January/February 2017 volume 13, issue 1 Advancing Biomedical Science, Education, and Health Care
New year brings a new Yale Cancer Center director Incoming leader plans to treatment of gastrointestinal cancers, after diagnosis, uncovered energy He completed his Fuchs has spearheaded clinical trials balance pathways that contribute to medical residency at direct advances in research that have resulted in FDA approval of the development and progression of Brigham and Wom- as well as clinical practice new drugs for patients. He estab- cancer, and identified new potential en’s Hospital, where lished one of the first large-scale targets for cancer therapy. he also served as Charles S. Fuchs, M.D., M.P.H., an molecular epidemiology laboratories, “Charlie’s scientific renown and chief medical resi- internationally renowned expert in characterizing an array of molecular contributions, which include dis- dent, and completed gastrointestinal cancers and cancer events in thousands of tumors. This coveries about the underpinnings of his medical oncol- epidemiology, has been named direc- ongoing project, which has yielded cancer, insights into prevention, and Charles Fuchs ogy fellowship at tor of Yale Cancer Center (YCC), one valuable information about patients developing new therapies, speak for Dana-Farber Cancer of just 47 National Cancer Institute- both before and after cancer diag- themselves,” says Robert J. Alpern, Institute. In 1994, he received his designated comprehensive cancer nosis, led to the finding that healthy M.D., dean and Ensign Professor of M.P.H. from Harvard School of Public centers in the nation and the only one individuals who took aspirin had a Medicine. “His considerable experi- Health. He has been professor of in Connecticut, and physician-in- significantly lower risk of developing ence will be an asset to the cancer medicine at Harvard Medical School chief of Smilow Cancer Hospital at colorectal cancer. It also led to the center as we build upon the solid and chief of the gastrointestinal oncol- Yale New Haven. identification of a molecular tumor foundation that already is in place.” ogy division and the Robert T. and Known for his research that profile that is connected to better Fuchs received his medical degree Judith B. Hale Chair in Pancreatic spans the prevention, biology, and patient outcomes with aspirin use from Harvard Medical School in 1986. Cancer at // Cancer Center (page 5) In memoriam: Carolyn Walch Slayman, Ph.D. School of Public Health welcomes Renowned geneticist and a new dean administrator was a pioneer Sten H. Vermund, among women in science M.D., Ph.D., an expert on HIV/HPV Carolyn Walch Slayman, ph.d., science and cervical deputy dean for academic and scien- cancer prevention, tific affairs at the School of Medicine, has been named Sterling Professor of Genetics, and dean of the School professor of cellular and molecular of Public Health. physiology, died on December 27 at Sten Vermund Vermund comes to Yale New Haven Hospital. She was Yale in February 79, and had been undergoing treat- after serving since 2005 on the fac- ment for recurrent breast cancer. ulty of Vanderbilt University School Slayman was a faculty member of Medicine, where he was professor and leader at the medical school for of pediatrics, medicine, health policy, almost 50 years. While she was stead- and obstetrics and gynecology;
fastly humble about her accomplish- TERRY DAGRADI the Amos Christie Chair in Global ments, her career was characterized who have passed through our doors,” Carolyn W. Slayman, a member of the Yale School Health; director of the university- of Medicine faculty for nearly 50 years, is warmly re- by a series of firsts. She was the first says Robert J. Alpern, M.D., dean and membered as a pioneering woman of science, skilled wide Vanderbilt Institute for Global woman to head a department at Yale Ensign Professor of Medicine. “We de- administrator, and mentor to young scientists. Health; and vice president for global School of Medicine when she was pended on her judgment and wisdom health of the Vanderbilt University named chair of the Department of to help guide every major decision.” did postdoctoral work in membrane Medical Center. Human Genetics (now Genetics) in After graduating from Swarthmore biochemistry at Cambridge University. “In the mid-1980s, Dr. Vermund 1984. In 1995, she became the school’s College in 1958 with highest honors in Following a brief stint as assistant helped establish an adolescent health first deputy dean for academic and biology and chemistry, Slayman earned professor of biology at Western Reserve clinic that provided some of the earli- scientific affairs, and the first woman a ph.d. in biochemical genetics under University (now Case Western est care to HIV-infected youth in New to hold a deputy deanship. Nobel Laureate E.L. Tatum at Rock- Reserve), she joined Yale as assistant York City,” noted Yale President Peter “It is difficult to overstate Caro- efeller University, where she was the professor in the departments of Salovey, Ph.D. ’86, and Dean and En- lyn’s influence on the School of only woman in her class. As a National microbiology and physiology in 1967. sign Professor of Medicine Robert J. Medicine and the many individuals Science Foundation Fellow, Slayman She helped to // Slayman (page 7) Alpern, M.D., // Public Health (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 William C. Sessa demonstrates that the New Haven, CT veins and arteries of the cardiovascular Permit No. 526 system are far more than passive plumbing. 3 Cancer as a complex system A multidisciplinary team at West Campus has begun intensive study of the biological systems that govern the spread of cancers. 5 An alumnus shows his gratitude Michael Singer, m.d. ’02, ph.d. ’00, says Yale was the catalyst for much success. His gift honors a mentor and a classmate. FOLLOW & SHARE twitter.com/YaleMed facebook.com/YaleMed instagram.com/YaleMed lifelines Appointments to ongoing endowed professorships
William C. Sessa has been Gary V. Desir, a leading figure in the transformation of vascu- M.D., becomes lar biology from a near- Paul B. Beeson afterthought to an essential aspect of biomedical re- Professor of In- search. Sessa’s discoveries ternal Medicine. have added to the under- standing of the role of veins He also is pro- and arteries in numerous fessor and chair biological functions, espe- cially their contribution of medicine, and to this country’s leading Gary Desir holds a second- cause of death, cardio- vascular disease. ary appointment at Yale School of Forestry & Environmental Studies. Joann B. Sweasy, Ph.D., William Sessa becomes Ensign harold shapiro Joann Sweasy Professor of Therapeutic Radiology. She Revealing the vascular system also is professor of genetics; vice chair of basic Investigator demonstrates “Vascular biology in the present More recently, based on his initial curi- research, thera- that veins and arteries are far world is really how blood vessels control osity provoked by the Palade article, peutic radiology; different aspects of organs—particu- he has worked to identify undiscov- and associate larly the brain, heart, and kidney,” says ered pathways through which ldl can more than passive plumbing Susan Kaech director, basic Sessa, director of the Vascular Biology damage blood vessels beyond those science, Yale In the late 1980s, William C. Sessa, ph.d., and Therapeutics Program since 2007. on which statins act. In June, Sessa Cancer Center. then a doctoral candidate in pharmacol- The control, he explains, starts with received a $1 million Merit Award from ogy, read an editorial by Nobel Laure- biochemical changes within endothelial the American Heart Association that Susan M. ate George E. Palade, m.d., professor, cells that protect blood vessels against will help him pursue that line of inquiry. Kaech, Ph.D., chair, and founder of Yale’s then-named potential antagonists, especially lipids. On Nov. 21, Nature Communications has been named section of cell biology. Palade argued While completing his doctorate in published his first report of progress, in Waldemar Von that long-held assumptions about the pharmacology at New York Medical which he described the protein alk1 as Zedtwitz Profes- biology of the endothelium, or inner College, Sessa crossed paths with Sir a promising target for reducing athero- sor of Immuno- lining, of blood vessels, had become John R. Vane, d.phil., who had won sclerosis, which remains this country’s Lucian Del Priore biology. Kaech questionable, and he urged investiga- the 1982 Nobel Prize in physiology or leading cause of death. joined the School tors to probe more deeply into the medicine for discovering how aspirin Sessa also took a recent sabbati- of Medicine faculty in 2004 as an unknowns of the vascular system. works. “I wrote to him and said I would cal, the first in his more than 20 years assistant professor of immunobi- Sessa, now Alfred Gilman Profes- love to do a postdoc in your lab,” Sessa at Yale. In the fall of 2015, he went to ology, and became a professor of sor of Pharmacology and professor of recalls. Soon the New Jersey native was Cambridge, Mass., where Pfizer made medicine, took Palade’s words to heart. working under Vane in London, studying him interim director of its global car- immunobiology in 2015. He wanted to know how particles of ldl the enzymatic pathway through which diovascular and metabolism unit. The Lucian V. Del Priore, M.D., (low-density lipoprotein) cholesterol endothelial cells produce nitric oxide, role forced Sessa to think in a new way has been named Robert R. Young morphed from floating hitchhikers in which relaxes blood vessel walls. about pharmaceutical development, Professor of Ophthalmology and the bloodstream to permanent lodgers “All endothelial cells make nitric oxide, involving him in decisions to initiate, Visual Science, in addition to his in artery walls, where their effect on and we know that with almost every car- augment, or terminate research proj- appointment as chair of oph- health can be profound. diovascular disease, they stop making it ects. “It is more complex than you think thalmology and visual science. Blood vessels had first caught to some degree,” Sessa says. During his it is,” Sessa says. “There are so many Del Priore arrived at the medical Sessa’s attention when he was an second postdoctoral fellowship, at the moving parts and very tight timelines in school in July from the Storm Eye undergraduate at Philadelphia College University of Virginia, Sessa cloned the drug development.” Institute at the Medical University of Pharmacy and Sciences. As part of gene for the enzyme that makes nitric He will apply lessons he took of South Carolina. a research lab course, Sessa measured oxide. “It was very competitive,” he says. from industry to CavtheRx, a biotech how the brain controls blood pressure, “Within three months, three papers came company he founded in 2014 to develop and he came away full of curiosity. out from major institutions and I was the a drug for the orphan disease uveitis, During that era, he says, science lone postdoc working on it.” inflammation of the eye wall. “I’ve sharp- characterized the body’s vasculature as When he started his lab at Yale in ened what we need to do to be success- Managing Editor Robert Forman a network of passive garden hoses that 1993, Sessa wanted to learn which mol- ful therapeutically,” he says. He also says Contributors Jeanna Canapari, Sonya Collins, Bill merely shuttled blood and nutrients ecule regulates the gene and enzyme he has renewed appreciation for the Hathaway, Ziba Kashef, Jill Max, Kathleen Raven, throughout the body. Three decades of responsible for generating nitric oxide freedom of inquiry he enjoys at his true Ashley Taylor, Jim Shelton, and Sarah C.P. Williams. Design Jennifer Stockwell inquiry have broadened that view. via the endothelial lining of vessels. professional home—his lab at Yale. Medicine@Yale is published four times each year by: Yale School of Medicine, Office of Communications 1 Church Street, Suite 300, New Haven, CT 06510-3330 Telephone: (203) 785-5824 Fax: (203) 785-4327 A new executive chair for Yale institutional review boards is chosen Email [email protected] Website medicineatyale.org John D. Roberts, M.D., professor of Roberts assumes the executive for increased ef- Copyright ©2017 by Yale University. All rights reserved. If you have a change of address or do not wish to receive medicine and medical director of the chair position as changes in IRB ficiency for sponsors future issues of Medicine@Yale, please write to us at the Yale New Haven Hospital Adult Sickle procedures are occurring nationwide. and researchers, and above address or via email at [email protected]. Postal permit held by Yale University, Cell Program, has been selected as “Clinical research has moved from creates challenges in 155 Whitney Avenue, New Haven, CT 06520 executive chair of Yale University’s predominantly single center studies, terms of maintain- Institutional Review Boards (IRBs), with oversight from a local IRB, to ing awareness of lo- the committees that work to ensure multicenter studies, often involving cal context research Robert J. Alpern, m.d. that all Yale human subjects research scores of institutions,” he says. Many oversight,” he says. Dean and Ensign Professor of Medicine is conducted ethically and accord- organizations involved in human sub- John Roberts “I look forward Charles Turner Associate Vice President for Development and ing to governmental and university jects research, including the National to working with all Director of Medical Development (203) 436-8560 requirements. His new role begins as Institutes of Health and industry of the IRB chairs and with Linda M. Mary Hu of the new year, with the retirement sponsors, are advocating use of central Coleman, J.D., the recently arrived direc- Associate Dean for Communications and Chief Communications Officer of his predecessor Maurice Jeremiah IRBs, which can oversee research at tor of the Yale Human Research Protec- Mahoney, M.D., J.D. many sites. “This offers opportunities tion Program, as Yale // IRBs (page 7) Printed on recycled paper ♻
2 www.medicineatyale.org advances Major grant accelerates cancer research Health & Science News Infections’ varying West Campus becomes a multidisciplinary invaluable. “Mathematical models can combine real terms reactions to foods and real quantities with unknown variables, giving us a center to explore how biological systems can model that has flexibility and outcomes that are both predict- aid—or block—aggressive cancer spread able and testable.” Says Rinehart of CaSB@Yale colleagues who have expertise beyond the biological sciences, “I really A $9.5 million, five-year grant from the National Cancer want to learn from them.” Institute (NCI) will fund an intensive multidisciplinary research Gunter P. Wagner, Ph.D., Alison Richard Professor of effort that seeks to better understand how cancer cells reach an Ecology and Evolutionary Biology, is looking for ways to aggressive state and begin to damage surrounding tissue. The use the knowledge of normal physiological aggressive cell initiative, called Cancer Systems Biology at Yale (CaSB@Yale), growth to understand and thwart the often-fatal metasta- is one of four new research centers in NCI’s Cancer Systems Bi- sis of cancers in humans. He hopes to find clues in certain ology Consortium, and is directed by Andre Levchenko, Ph.D., mammals for which the skin cancer melanoma has become the John C. Malone Professor of Biomedical Engineering and a chronic, non-malignant condition. “Given all the molec- director of the Yale Systems Biology Institute. ular biology tools we have at our disposal it would not be
istockphoto.com CaSB@Yale is based at the university’s West Campus and surprising if we could find the gene regulatory differences Many organisms experience a lack brings together investigators with varying research back- of appetite or avoid certain foods grounds from three schools and seven departments at the when they catch a virus or acquire university, and a variety of other institutes and programs. In harmful bacteria. A study led by particular, at the core of CaSB@Yale, the Yale Systems Biology Ruslan Medzhitov, ph.d., the David W. Institute on West Campus will join forces with the Yale Cancer Wallace Professor of Immunobiology, Biology Institute, the Raymond and Beverley Sackler Institute published Sept. 8 in Cell, suggests for Biological, Physical and Engineering that nutrition has different effects on viral versus bacterial infections. Sciences, the Yale Cancer Center, and Emory “When animals are infected, they University to address fundamental ques- stop eating and switch to a fasting tions at the core of cancer biology. Four of metabolic mode,” Medzhitov says. “The the 12 principal and primary investigators are question was whether fasting metabo- members of the School of Medicine faculty. lism is protective or detrimental.” The program will address the specific Fasting proved helpful for recovery problem of phenotypic plasticity of invasive stengelmelanie from fevers brought on by, for example, cancers. Cancer cells with the same Jesse Rinehart Andre Levchenko (left), director of Cancer Systems Biology at Yale, and Mark bacterial sepsis. However, eating food, genomic makeup can adopt different A. Lemmon say a large National Cancer Institute grant will spur far-reaching which provides glucose, aided the multidisciplinary research on the role of biological systems in the spread, or phenotypes, or characteristics, switching potential containment, of malignant cells. Yale is one of four institutions in the mice’s ability to recuperate from a viral from rapid division and growth to invasive country where major research centers have been established. infection. The findings suggest that various diet preferences may correlate migration and metastatic spread through that make the difference between cows and pigs on the one with different types of infections. Still, unknown mechanisms. Furthermore, hand, and humans,” Wagner says. the authors note, the old adage, “Starve different phenotypes may co-exist in the Wagner will draw from Levchenko’s expertise in examin- a fever, feed a cold,” might not apply same tumor, with cells exchanging signals ing aggressive cancers in the context of surrounding biological because the effect likely depends on among themselves and with surrounding matrix and normal stromal (connective tissue) cells. Levchenko specific infections. normal tissues. CaSB@Yale will explore Gunter Wagner views metastatic disease in military terms. “If you think about The findings of this study may in- this complexity of invasive cancer through a an invading army, it can be welcomed by the population or form clinicians’ decisions on nutrition range of novel techniques and approaches. resisted. A lot depends on the country that is being invaded and for intensive care patients who suffer CaSB@Yale will also be devoted to un- the population that lives there. Very similarly in cancer you can from acute infections. derstanding and manipulating the complex think about what happens with the cells that are normal and molecular networks governing complex experience the invasion of cancer cells. Are they going to resist? New type 2 diabetes cell behaviors. A key focus of the research Or are they going to promote the invasive spread?” protein target named will be on translational applications aimed Sidi Chen, Ph.D., assistant professor of genetics and systems at identifying new targets for therapeutic biology, will use his lab’s expertise in designing experimental Insulin resistance in type 2 diabetes is intervention and the development of new Sidi Chen models to benefit CaSB and the field. “My role in this grant is to linked to defects in the insulin recep- drugs targeting invading cells. build a platform to study cancer in animal models,” says Chen. tor in numerous organs, including the Says Levchenko, “Our approach will vary from the use “We have previously developed the CRISPR/Cas gene editing liver. The search for better drug tar- of synthetic biology to evolutionary approaches, and will rely technology in vivo in Cas9 transgenic mice. We want to utilize gets is an ongoing effort. Narendra heavily on advances in engineering, mathematics, and physics, this platform to build new mouse models to better study cancer.” Wajapeyee, ph.d., associate professor in addition to breaking new ground in biology and chemistry.” A hallmark of CaSB@Yale will be the opportunity for of pathology, and Gerald I. Shulman, m.d., ph.d., the George R. Cowgill Pro- “The next important goal in cancer therapeutics will be speed, efficiency, and new ways of attacking problems that fessor of Medicine (Endocrinology) to control or correct signaling networks rather than target- collaboration brings. The moment any lab makes tangible and professor of cellular and molecu- ing individual molecules, and CaSB@Yale brings unique sets progress, other investigators will know it. “We typically get to lar physiology, have led a study that of expertise and perspective together to do this,” says Mark interact with ideas and progress from other labs after it’s been identifies a promising protein target. A. Lemmon, Ph.D., co-director of the Yale Cancer Biology published,” says Rinehart. “Even when it’s a breakthrough, After a large-scale rna interfer- Institute and the David A. Sackler Professor of Pharmacology it’s something that the lab was working on in the past. Some- ence screen of more than 600 proteins at the medical school. times that may be five years ago. You really need to know that interact with E3 ubiquitin ligase, Other School of Medicine investigators who plan to take what they are doing now, and that’s exactly what we have.” another protein that is involved in full advantage of CaSB@Yale’s advanced resources and col- Levchenko compares this approach to a famous precedent— many cellular processes, the team laborative approach include Jesse Rinehart, Ph.D., associate the Manhattan Project—which brought together scientists from found march1 to be a highly influential professor of cellular and molecular physiology. Rinehart says many disciplines with the urgent goal of developing an atomic protein that degrades the surface of the insulin receptor—thus thwarting a portion of the grant will support a project that he and Farren bomb that could win World War II. “I don’t think a lot of the normal function of insulin, which J. Isaacs, Ph.D., an assistant professor of molecular, cellular, people thought it was possible to do what is already happening is to keep glucose levels from rising in and developmental biology in the Yale Combined Program in here, including identification of new lead compounds that have the bloodstream. To the researchers’ the Biological and Biomedical Sciences, have developed. the potential to become anti-cancer drugs, in just a few years of surprise, they found that obese people “We’ve combined our expertise in an area called synthetic our active work. We are dealing with one of the most difficult had noticeably higher levels of march1 biology and molecular biology, to build very, very unique bac- problems in medicine and the hope was that with harness- expression than non-obese people. terial cells,” says Rinehart. “They’re unique because they al- ing all the interdisciplinary approaches, this problem can be Their study was published Aug. 31 in low us to encode human genes and then endow those human solved—and the progress has been very impressive.” Nature Communications. genes with the same physiological function that you might Lemmon believes the benefits of collaboration, with an According to Wajapeyee, patients find in human cells. We recently demonstrated that we could emphasis on systems biology over studying components of need more treatment options because bring in genes that are responsible for small protein networks cancer in isolation, may bring progress that is “beyond expo- they face a catch-22. “Type 2 diabetes cannot initially be treated with insulin or genetic networks in cancer, and that we could accurately nential.” Argues Lemmon, “The emergent properties won’t because the glucose signaling is dis- model their properties in these bacterial cells.” emerge—you’ll never know what they are—unless you take a rupted,” he says. The team now will Rinehart, whose primary expertise is in signaling systems approach. So, if you’re actually trying to understand work to find a small molecule drug to networks, says that as the work proceeds, the presence of the properties of the system, you will never understand it by target march1. additional disciplines such as mathematical modeling will be looking at the parts.”
Medicine@Yale January/February 2017 3 out & about
1 June 8 The Precision Paradigm, held in New York City’s Hearst Tower, recognized how genomics research at Yale School of Medicine is helping to unravel the myster- ies of perinatal loss, birth defects, and cancer. 1. Mary Lake Polan, m.d. ’75, ph.d. ’70, m.p.h., clinical professor in obstetrics, gynecology, and reproductive sciences, and her
2 husband, Frank A. Bennack Jr., executive vice chair and former ceo of the Hearst
Corporation, hosted the event. 2. Susan terry dagradi Barber (left), a 1963 graduate of Yale August 11 At the Class of 2020 White School of Drama, talks with Cathy Sokil Coat Ceremony, Lillian Oshva, m.d. ’96, Milnikiewicz, a 1979 graduate of Yale the newly appointed chair of the Yale College, and Alessandro D. Santin, m.d., School of Medicine Alumni Fund, gave professor of obstetrics, gynecology, and personal stethoscopes to all first-year reproductive sciences and co-chief of students, including Maryam Ige (fore-
robert lisak (2) the section of gynecologic oncology. ground) and Daniel Jacobs.
September 12 Leader- 1 2 ship and staff gathered for the Long Ridge Medical Center’s Cen- ter for Musculoskeletal Care Grand Opening in
Stamford. From left to sembos jensen kelly right, Heather Eastman, interim facilities director of Greenwich Hospital; Sue
Brown, r.n., m.s.n., chief nursing officer and executive vice president of Green- julie brown harwood (2) wich Hospital’s operations and patient care services; Margie Guglin, vice October 10 To celebrate the John and Hope Furth Professorship in Psychiatric Neurosci- president of clinical project management at Yale New Haven Health System ence, a dinner was held at the Yale Club in New York City. 1. On the far left, Dean Robert (ynhhs); Marc Kosak, Greenwich Hospital’s senior vice president of adminis- J. Alpern, m.d., joins the Furths, along with (second from right) Hilary Blumberg, m.d., recipi- tration; Marna Borgstrom, ynhhs ceo and president; Norman Roth, Green- ent of the Furth professorship and professor of psychiatry, and (far right) John Krystal, m.d., wich Hospital president; Paul Taheri, m.d., m.b.a., Yale Medicine ceo; Mary Robert L. McNeil, Jr. Professor of Translational Research and professor of psychiatry. O’Connor, m.d., director of the Center for Musculoskeletal Care; Marie Follo, 2. Hope Furth, and her husband, John, hold replica wooden chairs that symbolize their gift. ynhhs director of practice management; Kimbirly Moriarty, chief strategy of- ficer of ynhhs; Prathibha Varkey, m.b.b.s., Northeast Medical Group ceo; and Thomas Madden, director of economic development for the City of Stamford. November 10 A large crowd turned out for a public symposium that celebrated September 16 In a panel discussion entitled Compas- the 10th anniversary of the Yale Stem sion, Meaning, and Joy in the Practice of Medicine, Cell Center. From left, Na Liu, ph.d., as- sponsored by the Yale Program on Medicine, Spirituality, sociate research scientist in cell biology; and Religion, Benjamin R. Doolittle, m.d., ma. div., as- Lauren Gonzalez, a doctoral student in sociate professor of medicine (general medicine) and of genetics at Yale University; Haifan Lin,
pediatrics hosted Sadhguru Jaggi Vasudev, a prominent robert lisak ph.d., director of the Yale Stem Cell Cen- yogi, visionary, and author from India, and discussed ter; Hongying Qi, ph.d., associate research scientist in cell biology; and Suping Peng,
john curtis john how physicians can combat stress and depression. ph.d., a postdoctoral associate at the Yale Stem Cell Center. New endowed professorship established in experimental pathology In the 1980s, Joseph A. Madri, M.D., of Pathology, who knowledge to the “We treat people who have par- Ph.D., professor of pathology; and have informed and understanding of oxysmal nocturnal hemoglobinuria in Leonard Bell, M.D. ’84, then a post- inspired his work. mitochondrial gene 50 countries, and now they have a life doctoral fellow; enjoyed lingering in “We felt strongly regulation and expectancy that parallels the average Madri’s lab after work and cooking that we should give metabolic stress person in their particular country, up plans to launch a biotech company back now that we signaling pathways. and they are productive members of one day. “We had a folder on the have the ability,” The lab’s ground- society,” says Madri. Mac called ‘Fantasy,’” Madri recalls. Madri says. “I am a breaking aging The company makes therapies Fantasy would become reality when strong proponent of Joseph Madri Gerald Shadel studies have shown that also treat the bone-softening Madri, Bell, and four colleagues met doing that through that mitochondrial disease hypophosphatasia, as well in 1991 at the Omni Hotel in New research that benefits the depart- respiration and reactive oxygen spe- as lysosomal acid lipase deficiency, Haven, and set a course that would ment’s research enterprise, so we cies signaling are key components of a condition in which uncontrolled bring a startup called Alexion to life came up with a professorship for an conserved longevity pathways. accumulation of cholesterol and tri- the following year. experimental pathologist.” Madri notes that in making his gift, glycerides leads to organ damage and Today Alexion is a global biophar- The professorship’s first occupant he had a particular desire to support a early death. maceutical company that employs is Gerald S. Shadel, Ph.D., who also mid-career researcher, and he is confi- “If I do nothing else in science, 3,000 people. It is a world leader in is professor of pathology and of ge- dent Shadel is the right choice. “He is an having helped thousands of people developing life-extending therapies netics, and director of the Yale Center outstanding investigator,” says Madri. live a long, productive life is more for people with rare, devastating, and for Research on Aging (Y-Age). “He has a true and abiding interest in than enough reward for me,” he says. potentially fatal diseases of the blood “Gerry Shadel is an ideal person developing the department, its research, The Madris have spent their en- and bone. to be the inaugural Madri professor, and its educational mission.” tire professional lives at Yale. Joseph The success of the company an outstanding scientist who is com- Madri also continues to pursue Madri arrived as a postdoc in 1975. he helped to found has inspired mitted to understanding the cellular his own abiding goal—to help people Lucille Madri held administrative Madri and his wife Lucille to and molecular mechanisms of aging,” worldwide whose health needs are roles at the university for 25 years. endow a new professorship at the says Robert J. Alpern, M.D., dean and often forgotten. The company he It is rare for a faculty member to School of Medicine—the Joseph A. Ensign Professor of Medicine. launched has worked hard to achieve endow a professorship, but Madri and Lucille K. Madri Professor of Shadel, who became a member that vision. says Yale and the Department of Experimental Pathology. of the faculty in 2004, researches the Alexion Pharmaceuticals extends Pathology deserve such a special Madri says he owes many profes- role of mitochondria—energy genera- the lives of people who are afflicted gift. “Yale is a unique place and the sional achievements to the faculty, tors within cells—in disease, aging, with two rare blood diseases: atypical postdocs and students who’ve cycled postdocs, and students in his lab and the immune system. Shadel’s hemolytic-uremic syndrome and par- through the lab have been outstand- and the medical school’s Department laboratory has contributed crucial oxysmal nocturnal hemoglobinuria. ing,” he says.
4 www.medicineatyale.org advances Alumnus Singer ’02 funds Yale programs Health & Science News Durable immune cells Serial entrepreneur and physician honors a headed by Pietro De Camilli, M.D., the John Klingenstein may protect for years Professor of Neuroscience and professor of cell biology, faculty mentor and a classmate as he salutes will administer the lectureship. Yale for inspiring his personal achievements Singer’s gift also memorializes a classmate and friend, Joshua “Josh” Gibson, M.D. ’01, who died in 2005 due to The School of Medicine will receive support for cardiac an unrecognized heart condition. The Joshua C. Gibson, research, a neuroscience lectureship, and a global health M.D., Memorial Fund for Heart Research will spon- fellowship; and a Yale College scholarship will honor a sor work in the laboratory of Daniel L. Jacoby, M.D. ’00, medical school faculty member, thanks to a large gift another contemporary and director of the Advanced Heart to Yale University by self-described “serial entrepreneur” Michael Singer, M.D. ’02, Ph.D. ’00, and his wife Baha- rak Asefzadeh, O.D., M.S. The gift is in thanks to Yale for the role it played in
istockphoto.com shaping Singer’s success.
Yale researchers have discovered Singer’s professional life is centered a population of cells that may help in Boston, where he has lived since he explain how the human immune sys- began a residency in ophthalmology tem can provide protection against at Harvard. He has founded a series pathogens for decades after a person of health-related companies there is first exposed. and also teaches at Harvard Medical The cells, a subset of tissue-resident School. Topokine, which produces a memory T (Trm) cells, are found topical treatment that acts on fat cells throughout the body—including in the to contour the face, was one of Singer’s blood, bone marrow, gut, and skin— privately held companies. In 2015, rather than just the lymphatic system Singer and Asefzadeh donated to Yale where many immune cells reside. A team led by Madhav Dhodapkar, Topokine shares then valued at over m.b.b.s., professor of medicine $1 million. This past spring, the multi- (hematology) and of immunobiology, national pharmaceutical company Al- found that some Trm cells in all these lergan purchased Topokine, providing tissues remain in a static resting Yale with immediate cash and rights
state, the G0 phase of the cell cycle, to future milestone payments. erik jacobs where they are neither dividing nor Yale University is “kind of where I grew up,” says Sing- Michael Singer and his wife Baharak Asefzadeh have donated to Yale in thanks preparing to divide. er, who also attended Yale as an undergraduate, earning for the university’s role in what Singer says is “everything positive that has This quiescent cell population, the happened to me” since he first arrived at Yale more than 25 years ago. They are a Bachelor of Science degree in 1995. “Everything positive funding a lectureship in integrative neuroscience at the School of Medicine, researchers reported in their Sept. 12 that has happened to me since depended on my arriving heart research, sponsorship for scholars from around the world to visit Yale, and Journal of Clinical Investigation paper, scholarships for Yale College undergraduates. at Yale back in 1991.” Singer credits Yale with fostering his has the ability to be mobilized into circulation when needed. creativity and encouraging him to pursue a wide array of Failure and Cardiomyopathy and General Heart Failure The new cells, because they are so ideas and habits of thinking that led him to become the programs. Singer and Gibson shared an interest in travel long lasting and tend to localize in tis- entrepreneur he is today. and global health, and during medical school both trav- sues, may be an attractive candidate Faculty, and fellow students alike, made a big impres- eled to less-developed countries to do health research for use in immune-based therapies sion on Singer. “The most important part of the Yale through Yale’s Downs Fellowship program. Another such as those designed to shrink experience is the people you meet,” he says. Accordingly, portion of the gift, also in Gibson’s name, will endow tumors, they suggested. each facet of the gift will recognize individuals who made what Singer thinks of as a “reverse Downs fellowship” to Singer’s time at Yale the formative experience it was. sponsor scholars from less-developed countries to visit As an undergraduate work-study student and then as Yale School of Medicine. Copycat proteins may a Ph.D. candidate, Singer studied the olfactory system in Singer’s next venture is Cartesian Therapeutics, a com- trigger type 1 diabetes the lab of Gordon M. Shepherd, M.D., D.Phil., professor of pany developing novel cancer therapies, and philanthropy neuroscience. Shepherd was more than a scientific mentor. is an ongoing priority. “I would like to begin a movement Despite the fact that it appears in “We also formed a very nice personal bond,” Shepherd recalls, to encourage more entrepreneurs and early-stage investors childhood and has several genetic risk noting that Singer was often a guest at his home. “My wife to donate their privately held stock to support charity and factors, autoimmune type 1 diabe- [Grethe Shepherd] enjoyed having him; she always enjoys institutes of higher learning,” he says. tes cannot be entirely predicted by having students come out, as they do from time to time.” The “[Singer] was thrilled and excited by every opportunity genetics. Only one identical twin may get the disease, for instance. New Shepherds were a “home-away-from-home” for him and for that was presented to him here,” says Charles A. Greer, research suggests how an environ- many Yale students, Singer says. In honor of the Shepherds, Ph.D., professor of neurosurgery and of neuroscience, and mental factor—gut bacteria—could part of the gift will endow an undergraduate scholarship, the director of the Interdepartmental Neuroscience Gradu- play a role. Gordon and Grethe Shepherd Scholarship Fund. ate Program. Greer, who will co-administer the Shepherd According to the study, led by Li Also in honor of Singer’s mentor, the donation will lectures, says the donations reflect Singer’s character. “You Wen, m.d., ph.d., senior research sci- endow a School of Medicine lectureship in integrative know, sometimes people can become rather indifferent entist in medicine (endocrinology), Fu- neuroscience, which Singer describes as “the hallmark of about opportunities being presented,” says Greer. “As they sobacteria in the guts of mice produce [Shepherd’s] long and distinguished career as a neuro- have a series of successes, they come to think that they proteins that mimic the structure of scientist.” That field, Shepherd says, is concerned with maybe deserve them in some way. Michael never exhibited molecules in insulin producing pancre- synthesizing different kinds of data that scientists gather that trait. Michael always treated any success, any gesture atic beta cells, the same cells that are about the nervous system into a greater understanding of or effort that was extended on his part with the greatest of destroyed in type 1 diabetes. As the number of Fusobacteria in the system as a whole. The Department of Neuroscience, gratitude and continues to do so.” mice increases, the immune system produces more T cells that recognize these molecules, spurring immune // Cancer Center (page 1) Dana-Farber and science at the cancer center and about the opportunity to continue to activity not only against the bacteria, Cancer Institute. will coordinate these efforts with expand the breadth and depth of but also against the pancreatic cells. After spending his entire ca- discoveries that emerge across Yale’s the clinical practice as well as the In mice with a genetic risk factor for reer in Boston, where he has led a research enterprise. His vision is to extraordinary cancer research ongo- type 1 diabetes, having excess Fusobac- clinical enterprise as well as research advance Yale’s capacity to do innova- ing at Yale to meaningfully improve teria in their guts accelerated the onset programs, Fuchs says he is now tive clinical, translational, popula- the outcome of patients.” of disease. Moreover, altering their ready to bring his work to an even tion, and basic science research to With the start of the new year, guts to decrease Fusobacteria reversed higher level in his new role at Yale. further enhance the cancer center’s Fuchs succeeds Peter G. Schulam, the development of type 1 diabetes, the researchers reported Sept. 12 in Journal “The opportunity to lead such an position as a leader in cancer preven- M.D., who served as interim director of Experimental Medicine. extraordinary center as Yale Cancer tion, biology, and treatment. of the Cancer Center for the past year, The new findings could eventually Center and Smilow will allow me “The cancer center and Smilow Schulam remains chair of the Depart- provide targets for new therapies in to do that,” he says. Fuchs plans to have had impressive growth over the ment of Urology and chief of urology humans with type 1 diabetes. continue to expand clinical trials past five years,” he says. “I am excited at Yale New Haven Hospital.
Medicine@Yale January/February 2017 5 Games for Serious Issues: Reducing High-Risk (nih), copd’s Average Attributable Fraction from Sexual Behavior in Adolescents Through a Mobile Multiple Chronic Conditions (caafe), 1 year, $39,925 Grants and contracts awarded Game App, 1.2 years, $74,995 • Walter Gilliam, The Lori Nathanson, Boys & Girls Clubs of America, Walton Family Foundation, Walton Mapping Club Charters for Boys and Girls Clubs of America, Project, 1 year, $311,661 • Emily Gilmore, Massachu- 1.2 years, $124,998 • Laura Niklason, Karen Hirschi, to Yale School of Medicine setts General Hospital, Established Status Epilepti- Connecticut Innovations, Engineered Arteries and cus Treatment Trial (esett), 1 year, $157,000 iPS-Derived Endothelium, 3 years, $748,926 • James Michael Girardi, Richard Lifton, Drs. Martin and Noonan, Charles H. Hood Foundation, Discovering December 2015–March 2016 Dorothy Spatz Charitable Foundation, Precision Gene Regulatory Networks in Early Human Brain Medicine Approach to the Treatment of ctcl, Development that Contribute to Autism Spectrum Federal Non-federal 1 year, $200,000 • Emily Goldberg, American Fed- Disorders, 2 years, $450,000 • Chirag Parikh, Emily Ansell, nih, Ecological Momentary Emily Ansell, Peter F. McManus Charitable Trust, eration for Aging Research, Impact of Ketone Northern California Institute for Research & Educa- Assessment of Cannabis Use Effects in Young Relationship Processes in Couples Coping with Metabolites on Age-related Inflammation, 1 year, tion (nih), Kidney Health Biomarker Panels for Drug Adults, 4.8 years, $2,339,320 • Albert Arias, nih, ptsd that Increase Risk for Hazardous Drinking, $51,000 • Andrew Goodman, Memorial Sloan- Toxicity and Prognosis in hiv Infection, 4.2 years, Zonisamide Treatment of Alcohol Use Disorder: 1 year, $50,000 • Alan Anticevic, BlackThorn Kettering Cancer Center (nih), Systems Biology of $122,895 • Abhijit Patel, Honorable Tina Brozman An Evaluation of Efficacy and Mechanism of Therapeutics, Characterizing the Neural Mecha- Microbiome-mediated Resilience to Antibiotic- Foundation, Consortium Grant Agreement-Stage Action, 5 years, $2,779,749 • Angelique Bordey, nisms Behind Cognitive and Motivational Deficits resistant Pathogens, 5 years, $476,920; Massachu- 1, 1 year, $17,947 • Ismene Petrakis, Brain & Behavior nih, Filamin A in tsc, 5 years, $1,831,119 • William in Psychiatric Disorders, 2.1 years, $1,996,452 setts Institute of Technology, Microbiome Varia- Research Foundation (formerly narsad), Effects Cafferty, nih, prg3 Drives Functional Plasticity in Renata Batista Brito, Brain & Behavior Research tion and Coumadin Function in Humans, 1 year, of Progesterone on Stress-Induced Craving in ptsd Intact Circuits After Spinal Cord Injury, 5 years, Foundation (formerly narsad), gabaergic Contri- $156,250 • Cary Gross, American Cancer Society, and aud, 1 year, $99,930 • Melinda Pettigrew, Duke $1,831,301 • Nancy Carrasco, nih, Mechanism of butions to Neural and Cognitive Dysfunction in a State Laws, New Breast Cancer Screening Modality University (nih), Antibacterial Resistance Leader- I-Transport by the Na+/I-Symporter (nis), 4 years, Genetic Model of Schizoprenia, 2 years, $70,000 Use and Cost-Sharing, 3 years, $590,000; Pfizer, ship Group (arlg), 1 year, $34,079 • Katerina Politi, $2,301,971 • Sreeganga Chandra, nih, Identifying Anton Bennett, American Heart Association U.S. Pharmaceuticals Group, Optimizing Patient Associazione Italiana per la Ricerca sul Cancro, the Neuronal Substrates of the Depalmitoylating (Founders Affiliate), Congenital Heart Disease Engagement in Reporting Outcomes Among Functional Validation and Analysis of Novel Muta- Enzyme ppt1, 2 years, $460,125 • Sandy Chang, Mechanisms by ptpn11/shp2, 3 years, $198,000 Women with Metastatic Breast Cancer, 2 years, tions In TKI-Resistant egfr Mutant Lung Adenocar- nih, Telomere Dysfunction and Genome Instabil- Ranjit Bindra, American Cancer Society, Pre- $357,985 • Patricia Gruner, Brain & Behavior cinomas; PI Anna Truini, 1 year, $39,641 • Angelica ity in Familial Melanoma, 2 years, $400,110; nih, clinical Development of Mibefradil as a Novel Research Foundation (formerly narsad), Obses- Ponguta, Jacobs Foundation, International Early Telomere Dysfunction Induced Breast Cancer Glioma Radiosensitizer, 4 years, $792,000; cavion, sions and Delusions: Probing Abnormalities in Childhood Development Program Implementa- Pathogenesis, 5 years, $1,914,446 • Kelly Cosgrove, Development of Biomarker Assay & Protocol for Causal Reasoning in Obsessive-Compulsive Disor- tion and Evaluation in Fragile and Vulnerable Set- nih, Imaging Molecular Mechanisms of Tobacco Commercialization of Mibefradil Dihydrochloride der (ocd), 2 years, $70,000 • Shangqin Guo, tings, 3 years, $160,585 • Lajos Pusztai, The Hope Smoking Withdrawal, 4.8 years, $3,639,011 as gbm Treatment, 1 year, $90,862; cavion, High- Charles H. Hood Foundation, Molecular Definition Foundation, Genomic Analysis of Inflammatory Sabrina Diano, nih, Central Prolyl Carboxypep- Content and High-Throughput Screening to of Cancer Cell-of-Origin in B-all, 2 years, $150,000; Breast Cancer (ibc) in swog S0800 Clinical Trial tidase (prcp) in the Regulation of Metabolism, Analyze a Library of Small Molecules in a Gilead Sciences, Molecular Definition of Leukemia Tissues to Identify Molecular Alterations that 5 years, $1,883,062 • Donald Engelman, nih, Microplate-Based Format, 1 year, $26,800 • Alfred Cell-of-Origin, 2 years, $130,000 • Abha Gupta, Underlie the Aggressive Biology of ibc and Could Mechanism and Uses of Transmembrane Helix Bothwell, Elsa U. Pardee Foundation, Development Connecticut Innovations, Human ipsc Modeling of Lead to the Development of New Diagnostic Tests Insertion by Soluble Peptides, 4 years, $2,289,780 of Human Lung Cancer Metastasis Model in Mice, Autism-associated Mutations in the Gene chd8, and Therapeutic Interventions, 1 years, $48,628 Kathryn Ferguson, nih, Analysis of Active and 1 year, $163,244 • Martina Brueckner, Children’s 2 years, $200,000 • David Hafler, National Multiple Yibing Qyang, Connecticut Innovations, Targeted Inactive egfr Conformations, 1.6 years, $220,945; Hospital, (Cincinnati), Administrative Coordinating Sclerosis Society, PI: Sharon Stoll; Clinical Care Fel- Investigation into the Causes and Amelioration of nih, Signaling Mechanisms of rtks with Center: Cardiovascular Development and Pediatric lowship Grant (nmss) Sharon Stoll (Fellow), 1 year, Vascular Proliferative Disease Using Patient-derived Membrane-Proximal Fibronectin Type III Domains, Cardiac Genomics Consortia, 10 months, $43,000 $65,000 • Kevan Herold, The Leona M. and Harry Induced Pluripotent Stem Cells, 4 years, $750,000 1.7 years, $58,789 • Carlos Fernandez-Hernando, Susan Busch, Patrick and Catherine Weldon Dona- B. Helmsley Charitable Trust, Studies of Diabetes John Rose, Albany Medical Center (nih), Highly nih, Role of micrornas in Lipid Metabolism ghue Medical Research Foundation, Reducing Inap- Development in an Index Case of Initially Discor- Attenuated Vesiculovirus Based Vectors as hbv and Cardiovascular Disease, 4 years, $1,724,378 propriate Use of Antipsychotic Medications in dant Triplets, 1 year, $152,000; Benaroya Research Therapeutic Vaccines, 3 years, $376,568 • Joseph Michael Girardi, nih, Local Immunoregulation of Nursing Homes, 2 years, $171,796 • William Caf- Institute (nih), ITN066AI Type 1 Extension Diabe- Ross, Bioethics International, The Pharma Integrity Cutaneous Carcinogenesis, 5 years, $1,987,679 ferty, Connecticut Innovations, Polyphosphate- tes Trial (t1des), 5.3 years, $117,584; Albert Einstein Index, 2.8 years, $80,649 • Douglas Rothman, Julie Goodwin, nih, Endothelial Glucocorticoid 5-phosphatases Enhance Functional Regeneration College of Medicine (nih), Women’s Interagency Cure Huntington’s Disease Institute Foundation Receptor Suppresses Vascular Inflammation, after Spinal Cord Injury, 2 years, $200,000 hiv Study (wihs-v), 1 year, $33,791 • Karen Hirschi, (chdi), Effects of Pan-htt Knockdown on Recently 5 years, $2,594,871 • Ya Ha, nih, Mechanistic Alberto Canfran-Duque, American Diabetes Connecticut Innovations, Generation of Human Identified 13C and 1H mrs Flux-based Biomarkers Studies of Intramembrane Protease GlpG, 4 years, Association, miR-33a/b in Type 2 Diabetes and Car- Hemogenic Endothelial Cells, 3 years, $750,000 of Mitochondrial Energetics and Neurotransmitter $1,337,902 • Mark Hochstrasser, nih, Function diovascular Disease, 3 years, $177,468 • Richard Tamas Horvath, American Diabetes Association, Cycling in Huntington’s Disease, 1 year, $243,074 and Assembly of Eukaryotic Proteasomes, 4 years, Carson, Pfizer, U.S. Pharmaceuticals Group, Radio- Breaking the Cycle of Hyperphagia and Hippocam- Alessandro Santin, Honorable Tina Brozman $1,356,907 • Barbara Kazmierczak, nih, Targeting chemistry Evaluation and Exploratory ind Compila- pal Damage, 3 years, $115,000 • Susan Kaech, Uni- Foundation, Consortium Grant Agreement-Stage 1, Intrinsic Resistance to Combat Multi-Drug Resis- tion and Regulatory Filing of [11C]PF-06809247, versity of Connecticut Health Center (nih), Cellular 1 year, $50,000 • Kurt Schalper, tesaro, Measure- tant P. aeruginosa, 2 years, $446,147 • Mustafa 1 year, $91,908 • Paul Cleary, University of Con- Mechanisms of Viral Control, 5 years, $140,287 ment of tim-3 Protein and Immune Contexture in Khokha, Martina Brueckner, Michael Choma, nih, necticut Health Center (dhhs), CT sim Model Test, Kristopher Kahle, March of Dimes, A Novel Kinase Human Solid Tumors Using Objective Methods, Cardiac Phenotyping of chd Candidate Genes 9 months, $123,500 • Andrew Cohen, Patrick and Switch of gaba Activity in Neurodevelopment and 1 year, $311,550; and Vasculox, Quantitative Meas- in Xenopus, 3 years, $1,588,354 • Kenneth Kidd, Catherine Weldon Donaghue Medical Research Disease, 2 years, $150,000 • Barbara Kazmierczak, urement and Biological Significance of cda47 National Institute of Justice/Department of Foundation, End-of-Life Care for Nursing Home University of Maryland (nih), Catheter Associated Protein Expression in Human Lung and Breast Justice, Powerful Forensic Markers Optimized for Residents with Guardians, 2 years, $109,634 • Joan Urinary Tract Infection by Pseudomonas Aerugi- Carcinomas, 1 year, $97,150 • Charles Sindelar, Massively Parallel Sequencing, 2 years, $1,146,143 Cook, Palo Alto Veterans Institute of Research nosa, 3 years, $94,063 • Richard Kibbey, Agios University of Pennsylvania School of Medicine Albert Ko, nih, Naturally Acquired and Vaccine- (nih), Improving and Sustaining cpt Delivery for Pharmaceuticals, In Vitro PK Activation, 1 year, (nih), Molecular Function of Myosin-1, 11 months, Mediated Immunity to Leptospirosis, 5 years, ptsd in Mental Health Systems, 10 months, $13,322 $68,672; American Diabetes Association, Cross $47,204 • Laura Skrip, Binational Science Founda- $4,003,326 • Priti Kumar, nih, Exploring Gianfilippo Coppola, Connecticut Innovations, Platform-Validated In Vivo 13C Flux Measures of tion, Markov Model of Risk Factors for Clinical Antibody-Fc Effector Function in Humanized Brain-on-Chip, 2 years, $199,979 • Jose Cortes- Cataplerosis and Anaplerosis and Oxidation in the Visceral Leishmaniasis in Northern Ethiopia, 1 year, Mouse Models of hiv Latency, 2 years, $464,478 Briones, Brain & Behavior Research Foundation Liver, 3 years, $345,000 • Jonathan Koff, Cystic $4,000 • Levi Smith, Pfizer, U.S. Pharmaceuticals Daeyeol Lee, nih, Neural Basis of Temporal (formerly narsad), Biomarker-based Estimation of Fibrosis Foundation (cff), Implementation of the Group, Pfizer Funding for 2016 Yale Graduate Bio- Decision Making, 5 years, $2,085,711 • Richard Relapse Risk in Schizophrenia, 2 years, $69,995 Depression and Anxiety Guidelines: Award for medical Career Fair, 2 months, $2,000 • Gwendolyn Lifton, nih, Yale Center for Mendelian Genomics, John Davis, Regents of the University of California A Mental Health Coordinator, 3 years, $121,500 Thomas, Robert Leet and Clara Guthrie Patterson 3.9 years, $11,966,861 • Alex Lipovsky, nih, Innate (nih), TB Surrogate Markers for Assessing Anthony Koleske, Brain & Behavior Research Foun- Trust, An Enhanced Behavioral Intervention to Immunity to hpv Infection, 1 year, $56,118 • Elias Response to Treatment (TB smart Study), 1 year, dation (formerly narsad), Substrate Identification Increase Daily Exercise Adherence in Breast Cancer Lolis, nih, Targeting cxcr5 for Angioimmuno- $47,819; Regents of the University of California, San for a Schizophrenia-Associated Protein Kinase, Survivors, 8 months, $85,001 • Derek Toomre, blastic T-cell Lymphoma, 2 years, $388,104 • Elan Francisco (nih), Single-sample Tuberculosis Evalua- 1 year, $100,000 • David Kovacevic, Theodore Nanoprobes (nih), Non-Antibody Labeling for Cor- Louis, nih, Environmental Epidemiology of Essen- tion to Facilitate Linkage to Care: The simple TB Blaine, American Shoulder and Elbow Surgeons, relative Superresolution and Electron Microscopy, tial Tremor, 5 years, $3,881,211 • Stefania Nicoli, Trial, 5 years, $14,809 • Pietro De Camilli, Mian Cao, Amniotic Fluid-Derived Allograft to Improve 1 year, $70,021 • Seyed Torabi, Damon Runyon nih, Integrating miR-107 into Signaling Pathways Michael J. Fox Foundation for Parkinson’s Research, Rotator Cuff Tendon-Bone Healing, 1 year, $19,967 Cancer Research Foundation, Evolution of Triplex- that Coordinate Neurogenesis and Brain Vas- Pathogenetic Mechanisms in Autosomal Recessive Peter Krause, Immunetics (nih), Babesia Antigen Forming rnas from Random Sequences: A Search cular Permeability, 5 years, $2,092,500 • Laura Early-Onset Parkinsonism Resulting from a Muta- Detection Assay for Blood Screening, 2 years, for Additional malat1-Like Triplex Motifs, 4 years, Niklason, nih, Hyaluronan Coatings for Engi- tion in Sac Domain of Synaptojanin1, 1 year, $50,100 • Diane Krause, Connecticut Innovations, $226,000 • Anthony Van den Pol, Connecticut neered Vessels, 4 years, $2,456,811 • John Pachan- $100,000 • Maria Teresa Dell’Anno, Marco Regenerative Medicine for Hypoparathyroidism, Innovations, Generation of Neurons Directly from kis, nih, A Unified Intervention For Young Gay and Onorati, Connecticut Innovations, Human Neuro- 3 years, $750,000 • Ifat Levy, Branding Science Glia with NeuroD1 Transcription Factor, 2 years, Bisexual Men’s Minority Stress, Mental Health, epithelial Stem Cells in Spinal Cord Injury, 2 years, International, Physician Risk Assessment Research, $200,000 • Christopher Van Dyck, University of and hiv Risk, 4.9 years, $4,422,608 • Jordan Pober, $200,000 • Jonathan Demb, University of Mary- 10 months, $43,400 • Zhuobin Liang, Damon California, San Diego (nih), Therapeutic Effects of nih, Human Vascular Cell Functions in Acute land (nih), Synaptic Transmission in the Rod Runyon Cancer Research Foundation, Mechanistic Exercise in Adults with Amnestic Mild Cognitive Allograft Rejection, 4 years, $2,047,964 • Tomoaki Pathway of the Mammalian Retina, 3 years, $293,218 Dissection of the Fanconi Anemia Pathway in Coor- Impairment (exert), 1 year, $107,950 • Narendra Sasaki, nih, Biochemical and Functional Charac- Kamil Detyniecki, Acorda Therapeutics, Demo- dinating R-loop Processing and dna Repair, 4 years, Wajapeyee, American Cancer Society, Metabolic terization of the Mutagenic Cytidine Deaminase graphics, Clinical Characteristics, Frequency, and $231,000 • Joseph Lim, University of Florida, The Drivers of Melanoma Initiation, Progression and apobec3b in the Context of Squamous Cell Lung Associated Outcomes of Seizure Clusters Among Prioritize Study: A Pragmatic, Randomized Study of Therapy Response, 4 years, $792,000; L2 Diag- Carcinoma, 3 years, $130,728 • Martin Schwartz, Outpatients with Epilepsy at Two Tertiary Care Oral Regimens for Hepatitis C: Transforming nostics (nih), Small Molecule Inhibitors Targeting nih, Endothelial Mechanisms of Flow Sensing Centers, 4 years, $48,872 • Nicole Deziel, American Decision-Making for Patients, Providers, and Oncogenic Drivers of Hepatocellular Carcinoma, and Atherosclerosis, 4 years, $1,695,427 • Joann Cancer Society, Exposure to Halogenated Aro- Stakeholders, 5 years, $317,100 • Haifan Lin, Con- 1 year, $131,323 • Lisa Walke, University of Colorado Sweasy, nih, dna Polymerase Beta Variants and matic Compounds and Risk of Thyroid Cancer, necticut Innovations, Continued Support and Denver, Practice Change Leaders for Aging and Cancer, 5 years, $2,118,864 • Narendra Wajap- 5 years, $729,000 • Marie Egan, Peter Glazer, W. Technology Development for Shared Core Facili- Health, 1 year, $4,500 • Shuo Wang, University of eyee, nih, A Novel Druggable Genetic Vulnerabil- Mark Saltzman, Cystic Fibrosis Foundation Thera- ties at the Yale Stem Cell Center, 1 year, $500,000 Pittsburgh (nih), Developmental Changes in Striatal ity Pathway in Melanoma, 5 years, $1,914,446; nih, peutics (cfft), Gene Editing using Nanoparticles Wu Liu, Elsa U. Pardee Foundation, Nanoparticle- Neurophysiology through Adolescence, 1.2 years, Anoikis Effectors as Drivers of Metastatic Mela- with Triplex-Forming pnas, 2 years, $334,263 enhanced Focused kV X-ray Radiotherapy: Monte $11,050 • Tobias Wasser, American Academy of noma, 2 years, $399,982 • Min Wang, nih, Cholin- Marie Egan, Cystic Fibrosis Foundation (cff), Carlo Dosimetry Modeling, 1 year, $106,665 • Chi Psychiatry and the Law, Introduction to Forensic ergic Influences on Neuronal Physiology in Dor- Depression and Anxiety: Barriers to Adherence, Liu, Philips Healthcare, Specific Research Plan for Psychiatry – A National Model for a Module- solateral Prefrontal Cortex, 4.9 years, $2,075,929 3 years, $121,500 • Marie Egan, Jonathan Koff, Imaging Small Lesions Using a Prototype Photon Based Curriculum, 1 year, $15,000 • Sherman Shannon Whirledge, nih, Environmental Exposure Cystic Fibrosis Foundation Therapeutics (cfft), Counting CT System, 2.1 years, $211,728 • Paul Weissman, Massachusetts General Hospital, to Genistein Regulates Signal Transduction in the Yale Cystic Fibrosis Therapeutic Development Lombroso, Emory University (nih), Anticipatory Dynamics of the In Vivo rna Transcriptional / Uterus, 3 years, $735,960 • Dianqing Wu, nih, Center, 1 year, $66,026 • Enric Esplugues, Crohn’s & Anxiety: Mapping Functional Microcircuits in the Translational Landscape in xdp Patient-Specific Signaling Mechanisms for Leukocyte Migration Colitis Foundation of America (ccfa), Controlling bnst, 4 years, $53,711 • Jun Lu, Connecticut Inno- Cells, 1 year, $198,064 • David Zenisek, University Regulation, 4 years, $1,992,868 • Xiaoyong Yang, Pathogenic TH17 Cells in Inflammatory Bowel vations, Novel Insights and Approaches toward of Texas (nih), Mechanisms of Neurotransmission nih, O-GlcNAc Signaling in Central Control of Disease, 3 years, $347,490 • Sorin Fedeles, pkd Accelerated Hematopoietic Regeneration, 4 years, in Vertebrate Retina, 1 year, $42,364 • Jiangbing Energy Balance, 3.9 years, $1,761,556 • Sarah Yip, Foundation for Research in Polycystic Kidney $750,000 • Walther Mothes, Dana Farber Cancer Zhou, Joseph Piepmeier, Connecticut Innova- nih, Neural Mechanisms of Galantamine Treat- Disease, Examining the Role of xbp1 in the Patho- Institute (nih), Conformational Landscape of tions, Patient Specific Neural Stem Cell Mediated ment for Cocaine Dependence, 5 years, $904,946 genesis of Protein Folding-Associated Polycystic the hiv-1 Envelope Glycoproteins, 1 year, $60,155 Combination Therapy for Malignant Gliomas, Jiangbing Zhou, nih, mif20-loaded Nanoparticles Kidney Disorders, 2 years, $160,000 • Richard Thiruvengadam Muniraj, University of Colorado, 4 years, $750,000 • Andrey Zinchuk, Robert Leet for tbi Treatment, 2 years, $460,125 • Z. Jimmy Flavell, Fondazione Cariplo, T Cell rna Signatures in 2016 Fellows Advanced Endoscopy Program Grant and Clara Guthrie Patterson Trust, Identification Zhou, nih, Functional Dissection of New Retinal Inflammatory Bowel Diseases, 2 years, $192,600 Application, 3 months, $1,000 • Terrence Murphy, and Validation of Clinically Relevant Obstructive Circuits, 3 years, $1,255,000 Aileen Gariepy, Society of Family Planning, Serious University of Massachusetts Medical School Sleep Apnea Phenotypes, 2 years, $110,000
6 www.medicineatyale.org Early career recognition goes to five Yale investigators A highly competitive new program Andrew Goodman, Ph.D., associate professor of microbial identifies and funds the most promising pathogenesis, is exploring the young scientists in the United States mechanisms that human com- mensal microbes—those normally Five School of Medicine scientists have been named found in the body—use to cooper- Howard Hughes Medical Institute (HHMI) Faculty ate, compete, and antagonize each Scholars in recognition of their potential to make other in the gut and how manipu- unique contributions to their fields. lating these communities could im- This newly established program—a joint endeavor prove drug responses in patients. of HHMI, the Bill & Melinda Gates Foundation, and Valentina Greco, Ph.D., associ- the Simons Foundation—supports early career basic ate professor of genetics, is inves- researchers with more than four and up to 10 years of tigating how stem cells initiate experience. The investigators were chosen based on and coordinate tissue regenera- their innovative approaches to solving biology-related tion to maintain healthy tissues problems that are relevant to human health. and restore damaged tissue after Daniel A. Colón-Ramos, Ph.D., associate professor injury, and how tissues respond of cell biology and neuroscience, is using Caenorhabditis to cells with cancer-promoting elegans, also known as roundworms, to explore the cel- mutations, which will shed light robert lisak lular mechanisms used to create, maintain, and modify on the earliest events that lead to cancer. In the first year of a program designed to identify and fund promising young investigators, (left to right) Valentina Greco, Andrew Goodman, synapses in order to further understanding of their role Carla V. Rothlin, Ph.D., associate professor of Carla V. Rothlin, Daniel A. Colón-Ramos, and Antonio J. Giraldez have in producing behaviors and storing memories. immunobiology and of pharmacology, is studying been named Howard Hughes Medical Institute Faculty Scholars. No Antonio J. Giraldez, Ph.D., professor of genetics, the biochemical mechanisms that control the im- medical school in the United States had a larger group chosen. seeks to understand how the cellular codes that mune response and lead to inflammation that can shape gene expression are used to turn a fertilized trigger autoimmune disorders or fuel cancer. that HHMI has chosen to support five of our most egg into a complex multicellular embryo. Using “Promising young faculty members are the back- accomplished investigators.” Yale’s five awardees, as zebrafish as a model system, he aims to shed light bone of our ability to continue to conduct ground- many as were chosen from any medical school, are on the mechanisms that initiate embryonic develop- breaking research,” says Dean Robert J. Alpern, among just 84 Faculty Scholars selected from a pool ment and specify different cell types in vertebrates. M.D., Ensign Professor of Medicine. “I am proud of more than 1,400 applicants.
// IRBs (page 2) addresses these issues.” has extensive experience in clinical // Public Health (page 1) in a joint simple technique to visually detect Prior to joining the Yale faculty trials, and was a co-investigator in a statement announcing Vermund’s cervical lesions and built a major in 2012, Roberts was professor of landmark study that demonstrated appointment. “His work showed screening program in Zambia that has internal medicine at Virginia Com- that chronic pain is common in adults that HIV was a risk factor for cervical become a global training center. monwealth University (VCU), where with sickle cell disease. cancer, which motivated routine cervi- In 2000, he founded the Centre he was an IRB member for nearly 20 Roberts earned his M.D. at the cal cancer screening for HIV-infected for Infectious Disease Research, now years. At VCU he also taught human University of Pennsylvania. In 2012, women worldwide.” one of Zambia’s largest NGOs, which subjects protection at the gradu- he received the Principal Investiga- Vermund received his medical de- currently supports more than 330 ate level. Shortly after his arrival at tor of the Year (Harry Hines Award) gree from Albert Einstein College of clinics that play an instrumental role Yale, he was appointed co-chair of from the Community Clinical Medicine in 1977. During his training in the prevention of maternal-fetal the Yale IRB Cancer Panel (Human Oncology Program of the National in pediatrics at Columbia University, HIV transmission and the imple- Investigations Committee I). Roberts Cancer Institute. he was exposed to many cases of mentation of antiretroviral therapy. preventable illness in underserved He also founded Friends in Global minority populations. “The more Health, an NGO in Mozambique and // Slayman (page 1) establish the gradu- A renowned scientist, Slay- preventable illness I saw, the more Nigeria that has provided HIV-related ate program in the nascent Department man was elected to the Institute of my passion for a public-health based care to over 140,000 individuals. of Human Genetics in 1972 and served Medicine (now the National Acad- orientation grew,” he says. Vermund has been a mentor to as director of graduate studies in ge- emy of Medicine) in 1995. She was He pursued this interest by com- scores of individuals who have gone netics from 1972 to 1984. In 1984, she recognized for her research on the pleting a master’s degree in commu- on to distinguished careers heading was named chair of the Department of proteins that transport nutrients nity health in developing countries major programs, including Ann E. Genetics, serving in that position for 11 across cell membranes and the genes at the London School of Hygiene Kurth, Ph.D., C.N.M., M.P.H., dean of years. In 1991, she was named Sterling that code for those proteins. She and Tropical Medicine, a diploma in Yale School of Nursing. He has also Professor of Genetics in recognition of served on numerous scientific boards public health at the Royal Institute written many grants through which her academic excellence. and panels, including the Howard of Public Health and Hygiene, and hundreds of individuals have received As deputy dean for academic and Hughes Medical Institute Scientific a Mellon Foundation-supported training in public health science. He scientific affairs, she focused her Review Board and the NIH Panel on fellowship in clinical epidemiology plans to draw upon this experience to attention on faculty recruitment and Scientific Review. at Columbia-Presbyterian Medical work closely with interested faculty development, and the creation and Slayman, who was passionately Center. He received his Ph.D. in epi- to help increase the number of Yale’s advancement of research programs committed to the training and educa- demiology from Columbia in 1990. public health doctoral trainees. and core facilities—including the Yale tion of young scientists, became a Vermund served as chief of the He adds that he plans to work Center for Genome Analysis at the mentor to many, relishing the op- Vaccine Trials & Epidemiology Branch tirelessly to expand Yale’s research West Campus—and was instrumental portunity to guide their research and in the Division of AIDS at the National enterprise for highly relevant dis- in Yale’s applications for many insti- careers. Megan C. King, Ph.D., as- Institute of Allergy and Infectious Dis- covery and to support faculty who tutional grants, such as the National sociate professor of cell biology, notes eases from 1988 to 1994, a time when are at the leading edge of health Institutes of Health (nih) Clinical that Slayman was instrumental in her AIDS activism had a major influence policy and reform. He also looks and Translational Science Award. earning an Early Outstanding Inves- on government policy. Recognizing forward to spearheading larger Slayman spearheaded the renovation tigator Award, which sustained King the need for prevention approaches, collaborative initiatives across the and modernization of the medical between grants, enabling her to move his branch launched HIVNET (HIV entire university, including climate school’s laboratory space in an effort from yeast to animal model systems Network for Prevention Trials), a major change and population projects to create a collaborative environment in her work on the role of a mechano- international research network that with the School of Forestry & that fosters the sharing of ideas. transduction pathway in cardiomy- evolved into several NIH-sponsored Environmental Studies, strengthen- “One of Carolyn’s strengths was that opathies and generate data that will networks focused on prevention. ing global health care systems with she never had any personal ego stake in allow her to continue this research. For the past two decades, Ver- the School of Management, and an outcome, other than what was going “She gave advice,” King says, “which mund, who is a member of the Na- collaborations on health ethics with to be the very best for the institution,” is a skill that most of us don’t have but tional Academy of Medicine (formerly Yale Divinity School. says Richard P. Lifton, M.D., Ph.D., which is increasingly important.” the Institute of Medicine), has focused “At Yale,” Vermund says, president of Rockefeller University and The School of Medicine plans to on global health issues. In develop- “the opportunities are immense former chair of the Department of Ge- hold a public memorial for Slayman ing countries, where Pap smears are to get involved with a variety of netics at the School of Medicine. in the coming weeks. not routine, his team promulgated a enterprises.”
Medicine@Yale January/February 2017 7 School welcomes chief diversity officer Awards & Honors Deputy dean arrives with were few African- racial, gender, ethnic, and socio- Madhav V. Dho- Americans and even economic diversity,” says Robert dapkar, m.b.b.s., long experience in areas of fewer students from J. Alpern, M.D., dean and Ensign Arthur H. Bunker recruitment and inclusion his modest socioeco- Professor of Medicine. “I am pleased and Isabel Bunker nomic background. that we have recruited such an ex- Professor of Medi- Darin A. Latimore, M.D., has been While serving as ceptional candidate to head our ef- cine (Hematology) and professor of appointed deputy dean for diversity associate program forts at promoting a culture in which immunology, has been named and inclusion, beginning in January director for the all members of our community feel an Outstanding Investigator by as the School of Medicine’s inaugural Darin Latimore UC Davis internal respected and included.” the National Cancer Institute. chief diversity officer. medicine program, At Yale, Latimore will coordinate Dhodapkar is also chief, section Latimore obtained his medical de- he noted that many of the students and with such groups as the Office of of hematology, department of gree at University of California, Davis residents with whom he worked shared Multicultural Affairs, the Minor- internal medicine; and Disease School of Medicine and completed his experiences of isolation and dis- ity Organization for Retention and Aligned Research Team leader, his residency in internal medicine at crimination, prompting him to write a Expansion (MORE), the Committee Hematology Program, Yale University of California, Davis Medi- job description that led to his inaugural on the Status of Women in Medicine Cancer Center. cal Center. He specialized in HIV care position as director of medical student (SWIM), the Committee on Diversity, as a physician with the Permanente diversity at UC Davis in 2008. He later Inclusion, and Social Justice, and the Medical Group in South Sacramento, became associate dean for student and newly formed Dean’s Advisory Coun- Naftali Kaminski, Calif., where he also trained medical resident diversity, developing initia- cil on LGBTQ Affairs. m.d., Boehringer students and residents before join- tives to increase the pipeline of socio- Latimore will aid with recruitment Ingelheim Phar- ing UC Davis as a volunteer clinical economically disadvantaged students, efforts to increase diversity within maceuticals, faculty member in 2002. residents, and faculty and spearheading School of Medicine faculty. In addi- Inc., Professor of His passion for promoting diver- programs to support and empower tion, he says, “I am looking forward to Medicine (Pulmo- sity and inclusion stems from his own underrepresented students interested in working with Yale’s student body to nary), professor experiences. As an undergraduate at attending medical school. develop programming that is more in- of pharmacology; and chief of University of California, Berkeley, he “The School of Medicine is clusive and to help underserved com- pulmonary, critical care, and sleep medicine, has received felt isolated on a campus where there strongly committed to promoting munities around the Yale campus.” the European Respiratory So- ciety Gold Medal in Interstitial Lung Disease, and been elected Albany Prize is awarded to investigator of proteins a Society fellow. Arthur L. Horwich, M.D., Sterling in a process called for his internship and residency Professor of Genetics, professor of “chaperone-mediated in pediatrics. He served as a Stefania Nicoli, pediatrics, and a Howard Hughes protein folding.” postdoctoral fellow first at Salk ph.d., assistant pro- Medical Institute investigator, is one “Protein folding Institute in the Tumor Virology fessor of medicine of three recipients of the 2016 Albany is a concept consid- Laboratory and then in the genet- (cardiology) and of Medical Center Prize in Medicine ered revolutionary ics department at the School of pharmacology, has and Biomedical Research, one of the in modern biology, Medicine, before joining the medi- received the 2016 most prestigious honors in medicine. with important cal school faculty in 1984. Springer Junior Investigator Award from the Horwich, F. Ulrich Hartl, M.D., Arthur Horwich implications for the He has received numerous honors of the Max Planck Institute, and treatment or delay including the Lasker Award for Basic North American Vascular Biol- ogy Organization. Nicoli is the Susan Lindquist, Ph.D., at the Mas- of Parkinson’s disease, Alzheimer’s Medical Research in 2011 and the first woman ever to receive this sachusetts Institute of Technology disease, Huntington’s disease, and Shaw Prize in Life Science and Medi- award, which was inaugurated will share the $500,000 prize for other neurodegenerative conditions, cine in 2012. He is a member of the in 2011. their discoveries about the biology of as well as cancer and drug resistance,” National Academy of Sciences and protein folding. says Vincent Verdile, M.D., the Lynne the National Academy of Medicine Proteins must be folded into a and Mark Groban, M.D. ’69, Dis- (formerly the Institute of Medicine). proper three-dimensional structure tinguished Dean of Albany Medical Horwich has studied ALS for Robert J. Touloukian, to carry out their functions, which College and chair of the Albany Prize several years, focusing on aspects m.d., professor are crucial to all life. The scientists National Selection Committee. that include protein quality control emeritus of surgery have shown that protein folding A Chicago native, Horwich mechanisms, in an effort to under- (pediatrics), has been named the inside cells does not occur sponta- received both his undergraduate stand exactly what causes the motor next president of neously as previously believed but and medical degrees from Brown failure and paralysis that are hall- the New England depends upon molecular “assistants” University, and then came to Yale marks of the disease. Surgical Society. His term begins in September 2017.
Taylor is elected to National Academy of Medicine Richard E. Carson, Hugh S. Taylor, M.D., Anita O’Keeffe Taylor earned a Bachelor of Arts research in repro- ph.d., professor of Young Professor and chair of the De- from Yale College in 1983, and his ductive medicine, radiology and bio- partment of Obstetrics, Gynecology, M.D. degree from the University of and was named medical imaging, and Reproductive Sciences; professor Connecticut School of Medicine in Mentor of the Year and of biomedical engineering; direc- of molecular, cellular and develop- 1988. He then returned to Yale for his by the American tor, Yale pet Center; mental biology; and chief of obstet- residency in obstetrics and gynecol- College of Obstetri- and director of rics and gynecology at Yale New ogy. His postdoctoral training at Yale cians and Gynecolo- graduate studies, Haven Hospital is one of 79 individu- included a fellowship in reproductive gists. In 2012, he biomedical engi- als elected in October to the National endocrinology and infertility as well Hugh Taylor was named Hon- neering; and D.S. Academy of Medicine (NAM). as a fellowship in molecular biology. oree of the Year by Fahmeed Hyder, Taylor’s clinical research centers He became an associate research the Endometriosis Association. ph.d., professor on implantation, endometriosis, and scientist in 1992 and joined the ladder The NAM (originally the Institute of radiology and menopause. His basic science research track faculty in 1998. of Medicine) was established in 1970 biomedical imaging and of bio- focuses on uterine development, the In 2015-2016, he served as presi- under the charter of the National Acad- medical engineering; technical regulation of developmental gene dent of the Society for Reproductive emy of Sciences to advise the nation on director, Magnetic Resonance Research Center; and program expression by sex steroids, endocrine Investigation, the leading academic medical and health issues. Members are director, Core Center for Quan- disruption, and stem cells. Taylor’s society in the field of obstetrics and elected by their peers for distinguished titative Neuroscience with work has led to, among other insights, gynecology, and presided over its contributions to medicine and health. Magnetic Resonance; have been a better understanding of endometrio- 2016 annual meeting. In 2013, he was At its annual meeting, NAM announced named Distinguished Investiga- sis, including its genetic cause and the awarded the IVI Foundation Inter- 70 new members from the United tors of the Academy of Radiol- role of stem cells in the disease. national Award for the impact of his States and nine international members. ogy Research.
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