december 2014 volume 10, issue 3 Advancing Biomedical Science, Education, and Health Care
Chair of biomedical engineering joins Institute of Medicine
Pioneering nanobiologist, in the fields of biomaterials, nano- that neurosurgeons biotechnology, and tissue engineer- implant in the brain to department founder, is ing, Saltzman has contributed to combat glioblastoma elected to prestigious corps the design and implementation of a multiforme (gbm), one number of clinical technologies that of the most aggressive W. Mark Saltzman, ph.d., Goizueta have become essential to medical types of malignant Foundation Professor of Chemical practice today. brain tumors. and Biomedical Engineering at the As a graduate student at the Saltzman has minia- School of Medicine, has been elected Massachusetts Institute of Technol- turized his slow-release to the Institute of Medicine (iom), ogy (mit), Saltzman built scaffolds polymers into spherical one of the most prestigious bodies in that could be seeded with cells to nanoparticles that can health and medicine. sculpt new replacement tissues. be taken up directly by Saltzman’s research at the inter- He also created drug-impregnated cells. In 2013, Saltzman section of basic science and trans- implants from polymers that slowly was part of an interdis-
lational research aims to promote and steadily release medicines for ciplinary Yale collabora- terry dagradi new methods for drug delivery and long periods—work that now helps tive team whose work led to a new W. Mark Saltzman, founding chair of the De- develop new biotechnologies to patients in the form of gliadel®, a treatment for gbm that has shown partment of Biomedical Engineering, is Yale’s combat human disease. A pioneer chemotherapy-loaded polymer wafer great promise in // IOM (page 4) newest member of the Institute of Medicine.
Neurosurgeon, a Taking a productive alliance further pioneer in genomic Renewing its commitment studies, is new chair to collaboration, an industry Murat Günel, m.d., leader bets on Yale science an accomplished neurosurgeon and In 2011 the School of Medicine geneticist, has been formed a research alliance with the named chair of the biopharmaceutical company Gilead School of Medi- Sciences, Inc. to accelerate the discov- cine’s Department ery and development of new drugs to of Neurosurgery treat cancer. Called “transformative” Murat Günel and chief of neuro- by then-Yale President Richard C. surgery at Yale- Levin, the collaboration included an New Haven Hospital (ynhh). initial commitment of up to $40 mil- Günel’s clinical expertise is in lion to support research at the medi- treating complex brain aneurysms and cal school over four years. vascular malformations, and brain tu-
Now, almost four years into the sacco william mors. His landmark genomic research collaboration, the commitment has has revealed the genetic risks for brain (Clockwise, from top left) Yale scientists Roy Herbst, Joseph Schlessinger, and Richard Lifton are been renewed for an additional three three of six members of the Yale-Gilead collaboration’s joint steering committee. The collabora- aneurysms, the mutational landscape years and supplemented with an ad- tion’s aim is to identify new molecular targets in order to develop new therapies for cancer. of brain tumors, and a multitude of ditional $30 million. genes fundamental in cortical develop- “Gilead is pleased to be continuing Since the collaboration’s incep- resistance—has fostered substantial ment. He succeeds Dennis D. Spencer, this important collaboration with Yale,” tion, scientists from Gilead and Yale and promising research. m.d., the Harvey and Kate Cushing said William Lee, ph.d., senior vice have engaged in a multidisciplinary In one part of the collaboration, Professor of Neurosurgery, who led president of research at Gilead. “Sig- research program to search for the ge- tumor samples are analyzed to iden- the department for 27 years and is a nificant progress has been made in this netic basis and underlying molecular tify gene mutations that disrupt nor- longtime mentor to Günel. first phase of our research partnership, mechanisms of many forms of cancer. mal cellular functions and promote “Murat is an exceptionally crea- and we will continue to work closely The goal—to identify new molecular the uncontrolled cell growth and tive scientist,” said Dean and Ensign with the team from Yale in an effort to targets in order to enable develop- metastasis seen in cancer. Thousands Professor of Medicine Robert J. Alpern, identify novel cancer therapies with the ment of novel targeted therapies, in- of genes from a diverse set of cancer m.d. “I am confident he’ll be a terrific potential to help patients.” cluding therapies that overcome drug types have been // Alliance (page 5) department chair. I am // Chair (page 5)
Non-Profit Org. inside this issue U. S. Postage 1 Church St., Suite 300, New Haven, CT 06510-3330 2 Lifelines www.medicineatyale.org paid Diagnostic radiologist Michele Johnson New Haven, CT pieces together clinical clues to solve Permit No. 526 medical mysteries. 3 Arming the immune system Research by Lieping Chen and colleagues is leading to a new class of cancer drugs. 5 The state of stem cells Connecticut’s support of stem cell research is a boon for School of Medicine scientists.
also Advances, pp. 3, 5 Out & About, p. 4
@YaleMed f /YaleMed
M@Y_October2014.indd 1 12/18/14 4:05 PM lifelines New pilot aims to help bridge gaps for new physicians
The School of A passion for solving prob- Medicine lems has fueled Michele has been Johnson’s career as a diag- named nostic radiologist. In 2014 by the she became the fi rst African- American woman named a Association of American Medi- full professor at the School cal Colleges (aamc) as one of of Medicine. 10 medical schools that will make up a pilot cohort to test the imple- mentation of the Core Entrustable Professional Activities (epas) for Entering Residency. These are new guidelines intended to help bridge the gap between patient care activities that new physicians should be able to perform on day
Michele Johnson shapiro harold one of residency training and those they feel ready to perform without direct supervision. The aamc released the new The mystery of medicine guidelines in June in response to Pursuing a passion for immediately saw the value in pairing finger trap. To restore blood flow in feedback from residency pro- problem solving, while X-ray clues with clinical knowledge to the brain after an acute stroke, she gram directors about the clinical diagnose patients: “I learned very early uses the contraption to snake through preparedness of entering residents, quietly making history that the more clinical information you vessels, latch onto blood clots, and pull and from emerging literature know and can apply, the stronger diag- them out the same way she went in. documenting a performance gap at As a college chemistry student in the nostician you are,” she says. One of the field’s biggest chal- the transition point between medi- 1970s, Michele H. Johnson, m.d., found After her internship and residency lenges, Johnson says, is training new cal school and residency training. herself intrigued by the television in diagnostic radiology at Temple Uni- radiologists to apply established The School of Medicine was show “Quincy, m.e.,” about a crime- versity and fellowship in neuroradiol- fundamentals in using newer, non- one of more than 70 aamc mem- solving forensic pathologist. In one ogy at the University of Pennsylvania, invasive technologies. Trainees need ber schools to apply for a spot in episode “they found a femur, and in Johnson returned to Temple to join the to develop the ability to take two- the pilot. The high number of a television hour, they came up with diagnostic radiology faculty. It was an dimensional images and make them applications “demonstrates the the drawing of the person. This is so exciting time to be in radiology, she three-dimensional in their heads. “Our signifi cant energy and commit- hokey,” Johnson says, but the show led says. Bolstered by the appearance of challenge as faculty is to teach that ment within academic medicine her to an idea: “Could I use chemistry non-invasive technologies like comput- effectively,” she says. toward closing the gap between to solve medical problems?” erized tomography (CT) and magnetic In 2012 Johnson completed a fellow- expectations and performance for Since then, problem-solving has resonance imaging (mri), the field ship in medical education through the residents on day one,” said Darrell formed the backbone of Johnson’s blossomed in the late 1970s and 1980s. medical school’s Teaching and Learning G. Kirch, m.d., aamc president own narrative. She has also followed in In 1999 Johnson came to Yale Center, to stay abreast of pedagogical and ceo. the footsteps of her mother, a chemist, School of Medicine (ysm), where today trends. She challenges students and The aamc is a not-for-profi t and her father, a neurochemist and she confronts medical mysteries rou- residents to think creatively and coop- association representing all 141 ac- the first African-American to receive a tinely. As professor of diagnostic radi- eratively when faced with novel situ- credited U.S. and 17 accredited ph.d. in chemistry from the University ology, neurosurgery, and surgery, like ations. “I try to teach trainees that it’s Canadian medical schools; nearly of Delaware. After earning her b.a. in any good detective, she throws herself more effective to be collaborative than 400 major teaching hospitals and chemistry at the same institution, she into every case. “We’re not just sitting confrontational,” says Johnson. “You health systems, including 51 De- entered medical school at Temple Uni- in a dark room looking at films,” says might even have fun in the process.” partment of Veterans Affairs medi- versity, where a medical “mystery” on Johnson. “We’re part of the patient In 2014, Johnson became the first cal centers; and nearly 90 aca- a rotation struck a familiar chord. care team, and I’m very proud that African-American woman named a full demic and scientifi c societies. It At St. Christopher’s Hospital for that’s an important part of what I do.” professor at ysm, but she doesn’t dwell represents 128,000 faculty mem- Children in Philadelphia, Johnson Johnson shows off photos on her on the subject. “I can teach technique bers, 83,000 medical students, and watched Marie Capitanio, m.d., chief ever-buzzing phone of one of the and anatomy,” she says. “Can I teach 110,000 resident physicians. of radiology, use a single chest X-ray latest advances in neuroradiology, students to work together successfully to diagnose both cystic fibrosis and a clot retrieval tool no wider than a for the patient’s benefit? That would sickle-cell disease in a teenager. She blood vessel that resembles a Chinese be the real legacy I’d aspire to.” Managing Editor Charles Gershman Contributors Divyansh Agarwal, Jenny Blair, Tim Cusack, Michael Fitzsousa, Sarah C.P. Williams Design Jennifer Stockwell For Yale’s renowned m.d./ph.d. Program, a changing of the guard Medicine@Yale is published four times each year by the Office of Institutional Planning and The School of Medicine’s Medical Tri-Institutional director for basic Communications, Yale School of Medicine, 1 Church St., Suite 300, New Haven, CT 06510-3330 Scientist Training Program (mstp), Program. She com- science of the m.d./ Telephone: (203) 785-5824 Fax: (203) 785-4327 known on campus as the m.d./ph.d. pleted residency ph.d. Program. E-mail [email protected] Program, has undergone a change in and fellowship train- Established in Website medicineatyale.org leadership for only the fi fth time in ing at the University 1969, the m.d./ Copyright ©2014 by Yale University. All rights reserved. If you have a change of address or do not wish to receive its 45-year history. James D. Jamie- of California– ph.d. Program future issues of Medicine@Yale, please write to us at the son, m.d., ph.d., professor of cell San Francisco. graduated its fi rst above address or via e-mail at [email protected]. biology and the program’s director Kazmierczak students in 1971. Postal permit held by Yale University, 155 Whitney Avenue, New Haven, CT 06520 for more than 30 years, stepped down has studied the Barbara Kazmierczak James Jamieson Jamieson led the this past summer. His successor is pathogen Pseudomo- program from 1974
Barbara Kazmierczak, m.d., ph.d. nas aeruginosa extensively, focusing to the present, with the exception Robert J. Alpern, m.d. Kazmierczak, associate professor on bacterial factors important for of the years 1983 to 1992, when he Dean and Ensign Professor of Medicine Charles Turner of medicine and microbial pathogen- establishment of disease and on host chaired the Department of Cell Biol- Director of Medical Development (203) 436-8560 esis, earned her bachelor’s and mas- responses to infection. She came to ogy. The program’s extraordinary Mary Hu ter’s degrees at the University of Chi- Yale in 2001 and has served as direc- success under Jamieson is refl ected Director of Institutional Planning and Communications cago, and her m.d./ph.d. at the Weill tor of graduate admissions for the by its 40 years of continuous support Cornell/Rockefeller/Sloan-Kettering microbiology track and as associate by the National Institutes of Health. Printed on recycled paper ♻
2 www.medicineatyale.org
M@Y_October2014.indd 2 12/18/14 4:05 PM advances Tackling cancer with a new paradigm Health & Science News Better predicting a Designed to guide the immune system in immunotherapeutic and chemotherapeutic agents. But fighting cancer, a new class of drugs is it also means researchers like Chen foresee a day when tumor’s treatability immunotherapy will replace chemo as a first-line altering the landscape of cancer treatment treatment for cancer. “The direction is very clear,” says Chen, also professor of immunobiology, dermatology, In the 1980s, immunotherapy researcher Lieping Chen, and medicine. m.d., ph.d., embraced the career goal of curing one cancer. Studies that place the burden of a cure solely on immuno- That lofty-seeming goal is beginning to look more modest therapeutic agents are already under way. Scott N. Gettinger, today. Recent clinical trials have shown that one cancer m.d., associate professor of medicine, for example, is studying after another is vulnerable to immune modulation therapy, nivolumab alone or in combination with other agents in
istockphoto a cancer-fighting strategy Chen pioneered that for years advanced lung cancer, with promising early results. Predicting whether a patient’s tumor was considered marginal. PD-1/PD-L1 inhibitors work by disrupting an immune will shrink in response to a treatment “Now it seems like I should retire, because I think these “shutdown” caused by tumors. Typically, when the immune has often been a bit of a guessing drugs can probably cure multiple cancers,” says Chen, the system’s T-cells arrive at cancer sites, they secrete cytokines, game. But this may be changing: Yale United Technologies Corporation Professor in Cancer which causes tumors and related tissues to make the protein researchers have identified a way to Research at the School of Medicine. “This is way beyond PD-L1. The PD-L1 then binds to PD-1, a receptor on the determine ahead of time whether a my expectations already. I’m very happy.” wide range of cancers will respond The drugs Chen refers to are a to mpdl3280A, an experimental group of immune modulation agents drug which blocks the protein PD-L1, called PD-1/PD-L1 inhibitors. These a critical “checkpoint” for the body’s are antibodies that allow the immune immune response to cancer. system to attack tumors by blocking a Roy S. Herbst, m.d., ph.d., Ensign pathway that paralyzes the immune re- Professor of Medicine, and colleagues sponse, and they’ve achieved dramatic monitored 175 patients before and clinical trial results for melanoma. after treatment with mpdl3280A. In September the fda approved pem- Across patients with a variety of brolizumab (marketed as Keytruda) tumors—including melanomas and for advanced melanoma, while Japan cancers of the lungs, kidneys, and co- approved nivolumab for the cancer lon—those with higher levels of PD-L1 in July. These drugs have also shown in their immune cells at the study’s startling effects in kidney and lung start responded better to treatment. cancer—the latter result a game- The findings, published Nov. 27 changer, since lung cancer is responsible in Nature, suggest a way of selecting for more deaths than any other cancer. patients for whom the new drug will These advances appear to be just work best and highlight the role of the start. Alone and in combination immune cells in the drug’s mecha- with many other agents, PD-1/PD-L1 nism. The research “could help us inhibitors are currently under intense
design new combination therapies,” scrutiny in hundreds of studies around shapiro harold Herbst says. the world, showing promise for treating Hodgkin’s Lieping Chen, the United Technologies Corporation Professor in Cancer lymphoma, bladder, stomach, ovarian, and head and neck Research, is a pioneer of immune modulation therapy, a cancer-fighting cancers. At Yale, researchers are building on groundbreak- strategy that employs antibodies to guide the immune system in To end brain tumor ing results from the last several years to study these agents fighting tumors. Research by Chen and School of Medicine colleagues has led to a new class of drugs that are proving to be more effective and growth: a switch? in a wide variety of solid and hematologic tumors. better tolerated than chemotherapy. Glioblastomas are among the most In July, Mario Sznol, m.d., professor of medicine, up- deadly cancers: fewer than 5 percent dated colleagues at the annual conference of the American arriving T-cells, paralyzing the immune response at the of those diagnosed with the brain Society of Clinical Oncology (asco) on a remarkable tumor site. PD-1/PD-L1 inhibitors come in two types: tumors will survive more than five Phase I melanoma trial. It combines nivolumab and another drugs that consist of antibodies to PD-1, such as nivolumab, years. Researchers know that multiple antibody, ipilimumab, in advanced melanoma patients. and drugs that consist of antibodies to PD-L1, such as different molecular pathways work in While ipilimumab acts on the unrelated ctla-4 checkpoint, MPDL3280A. Both types counteract this immune shutdown, concert to help the tumors grow, and together the drugs affect the immune system synergistically. allowing T-cells to proceed with the destruction of cancer they’ve struggled to find drugs that Nivolumab produces an already impressive 63 to 73 percent cells. (Incidentally, Chen discovered PD-L1 in 1999 at the block these cancer-enabling factors one-year survival rate, but when combined with ipilimumab Mayo Clinic.) all at once. the rates rose to 85 percent at one year and 79 percent at two The PD-1/PD-L1 inhibitors offer multiple and distinct Now, a team of School of Medi- years. (By comparison, chemotherapy offers this population advantages. Not only do they halt and shrink so many cine scientists has discovered a single of patients a two-year survival rate of around 20 percent.) advanced cancers, their effects also last much longer than protein that can simultaneously Early results appeared in 2013 in the New England Journal of those of chemotherapy, since the inhibitors bolster the weaken glioblastomas and make the Medicine. If confirmed in Phase III trials, Sznol says, “this patient’s immune system against his own cancer. And environment around the tumors less would be the most active combination that we’ve ever because the immune boost happens at tumor sites, most welcoming to the cancer. developed for melanoma.” side effects are minor or readily manageable, so the drugs Sourav Ghosh, ph.d., assistant Another PD-1/PD-L1 inhibitor, mpdl3280A, is in trial as are better tolerated than chemotherapy. “Patients don’t professor of neurology, Carla V. Roth- well. Half of a group of patients with advanced bladder even have to be hospitalized,” Chen says. “They walk in, sit lin, ph.d., assistant professor of im- cancer—who haven’t responded to standard therapy—have for a half-hour or one hour, and then leave.” munobiology, and colleagues showed responded to mpdl3280A, says investigator Daniel P. Yale researchers hope to develop biomarkers to identify that blocking the protein—called Petrylak, m.d., professor of medicine and urology. That, he the patients most likely to benefit from immunotherapeu- atypical protein kinase (apkc)—inac- says, “has been pretty much unheard of,” since no chemo- tic agents from those less likely, so they’re taking biop- tivated growth pathways in glioblas- therapeutic agent currently exceeds a 20 percent response sies from responders and non-responders to look for key tomas and reduced inflammation rate. Some patients’ tumors have become radiologically differences (see related story, “Better predicting a tumor’s in the surrounding tissue. In mice undetectable, and responses have lasted more than 18 treatability,” at left.). Some tumors, for example, express with glioblastomas, they discovered, months. Similarly, in 2013, Roy S. Herbst, m.d., ph.d., more PD-L1 than others, and so are more apt to respond to administering a drug targeting apkc Ensign Professor of Medicine, professor of pharmacology, an anti-PD-1/PD-L1 agent. shrunk tumors by more than half and chief of medical oncology at Yale Cancer Center and Researchers also plan to develop effective combina- in just a week. And in people with Smilow Cancer Hospital at Yale-New Haven, reported at tions with other immune modulatory agents as yet unde- glioblastomas, higher levels of apkc asco that mpdl3280A was durably shrinking advanced veloped and with other immunotherapy strategies. From were correlated with poorer progno- solid and hematologic tumors in 21 percent of patients. here, the possibilities seem nearly limitless. sis, they reported in the Aug. 12 issue Such results are prompting oncologists to rethink the “We used to have a paradigm in oncology that the of Science Signaling. role of chemotherapy, which damages the immune system amount of excitement is inversely correlated to the amount The findings suggest that drugs as it targets fast-dividing cancer cells. Immunotherapy, of clinical data that you have,” Sznol says. “Here, the excite- blocking apkc in humans could be an by contrast, relies on intact immunity. That difference ment is actually driven by very good clinical data. We’re just effective treatment for glioblastomas. makes it problematic to design trials that combine at the beginning of what we can do with these drugs.”
Medicine@Yale December 2014 3
M@Y_October2014.indd 3 12/18/14 4:05 PM out & about
May 30–June 1 Reunion Weekend drew more than 320 alumni and friends to cam- August 15 At the White Coat Ceremony, an annual event at which incoming medical pus. 1. (From left) Christiane Nockels Fabbri, p.a. ’84, ph.d. ’06; Remo Fabbri, m.d. ’64, students receive physicians’ jackets, the School of Medicine formally welcomed the 104 David Leof, m.d. ’64, and Colleen Leof recon- members of the Class of 2018. 1. The ceremony was held for the first time at Yale’s Wool- nect at their 50th reunion dinner. 2. (Back, 1 sey Hall. Pictured in the front row (from left) are Amber Anders ’18, Prince Antwi ’18, Wardah from left) Forrester A. “Woody” Lee, m.d. Athar ’18, Daniel Barson ’18, and William Biche ’18. 2. Nidharshan Anandasivam ’18 receives ’79, professor of medicine and assistant his white coat from Barbara I. Kazmierczak, m.d., ph.d., associate professor of medicine dean for multicultural affairs, with Dana and microbial pathogenesis and director of the m.d./ph.d. Program. 3. Sarah Amalraj ’18 Ugwonali, her husband Obi Ugwonali, m.d. (center) with her parents, Rajam and David Amalraj. 4. Robert J. Alpern, m.d., dean and ’79, Donald Moore, m.d. ’80, Sherri Sandifer, Ensign Professor of Medicine, with Katherine Chuang ’18. 5. Jonathan Marquez ’18 (second m.d. ’99, and Dannie Liggans. Front, from from right) with (from left) his grandmother Maria Zavala, aunt Natalia Ehlert, and mother,
left: Gabriella, Alex, and Nate Ugwonali. mike ross Maria Marquez.
2 1 2
3
4 5 john curtis
1 terry dagradi (5)
September 3 More than 100 people attended 2 ‘Just Blue It Up’, an event organized by members of the Section of Pulmonary, Critical Care and Sleep Medicine (pccsm) to raise money for the Pulmonary Fibrosis Foundation. 1. (From left) Erica L. Herzog, m.d., ph.d., associate professor of medicine; Danielle E. Antin-Ozerkis, m.d., as- sociate professor of medicine; Naftali Kaminski, m.d., the Boehringer-Ingelheim Professor of Medicine and chief of pccsm; Diane Reichert, creator of the Just Blue It Up campaign; Mridu 3 Gulati, m.d., assistant professor of medicine; and Issahar Ben-Dov, m.d., clinician. 2. Jennifer
Novicki (left) and Rochelle Goodwin, both senior john curtis administrative assistants. 3. Chad R. Marion, September 5 A friendly therapy dog named Finn receives some attention from Katie Hart, d.o., clinical fellow in medicine (left), with his senior administrative assistant at the Cushing/Whitney Medical Historical Library. Finn, a son, Myles, and Lauren Ferrante, m.d., clinical three-year old rescue and certified therapy dog, makes frequent visits around campus. Finn’s
fellow in medicine. john curtis (3) owner is Krista Knudson, r.n., a doctoral student at the School of Nursing.
// IOM (from page 1) animal studies. of the technology in humans with Robert J. Alpern, m.d. “Mark is not Saltzman’s achievements in the The treatment method involved de- gbm. In other projects with medical only a dynamic leader, but a resource- classroom have been recognized livering the fungicide dithiazanine colleagues, Saltzman is synthesizing ful and innovative collaborator. We are throughout his career, with teaching iodide via nanoparticle “carriers” and testing nanoparticles to deliver very proud of his election to the iom, awards from Johns Hopkins, Cornell, infused directly at the tumor site. gene-editing agents, novel anti-can- an honor he has truly earned.” and Yale, as well as the Distinguished Saltzman and his colleagues Joseph cer agents that block micrornas, mi- Saltzman received his b.s. in Lecturer Award from the Biomedical M. Piepmeier, m.d., Nixdorff- crobicides for preventing infectious chemical engineering from Iowa Engineering Society. German Professor of Neurosurgery, disease, and targeted approaches for State University and earned an m.s. The iom is an honorific mem- and Jiangbing Zhou, ph.d., assistant treating vascular disease. in chemical engineering and ph.d. bership body that also advises professor of neurosurgery and bio- “Mark Saltzman embodies the in medical engineering from mit. In lawmakers, health professionals, medical engineering, reported in the spirit of collaboration and innovation 2002, after serving on the faculties at and the public on health care and Proceedings of the National Academy that we prize at the School of Medicine, The Johns Hopkins University and health policy. Saltzman is one of of Sciences that the technology had which is so essential to the develop- Cornell University, Saltzman came to 37 School of Medicine scientists cured eight of 12 rats with tumors— ment of novel treatments for disease in Yale, where he was named founding who are members. He is among an unprecedented rate of success. today’s scientific climate,” says Dean chair of the Department of Biomedi- 70 new members and 10 foreign The team is now exploring the use and Ensign Professor of Medicine cal Engineering in 2003. associates elected to the iom.
4 www.medicineatyale.org
M@Y_October2014.indd 4 12/18/14 4:05 PM advances Yale stem cell research boosted by state Health & Science News A new piece of With seven grants, Connecticut’s Lawrence J. Rizzolo, ph.d., for instance, is using stem cells to research the retinal pigment epithelium (rpe), a the diabetes puzzle commitment to innovative research layer of cells in the human eye that protects the retina from strengthens Yale stem cell biology stray light, nourishes it, and maintains the light-sensitive cells. His eventual goal is to use stem cells to bioengineer Although a young and sometimes controversial field, stem a 3-D culture model of the retina, which would enable cell research has been hailed for its medical importance: scientists “to test new drugs, and could be transplanted into increasingly, medicine has turned to stem cell biology in diseased eyes to treat age-related macular degeneration,” treating a variety of human diseases—ranging from the says Rizzolo, associate professor of surgery and of ophthal- treatment of neuromuscular and liver diseases to the gen- mology and visual science.
istockphoto eration of skin grafts for burn victims. Funding from the state, federal sources, and private Since the 1990s, researchers have Weimin Zhong, ph.d., associate professor of molecular, donors, such as the Li Ka Shing Foundation and the G. struggled to explain how leptin, an cellular, and developmental biology, is getting at the root of enzyme that monitors how much en- what makes stem cells so medically valuable, studying how ergy our bodies generate, lowers high they balance their abilities to self-regenerate indefinitely, blood glucose in diabetic mice. Under- on one hand, and to develop into any kind of bodily cell or standing this mechanism, they’ve tissue, on the other. To better understand stem cell known, could pave the way for new regulation, the team is inducing mouse nerve stem cells to therapies for patients with type 1 and deviate from their normal patterns of replication. type 2 diabetes (T1D and T2D). Zhong’s research is being supported by a new grant In the July 2014 issue of Nature from the state of Connecticut, which this past June award- Medicine, members of the lab of Ger- ed $3.6 million to Yale stem cell researchers. While the ald I. Shulman, m.d., ph.d., George R. federal government has not always been fully supportive of Cowgill Professor of Medicine, report- stem cell research (between 2001 and 2009, federal fund- ed on a mechanism by which leptin ing for human embryonic stem cell research was restricted
mediates its action. The team ob- to a group of four cell lines), the state—partly in reaction to photo courtesy of lawrence rizzolo served that fasting T1D and T2D mice the federal restrictions—has staunchly supported stem cell Lawrence Rizzolo (left) aims to use stem cells to had low levels of leptin, and increasing research for nearly a decade. create a three-dimensional culture model of the human retina. (Above) The retinal pigment epithe- leptin levels reversed hyperglycemia. The grants are part of a 10-year $100 million commit- ment to stem cell research begun in 2006. Connecticut’s lium (rpe) sits on a bed of leaky capillaries (bottom They found that leptin inhibits the of image). To form a blood-retinal barrier, the rpe is hypothalamic-pituitary-adrenal (hpa) program aims “to foster an environment in our state where polarized. One protein (red) anchors other proteins axis, a critical neuroendocrine pathway scientists can pursue innovative research–work that is in the microvillar pole, to interact with photorecep- that regulates body processes such as already promising new therapies for debilitating diseases,” tors. In the basal pole, the green protein converts signals secreted by the capillaries. stress response. said Gov. Dannel P. Malloy. The results suggest “leptin The grants will fund seven projects at the Yale Stem could be an additional therapy [with Cell Center (yscc). Among these, the yscc received one Harold and Leila Y. Mathers Charitable Foundation, “has insulin] that could vastly improve of only two “core” grants of approximately $500,000 each, been integral in the growth of stem cell research at Yale blood glucose control” in diabetics, for continued support and technological development of from our beginning almost a decade ago,” says Haifan Lin, says lead author Rachel J. Perry, ph.d., the yscc’s shared facilities, including its five core labs. ph.d., professor of cell biology and genetics and yscc di- postdoctoral fellow in medicine. Some of the grants are funding research into understand- rector. “The state of Connecticut has been a critical partner, ing fundamental stem cell biology, such as Zhong’s project. enabling research that will help us better understand basic A step forward in Others are funding work targeted at specific disease states. biology and treat human disease.” treating Alzheimer’s // Alliance (from page 1) sequenced as a Professor of Medicine, professor of // Chair (from page 1) also grateful to Researchers have known that direct result of projects undertaken pharmacology, and chief of medical Dennis Spencer for his many years of STriatal-Enriched protein tyrosine as part of the collaboration. Rigor- oncology at Yale Cancer Center and outstanding leadership and service.” Phosphatase (step), an enzyme key ous analysis of these sequences has Smilow Cancer Hospital at Yale-New The Nixdorff-German Professor to regulating learning and memory revealed several recurring mutations, Haven; and Richard P. Lifton, m.d., of Neurosurgery, Günel led the largest in the brain, also plays a role in dis- believed to underlie the development ph.d., chair and Sterling Professor of international genome-wide associa- eases marked by cognitive defects: in of drug resistance in cancer, provid- Genetics, professor of medicine, and a tion studies of intracranial aneurysms, people with Alzheimer’s, Parkinson’s, ing key insights into the processes Howard Hughes Medical Institute in- identifying several susceptibility loci, schizophrenia, and other diseases, driving cancer progression. The find- vestigator. Also on the jsc are Gilead as published in two papers in Nature high levels of step disrupt the normal ings serve as an important catapult scientists Howard S. Jaffe, m.d., a 1982 Genetics. Through international col- development and strengthening of for further scientific discovery aimed alumnus of the School of Medicine laborations, his lab identified several the brain’s neurons. at finding potential cures. and president and chair of the board genes mutated in malformations of cer- Now, a team led by Paul J. Lom- The renewal agreement allows the of the Gilead Foundation; William ebral cortical development. The work broso, m.d., the Elizabeth Mears and collaboration to continue growing A. Lee, ph.d., senior vice president, resulted in publications in Nature and House Jameson Professor in the Child on several fronts. In addition to the research; and Linda Slanec Higgins, Nature Genetics, and recently in Cell and Study Center, has developed a drug sequencing initiative, Yale has also ph.d., vice president, biology. Neuron, in which a team led by Günel that inhibits step’s negative effects. launched biochemical and pharmaco- Under the terms of the initial identified mutations in the clp1 and For five years, Lombroso’s team logical studies to identify compounds agreement, the collaboration may katnb1 genes in patients with com- screened more than 150,000 com- that may lead to therapeutic candi- be renewed for up to 10 years and plex, structural brain abnormalities. pounds in search of one that blocks dates for certain cancers. These ef- funded with a total of up to $100 mil- In 2013 Günel was the senior author step activity. Eventually they landed forts have yielded promising results, lion, the largest corporate commit- of a pivotal manuscript published in on a drug called TC-2153. In the Aug. which will be further expanded in ment in Yale’s history. Yale maintains Science, which unveiled that somatic 5 issue of PLoS Biology, Lombroso’s this new phase of the collaboration. ownership of all intellectual property mutations in just five genes, including team reported that TC-2153 reversed Greater focus will also be placed on generated by School of Medicine re- two that have never been implicated in memory deficits in mice with an finding a single therapy that could be search, and Gilead has the first option abnormal tissue growth, or neoplasia, animal version of Alzheimer’s disease. used in multiple cancers. to license and develop any compound can explain the mutational landscape By entering the brain and effectively “We could not have asked for a it deems promising. of a majority of meningiomas, the most binding to and inhibiting step, the better start to our partnership with “The pace of scientific exchange common type of brain tumor. This and drug prevented the protein from dis- Gilead,” says Joseph Schlessinger, and innovation spurred by our work other genomic studies have formed the rupting synaptic activity in neurons. ph.d., chair and the William H. Pru- together is unlike anything I have basis of personalized treatments for The researchers are now testing soff Professor of Pharmacology, di- seen before,” Schlessinger says. brain tumor patients now ongoing at the compound in other animals with rector of the Cancer Biology Institute “If our accomplishments over the the School of Medicine and ynhh. cognitive defects. “Successful results on Yale’s West Campus, and chair of past three years are any indication, Also professor of genetics and will bring us a step closer to testing a the collaboration’s six-member joint we are confident that our future neurobiology, Günel earned his medi- drug that improves cognition in hu- steering committee (jsc). endeavors will significantly advance cal degree from Istanbul University mans,” says Lombroso, also professor Yale’s jsc members also include our current understanding and and completed his internship and of neurobiology and psychiatry. Roy S. Herbst, m.d., ph.d., Ensign treatment of cancer.” residency in neurosurgery at ynhh.
Medicine@Yale December 2014 5
M@Y_October2014.indd 5 12/18/14 4:05 PM 5 years, $2,081,250 • Naftali Kaminski, nih, Oncolytic Virotherapy with Type III Interferon, Grants and contracts awarded Gene Networks beyond Organ Boundaries: 2 years, $391,701; nih, A New Humanized Heart, Lung and Pulmonary Vascular Disease, Mouse Model of Chronic Hepatitis B, 2 years, 1.8 years, $1,025,715 • Erdem Karatekin, nih, $456,349 • John Rose, nih, R56 Development of to Yale School of Medicine Nucleation and Dynamics of Exocytotic Fusion Chimeric Vesiculo/Alphaviruses as an Alphavi- Pores, 5 years, $2,236,569 • Kenneth Kidd, rus Vaccine, 2 years, $1,156,616 • Marc Rosen, July 2013–February 2014 Department of Justice, High Resolution snp nih, sbirt (Pain Management) for Veterans Panels for Forensic Identification of Ancestry, Filing Compensation Claims, 2.8 years, Family, and Phenotype, 2 years, $952,255 • Tae $554,003 • Craig Roy, nih, Modulation of Host Federal Hoon Kim, nih, Nuclear, Genomic and Molecu- Cell Function by Coxiella Burnetii, 1 year, Chadi Abdallah, nih, Examining the Effect Inflammasome Driven Immune-Metabolic lar Regulation of Type I Interferon Transcription, $416,250 • Robert Schonberger, nih, Integrat- of Ketamine on Glutamate/Glutamine Cycling, Interactions, 1.9 years, $524,616; nih, Thymic 2 years, $445,290 • Harriet Kluger, nih, A ing Perioperative Care into Treatment of Hyper- 5 years, $907,630 • Clara Abraham, nih, Adipogenesis and Age-Related Thymic Demise, Research and Training Program for Junior Clini- tension, 5 years, $688,165 • William Sessa, nih, Functional Outcomes of Inflammatory Bowel 1.8 years, $391,275 • Ronald Duman, nih, cians in Treating Metastatic Melanoma, 5 years, Phosphorylation and Endothelial Nitric Oxide Disease Associated Variants, 4.7 years, Research Training–Biological Sciences, 5 years, $780,420 • Monica Lee, nih, An Isoform- Production, 4 years, $1,645,020 • Gerald $1,810,690 • Serap Aksoy, nih, Expanding $1,474,532 • James Duncan, nih, Integrated Specific, Conditional Deletion Approach to Deci- Shadel, nih, Nuclear Control of Mitochondrial the Toolbox for Tsetse Reproductive Biology, RF and B-Mode Deformation Analysis for 4D pher Akt1 and Akt2 Function, 3 years, $157,590 Gene Expression, 4.7 years, $1,661,695 • Robert 2 years, $427,572; nih, Tsetse Transmitted Stress Echocardiography, 4 years, $3,587,112 Robert Leeman, nih, Testing Automatic Action- Sherwin, nih, Glucoregulatory Hormone Inter- African Trypanosomiasis, 5 years, $1,216,240 Stephanie Eisenbarth, nih, Regulation of Tendency Retraining in Heavy Drinking Young actions in Diabetes, 4.9 years, $2,964,725 Nadia Ameen, nih, Functional Relevance of Adaptive Immunity by the nod-like Receptor Adults Using a Novel Self-Administration, Frederick Shic, nih, Gaze Modification Strate- cftr Trafficking In Vivo to Intestinal Disease, nlrp10, 5 years, $2,081,250 • Shawn Ferguson, 2 years, $141,900 • Chiang-Shan Li, nih, Cere- gies for Toddlers with asd, 2 years, $457,875 5 years, $1,810,690 • Amy Arnsten, nih, nih, Molecular Mechanisms that Match Lyso- bral Correlates of Early Habitual Drinking, Frederick Sigworth, nih, Cryo-EM Structure of Highly Evolved Brain Circuits in Primates: some Function to Cellular Demand, 4.7 years, 5 years, $1,189,310; nsf, A Computational and a Membrane-Embedded Glutamate Receptor, Molecular Vulnerabilities for Disease, 4.7 years, $1,570,517 • Carlos Fernandez-Hernando, nih, Neuroimaging Investigation of Prediction and 2 years, $454,550 • Michael Simons, George $4,162,499; nih, Potential mGLuR Treatment Caveolin-1 in Lipoprotein Metabolism and Ath- Learning in Cognitive Control, 3.8 years, Tellides, nih, Angiogenesis and Ischemia, of Age-Related Cognitive Decline, 4.7 years, erosclerosis, 3 years, $1,404,348; nih, Role of $489,315 • Richard Lifton, nih, Genetics and 4 years, $2,274,578 • Michael Simons, Anne $3,201,204 • Peter Aronson, nih, Methods Microrna in Lipid Metabolism and Cardiovascu- Genomics of Human Disease, 4.7 years, Eichmann, nih, Syndecan Function in Endothe- in Nephrologic Research, 5 years, $2,147,254 lar Disease, 2 years, $966,307 • Karin Finberg, $1,570,470 • Kasia Lipska, nih, Toward Person- lial Cells, 3.9 years, $1,973,462 • Rajita Sinha, Renata Belfort De Aguiar, nih, Effect of Circu- nih, Identification of Novel Genes that Modu- alized Diabetes Care: Understanding Hypogly- Carlos Grilo, Robert Sherwin, nih, Food Cues, lating Glucose on Eating Behavior and Brain late Systemic Iron Homeostasis, 11 months, cemia in Older Adults, 2 years, $166,500 Stress and Motivation for Highly Palatable Activation in Diabetes, 3.8 years, $594,071 $157,699 • Helen Fox, nih, Stress System Xingguang Luo, nih, Deep Sequencing of Genes Foods, 5 years, $3,012,326 • Mehmet Sofuoglu, Titus Boggon, nih, Molecular Assembly and Changes in Alcoholics with and without in Ethanol-Metabolism Pathway in Alcoholism, nih, Cholinergic Enhancement as Treatment for Regulation of the Cerebral Cavernous Malfor- Depressive Symptomatology, 1.9 years, $141,900 2 years, $343,613 • Charles Lusk, nih, Establish- Nicotine Addiction, 2 years, $376,106 • Mark mation Complex, 5 years, $1,821,095 • Pramod James Freeman, nih, Comparative Effective- ing a Blueprint for Nuclear Pore Complex Solomon, nih, Biochemistry of the Anaphase Bonde, nih, Characterization and Safety ness of Catheter Ablation Compared with Assembly, 4.8 years, $1,568,666 • Thomas Promoting Complex-Mediated Ubiquitination, Profiling for Wireless lvads, 2 years, $419,354 Medical Therapy for Atrial Fibrillation, 4.7 years, Lynch, Henry Durivage, nih, Yale Comprehen- 3.8 years, $1,262,872 • Stefan Somlo, nih, Angelique Bordey, nih, tsc-mtor on Neuron $787,160 • Alison Galvani, nih, Evaluating the sive Cancer Center Support Grant, 4.9 years, Mechanisms of Polycystin and Cilia Function in Development, 5 years, $1,835,806 • Elizabeth Social Influences that Impact Vaccination Deci- $12,405,033 • Shuangge Ma, nih, Development adpkd, 4.7 years, $1,810,690 • Serena Spudich, Bradley, dhhs, Yale Training Program in Health sions, 4.7 years, $1,550,019 • Kseniya Gavrilov, of Integrated Analysis Methods and Applica- nih, Central Nervous System Events in Primary Services Research, 5 years, $1,477,429 • Judson nih, Suppression of bcr-abl by sirna-loaded tions to tcga Data, 2 years, $166,500 hiv Infection, 1.8 years, $349,559 • Vinod Brewer, nih, Augmenting Mindfulness Training Nanoparticles for the Treatment of Chronic Kathleen Martin, nih, Regulation of Vascular Srihari, nih, step-ed: Reducing Duration of Through Experience-Driven Neurofeedback Myeloid Leukemia, 2.9 years, $127,584 • Joel Smooth Muscle Cell Plasticity, 4 years, Untreated Psychosis and its Impact in the U.S., Devices (attend), 5 months, $316,350 • Richard Gelernter, nih, Genetics of Opioid Dependence, $1,665,000 • Kathleen Martin, nih, Novel 4.9 years, $3,690,681 • Mario Strazzabosco, Bucala, nih, Mechanisms of Rheumatoid Syno- 4.9 years, $4,665,445 • Thomas Gill, nih, Aca- Targets of Rapamycin in vsmc, 5 years, nih, Epithelial Angiogenic Signaling in Polycys- vial Fibroblast Activation, 4.9 years, $1,769,065 demic Leadership Award in Disability and Dis- $2,061,270 • Graeme Mason, nih, Brain tic Diseases of the Liver, 4.8 years, $1,810,690 Christopher Burd, nih, Sorting and Trafficking abling Disorders, 5 years, $644,564 • Antonio Acetate and Ethanol Metabolism in Alcohol Samantha Streicher, nih, Genome-Wide Case- in the Endosomal System, 3.9 years, $1,465,200 Giraldez, nih, The Role of Micrornas in Verte- Dependence and Abuse, 5 years, $2,730,603 control Association Study of Pancreatic Cancer David Calderwood, nih, Filamin Interactions in brate Development, 4 years, $1,265,400 • Elena Aditi Mathur, nih, Role of Plexin C1 in Sclero- in Jews, 2 years, $84,464 • Yajaira Suarez, nih, Differentiation, Invasion and Disease, 3.8 years, Grigorenko, National Institute of Justice/ derma Related Interstitial Lung Disease, Micrornas in Endothelial Cell Activation, $1,378,140 • Michael Caplan, nih, Training Department of Justice, Trends in Juvenile 9 months, $51,185 • Sherry McKee, nih, Does 3 years, $1,454,067 • Denis Sukhodolsky, nih, Program in Molecular Medicine, 5 years, Criminal Case Processing and Education, 1 year, Guanfacine, an Alpha2 Adrenergic Agonist, Using cbt to Examine Circuitry of Frustrative $811,453 • Jessica Cardin, nih, gabaergic Contri- $39,976 • Jhumka Gupta, United States Insti- Attenuate Stress-Induced Drinking? 4 years, Non-Reward in Aggressive Children, 4 years, butions to Neural Circuit Deficits in Schizophre- tute of Peace, Adapting Innovative Programs $1,498,500 • James McPartland, nih, Neural $1,665,000 • Patrick Sung, nih, Formation and nia, 5 years, $2,081,250 • Owen Chan, nih, for Women’s Social and Economic Empower- Markers of Shared Gaze during Simulated Social Resolution of Recombination Intermediates, Mechanisms of Counter-Regulatory Failure, ment and Reduction of Gender-Based Violence Interactions in asd, 2.8 years, $1,248,750 3.7 years, $1,191,308 • Richard Sutton, nih, Host 4.8 years, $1,810,690 • Sreeganga Chandra, in Abidjan, Côte d’Ivoire, 1 year, $108,706 Wajahat Mehal, nih, Regulation of Hepatic Genetic Control of hiv, 4.7 years, $3,710,300 nih, Roles of the cspalpha Chaperone Complex Stephanie Halene, DoD, Assessing the Mecha- Repair Response by Metabolites of the Uric Acid Seyedtaghi Takyar, nih, mir-1 is a Critical Regu- in Presynaptic Maintenance and ancl, 5 years, nisms of mds and its Transformation to Leuke- Pathway, 1 year, $333,000 • Ana-Claire Meyer, lator of vegf-Induced Angiogenesis, 3 years, $1,821,795 • Sandy Chang, nih, Telomere Repli- mia in a Novel Humanized Mouse, 2 years, nih, Treatment of hiv- Associated Cognitive $735,048 • Peter Tattersall, Susan Cotmore, cation and Maintenance of Genome Stability, $399,600 • Marc Hammarlund, nih, Identifica- Impairment, 3 years, $405,299 • Wang Min, nih, Molecular Genetics of Parvoviral dna Repli- 2 years, $457,875 • Katarzyna Chawarska, nih, tion of Transcriptional Targets of the dlk-1 nih, The Role of Signaling Molecule aip1 in cation, 5 years, $2604392 • Nicholas Theodo- Components of Emotional Processing in Tod- Axon Regeneration Pathway, 2 years, $480,811 Pathological Angiogenesis, 3.9 years, $1,657,751 sakis, nih, Evaluation of braf-Inhibitor Induced dlers with asd, 4.7 years, $3,412,696; DoD, Edward Herman, nih, The Role of Follicular Andrew Miranker, nih, Predoctoral Program in Alterations in Glucose Metabolism, 3 years, AR120201 Subtyping of Toddlers with asd Based Helper T Cell Cytokines in the IgE Response, Biophysics, 5 years, $2,634,620 • Lauren Moore, $141,696 • Mary Tinetti, Heather Allore, nih, on Patterns of Social Attention Deficits, 3 years, 3 years, $122,628 • Amanda Hernandez, nih, nih, Mechanistic and Biomarker Studies on Health Outcome Effects of Common Medica- $665,455 • Michael Choma, nih, Quantitative Sodium Chloride Induced Dysregulation of Cancer Progression and Taxane Resistance, tions in Elders with Multiple Conditions, Optical Imaging of Cilia-Driven Fluid Flow, CD4+CD25+ Regulatory T Cells in MS, 2 years, 3 years, $106,705 • Brent Moore, nih, Auto- 1.7 years, $457,875 • Susumu Tomita, nih, Regu- 4.9 years, $2,052,945; nih, Development of a $80,249 • Kevan Herold, nih, Analysis of Beta mated Recovery Line for Medication-Assisted lation of Glutamate Receptors by Calcium- New Light Source for Parallel Optical Coherence Cell Death in Type 1 Diabetes, 2.9 years, Treatment, 2.9 years, $1,073,006 • Evan Morris, Dependent Protein Kinase, 2 years, $832,500 Tomography, 2 years, $435,006 • Geoffrey $806,617 • Raimund Herzog, nih, Human nih, Endotoxin-Induced Inflammation Affects Derek Toomre, nih, Dynamics of Exocyst Chupp, nih, Longitudinal Analysis of Transcrip- Brain Ketone Metabolism in Type 1 Diabetes Striatal Dopamine: A Raclopride pet Study, Recruitment and Assembly, 3 years, $1,048,950 tomic Endophenotypes in Asthma, 3.8 years, and Hypoglycemia, 2 years, $164,219 • Karen 1.7 years, $457,875; nih, pet Imaging of Naltrex- Alda Tufro, nih, Function of Semaphorin3a in $3,144,566 • Daniel Cifuentes Buira, nih, Hirschi, nih, Neurovascular Regeneration, one Occupancy of Kappa Receptors in Heavy Diabetic Nephropathy, 3.9 years, $999,000 Analysis of the Molecular Machinery of 5 years, $4,751,619 • Mark Hochstrasser, nih, Drinkers, 5 years, $3,219,529 • Richard Nowak, Benjamin Turk, nih, Modeling Human Phos- Microrna-Processing Pathways, 2 years, Functions and Mechanisms of Deubiquitinating David Hafler, Jonathan Goldstein, nih, A Phase phorylation Networks through Kinome-Wide $217,334 • Victoria Clark, nih, Characterizing Enzymes, 3.7 years, $1,334,722 • Rafaz Hoque, II Trial of Rituximab in Myasthenia Gravis, Profiling, 4.7 years, $2,401,355 • Flora Vacca- the Genomic Architecture and Molecular Mech- nih, gpr81 & gpr109a Regulate Innate Immune 3.9 years, $4,125,866 • Chirag Parikh, nih, Pro- rino, nih, Genomic Mosaicism in Developing anisms Driving the Formation of Non-NF2 Injury in Sterile Inflammation, 2 years, gression of Acute Kidney Injury to Chronic Human Brain, 5 years, $3,515,307 • Wendilywn Meningiomas, 3 years, $137,345 • Robert $166,500 • Mark Horowitz, nih, Myeloid Kidney Disease, 4.9 years, $2,379,999 • Godfrey Walker, Richard Sutton, nih, Investigating the Constable, nih, O-Space Imaging-Accelerating Lineage Differentiation and Osteoclast Priming Pearlson, nih, 3/4 Psychosis and Affective Genetic Basis of CD4-Intrinsic hiv Control, mri with Z2- Gradient Encoding, 3.9 years, by a Novel Pax5 Cytokine, 2 years, $389,193 Research Domains and Intermediate Pheno- 5 months, $76,614 • Rong Wang, nih, Compar- $2,004,429 • Kelly Cosgrove, nih, Microglial Yiyun Huang, Nabeel Nabulsi, Richard Carson, types, 2.9 years, $782,105 • Manoj Pillai, nih, ative Effectiveness of Treatments for Acute Activation in Alcohol Dependence: A[C-11]pbr28 Wendol Williams, nih, Novel pet Tracers for Role of Micornas in Regulation of the Marrow Myeloid Leukemia in the Elderly, 2 years, pet Study, 2 years, $429,882 • Pietro De Camilli, Imaging Kappa Opioid Receptor, 3 years, Microenvironment (R01HL104070), 2.6 years, $164,003 • Sherman Weissman, nih, Cytokines nih, ocrl and the Pathogenesis of Lowe Syn- $2,030,642 • Natalia Ivanova, nih, Epigenetic $1,416,035 • Lori Post, National Institute of and Lineage Choice in Hematopoietic Precur- drome and Dent Disease, 4 years, $1,158,840 Control of the Pluripotent State by Chromatin- Justice/Department of Justice, Evaluation of sors, 2.8 years, $869,130 • Nicole Wilson, nih, Jonathan Demb, nih, Neural Circuits and Syn- Associated Factor Dppa2, 5 years, $1,644,190 the Domestic Violence Homicide Prevention Ini- Elucidating the Connections between the sumo apses for Early Visual Processing, 5 years, Joshua Johnson, nih, Use of Fragile X Premuta- tiative, 4 years, $1,899,856 • Marc Potenza, Pathway and the ER Stress Response, 2 years, $2,081,250 • Francesco D’Errico, Department tion Knock-In Mouse to Study fxpoi, 1.8 years, nih, Neural Mechanisms of cbt in Cocaine $52,464 • Adam Wisnewski, dhhs, Biochemis- of Homeland Security, ari-ma Superheated $480,739 • Elizabeth Jonas, Hongmei Li, Dependence, 4 years, $2,393,220 • Helen Push- try Connecting Glutathione and Isocyanate Emulsions for Nuclear Material Detection, Kambiz Alavian, nih, Role of Bcl-xL in Neuronal karskaya, nih, Neural Correlates of the Uncer- Asthma, 2 years, $452,011; dhhs, Signature 2 years, $155,011 • Sabrina Diano, nih, Role of Mitochondrial Calcium Dynamics, 2 years, tainty Intolerance in Obsessive Compulsive Dis- Peptide Approach to Biomonitor mdi Exposure, Peroxisome Proliferation in Leptin Resistance, $455,793 • Celina Juliano, nih, Identifying order, 4.3 years, $730,772 • Yibing Qyang, nih, 2 years, $448,083 • Dianqing Wu, nih, Sus- 3.9 years, $1,448,552 • Vishwa Dixit, nih, Targets of the Piwi/pirna Pathway in Stem Human Tissue-Engineered Blood Vessels Using tained Signaling for Fibroblast Migration, Impact of Obesity and Weight-Loss Interven- Cells, 4 years, $474,660 • Michael Jurczak, nih, Induced Pluripotent Stem Cells, 4.8 years, 3.8 years, $1,636,695 • Qin Yan, DoD, Targeting tions on Immune-Surveillance Mechanisms, Parkin’s Role in Hepatic Mitochondrial Turnover $2,061,270 • Lynne Regan, nsf, Stimuli- Epigenetic Regulator jarid1b in Malignant Mel- 1 year, $822,374; nih, Impact of Calorie Restric- and Steatosis and Insulin Resistance, 2.8 years, Responsive Nano-Materials from Designed Pro- anoma, 2 years, $399,600 • Jun Yu, nih, Role of tion on Thymopoiesis in Humans, 3 months, $441,339 • Amy Justice, nih, chaart Consortia teins, 3 years, $450,000 • Valerie Reinke, nih, rtn-4 in Artherosclerosis, 11 months, $416,250 $66,150; nih, Inflammasomes and the Mecha- Scientific Meetings, 3 years, $226,365 • Arie Deciphering Mechanisms Governing Functional Christina Yuan, dhhs, Understanding How nisms of Thymic Demise in Aging, 5 years, Kaffman, nih, Microglia Play a Critical Role in Partitioning of the C. elegans Genome, 4 years, Social Influence and Social Networks Affect emr $1,837,398; nih, Impact of CR on the Long-Term Sequelae of Early Life Stress, $1,265,399 • Michael Robek, nih, Enhancing Implementation, 1.3 year, $39,853
6 www.medicineatyale.org
M@Y_October2014.indd 6 12/18/14 4:05 PM Non-federal Treatment Network (uitn), 1 year, $36,921 $176,395; Nancy Taylor Foundation for Chronic $227,546 • Priti Kumar, Connecticut Innova- Chadi Abdallah, American Psychiatric Associa- Yung-Chi Cheng, National Foundation for Diseases, Human Genetic Variation in Cytokine tions, Human ES-Derived Neuronal Cell Culture tion, Examining the Effect of Ketamine on Glu- Cancer Research, nfcr Fellow Renewal, 3 years, Signaling Pathways and Susceptibility to Auto- Systems for Investigating West Nile Virus Patho- tamate/Glutamine Cycling in Healthy Subjects, $225,000 • Keith Choate, Doris Duke Charita- immune Disease, 2 years, $230,000; Dana genesis, 2 years, $200,000 • TuKiet Lam, Cerno 3.1 years, $45,000 • Parwiz Abrahimi, The Paul ble Foundation, Genetics and Pathobiology Farber Cancer Institute (nih), Project 3: T:B Col- Bioscience (nih), High Accuracy and High & Daisy Soros Foundation, The Paul & Daisy of Mosaic Skin Disorders, 1.5 years, $64,800 laboration and Induction of Autoimmune Throughput MS Screening for Large Numbers of Soros Fellowship for New Americans, 2 years, Hyung Chun, American Diabetes Association, Tissue Inflammation, 5 years, $35,279 • James Compounds in Complex Food Samples, $40,000 • Fuad Abujarad, Michigan Licens- Role of gpcr Mediated FoxO1 Regulation in Dia- Hansen, Radiological Society of North 10 months, $39,023 • Eli Lebowitz, Brain & ing and Regulatory Affairs (dhhs), Michigan betic Endothelial Dysfunction, 3 years, America, Targeting Glioblastoma with a Lupus Behavior Research Foundation, Motion Track- Workforce Background Check-Enhancement, $310,500; American Heart Association, Endo- Autoantibody, 2 years, $152,000 • Kevan ing for the Study of Avoidance in Anxiety Disor- 2.6 years, $468,911 • Meenakshi Alreja, Foun- thelium in Health and Disease: Pursuit of Novel Herold, jdrf, Epigenetic Modifications of the ders, 2 years, $58,121 • Patty Lee, Flight Atten- dation for Prader-Willi Research, Oxytocin Mechanisms to Promote Vascular Homeostasis, Insulin Gene in Response to Beta Cell Stress, dant Medical Research Institute, tlr4-Medi- Actions on Prefrontal Cortical Circuits in a 5 years, $400,000 • Elizabeth Claus, Acoustic 5 years, $739,564; Albert Einstein College of ated Emphysema: Role of Aging, 3 years, Mouse Model of Prader-Willi Syndrome, 2 years, Neuroma Association, Genetic Epidemiology of Medicine (nih), Impact of hsv-2 on Female $325,500 • Chun Geun Lee, Brown University $108,000 • George Anderson, University of Acoustic Neuroma, 2 years, $49,199 • Eve Genital Tract Mucosal Immunity and hiv Infec- (nih), mapGen-Yale and Collaborators Supple- Southern California (DoD), Altered Placental Colson, The Doctors Company Foundation, tion, 1.2 years, $103,230; Juvenile Diabetes mental Proposal, 10 months, $16,925; Brown Tryptophan Metabolism: A Crucial Molecular Reform Health Professional Curriculum at Yale, Research Foundation International, ITN027AI University (nih), Distinct and Overlapping Pathway for the Fetal Programming of Neuro- 3 years, $200,000 • Gianfilippo Coppola, Brain Follow up Study Proposal, 2 years, $211,284; Pathways of Fibrosis and Emphysema in Ciga- developmental Disorders, 1 year, $68,761 • Emily & Behavior Research Foundation, Integrative Juvenile Diabetes Research Foundation Inter- rette Smokers, 10 months, $81,322 • Rafael Ansell, George Mason University (nih), Parent- Regulatory Network Analysis of ipscs Derived national, Phase II Trial of Bydureon in Patients Lefkowitz, University of Washington, Seattle Adolescent Iterations and Substance Abuse Risk: Neuronal Progenitors from Macrocephalic asd with Established Type 1 Diabetes, 3 years, (dhhs), Assessing Hearing Conversation Effec- Gender Differences, 4 years, $205,401 • Nicolas Individuals in a Family-based Design, 2 years, $2,221,714 • Erica Herzog, Bristol-Myers Squibb tiveness, 1 year, $225,200 • Judith Lichtman, Baeyens, American Heart Association (Found- $60,000 • Philip Corlett, International Mental Company, Innovative Studies of Pulmonary American Heart Association (Founders Affili- ers Affiliate), Mechanism of Directional Flow Health Research Organization, Potassium Fibrosis, 3 years, $250,000 • Michael Higley, ate), Preventable Readmission after Ischemic Sensing by Endothelial Cells and Atherogenesis, Channels and Prediction Error: Targeting Schizo- Simons Foundation, Regulation of Cortical Cir- Stroke in the Elderly, 3 years, $197,248 2 years, $92,300 • Sviatoslav Bagriantsev, phrenia with Retigabine, 3 years, $150,000 cuits by tsc1 in gabaergic Interneurons, 1 year, Janghoo Lim, National Multiple Sclerosis American Heart Association, Studying a Novel Joseph Craft, University of Massachusetts $69,443 • Erin Hofstatter, Terri Brodeur Breast Society, The Role of Nemo-like Kinase in Oligo- Role for K2P Channels as Excitatory Conduits (nih), Toll-Like Receptors in Systemic Autoim- Cancer Foundation, Evaluation of Age-related dendrocyte Development, 1 year, $44,000 in the Heart and Brain, 4 years, $308,000 mune Disease, 9 months, $198,163 • Larry Epigenetic Changes in the Breast as Risk Factors Haifan Lin, Diane Krause, Connecticut Innova- Oscar Bartulos-Encinas, Connecticut Innova- Davidson, New York University (nih), Person for Breast Cancer Development, 2 years, tions, Continued Service and Technology Devel- tions, Cell Therapy with ISL1+ Cardiovascular Centered Care Planning and Service Engage- $100,000 • Rafaz Hoque, The Global Fibrosis opment at the Yale Stem Cell Center Cores, Progenitor Cells for Cardiac Repair after Myo- ment, 1.3 years, $203,565 • Vishwa Dixit, Albert Foundation, gpr109a and gpr81 Agonists as 1 year, $500,000 • Yi-Hwa Liu, American Heart cardial Infarction, 2 years, $200,000 • Chyrell Einstein College of Medicine (nih), Glia- Novel Therapies for Pancreatic Injury and Fibro- Association (Founders Affiliate), Detection, Bellamy, Patient-Centered Outcomes Research Neuron Interaction via ikk-beta/NF-kappaB in sis, 1 year, $30,000 • Tamas Horvath, Vander- Correction and Quantification Methods for Institute, Increasing Health Care Choices and Obesity and Related Pre-T2D, 3 months, $25,752 bilt University (nih), Molecular and Cellular Molecularly Targeted spect/CT Imaging of the Improving Health Outcomes Among Persons Seth Dodds, OMeGA Medical Grants Associa- Basis for the Efficacy of Bariatric Surgery, 1 year, Heart, 3 years, $198,000 • Chi Liu, American with Serious Mental Illness, 3 years, $2,080,934 tion, OMeGA Grant for Orthopaedic Grand $47,388 • Jeannette Ickovics, Patrick and Cath- Heart Association, Quantitative Dynamic Michael Bloch, Brain & Behavior Research Rounds and Visiting Professorship, 11 months, erine Weldon Donaghue Medical Research spect/CT Imaging of Cardiac Sympathetic Foundation, Double-Blind, Placebo-Controlled $2,500 • Deepak D’Souza, Brain & Behavior Foundation, Evaluation of the Early Consumer Innervation, 3 years, $197,859 • Arya Mani, Trial of N-Acetylcysteine for Pediatric Obsessive- Research Foundation (formerly narsad), Con- Experience Enrolling into Access Health CT, American Diabetes Association, The Mecha- Compulsive Disorder, 2 years, $58,254; Robert sequences of Chronic, Heavy, Early Cannabis 9 months, $15,000 • Melinda Irwin, Breast nisms of Combined Hyperlipidemia Caused by E. Leet and Clara Guthrie Patterson Trust, A Use, 2 years, $99,185 • Lydia Dugdale, Univer- Cancer Research Foundation, Biological and Altered Wnt Signaling, 3 years, $310,500 Randomized, Placebo-Controlled Crossover Trial sity of Chicago, Care of the Dying Patient: Rec- Biochemical Effects of Exercise and Diet on Robin Masheb, The John B. Pierce Laboratory of an N-methyl-D-aspartate Antagonist in the onciling Paradox, 2 years, $218,730 • Stephanie Breast Tissue, 1 year, $240,000 • Daniel Jane- (nih), The Gut-Brain Axis: A Novel Target for Treatment of Social Anxiety Disorder, 2 years, Eisenbarth, Charles H. Hood Foundation, Tar- Wit, American College of Cardiology, Develop- Treating Behavioral Alterations in Obesity, $100,000 • Marcus Bosenberg, Harriet Kluger, geting Dendritic Cells to Block Allergen Sensiti- ing Novel Diagnostic Methods and Therapeutics 3.8 years, $31,428 • Wajahat Mehal, Dynavax Sanford-Burham Medical Research Institute zation in Asthma, 2 years, $150,000 • William for Cardiac Allograft Vasculopathy, 1 year, Technologies (nih), The Development of tlr (nih), pdk1 as a Novel Target in Melanoma, Elam, American Heart Association, Regulation $70,000 • Ryan Jensen, Ovarian Cancer Antagonists for Therapy of Liver Fibrosis and 11 months, $70,822 • Lidia Bosurgi, American- of Cofilin Activity by Phosphorylation and Research Fund, A ‘Cellular Switch’ to Modulate Cirrhosis, 1.1 years, $135,000 • Lauren Metskas, Italian Cancer Foundation, Reprogramming Actin-Binding Proteins, 2 years, $87,600 brca2-Mediated Tumor Progression, 3 years, American Heart Association, Dynamics of the Macrophage Polarization through tam Signal- Adrienne Ettinger, University of New Mexico $450,000 • Susan Kaech, Mayo Clinic College Cardiac Troponin I C-Terminus: The Effect of ing in Inflammation-Driven Cancer, 1 year, (dhhs), Continuing Prospective Birth Cohort of Medicine (nih), Effects of Aging on stat3 Hypertrophic Cardiomyopathy Mutations on $35,000 • Elizabeth Bradley, Leslie Curry, Study Involving Environmental Uranium Expo- Function in T Cells, 1 year, $96,978 • Amanda Contact Rates in Troponin Complexes and Thin Robert Wood Johnson Foundation, Health and sure in the Navajo Nation, 1 year, $45,951 Kallen, Washington University in St. Louis Filaments, 2 years, $44,000 • Ana-Claire Social Service Spending and Health Outcomes: Thomas Fernandez, Regents University of Cali- (nih), H19 lncrna-Mediated Regulation of Gene Meyer, World Federation of Neurology, Aug- A State-level Analysis, 2 years, $483,056 • Janet fornia, San Francisco (nih), 4/4 The Autism Expression in Granulosa Cells, 1 year, $135,000 menting Human Resources for Neurological Brandsma, University of Texas Health Science Sequencing Consortium: Autism Gene Discovery Naftali Kaminski, University of Pittsburgh Care in East Africa: Developing a Foundation Center at San Antonio (nih), Secondary in the >20,000 Exomes, 1 year, $56,901 (nih), Lung Tissue Research Consortium (ltrc): for Post-Graduate Neurology Training Program, Screening of hpv16+ Women using hpv16 Romina Fiorotto, psc Partners Seeking a Cure, Clinical Centers Core, 1.4 years, $11,223; Univer- 1 year, $49,600 • Wang Min, Oklahoma dna Methylation Biomarkers, 1 year, $88,250 Role of Epithelial Toll-Like Receptor-Dependent sity of Pittsburgh (nih), Implications and Sta- Medical Research Foundation (nih), The Role of Cynthia Brandt, Connecticut Children’s Innate Immune Responses in the Pathogenesis bility of Clinical and Molecular Phenotypes of Signaling Adaptor Protein Epsin in Atherosclero- Medical Center, Using the Adverse Event and Treatment of psc, 2 years, $60,000 • Helen Severe Asthma, 11 months, $11,885; University sis, 5 months, $9,420 • Pramod Mistry, Mount Reporting System: Can Analysis be Stream- Fox, Emily Ansell, Peter F. McManus Charitable of Pittsburgh (nih), Sarcoidosis and mat Sinai School of Medicine (nih), Understanding lined by Text Processing? 11 months, $64,123 Trust, Immune System Adaptations Underpin- Genomics & Informatics Center, 1.4 years, the Skeletal Phenotype of Gaucher Disease, Ketan Bulsara, Stryker Instruments, Skull Base ning the Transition from Social to Hazardous $553,612 • Kaveh Khoshnood, Bhutan Founda- 1 year, $238,291 • Ruth Montgomery, Mayo Cerebrovascular Dissection Fund #2, 1 year, Drinking, 1 year, $49,781 • Carlos Fragoso, Uni- tion, Training the Royal Institute of Health Sci- Clinic of Rochester (nih), Influenza Tetramers $9,999 • Susan Busch, Cambridge Health versity of Florida (nih), mtdna Variant Modifi- ences Faculty and Students in Capacity and Cur- and Cy tof, 1 year, $56,239; Mayo Clinic of Roch- Alliance (dhhs), Comparative Effectiveness ers of Cardiopulmonary Responsiveness to riculum Development for New Public Health ester (nih), Deciphering the Role of Natural Research Diffusion and Mental Health Care Physical Activity, 1 year, $16,442 • Nicola Programs in Bhutan, 1 year, $53,748 • Tae Hoon Killer Cells in Resistance to Infection with West Disparities, 1 year, $33,333 • Sonia Caprio, Gagliani, Cancer Research Institute, Targeting Kim, Connecticut Innovations, Pluripotency Nile Virus, 1.5 years, $101,998 • Ruth Montgom- Wake Forest University School of Medicine Th17 Cell Plasticity to Control Colorectal Cancer and Heterochromatin Topology, 4 years, ery, Xiaoling Yuan, Mayo Clinic of Rochester (nih), B-Cell Function and Cognition in the Development, 3 years, $164,500 • Kathleen $750,000 • Joseph Kim, Conquer Cancer Foun- (nih), Enabling Advanced High and Low Level Restoring Insulin Secretion (rise) Study, 1 year, Garrison, American Heart Association, Mobile dation, Systematic Evaluation of Immune Mod- Analytics for Luminex Technology, 1 year, $31,259 • Jessica Cardin, Simons Foundation, Mindfulness Training for Smoking Cessation, ulatory Effect of Radium 223, 1.5 years, $52,637 $4,995 • Evan Morris, Duke University (nih), gabaergic Contributions to Neural Deficits in 2 years, $154,000 • Mark Gerstein, Valerie Roger Kim, American Society of Nephrology, Fast-Fail Trials in Mood and Anxiety Spectrum a Genetic Model of Autism, 2 years, $249,955 Reinke, University of Washington, Seattle The Effects of Dopamine and Angiotensin-II on Disorders (fast-mas), 1.2 years, $863,095; Pfizer, David Carlson, Dartmouth College, In Vivo (nih), Comprehensive Identification of Worm nhe3 Patterns of Phosphorylation, 11 months, U.S. Pharmaceuticals Group, Receptor Occu- Electron Paramagnetic Resonance (epr) Tooth and Fly Transcription Factor Binding Sites, 10 $52,000 • Steven Kleinstein, Fred Hutchinson pancy of PF-06659286 at gabaa-bzrs in Non- Dosimetry for Rapid Point-of-Care Diagnostic months, $680,604 • Mark Gerstein, Kei-Hoi Cancer Research Center (nih), Development of Human Primates Using (11C) Flumazenil pet, Assessment of Absorbed Doses of Ionizing Cheung, Philip Askenase, Baylor College of the hipc Database and Research Portal, 2 months, $235,265 • Alan Morrison, North- Radiation, 7 months, $84,331 • Richard Carson, Medicine (nih), Data Management and 11 months, $75,374; Mayo Clinic of Rochester western University, Macrophage B3 Integrins Astellas Pharma U.S., Evaluation of hsd1 with Resource Repository for the exrna atlas, 1 year, (nih), Integration of hipc Data to ID Common Signal Through Non-Muscle Myosin IIA Modu- C-11-AS2471907-CL, 4 months, $292,957; Astellas $721,737 • Mark Gerstein, Jackson Laboratory Signatures of Influenza Vaccination Response, late vegf-A Protein Levels During Ischemia- Pharma U.S., CMC Preparation for [11C]hdd- (nih), An Integrative Analysis of Structural Vari- 1 year, $84,279; Mayo Clinic of Rochester (nih), Induced Arteriogenesis, 1.6 years, $500 1683, 1.5 years, $30,719; Pfizer U.S. Pharmaceu- ation for the 1,000 Genomes Project, 2.9 years, Development of hipc Data Standards, 1 year, Walther Mothes, Drexel University College of ticals Group, Evaluation of PF-06266047 with $333,829 • Thomas Gill, University of Florida $229,177 • Steven Kleinstein, Kei-Hoi Cheung, Medicine (nih), Structure-Based Antagonism lps and [11C]pbr28, 1 year, $318,348; Bristol- (nih), The life Study, 1 year, $477,703 • Elena Stanford University (nih), Enabling Systems of hiv-1 Envelope Function in Cell Entry, Myers Squibb Company, IM136-106; Evaluation Gracheva, Rita Allen Foundation, Mammalian Immunology through Ontological Normaliza- 4.9 years, $435,537 • Adam Naples, Autism and Development of lpa1 Receptor Ligand, Hibernation as a Model to Understand Temper- tion and Analysis of Literature Based Standards, Science Foundation, Cross-Modal Automated 1 year, $117,882 • Eda Cengiz, Juvenile Diabetes ature Sensitivity, 5 years, $500,000; Alfred P. 1.1 years, $133,200 • Yuval Kluger, New York Assessment of Behavior during Social Interac- Research Foundation International, Accelera- Sloan Foundation, Sloan Foundation Fellow- University School of Medicine (nih), Role of tions in Children with asd, 1 year, $5,000 tion of Insulin Action by Hyaluronidase during ship, 2 years, $83,250 • Liqiong Gui, Rensselaer Nuclear Organization in Protecting Genome Kevin O’Connor, Myasthenia Gravis Founda- Closed-Loop Therapy, 2 years, $722,341 • Anees Polytechnic Institute (nih), Differentiating Stability during Recombination, 1.2 years, tion of America, epitome (Efficacy of Predni- Chagpar, Connecticut Breast Health Initiative, Embryonic Stem Cells Toward Arterial and $21,595 • Albert Ko, Vanderbilt University sone in the Treatment of Ocular MyasthEnia), Understanding Intratumoral Heterogeneity Venous Endothelial Cells for Vascular Regenera- (nih), meph: Odetunde Site Support, 1 year, 1 year, $50,000; emd Serono, B Cell-Mediated in Breast Cancer, 1 year, $50,000 • Toby Chai, tion, 4.8 years, $137,711 • Ann Haberman, Uni- $11,664 • Harlan Krumholz, Robert Wood Autoimmunity in MS: Understanding Autoan- New England Research Institutes (nih), Plasma versity of Pittsburgh (nih), Murine Memory B Johnson Foundation, The rwjf Clinical Scholars tibody Production and Defects in B-Cell Toler- ntx and Vitamin D Levels as Prognostic Factors Cell Development and Function, 1 year, $164,121 Program: First Year Cohort (2013-2015), 2 years, ance Mechanisms, 2 years, $280,000 • Elaine for Surgical Outcomes after Midurethral Slings, David Hafler, Dana Farber Cancer Institute $747,498 • John Krystal, University of Texas O’Keefe, Central CT Health District, Central 5 months, $106,212; New England Research (nih), Antigen Presentation and T Cell Program- Health Science at Houston (DoD), cap- CT Health District Workforce Development Institutes (nih), Urinary Incontinence ming in Human Autoimmune Diseases, 5 years, Biomarkers Core (Neuroimaging), 1 year, Plan, 5 months, $12,000 // Grants (page 8)
Medicine@Yale December 2014 7
M@Y_October2014.indd 7 12/18/14 4:05 PM Foundation recognizes geneticist’s promise Two on faculty assume new leadership roles Panteleimon Rompolas, ph.d., mba, The new academic year has seen a postdoctoral fellow in genetics, is the shifting of roles within Yale’s largest recipient of a 2014 Blavatnik Regional graduate program with the appoint- Award for Young Scientists in the ment of its director, Lynn Cooley, category of life sciences. ph.d., as dean of Yale’s Graduate The award, which carries an School of Arts & Sciences (gsas). unrestricted cash prize of $30,000, Cooley, the C.N.H. Long Profes-
honors Rompolas’ contributions to the sor of Genetics, stepped down as carl kaufman
understanding of tissue development terry dagradi leader of the Combined Program in Anthony Koleske (left) succeeds Lynn Cooley and regeneration. His research, con- Panteleimon Rompolas (left) is a postdoctoral Biological and Biomedical Sciences (right) as director of the Combined Program in ducted in the lab of Valentina Greco, fellow in the lab of Valentina Greco (right). (bbs) July 1 to assume the deanship Biological and Biomedical Sciences. ph.d., associate professor of genetics the Merton Bernfield Memorial Award of gsas. She is succeeded as bbs for genetic and molecular analysis of and dermatology, includes examining from the American Society for Cell director by Anthony J. Koleske, ph.d., genes in the fruit fly Drosophila. hair follicle stem cell behavior. Biology. He earned his b.sc. at the professor of molecular biophysics and Koleske has served as director To directly address how stem cells National and Kapodistrian University biochemistry and of neurobiology. of graduate admissions for the bbs maintain and regenerate adult tis- of Athens in Greece, and his ph.d. and Cooley, also professor of cell biol- Program’s Molecular Biophysics and sues, he developed a system that es- mba at the University of Connecticut. ogy and of molecular, cellular, and Biochemistry track and its succes- tablished for the first time the ability The Blavatnik Regional Awards for developmental biology, had served as sor, the Biochemistry, Biophysics, to visualize stem cells in their native Young Scientists were established in bbs director since 2001. She received and Structural Biology track. He is a environment in real-time in mamma- 2007 to honor outstanding postdoctor- her b.a. from Connecticut College, member of the executive committees lian skin. This research, published in al scientists in Connecticut, New York, and earned her ph.d. at the Uni- of the Interdepartmental Neurosci- 2012 and 2013 in the journal Nature, and New Jersey. They are administered versity of Texas for research carried ence Program and the Cellular and has enhanced our understanding of by the Blavatnik Family Foundation, out with Dieter Söll, ph.d., Sterling Molecular Biology Training Program. stem cell function in live mammalian which is led by industrialist and phi- Professor of Molecular Biophysics Koleske earned his ph.d. and tissue, and the influence of cell posi- lanthropist Len Blavatnik, and the New and Biochemistry and professor of completed a postdoctoral fellowship tion on cell behavior and fate. York Academy of Sciences, an inde- chemistry. She was a postdoctoral at mit. His research is focused on the Rompolas is a current Drucken- pendent non-profit group committed fellow at the Carnegie Institution for mechanisms underlying cell adhesion miller Fellow with the New York Stem to advancing science, technology, and Science, where she established new and how these processes break down in Cell Foundation and in 2013 received society worldwide. methods using transposable elements cancer and neurodegenerative diseases.
// Grants (from page 7) Darren Opland, Hilda 2 years, $200,000 • Gerard Sanacora, Massa- $200,000 • Richard Sutton, Texas Tech Univer- Nuclear Lamina-Associated Chromatin in & Preston Davis Foundation, Exploring Sex Dif- chusetts General Hospital (nih), Double-Blind, sity (nih), Investigating the Genetic Basis of Human ES Cells, 2 years, $200,000 • Lawrence ferences in Anticipatory Negative Contrast Placebo-Controlled, Proof-of-Concept (poc) Trial CD4-Intrinsic hiv Control, 7 months, $5,928 Young, American Heart Association (Founders Behavior by Manipulating Labeled Neural of Ketamine Therapy in Treatment-Resistant Joann Sweasy, University of Southern Califor- Affiliate), The ddt Pathway in the Ischemic Ensembles, 3 years, $153,000 • Nicole Over- Depression (trd), 1.7 years, $354,237 • Lauren nia (nih), dna Polymerase Fidelity Mechanisms: Heart, 3 years, $198,000 • Zhong Yun, Con- street, Fordham University (nih), Ethical Consid- Sansing, Robert E. Leet and Clara Guthrie Pat- Theory and Experiment, 1 year, $155,975 • Jean- necticut Innovations, Hypoxia and Mainte- erations in Intimate Partner Violence Research: terson Trust, Monocyte Differentiation and Leon Thomas, Connecticut Innovations, Vascu- nance of Human Cancer Stem Cells, 2 years, Examining the Role of Stigma, 10 months, Outcome after Intracerebral Hemorrhage, lar Growth Factor Signaling in Human Neural $200,000 • Hai Feng Zhang, American Heart $19,175 • John Pachankis, Hunter College, City 2 years, $25,000 • Carolyn Sartor, Robert E. Leet Stem Cells, 2 years, $200,000 • Mary Tinetti, Association, Function of ccm3 in Pericyte/SMC: University of New York (nih), Multicomponent and Clara Guthrie Patterson Trust, The Contri- John A. Hartford Foundation, Improving the Mechanism and Disease Model, 4 years, Intervention to Reduce Sexual Risk and Substance butions of Genetic Liability, Parenting and Child- Care of Persons with Complex Health Needs: $308,000 • Yongli Zhang, Brain Research Use, 1 year, $8,500; Hunter College, City Univer- hood Trauma to the Development of Problem Realigning the Patient, Primary Care, and Spe- Foundation, Structures, Stabilities, and Forma- sity of New York (nih), Compulsive Behaviors, Substance Use in Young African-American and cialty Care Relationship toward Patient-Cen- tion Kinetics of Amyloid Beta Precursors and Mental, Health, and hiv Risk, 1.6 years, $8,000 White Women, 2 years, $100,000 • Mark tered Care, 1.5 years, $497,734; American Feder- Oligomers, 1 year, $50,000 • Jing Zhou, Ameri- Chirag Parikh, University of Pittsburgh (nih), Schlesinger, Robert Wood Johnson Foundation, ation for Aging Research, John A. Hartford can Heart Association, Graft-Related Host Biomarker Collection and Analysis in the pre- Encouraging Physicians’ Precommitment to Less- Foundation’s Center of Excellence in Geriatric Cardiovascular Disease, 4 years, $308,000 serve Trial Cohort, 1 year, $55,565 • John intensive Care to Reduce Use of Clinical Services Medicine and Training, 1 year, $88,000 Lingjun Zuo, Alcoholic Beverage Medical Pawelek, Access Business Group International, of Low or Questionable Value, 2 years, $213,652 Tamara Vanderwal, American Academy of Research Foundation (abmrf), Post-gwas Hyperpigmented Disorders of the Skin; Pathol- William Sessa, American Heart Association, Child and Adolescent Psychiatry, Intrinsic Con- Search for Risk Loci for Alcohol and Nicotine ogy and Model Development, 3 years, $174,825 Identification of Novel Mechanisms of ldl nectivity Networks in Young Children, 2 years, Co-Dependence Using Third-Generation Kevin Pelphrey, University of Texas at Dallas, Uptake into Endothelium, 2 years, $150,000 $60,000 • Pamela Ventola, Autism Science Sequencing, 2 years, $100000 Virtual Reality Social Cognition Training for Gerald Shadel, Connecticut Innovations, Testing Foundation, Sex Differences in the Neural Adults with Autism Spectrum Disorders, the Oxidative Stress Theory of Ataxia-Telangiec- Mechanisms of Treatment Response, 1 year, 10 months, $20,000 • Rafael Perez-Escamilla, tasia Pathology Using Induced Pluripotent Stems $5,000 • Narendra Wajapeyee, International Awards & Honors Baylor College of Medicine (dhhs), latch: Lacta- Cells, 2 years, $200,000 • Yushane Shih, Ameri- Association for the Study of Lung Cancer, Tar- tion Advice thru Texting Can Help, 2 years, can Heart Association (Founders Affiliate), geting Metabolic Drivers of Lung Cancer, Three Yale scientists $250,000 • Melinda Pettigrew, Duke University Optimizing Tissue Engineered Grafts by Compu- 2 years, $80,000 • Emily Wang, Robert E. Leet are among 50 re- (nih), Antibacterial Resistance Leadership Group tational Modeling, 1 year, $22,000 • Gerald and Clara Guthrie Patterson Trust, Risk of Mor- cipients of the 2014 (arlg), 1 year, $34,202; State University of New Shulman, American Diabetes Association, Role bidity and Mortality Upon Release from Correc- National Institutes of York at Buffalo (suny) (nih), Persistent H. Influ- of Apolipoprotein A5 in the Regulation of Ectopic tional Facilities Among Medicare Beneficiaries, Health Director’s New enzae in copd: Virulence Vaccines and Antibiotic Lipid and Insulin Resistance, 2 years, $124,140; 2.5 years, $100,000 • Stephen Waxman, Yang Innovator Awards. The Resistance, 11 months, $86,022 • David Pitt, Georgia Regents University (nih), Energy Expen- Yang, Connecticut Innovations, Modeling $1.5 million awards Novartis Pharmaceuticals Corporation, Expres- diture Working Group Collaborative Project, Chronic Pain Condition with iPS Cells from support innovative ap- sion of S1P Receptors in Multiple Sclerosis Lesions, 1 year, $24,975 • Alexa Siddon, Cap Foundation Patients with “Man on Fire” Syndrome for 2.2 years, $250,340; Dana Farber Cancer Insti- Scholars Program, Implementation of a Novel Better Pharmaco-Genomic Analysis and Drug proaches to major chal- tute (nih), Regulation of T Cell Immunity by Flow Cytometric Assay for Assessing Patients Testing, 2 years, $200,000 • Stephen Waxman, lenges in biomedical Stromal Cells in Autoimmune Tissue Inflamma- with Suspected Hemophagocytic Lymphohistio- European Commission, Propane Study, 3 years, research today. With tion, 1 year, $5,645 • Cristina Ramirez-Hidalgo, cytosis, 1 year, $8,832 • Wendy Silverman, $1,111,851 • Jadon Webb, American Academy of the award’s support, American Heart Association, Role of miR33 Florida International University (nih), Attention Child and Adolescent Psychiatry, Meta-Analy- Murat Acar, ph.d. (top), during Progression and Regression of Atheroscle- Bias Modification Training in Child Anxiety cbt sis: Do Stimulants Work as “Smart Pills”? The assistant professor of rosis, 4 months, $15,305 • Anna Rhoades, Uni- Nonresponders, 2.5 years, $38,463 • Megan Cognitive Effects of Stimulants in Healthy molecular, cellular, and versity of Minnesota (nih), Modeling Synaptic Smith, Community Foundation for Greater New Adults without adhd, 1.2 years, $24,975 Li Wen, developmental biology Vesicles: How Does Alpha-Synuclein Inhibit Haven, New Haven moms Partnership, 3 years, iacocca Family Foundation, Dampening Diabe- and of physics, will Fusion, 4.9 years, $187,305 • David Rimm, Breast $130,000 • Serena Spudich, Brigham and togenic Commensal Bacterial to Prevent and work to uncover novel Cancer Research Foundation, Whole Exome Women’s Hospital (nih), aids Clinical Trials Treat Type 1 Diabetes, 1 year, $99,990; Ameri- Sequencing of Cancer Samples from the Neo- Group (actg) Leadership and Operations Center, can Diabetes Association, Innate Immunity connections between altto Clinical Trial and Studies of Immunologic 11 months, $31,993 • Hanna Stevens, Klingen- and Dendritic Cells in Obesity of Mouse and single-cell aging and Targets in Breast Cancer, 1 year, $240,000; Board stein Third Generation Foundation, Gene-Envi- Man, 3 years, $310,500 • Scott Woods, TeleS- cellular metabolism, of Trustees of the Leland Stanford (nih), High- ronment Interaction and adhd: Translation age (nih), mpsy irt-Base Self-Report Screener chromosome insta- Content Pathology with Confocal Microscope Between Rodent and Human Models of Prenatal for Prodrome Schizophrenia Early Psychosis- bility, and protein Arrays, 10 months, $83,250 • Panteleimon Stress, Genetic Risk, and Postnatal Environment, Phase II, 2 years, $26,541 • Andrew Xiao, Con- misfolding. Chenxiang Rompolas, Connecticut Innovations, Elucidating 2 years, $60000 • Stephen Strittmatter, necticut Innovations, Improving the Fidelity of Lin, ph.d. (middle), as- the Role of Stem Cells in the Skin Tumor Alzheimer’s Association, Signaling by Aß Human iPSC with Epigenetic and Chemical sistant professor of cell biology, will aim Pilomatricoma by In Vivo Imaging, 2 years, Oligomer in the Post-Synaptic Density, 3 years, Genetic Approaches, 3 years, $532,500 to generate artificial membranes to bet- $200,000 • James Rothman, G. Harold and $449,997; Axerion Therapeutics (nih), Small Yong Xiong, Veterans Medical Research Foun- ter study membrane trafficking in cells. Leila Y. Mathers Charitable Foundation, Mecha- Molecule Development of PrPc Antagonists dation (nih), Inhibiting Immune Evasion by nism of Membrane Fusion by snare Proteins in for the Treatment of Alzheimer’s Disease, hiv-1 Nef to Facilitate Eradication, 2 years, Matthew Simon, ph.d. (bottom), as- Glucose Homeostasis and Exocytosis, 1 year, 8 months, $165,741 • Sumati Sundaram, $108,225 • Qin Yan, American Cancer Society, sistant professor of molecular biophysics $481,855 • Nancy Ruddle, Matthew Rodeheffer, Connecticut Innovations, Potential of Human Functional Analysis of Histone Demethylase and biochemistry, will use organic chem- Connecticut Innovations, The Role of Adipocyte Pluripotent Stem Cell-Derived Mesenchymal rbp2 in Breast Cancer, 4 years, $720,000 istry and enzyme engineering to research Stem Cell in Lymphatic Vessel Differentiation, Stem Cells for Lung Tissue Engineering, 2 years, Jie Yao, Connecticut Innovations, Characterize rna dynamics in the cell.
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