor of Comparative Medicine approved immunotherapy treatment time, ranging from several months to research time, as well as time to mentor Tamas L. Horvath, D.V.M., Ph.D., for advanced stomach cancer. more than a year. medical students who are interested in chair, Department of Comparative The drug, pembrolizumab (Key- “The responses really are quite Medicine; professor of neuroscience ophthalmology. “We need a genera- and of obstetrics, gynecology & repro- truda®), was approved by the U.S. robust and far longer than you would tion of physicians who can push the ductive sciences Food and Drug Administration (FDA) see with any cytotoxic chemotherapy envelope,” he says, noting that the vast for adult patients diagnosed with agent,” says Fuchs. David W. Wallace Professorship majority of his patients benefit from Now vacant. Most recently held, until advanced stomach cancer or gastro- Prior to pembrolizumab, the only advances that have been developed 2016, by Ruslan M. Medzhitov, Ph.D., esophageal junction cancer showing FDA-approved drug for non-responsive during the course of his career. “We Sterling Professor of Immunobiology PD-L1 positive tumors, in cases where stomach cancer was ramucirumab have to train people who can think out- Fergus F. Wallace Professor the cancer has progressed despite two (Cyramza®), a monoclonal antibody side the box and approach problems in of Genetics or more prior lines of treatment with whose benefits to patients have been a new way.” Medical students under his Antonio J. Giraldez, Ph.D., chair, standard therapies. Pembrolizumab classified as “modest” by the National guidance have conducted research on Department of Genetics works by increasing the ability of the Cancer Institute. the thinning of the retina and the gen- Jean McLean Wallace Professor body’s immune system to help detect Fuchs says progress against ad- eration of stem cells from skin biopsies of Pediatrics and fight tumor cells. vanced stomach cancer has been less in patients with macular degeneration, George Lister, M.D., professor of The FDA made its approval on an robust than he would like because and the use of medical marijuana in pa- cellular and molecular physiology accelerated basis, deciding to forego very few drugs have been developed to tients with poorly controlled glaucoma. Robert R. Young Professor of Phase III clinical trials after a Fuchs-led address the particular biology of the Wallace’s ties with Yale date back Ophthalmology and Visual Science Phase II trial of pembrolizumab had cancer. “Most commonly,” he explains, to his undergraduate days, when Lucian V. Del Priore, M.D., Ph.D., chair, demonstrated the value of the drug for “we use anticancer drugs that are Department of Ophthalmology & he resided at Branford College. His Visual Science patients with the PD-L1 mutation. used to treat other cancers and apply studies were interrupted by World Persuasive data from the trial, them to patients with stomach cancer War II, during which he served as Anita O’Keeffe Young Professor called KEYNOTE-059, were present- because we just don’t have dedicated of Women’s Health an officer in the 1st Infantry Division Hugh S. Taylor, M.D., chair, Depart- ed last September at the European So- efforts to develop drugs specific for and was awarded the Purple Heart. ment of Obstetrics, Gynecology & ciety for Medical Oncology (ESMO) stomach cancer.” That is a deficit he He received his bachelor’s degree Reproductive Sciences annual meeting. Sixteen percent of hopes to continue to rectify.

Medicine@Yale February/March 2018 7 Chair named for Radiology & Biomedical Imaging Awards & Honors

Extensive experience in the tracers, and 3D critical test result reporting system, and US and UK shapes plans image manipula- identified mechanisms to improve the tion. By including radiology peer review process. Build- for research and clinical care industry partners, ing upon his experience implementing he is eager to a Picture Archive and Communication Rob Goodman, MB BChir, M.B.A., expand the depart- System (PACS) in the UK, he now will has been appointed chair of the De- ment’s translational be involved in the implementation of a Hilary P. Blumberg, M.D., John and partment of Radiology & Biomedical research program to new enterprise PACS across Yale New Hope Furth Professor of Psychiatric Imaging and chief of Radiology and Rob Goodman help convert basic Haven Health. As well as improving Neuroscience and professor of psy- Biomedical Imaging at Yale New science discoveries clinical efficiency, this cutting-edge chiatry, in the Child Study Center, and of radiology and biomedical imaging, Haven Hospital. Goodman, professor into clinical applications that improve tool will have the potential to augment has been awarded the Colvin Prize for and section chief of pediatric radiol- patient care. departmental machine learning/artifi- Outstanding Achievement in Mood ogy served for six years as vice chair Goodman joined Yale in 2004 from cial intelligence research. Disorders Research, by the Brain & for clinical affairs for the department the John Radcliffe Hospital in Oxford, “What I find inspiring about radi- Behavior Research Foundation. and recently completed two years as UK, where he was lead clinician for its ology is that we touch every medical its executive vice chair. Before his ap- radiology department. When he came and surgical specialty,” says Goodman. pointment took effect on Jan. 1, he had to the United States, he was struck by “Any improvements we make have a served as interim chair. the marked differences in radiation trickle-down effect throughout the “As chair, Rob will build upon awareness between the two countries, entire medical enterprise.” his many experiences in radiology which is especially relevant in pediatric Goodman obtained his medical to enhance and integrate the depart- radiology due to children’s susceptibil- degree from Cambridge University in Hal Blumenfeld, M.D., Ph.D., the Mark ment’s world-class research and clinical ity to the effects of radiation. He has 1988 and an M.B.A. in health care from Loughridge and Michele Williams strengths,” says Robert J. Alpern since played a major role in the move- Yale in 2017. Upon completing his resi- Professor of Neurology and professor of M.D., dean and Ensign Professor of ment to reduce radiation exposure from dency at the Central Oxford Hospitals neuroscience and of neurosurgery, has Medicine. “I’m delighted that he will CT scans in children, as well as adults. in the UK, he did a fellowship in pedi- received a Jacob Javits Neuroscience Investigator Award from the National lead the department and look forward During his tenure at Yale, Good- atric radiology at the Hospital for Sick Institute of Neurological Disorders and to working with him.” man has overseen the expansion of pe- Children in Toronto. He is the Pediatric Stroke, recognizing him as a scientist Research areas on which Goodman diatric radiology services, spearheaded Community of Practice President for with “superior competence and out- plans to focus include such areas as the installation of a dedicated pediatric the American Institute for Ultrasound standing productivity.” Blumenfeld also novel MR pulse sequences, functional MRI scanner at Yale New Haven in Medicine, which recently elected has received the American Epilepsy So- ciety’s 2017 Clinical Scientist Research MRI, MR spectroscopy, novel PET Children’s Hospital, implemented a him to its Board of Governors. Recognition Award.

New program makes the addiction crisis a priority A collaboration to treat patients, train practitioners, Sonia Caprio, M.D., professor of pe- diatrics (endocrinology) has received and investigate addiction the Samuel J. Fomon Nutrition award from the American Academy of Pedi- The School of Medicine’s Section of atrics, for outstanding achievement in research relating to the nutrition of General Internal Medicine has estab- infants and children. lished the Yale Program in Addiction Medicine, a multidisciplinary clinical, educational, and research program. The program is intended to enhance Yale’s portfolio of state-of-the-art ad- diction research and patient care, while increasing the pipeline of physicians trained in evidence-based strategies Lieping Chen, M.D., Ph.D., United to tackle the opioid crisis and other Technologies Corporation Professor in Cancer Research and professor addiction-related health issues. of immunobiology, of dermatology, The program will emphasize re- and of medicine (medical oncology), search on topics that include improv- has received the Warren Alpert ing the recognition of, and access to Foundation Prize for transform- treatment for, substance use disorders ative discoveries of anti-PD-1/ PD-L1 cancer immunotherapy. in primary care, emergency depart- robert a. lisak ments, and hospitals; addressing the The establishment of the pro- David Fiellin has been put in charge of the multi- disciplinary Yale Program in Addiction Medicine, quality of addiction treatment; and gram comes at a time when addiction established to serve clinical, educational, and re- technology-based prevention in youth. to opioids and other substances is search needs as the United States faces rising levels The Yale Program in Addiction widely seen as a crisis. Drug over- of substance abuse and addiction. Medicine includes collaborations with dose deaths nearly tripled during and Gail D’Onofrio, M.D., chair and Yale School of Public Health and the 1999–2014, according to the Centers professor of emergency medicine, led Departments of Emergency Medicine for Disease Control and Prevention. the effort to make addiction medicine Roberta L. Hines, M.D., chair and Nicho- and Psychiatry. Its director is David From 2014 to 2015, the death rate an official medical subspecialty in 2016. las M. Greene Professor of Anesthe- A. Fiellin, M.D., professor of medicine from synthetic opioids increased by This landmark change will increase siology, has received the SEA/Duke Award for Excellence and Innovation in (general medicine), of emergency 72.2 percent, and heroin death rates the number of physicians in a variety of Anesthesia Education, from the Society medicine, and of public health. increased by 20.6 percent. Death rates primary care and other medical special- for Education in Anesthesia. “Since the use of opioid, tobacco, rose across all demographic groups ties, including psychiatry, to be trained alcohol, marijuana, and other sub- and regions, and in many states. and certified as specialists in addiction stances is common in general medical Yale School of Medicine was one of prevention and treatment. settings, and often goes undetected the first medical institutions to estab- “The current opioid epidemic, along and untreated, we need a medical lish an accredited fellowship program with the high prevalence of a variety system that does a better job of making in addiction medicine. It began accept- of substance use disorders, demands sure that all health care professionals ing trainees in 2015. innovative and creative approaches in implement effective prevention, screen- In addition, Patrick G. O’Connor, prevention, treatment, and medical Kevin N. Sheth, M.D., associate profes- sor of neurology and of neurosurgery, ing, treatment, or referral practices, and M.D., the Dan Adams and Amanda education,” says O’Connor. “Yale is has received the Derek Denny-Brown treat addiction as they do other medical Adams Professor of General Medicine uniquely positioned to provide national Young Neurological Scholar Award from conditions,” Fiellin says. and chief of general internal medicine, leadership in this critical area.” the American Neurological Association.

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