october/november 2015 volume 11, issue 2 Advancing Biomedical Science, Education, and Health Care

Life-changing care forges a -physician bond Following a global trek for after more than a decade of research family who earlier this year en- on the mechanisms of conscious- dowed his professorship. the right care, a family finds ness loss in focal seizures, including Meghan Loughridge’s , success, and calm, at Yale a landmark article recently published Mark Loughridge, and stepmother, in Neuron, as well as research on the Michele Williams, had taken Meghan Hal Blumenfeld, m.d., ph.d., the physiological changes in what are around the world looking for a way recently named Mark Loughridge called absence seizures and generalized to control her epilepsy. Eventually and Michele Williams Professor of tonic-clonic seizures. they found themselves in Houston, Neurology, has spent his career try- Says Blumenfeld, “My research at another hospital, waiting for yet ing to prevent loss of consciousness is one hundred percent motivated another test. Meghan was scared, but in people with epilepsy. [by a desire to] improve the lives of this was nothing unusual. Earlier this year his team reported people with epilepsy. Consciousness Mark describes Meghan’s life as in the journal Epilepsia that impaired impacts their ability to drive a car “a movie with every fifth frame miss- consciousness during and after fo- and to function at school or in other ing.” She would have 30 seizures in

cal seizures can be reversed by deep social situations.” a single minute and one daily grand terry dagradi brain stimulation. Now he is working Blumenfeld is making signifi- mal seizure, the kind characterized Inspired by the care their received, toward making the treatment avail- cant progress, and few know better by a loss of consciousness and violent Mark Loughridge and Michele Williams have able for patients. The discovery comes how important that is than the muscle contractions. // Chair (page 7) endowed a new professorship in neurology.

Foundation enables A more precise approach to dyslexia continued progress Pediatrician aims to reduce in stem cell research the impact of a broad range Earlier this year, Haifan Lin, ph.d., of learning disabilities director of the Yale Stem Cell Center (yscc), and colleagues discovered a Jeffrey R. Gruen, m.d., professor of potentially unique ability of stem cells: pediatrics and genetics, is taking a they can avert the damaging effects of holistic view in working to remedy stress better than regular cells. Stem learning disabilities. Focusing on cells are biologically valuable because reading, attention, and mathematics they can both differentiate into other disabilities, Gruen and his colleagues kinds of cells and divide to produce are preparing to follow around 3,200 more stem cells. The team’s findings first-graders in New Haven Public suggest that stem cells are designed to Schools (nhps) over five years. avoid passing on damaged dna that The new study, called the New could cause molecular-level irregulari- Haven Lexinome Project (nhlp) and ties, like cancer. The research was pub- supported by a grant from the New lished in the journal Stem Cell Reports. York-based Manton Foundation, A $1.86 million grant from the Li focuses on “genes-by-environment” Ka Shing Foundation made to yscc effects: Gruen’s team is studying how earlier this year will help the Center home and cultural environments marsland michael continue similarly innovative research. interact with a ’s genetics to Using “precision education,” a team led by Jeffrey Gruen (left) is collecting data on about 3,200 The grant will help fund new research influence his or her learning. first-graders in New Haven schools to further our understanding of and ability to predict and ad- equipment and strengthen collabora- Says Gruen, “Disabilities in dress dyslexia. A gift from the Manton Foundation is supporting the team’s research. tions between Yale and Shantou Uni- schoolchildren cost billions for versity (stu), in southeastern China. federal, state, and local interven- precisely match them with their opti- of just a handful of genes associated The Hong Kong businessman Li tion programs. We hope to improve mal intervention.” with dyslexia—as the fifth most im- Ka-shing founded stu. A self-made the effectiveness of those efforts The nhlp builds on Gruen’s portant breakthrough of that year. billionaire, Li dropped out of high by harnessing the predictive tool previous work in the field. In 2005 In 2008 Gruen coined the term school to help earn money for his fam- of genetics to target the kids who the journal Science described his human lexinome to capture all of the ily. He has spent his career building his can benefit most from help, and to discovery of the gene dcdc2—one genes and specific // Dyslexia (page 8) company, which he // Stem Cell (page 7)

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 Akiko Iwasaki has built a career around New Haven, CT challenging accepted tenets in her field. Permit No. 526 3 A treasure on West Campus The Yale Center for Molecular Discovery helps scientists identify the compounds they need to take their research forward. 5 Addressing Alzheimer’s A new federally-funded center coordinates research on and clinical care for Alzheimer’s disease across the university.

also Advances, pp. 3, 5 Out & About, p. 4 @YaleMed f /YaleMed lifelines School of Nursing alumna returns to lead the school

Ann Kurth, ph.d., m.p.h., r.n., Akiko Iwasaki enjoys asking m.s.n., a global basic science questions health expert and whose answers might be a Yale School of right under our noses, or Nursing (ysn) inside them. Her research on the immune system’s inter- alumna, will actions with the rhinovirus return to Yale as made national headlines Ann Kurth YSN’s new dean on earlier this year. Not satis- January 1, 2016. fi ed to focus on one area of Kurth, associate dean for research, her work spans a range of immunologic topics, research at New York University including the herpes simplex College of Global Public Health virus and autophagy. and the inaugural Paulette God- dard Professor of Global Health Nursing at New York University College of Nursing (NYUCN), is a

Akiko Iwasaki eddie torres clinically trained epidemiologist with a career-long interest in the prevention, detection, and care of HIV and other sexually transmit- Heeding the call of basic research ted infections. A willingness to question viruses evolved to function best in received the Wyeth Lederle Young “[Kurth’s] leadership in pro- dogma keeps a Yale cooler climes—and in the nasal cavity, Investigator award from the Infectious moting health care around the usually colder than the rest of the Diseases Society of America. The Bur- world fi ts ... with the ysn mission immunologist motivated body. But when her team incubated roughs Wellcome Fund recognized her of promoting better health for all,” the virus in airway cells in a warm research on the pathogenesis of infec- Yale President Peter Salovey wrote For as long as she could, Akiko Iwasaki, environment, it not only survived, but tious diseases in 2005. The American to the University community. ph.d., resisted a call to basic science grew, when the host’s immune cells Association of Immunologists awarded At NYUCN Kurth is also pro- research. She grew up outside Osaka, lacked key defense genes. her the BD Biosciences Investigator fessor of medicine and executive in the Kensai region of Japan, with a These studies suggested it may Award in 2011. And in 2012 the Ameri- director of NYUCN Global, which physicist father who spent long nights be the host immune response, rather can Society for Microbiology honored supports research and improved studying. The lifestyle initially did not than the virus, that determines the her work on the role of autophagy, health care infrastructure globally. appeal to her. But later, as an under- virus’s growth. The immune system or “self-eating,” in antiviral immunity In addition to her m.s.n. from graduate at the University of Toronto, itself appears “impaired at the lower with the Lilly Research Award. ysn, she holds an a.b. magna cum she discovered immunology, and found body temperature compared to the What drives Iwasaki’s productiv- laude from Princeton University, she could no longer deny her innate core body temperature,” Iwasaki says. ity? “The fun of it,” she says. Next, she an m.p.h. from Columbia Univer- attraction to science. The findings, published in Proceedings wants to figure how to fight viruses sity, and a ph.d. in epidemiology Iwasaki, professor of immunobiol- of the National Academy of Sciences by harnessing the infection-fighting from the University of Washing- ogy and of molecular, cellular, and last January, suggest that colder tem- power of T cells, rather than relying ton. She is a fellow of the National developmental biology and a Howard peratures “dampen” cell receptors only on antibodies, as most current Academy of Medicine and a mem- Hughes Medical Institute investigator, designed to detect rhinoviruses, and vaccines do. Such work could have ber of the U.S. Preventive Services has built a career asking research ques- therefore the immune system never implications for the treatment of hiv Task Force that sets screening tions that examine accepted tenets gets a memo to attack. and the herpes simplex type 2 virus. guidelines for the country. within the field of immunology. Her In parallel, Iwasaki’s team is inves- At home, Iwasaki can puzzle out Kurth succeeds Margaret Grey, doctoral thesis, also at the University tigating the immune defense against experiments with her , Ruslan dr.ph., r.n., the Annie W. Good- of Toronto, created a wave of surprise influenza viruses, particularly among M. Medzhitov, ph.d., the David W. rich Professor of Nursing, who in 1998 by suggesting that vaccines older adults. In the U.S., more than 90 Wallace Professor of Immunobiol- stepped down in August. Holly work by presenting antigens to T cells percent of deaths from influenza occur ogy and a Howard Hughes Medical Powell Kennedy, ph.d., executive through white blood cells—not muscle among adults over 65. A vaccine that Institute investigator. And their two deputy dean and the Helen Varney cells, as previously thought. helps older adults fight the flu would , ages 5 and 7, routinely drop Professor of Midwifery, is serving More recently, Iwasaki and her lab mark a huge breakthrough—and immunology-related vocabulary into as interim dean. members set out to challenge conven- Iwasaki is hopeful that will come. conversation, she says. tional thought about why the common Since she started her lab at Yale in This suggests yet another accom- cold spreads more readily in the winter 2000, Iwasaki’s peers have frequently plishment: she’s passed on the fun months. Researchers assumed rhino- recognized her work. In 2003 she of science.

Managing Editor Charles Gershman Contributors Jenny Blair, Jeanna Canapari, Dan Hebert, Angelika Hofmann, Jill Max, Kathleen Raven, International collaboration opens doors for student researchers Colleen Shaddox, Sarah C.P. Williams, Karen Zusi Design Jennifer Stockwell When Daniel Colón-Ramos, Ph.d., Colón-Ramos has spearheaded a Medicine@Yale is published four times each associate professor of cell biology, ar- new M.d./Ph.d. collaboration with year by the Office of Institutional Planning and Communications, Yale School of Medicine, rived from Puerto Rico as a freshman the University of Puerto Rico (Upr). 1 Church St., Suite 300, New Haven, CT 06510-3330 at Harvard in 1994, things didn’t Starting this year, students accepted Telephone: (203) 785-5824 Fax: (203) 785-4327 quite go as planned. Once in his in the m.d. program at upr can E-mail [email protected] dorm room, he felt dizzy and recalls apply to Yale’s Combined Program Website medicineatyale.org Copyright ©2015 by Yale University. All rights reserved. telling his roommate, “I’m dying. You in the Biological and Biomedical Sci- If you have a change of address or do not wish to receive

have to take me to the hospital.” ences and will be assigned mentors marsland michael future issues of Medicine@Yale, please write to us at the above address or via e-mail at [email protected]. The hospital physicians sus- while studying for their ph.d.s in Peter Salovey (left) and University of Puerto Postal permit held by Yale University, pected meningitis, but results on a New Haven. After completing their Rico President Uroyoán Walker at an event 155 Whitney Avenue, New Haven, CT 06520 spinal tap were negative. Following a research, they will return to Upr for celebrating the universities’ collaboration. phone call between Puerto Rican and the fi nal year of medical school. will also bring their island experienc- Robert J. Alpern, m.d. American physicians, it came to light The training that Upr students es to enrich the environment at Yale. Dean and Ensign Professor of Medicine Charles Turner that “these were all the symptoms of receive at Yale will prepare them for “We’re training our next genera- Director of Medical Development (203) 436-8560 dengue fever. I was coming in with a careers as physician-scientists, cur- tion,” says Uroyoán Walker, ph.d., Mary Hu tropical disease,” Colón-Ramos says. rently a small community in Puerto president of Upr. “And when I say Director of Institutional Planning and Communications With this global context in mind, Rico’s medical community. But they ours, I mean the world’s.” Printed on recycled paper ♻

2 www.medicineatyale.org advances The art, and science, of collaboration Health & Science News What’s not behind A world-class center on Yale’s West Campus a Ycmd pilot grant and began investigating drugs that would block Dna repair in tumors. Standard therapies— a rare lymphoma is ‘on-call’ for scientists, offering tools and chemotherapy and radiation—largely tackle cancer by services critical for precision medicine damaging cellular Dna, but cancer cells have Dna repair mechanisms that can diminish the therapies’ effectiveness. In the field of cancer research, one of the most significant Bindra’s team is seeking a class of compounds that inhibit discoveries in the last two decades is the finding that most these repair mechanisms, making the cancer more suscep- cancers are caused by overactive cell division due to genetic tible to treatment. mutations. The concept of “precision medicine” now uses “It’s easy to think you could do it all yourself,” Bindra a patient’s specific mutations to help treat his or her cancer. says, “but you really need a screening, like these folks, who

istockphoto.com For a subset of patients, this approach—matching patients are going to keep you on track and make sure you design While most cancers are caused by with appropriate targeted drugs—works exceedingly a screen which will get you meaningful hits.” Bindra’s lab mutations in single nucleotides of well. But unfortunately, many patients develop treatment has worked on four different projects with the Ycmd, two dna, like changing some letters in a resistance over time, after which the cancer can make an of which are currently running. His work has generated two sentence, cutaneous T cell lymphoma aggressive return. “For people like me in the signaling manuscripts, and Bindra plans to use the preliminary data in is often driven by large deletions of field, it was a pretty major disappointment that resistance an application for federal grant funding. whole genes, like removing whole can readily develop,” says David F. Stern, ph.d., professor An initial project with the Ycmd often leads to funding pages from a book. A better under- of pathology and associate director of shared resources at from larger institutions, as Qin Yan, Ph.d., associate profes- standing of how these deletions Yale Cancer Center (ycc). “And it’s been a real practical sor of pathology, discovered when he began research at Yale. cause the rare lymphoma, which problem for the clinicians.” Like Bindra, Yan was awarded a Ycmd pilot grant shortly affects skin cells and causes rashes, Cancer cells, just like healthy cells, try to maintain inter- could lead to better treatments. nal stability, or homeostasis. When single drugs are intro- To gain insight, Yale researchers duced that interfere with the cells’ division pathways, many studied blood samples from 40 pa- eventually switch to parallel pathways that cause the cells to tients with cutaneous T cell lym- continue dividing. phoma. Comparing dna sequences in For Stern, who was researching melanoma, it eventually cancerous cells with those in healthy became clear that these single- cells revealed that the large deletions agent therapies weren’t affected 17 different genes. Many of going to work well enough. the genes, the team reported July 20 He needed to find a cock- in Nature Genetics, control similar mo- tail of drugs that could hit lecular pathways, suggesting that the enough targets in the cell misregulation of these pathways may to shut down the cancer be key to causing the lymphoma and for good. Six years ago, he suggesting that drugs targeting these and collaborator Marcus W. denton hoyer Bosenberg, m.d., ph.d., as- pathways could help treat it. (Above) Biologists and “This cancer has a very distinctive sociate professor of derma- chemists at the Yale biology,” said Jaehyuk Choi, m.d., tology and pathology, turned to the Yale Center for Molecular ph.d., assistant professor of derma- Center for Molecular Discovery (ycmd) Discovery (ycmd) special- tology and lead author of the study. for help. “We brought the project to ize in molecular screening them and they said, ‘Yes, we can do and development to aid biomedical research at this,’ even though no one had done this Solving a multiple Yale. From left: Shelia kind of combination screening here, or Umlauf, Will Hungerford, sclerosis mystery really anywhere,” Stern recalls. Jacquelyn McGrath, Peter In the autoimmune disease multiple The ycmd, one of the core resource Gareiss, Mark Plummer, facilities on Yale’s West Campus in Janie Merkel, Yulia Sur- sclerosis (MS), the immune system’s ovtseva, Laura Abriola, T cells attack the myelin sheaths West Haven, Conn., specializes in drug and Denton Hoyer. Using surrounding nerve cells, potentially screening and development. “We help fluorescence microscope leading to neurodegeneration. But faculty access and correctly implement imaging, dyes, and stains, the reasons T cells attack in cases of a suite of technologies for early-stage ycmd staff stain cells for drug design,” explains Janie Merkel, analysis, including (left) MS have eluded researchers for years. breast epithelial MCF10A Now, scientists from Yale and mit Ph.d., director of biology at the Ycmd. cells and (above left) hu- have found a piece of the puzzle. The ycmd’s staff includes both bi- man epithelial HeLa cells. The team generated over 14,000 ologists and chemists with industry ex- T cell libraries using blood samples perience. The Center has a range of technologies to screen after he joined the medical school’s faculty in 2008. He had from 23 MS patients and 22 healthy small molecules for particular effects and to quantify the discovered a category of enzymes that act as major epigenetic controls, and discovered that T cells results in almost any small study system, from plant seeds regulators, altering gene expression globally—and realized from MS patients caused more in- to nematode eggs to cell lines. Its library contains 150,000 that inhibiting these enzymes might lead to a potential flammation than those from healthy compounds, covering a wide swath of chemical structures cancer treatment. Searching for a compound to do so, he first patients. In MS patients, autoreactive that can pass through the cell membrane. Once useful screened 15,000 compounds at the Ycmd, then increased that T cells produce factors that signal compounds are identified in a screen, the chemists take number to 106,000 in a second screen, looking for samples the body’s inflammatory immune over, tinkering with their molecular structures to maxi- where the enzymes had failed to react. His lab discovered response, but those same autoreac- mize their effectiveness. a handful of candidates, which later led to a patent and the tive cells in healthy patients secrete When Stern and Bosenberg brought their project to the promise of related research projects. He has successfully ap- anti-inflammatory agents instead. Ycmd, they started with a small single-agent screen on a plied for two Department of Defense grants as an extension “In most people, these T cells are melanoma cell line, then worked up to a much larger assay of the work he did at the Ycmd and has developed a partner- acting to repair tissue, but in MS using 41 different agents in combination with each other. ship with the National Cancer Institute. patients, they do damage to the “The advantage of having the screening center here is The Ycmd not only provides assay development and drug nervous system,” said David Hafler, that we developed this whole system,” he says. “Nobody screening technologies, but also consults on projects and m.d., chair and the William S. and Lois showed us how to do it. Five or six years ago, there was little provides grant-writing assistance. The Center is subsidized to Stiles Edgerly Professor of Neurology, published literature in combination work.” It took his team provide the best possible costs to School of Medicine fac- professor of immunobiology, and nearly a year to analyze their data: they have since published ulty. For many researchers, it adds translational potential to senior author of the study, published their work in the journal Cancer Discovery and are hoping their basic science research. And its highly trained staff pride in Science Translational Medicine in to move into clinical trials, while also coordinating similar themselves on creating long-term relationships and offering a May. The authors contend that the projects using lung and pancreatic cancer cell lines. custom approach to help develop any research project brought anti-inflammatory agents produced Early-career researchers at the School of Medicine have to their doorstep. “We’ll be emailing Saturday at seven a.m. by healthy controls may limit disease also benefited substantially from collaborations with the going back and forth,” Bindra says. “They’re almost on-call, progression. The findings suggest a Ycmd. Ranjit Bindra, M.d., Ph.d., assistant professor of [as if] we’re in the hospital.” similar mechanism may be at work in therapeutic radiology and of pathology, met with Merkel Says Denton Hoyer, Ph.d., director of chemistry at the other autoimmune diseases. before joining the faculty three years ago. He received Ycmd, “It starts with a conversation. Just call us.”

Medicine@Yale October/November 2015 3 out & about

March 27–29 Entrepreneurs, physicians, 1 May 5 At Student Research Day, medical and engineering students convened at students presented their thesis research a Hackathon sponsored by Yale’s Center for members of the community. m.d./ for Biomedical and Interventional Tech- ph.d. student Genevieve Yang ’17 (left) nology (cbit) and Center for Outcomes stands in front of her poster on schizo- Research and Evaluation (core) to brain- phrenia research while m.d./ph.d. storm ways to improve clinical care. student Wendy Xiao ’17 (right) discusses 1. Yale University President Peter Salovey, her research project, showcasing data on ph.d., the Chris Argyris Professor of Psy- consciousness collected from electrodes chology, delivered opening remarks. john curtis implanted in the brains of patients. 2. Winners of the Best Patient Experi- 2 ence Solution Award included (from left) nursing student Angela Hasler ’16; Catherine Jameson, Yale College ’16; May 18 At the School of Medicine’s Commencement Ceremonies, Howard Koh, m.d. ’77, Justin Koufopoulos; and graduate the Harvey V. Fineberg Professor of the Practice of Public Health Leadership at Harvard student Linda Fong ’17. 3. A group University’s T.H. Chan School of Public Health, encouraged members of the Class of 2015 presented its project to judges. (From to stay humble. 1. (From left) Adriana Blakaj and Christopher Bartley graduated from the Program. poses with left) Shervin Etemad; Dylan Visher, Yale 1 m.d./ph.d. 2. Jessica S. Wang College ’16; Malipeddi Phanindra Kumar her diploma. 3. (From left) Ryan Aronberg, Katherine Reddy; Katia Barnave; and Iulia Tamas, Davis, Nour Kibbi, Abhijeet Gumadavelli, and Brian Letzen. Yale College ’16. 3 3

2 john curtis (1), terry dagradi (2)

william sacco (3) sacco william 1 2 3

1 2

4 May 29 Scores of alumni returned to campus on Reunion Weekend. 1. (From left) Kim Fish and her husband Guy Fish, m.d. ’85, with classmates Julie Danaher, m.d. ’85, and Sara Cartmell, m.d. ’85. 2. (From left) Linda Maxwell, m.d. ’00; Robert H. Gifford, m.d., former deputy dean for education; and Oscar R. Colegio, m.d. ’00, ph.d. ’00, assistant professor of 3 dermatology. 3. (From left) Ben Zabar,

john curtis (1), terry dagradi (3) m.d. ’11; Natalie Spicyn, m.d. ’11; Barbara Ann (Hirschman) Chaiyachati, m.d. ’15, ph.d. ’15; and her husband, Krisda Chaiyachati, m.d., m.p.h. 4. James W. Bonz, m.d., assistant professor of emergency medicine, gave a demonstration at the Yale Center for Medical Simulation.

July 20 At a reception for the

john curtis (3) Covidien Clinical Immersion Program, engineers and workers at the medical May 21 Medical Education Day gave members of Yale’s medical community a chance device company Covidien were recog- to share educational projects and research as well as engage in numerous educa- nized for their successful completion tional sessions. 1. (From left) David M. Irby, ph.d., keynote speaker and professor of of a yearlong program that includes medicine at the University of California, San Francisco; Janet P. Hafler, ed.d., professor observing surgeries at Yale-New Ha- of pediatrics, associate dean for educational scholarship, and director of the Teach- ven Hospital and attending lectures ing and Learning Center (tlc); Richard Belitsky, m.d., the Harold W. Jockers Associate kathleen raven given by School of Medicine faculty Professor of Medical Education, associate professor of psychiatry, and deputy dean and hospital administrators. (From left) Justin Williams, Mark Rodbourn, Corrie O’Donnel, for education; and Michael L. Schwartz, ph.d., associate professor of neuroscience Jeff Varesio, Brett Roesler, Matthew Chowaniec, Rob Satti, Rich Fillion, and Dave Jermine. and associate dean for curriculum. 2. Participants at a workshop included Andrea G. Asnes, m.d., m.s.w., associate professor of pediatrics, and Benjamin Doolittle, m.d., associate professor of medicine and pediatrics. 3. A panel of judges made up of stu- dents, faculty, and staff from Yale School of Medicine, Yale School of Nursing (ysn), July 21 Carina Dehner, m.d. (second and Yale School of Public Health evaluated poster presentations. (From left) Rosana from left), postgraduate fellow in Gonzelez-Colaso, pharm.d., m.p.h., assistant professor of medicine; Susan H. Forster, immunobiology, attended the Lindau m.d., associate clinical professor of nursing; ysn student Eileen Condon ’20; Monica R. Nobel Laureate Meeting in Germany Ordway, ph.d., aprn, assistant professor of nursing; Kathleen H. Ang, m.d., clinical fel- as a Young Scientist Fellow. Dehner low in pediatric endocrinology; Oladoyin Oladeru, m.p.h. ’15; John A. Encandela, ph.d., joined Peter C. Doherty, ph.d. (center), assistant professor of psychiatry and associate director for curriculum and educator a 1996 recipient of the Nobel Prize in Assessment at the tlc; Dippy Bhattacharya ’18; Jake Wang ’17; and Tracie Addy, ph.d., Physiology or Medicine, and colleagues assessment program manager at the tlc. courtesy of carina dehner for a lunch.

4 www.medicineatyale.org advances Alzheimer’s research accelerates at Yale Health & Science News Addiction treatment A federally funded research center will will study a key signal-receptor protein in neurons called mGluR5, one that could be targeted by new drugs. Finally, can start in the ED support interdisciplinary efforts and pool Chun-Hay Alex Kwan, Ph.d., assistant professor of psychiatry resources to focus on Alzheimer’s disease and neurobiology, will study how circuits of neurons involved with the neurotransmitter gaba may play a role in the disease. 2015 has been a banner year for the study of Alzheimer’s The Adrc will also establish five new cores, including a disease (AD) at Yale. School of Medicine researchers Clinical Core built upon the 24-year-old Adru, and a Bio- recently published papers about an experimental drug that marker/Pathology Core that will develop new ways to monitor helps mice with a form of the disease, the role of immune the disease. Both cores will also aggregate samples like blood, cells in warding it off, and how cellular “garbage disposal” brain tissue, and stem cells for broad sharing and study. An

istockphoto.com systems may be involved. In June, those discoveries and Outreach Core will recruit subjects and conduct Alzheimer’s- Opioid-addicted patients who show several recent expansions and investments in research, equip- related community education, particularly for minorities. up in the emergency department (ED) ment, and faculty helped win the university an $8.9 million, Changes at Yale in recent years have paved the way for the are typically treated for symptoms five-year grant from the National Institutes of Health to fund As the principal investiga- then referred elsewhere for follow-up. a new Alzheimer Disease Research Center (adrc). tors of the Alzheimer’s Now, new research from Yale shows Stephen M. Strittmatter, M.d., Ph.d., the Vincent Coates Disease Research Center that ED-initiated buprenorphine, a Professor of Neurology, professor of neurobiology, and found- (adrc), Stephen Strit- ing director of the Yale Memory Disorders Clinic (ymdc), tmatter, m.d., ph.d. (cen- medication used to treat opioid de- ter), and Christopher Van pendence, could help expand access is the grant’s principal investigator. He leads the adrc with Dyck, m.d. (right), will to addiction treatment. co-director Christopher H. Van Dyck, m.d., professor of psy- spearhead cross-campus Gail D’Onofrio, m.d., m.s., chair chiatry, neurology, and neurobiology and the director of the research efforts. Arash and professor of emergency medicine, Alzheimer’s Disease Research Unit (Adru). The two will help Salardini, m.d. (left), is associate leader of the and David A. Fiellin, m.d., professor coordinate a small army of Yale physicians and scientists to harold shapiro harold adrc’s Clinical Core. of medicine and public health, and accelerate research on this debilitating form of dementia. colleagues randomly assigned 329 As one of 29 federally funded AD research centers around university to become a center for Alzheimer’s research. For opioid-dependent ED patients. About the U.S., the Yale adrc will coordinate the efforts of clini- example, hiring in the Department of Neurology has increased a third of the patients received infor- cal and research units across the university, among them the since David Hafler, M.d., the William S. and Lois Stiles Edg- mation about treatment resources, a Adru; the Program in Cellular Neuroscience, Neurodegen- erly Professor of Neurology, became chair: its full-time mem- third participated in interventions be- eration and Repair (Cnnr); the Yale/nida Neuroproteomics bers now number 50, compared with 20 or fewer a decade ago. fore receiving information and help in Center; the Program on Aging; and the ymdc. It will also of- The ymdc was founded in 2013 under Strittmatter’s direction. attending a treatment program, and a fer mentorship and pilot funding to up-and-coming research- Last year, the medical school made an $8.8 million investment third were given buprenorphine in the ers who are interested in Alzheimer’s. in imaging technologies like magnetic resonance (MR) and ED and follow-up care afterward. Three major lines of research, with an emphasis on the positron emission tomography (pet). And a general expansion ED-initiated buprenorphine, the cell biology of Alzheimer’s disease, will headline the adrc’s of basic neuroscience research, Van Dyck says, has also made a team reported April 28 in Journal of efforts. One, headed by Shawn M. Ferguson, Ph.d., assistant crucial difference the American Medical Association, professor of cell biology, will study how nerve fibers’ waste- “With the Cnnr and other people ... increasingly getting increased engagement in addiction processing units, or lysosomes, can malfunction, potentially involved, it really gave us the critical mass to be able to do treatment, reduced self-reported contributing to AD. In the second, Strittmatter and Van Dyck this,” Van Dyck says. “It’s a huge achievement.” illicit opioid use, and decreased use of inpatient treatment services. Team-based science is the focus of new clinician-scholars program Editing away a When the Robert Wood Johnson Foun- genetic disorder dation (Rwjf) ended its longstanding The genetic disease cystic fibrosis is Clinical Scholars Program last year, the caused by a mutation in the cystic fi- city of New Haven stood to lose deep brosis gene cftr, normally involved in health care expertise and free help. the production of digestive fluids and The national program began in mucus. Patients can have difficulty 1972 with the goal of bringing an breathing, frequent lung infections, academic approach to the training and other complications, and while of clinician-investigators. Yale was symptoms can be managed, the disor- one of the earliest participants in the der has no known cure. program, starting in 1974 under the New research reported April 27 in leadership of the late Alvan R. Fein- Nature Communications by Yale sci- stein, m.d., the Sterling Professor of entists suggests that inhaling a nasal Medicine and Epidemiology. spray containing tiny nanoparticles, Since then, more than 175 rwjf lisak robert specially engineered to carry genetic scholars at Yale have worked on di- The newest members in what will be the last cohort of Robert Wood Johnson Foundation Clinical information, might be the next big verse projects, with a common theme Scholars include (from left) Sanket Dhruva, Courtney McMickens, Alicia Agnoli, Joshua Elder, Dowin Boatright, Alon Peltz, Anita Arora, and Carolyn Presley. treatment for cystic fibrosis. of translating research into action. The team, led by Marie E. Egan, Scholars have conducted community- professor of medicine and co-director medical homes—which bring together m.d., professor of pediatrics and of based research on a range of topics of the new National Clinician Schol- physicians, nurses, physician associ- cellular and molecular physiology, including the availability of healthy ars Program (Ncsp) at Yale. “That ates, and others to care collaboratively Peter M. Glazer, m.d., ph.d., chair and foods, Hiv/aids status, gun violence, is why we simply had to find a way to for patients—are increasingly com- professor of therapeutic radiology, immigrant and refugee health, and ac- continue training the next generation mon. “Team-based care is a common and W. Mark Saltzman, ph.d., the cess to health care for the homeless. of scholars who will lead our efforts to and effective part of our health care Goizueta Foundation Professor of Bio- Though the Rwjf decided last year improve the health care system and en- system, yet we’re still struggling to medical Engineering, designed bits of to stop funding the Clinical Scholars hance the health of individual patients, learn how to do it well,” says Gross, dna that cause cells to turn on their Program, four host sites—the University our communities, and the nation.” who is leading the planning of the gene-editing program and repair the of California Los Angeles; University of The Ncsp, which will start in 2016, Ncsp at Yale. cftr mutation. When they implanted Michigan; University of Pennsylvania; shares many features of the original The decision to include nurse- these molecules inside nanoparticles and Yale—took up the mantle to begin a program but incorporates changes scholars in the Ncsp builds on the and applied the nanoparticles to the new, independent fellowship similar in that consider today’s changing health interdisciplinary framework of the noses of mice, close to 10 percent spirit to the original program. care landscape. Among these, it Rwjf program, which trained physi- of the animals’ airway cells became “I feel fortunate to be part of a emphasizes team-based approaches to cians from various specialties, includ- mutation-free—enough to change training program that is blessed with research and clinical care. As a result, ing internists, surgeons, pediatri- airway function. so much loyalty, appreciation, and the Ncsp will train doctoral-level cians, and others, together. “The technology could be used as a dedication among the alumni, the fac- nurse-scientists alongside physicians. “No profession can do it all them- way to fix the basic genetic defect in ulty, and the institutional and commu- In clinical practice, team-based selves, and we each have important cystic fibrosis,” Egan said. nity partners,” says Cary Gross, M.d., models such as patient-centered roles to play in the // Scholars (page 7)

Medicine@Yale October/November 2015 5 Postpartum Smoking, 4 years, $1,779,556 Warwick, Evaluating the Feasibility of the who Grants and contracts awarded Benjamin Toll, nih, Novel Treatments to Enhance 2020 Goal for hat Elimination, 3.2 years, $381,071 Smoking Cessation before Cancer Surgery, Thomas Gill, University of Massachusetts (nih), 1.9 years, $398,352 • Vasilis Vasiliou, nih, A Novel Advancing Geriatrics Infrastructure and Network to Yale School of Medicine Aldehyde Dehydrogenase (aldh16A1) in Gout, Growth, 3.6 years, $39,620 • David Glahn, Uni- 2 years, $396,401; nih, Mouse Models for Alcohol versity of Southern California (nih), enigma September 2014–December 2014 Metabolism and Tissue Injury, 3.3 years, Center for Worldwide Medicine, Imaging and $1,084,055; nih, Role and Molecular Mechanisms Genomics, 8 months, $61,845; Brain & Behavior Federal of Corneal Aldehyde Dehydrogenase, 7 months, Research Foundation (formerly narsad), Testing Clara Abraham, nih, Mechanisms Regulating Shilpa Hattangadi, nih, Elucidating the Role of $225,752; nih, The Role of gsh in Cornea and Lens the Influence of the Glutamatergic Gene Pathway Innate Immune Responses, 1 year, $416,250 Nuclear Protein Export in Erythroid Nuclear Con- Development, 8 months, $132,591 • Narendra on Neurocognitive and Neuroimaging Endophe- Alan Anticevic, nih, Neuropsychiatric Classifica- densation, 3.8 years, $1,332,000 • Raimund Wajapeyee, nih, Metabolic Drivers of Melanoma notypes for Schizophrenia, 2 years, $98,464 tion via Connectivity and Machine Learning, Herzog, nih, Regulation of Brain Glucose Metabo- Initiation, Progression and Therapy Response, Fred Gorelick, University of California, Los 1.9 years, $145,022 • John Beckmann, United lism by Alternate Fuels in Type 1 Diabetes, 2 years, $398,352 • Scott Woods, nih, 8/9 Predic- Angeles (nih), Organelle Disorders in Pancreatitis, States Department of Agriculture, Molecular 4.8 years, $1,873,125 • Robert Hill, nih, Cellular tors and Mechanisms of Conversion to Psychosis, 1 year, $251,108 • Jaime Grutzendler, Alzheimer’s Mechanism of Cytoplasmic Incompatibility Mechanisms of Cortical Myelin Plasticity and 5 years, $2,306,236 • Dianqing Wu, nih, Mecha- Association, Angiophagy a Mechanism Linking and Insect Control, 2 years, $150,000 • Maria Regeneration In Vivo, 3 years, $165,354 nisms for Wnt Signaling, 3.7 years, $1,465,200 Microvascular and Alzheimer’s Pathologies, Bonarrigo, nih, Recovery-Oriented Structures, Elizabeth Jonas, nih, Mitochondrial Ion Channels Mingyi Xie, nih, Noncanonical microrna Biogen- 3 years, $250,000 • Mihaly Hajos, Forum Phar- Practices and Outcomes in cmhcs: A National in Hypoxic Neurons, 3.8 years, $1,665,000 esis and Function in a Gamma Herpesvirus and maceuticals, Inc. (formerly En Vivo Pharmaceuti- Study, 3.8 years, $2,893,919 • Jessica Brown, nih, Naftali Kaminski, nih, Mir-29 Mimicry as a Mammals, 2 years, $177,895 • Xiangru Xu, nih, cals, Inc.), Proposal for Developing in Vivo Efficacy Elucidating the Inhibitory Mechanisms of rna Therapy for Pulmonary Fibrosis, 1.8 years, Study dna Methylation Changes in Brain Aging Assays for a7 nAChR Agonist Studies to Support Triple Helices in Nuclear Decay, 1.9 years, $177,894 $2,729,729 • Min-Jong Kang, nih, nlrx1 and mavs and Rapamycin Treatment, 1 year, $248,997 PK/PD Modeling and Establishing Neurophysiol- Nancy Carrasco, nih, Molecular Characterization in Cigarette Smoke-Induced Inflammation and Qin Yan, DoD, Targeting an Epigenetic Regulator ogy-Based Translational Biomarkers, 1 year, of the Sodium/Iodide Symporter (nis), 3.8 years, Alveolar Remodeling, 1 year, $428,498 • Robert to Suppress Breast Cancer Metastasis, 3 years, $402,241 • Ilan Harpaz-Rotem, Icahn School of $1,710,869 • Xi Chen, nih, Old-Age Pension, Kerns, nih, Pain, Care, Quality and Integrated and $1,165,498 • Wei Zhang, nih, The Essential Role of Medicine at Mount Sinai (ismms) (nih), Fear Behavior Change and the Well-Being Complementary Health Approaches, 5 years, Gamma-Secretase in Human Papillomavirus Learning and Reconsolidation After Trauma Expo- of the Elderly, 2 years, $333,000 • Won-Kyung $2,258,491 • Kenneth Kidd, National Institute Infection, 3 years, $159,906 sure - A Computational Approach, 1 year, $239,977 Cho, nih,Interleukin-13-Mediated Mechanisms of of Justice/Department of Justice, Continued Kevan Herold, L2 Diagnostics, llc (nih), sttr Pulmonary Vascular Remodeling, 5 months, Development of frog-kb: A Forensic Resource/ Non-federal Phase 2: Measurement of Beta Cell Death in Dia- $133,514 • Geoffrey Chupp, nih, Pre-Clinical Devel- Reference on Genetics Knowledge Base, 2 years, Clara Abraham, Pfizer Inc., U.S. Pharmaceuticals betes, 1 year, $277,551; Kevan Herold, David opment of a Novel Anti-YKL-40 Biologic to Treat $314,468 • Michael Koelle, nih, Neuromodulator Group, jak-Dependent Modulation of Pattern Hafler, Juvenile Diabetes Research Foundation Severe Asthma, 1.8 years, $3,311,540 • Mark Cicero, Signaling and Activity in the C. Elegans Egg- Recognition Receptors in Human Myeloid-Derived International, Cellular Biomarkers of Progression dhhs, Computer-Based Simulation Pediatric Laying Circuit, 3.9 years, $1,426,617 • Diane Cells, 2 years, $200,000; Icahn School of Medi- in the T1D At-Risk Setting, 2 years, $175,000 Disaster Triage Training for Emergency Medical Krause, nih, Molecular Basis of Dominantly Inher- cine at Mount Sinai (ismms), rna Sequencing of Michael Higley, Tuberous Sclerosis Alliance, Anal- Services Providers, 3 years, $720,455 • Gary Cline, ited Kidd-Null Phenotype, 2 years, $457,875 Human Monocyte-Derived Macrophages, ysis and Treatment of Altered Cortical Network nih, Imaging Pancreatic Beta-Cells with pet Eli Lebowitz, nih, Explanatory Clinical Trial of a 8 months, $39,060 • Heather Allore, Ramachan- Dynamics in tsc, 2 years, $150,000 • James Howe, Neuroimaging Agents, 2.9 years, $496,756 Novel Intervention for Childhood Anxiety, dran Ramani, Icahn School of Medicine at University of Texas Health Science at Houston Theodore Cohen, nih, Evaluating Health and 3.9 years, $702,893 • Becca Levy, nih, Stress Bio- Mount Sinai (ismms) (nih), Trajectory of Recovery (nih), tarp Modulation of ampa Receptors, 1 year, Economic Effects of Targeted Strategies in tb/hiv, markers as a Potential Link Between Age Benefits in the Elderly, 1.6 years, $73,723 • Alan Anticevic, $53,280 • Yiyun Huang, ucb Pharma S.A., 3.8 years, $2,583,370 • Christian Connell, Jacob and Health, 1.8 years, $332,999 • Aaron Levy, nih, Vanderbilt University (nih), Thalamocortical Net- pet Imaging of SV2A Receptors with [11C]UCB-J Tebes, dhhs, mpsy Rhode Island Child and Family Integrin-Arg-shp2 Signaling Regulates nmdar works in Psychosis, 11 months, $18,939 • Marc ([11C]APP311)), 7 months, $258,313 • Christoph Wellbeing: Wraparound Services for cps-Identified Function and Neuron Morphology, 3 years, Auerbach, R Baby Foundation, Mobile Pediatric Juchem, National Multiple Sclerosis Society, , 3 years, $250,000 • Charles Dela Cruz, $90,978 • Chiang-Shan Li, nih, Cognitive Control Simulation: Impacts, 1.4 years, $169,800 • Mary Study of MS Tissue Injury and Repair with In Vivo nih, Host-Pneumococcal Interaction in the Lung, and Cocaine Dependence: Thalamic Noradrener- Bailey, University of California, San Francisco Magnetic Resonance Spectroscopy of Lipids and 5 years, $2,090,555 • Kumar Dharmarajan, nih, gic Processes, 5 years, $2,621,904 • Chenxiang Lin, (nih), Treatment of Multiple Sclerosis with Siponi- Proteins, 1 year, $43,944 • Naftali Kaminski, Uni- Geriatric Conditions and Readmission after Acute nih, Cell-Free Membrane Remodeling Guided by mod, 8 months, $11,409 • Brian Biroscak, Univer- versity of Pittsburgh (nih), Center for Casual Myocardial Infarction, 4.8 years, $861,382 dna Nano-Templates, 4.8 years, $2,497,500 sity of South Florida (dhhs), Community-Based Modeling and Discovery of Biomedical Knowledge Vishwa Dixit, nih, Thymic Adipogenesis and Kasia Lipska, nih, Predicting Severe Hypoglycemia Prevention Marketing for Systems Change: Reduc- from Big Data, 7 months, $108,761 • Steven Age-Related Thymic Demise, 4 years, $1,665,000 among Older Adults with Diabetes, 4.8 years, ing Disparities, 1 year, $59,507 • Demetrios Kleinstein, Stanford University (nih), The Center Gail D’Onofrio, samhsa, Yale-sbirt Medical $777,933 • Shuangge Ma, nih, Penalization Braddock, Connecticut Innovations, Inc., Valida- for Expanded Data Notation and Retrieval (cedr), Health Professional Training Program, 3 years, Methods for Identifying Gene Environment Inter- tion of npp1 Enzyme Replacement to Treat Dis- 7 months, $94,316; U.S.-Israel Binational Science $943,785 • Ronald Duman, nih, Synaptic Mecha- actions and Applications to Melanoma and eases of Ectopic Bone Mineralization, 2 years, Foundation, Models and Methods for Mining B nisms Underlying the Rapid Antidepressant Other Cancer Types, 3 years, $434,565 • John $500,000 • David Calderwood, Benjamin Turk, cell Repertoire Dynamics from Next-Generation Actions of Scopolamine, 4.8 years, $2,207,943 MacMicking, nih, gbps as New Inflammsome Gilead Sciences, Gilead-Yale Collaboration in Sequencing Studies, 4 years, $105,000 • Peter Leigh Evans, Lori Post, DoD, Evaluation of the Regulators during Mammalian Host Defense, Cancer - Genome Wide shrna Screening, 2 years, Krause, Columbia University (nih), Babesiosis Effectiveness of ltr Training versus Simulation 5 years, $2,081,250 • Mark Mamula, nih, Post $2,306,716 • Mian Cao, Parkinson’s Disease Foun- Emergence in the United States, 1 year, $43,054 Training and Stress Inoculation, 6 months, Translational Modifications in Tolerance and dation, Functional Study of the Newly Identified Diane Krause, Burroughs Wellcome Fund, Collab- $417,751 • Jorge Galan, nih, Typhoid Toxin and Autoimmunity, 5 years, $2,081,250 • Arya Mani, Autosomal Recessive Early-Onset Parkinsonism- orative Studies for Single Cell Epigenetic Analyses, Salmonella Typhi Pathogenesis, 5 years, nih, Hepatic Wnt/lrp6 Regulation of Plasma Associated Mutation in Sac1 Domain of Synapto- 1 year, $12,000 • Michael Krauthammer, suny $2,526,770 • Patrick Gallagher, nih, Regulation of Lipids, 4 years, $2,080,864 • Darryl Martin, DoD, janin1, 1 year, $50,000 • Michael Caplan, Epigen Stony Brook (nih), Tools to Analyze Morphology Erythrocyte Volume Homeostasis, 2 years, Targeting Prostate Cancer with Multi-Functional Biosciences, Inc. (nih), Development of Novel and Spatially Mapped Molecular Data, 5 years, $412,088 • Alison Galvani, nsf, rapid: Optimal Nanoparticles, 3 years, $374,625 • James Mazer, Agents for the Treatment of Renal Fibrosis, 1 year, $6,290 • Haifan Lin, G. Harold and Leila Y. Allocation of Both Non-Pharmaceutical and Phar- nih, crcns: Model-Driven Single-Neuron Studies $143,180 • David Carlson, Dartmouth College Mathers Charitable Foundation, Applying Nono- maceutical Interventions toward Controlling of Cortical Remapping, 2.9 years, $666,000 (niid), Comparing In Vivo Biodosimetry with epr Physics to Epigenetics: Solving the Structure of Ebola Transmission in West Africa, 1 year, Don Nguyen, nih, A Novel Lineage Pathway to Independent Physical Dosimetry Methods, Piwi-pirna-Chromatin Complex by Atomic Force $199,890 • Mary Germino, nih, Hybrid Paramet- Controls Metabolic Adaptation by Metastatic 9 months, $50,000 • Keith Choate, Doris Duke Microscopy, 4 years, $1,708,593 • Kasia Lipska, ric/Non-Parametric Direct Reconstruction for Lung Cancers, 5 years, $1,901,390 • Michael Charitable Foundation, Genetics and Pathobiol- American Federation for Aging Research, Predict- Dynamic pet, 2 years, $72,552 • David Glahn, DoD, Nitabach, nih, Synaptic Microcircuits Controlling ogy of Cutaneous-Skeletal Hypophosphatemic ing Severe Hypoglycemia among Older Adults Genetic and Diagnostic Biomarker Development Sleep, 4.8 years, $2,029,622 • In-Hyun Park, nih, Syndrome and Erythrokeratodermia Variabilis, with Diabetes, 4.7 years, $50,000 • Elias Lolis, in asd Toddlers Using Resting-State Functional Investigation of the Function of Methylated dna 1.5 years, $64,800 • Theodore Cohen, Harvard U.S.-Israel Binational Science Foundation, CD74 mri, 2 years, $187,935; nih, Gene Networks Influ- Binding Protein in Reprogramming, 5 years, University (nih), midas Center for Communicable Intracellular Domain (icd) as a Transcription encing Psychotic Dysconnectivity in African Amer- $1,602,565 • Dana Peters, nih, Detection of Atrial Disease Dynamics, 11 months, $143,300 • Zachary Factor- Structure and Function, 4 years, $105,000 icans, 5 years, $3,880,154 • Peter Glazer, nih, Remodeling by mri: Validation and Emerging Sig- Cooper, Commonwealth Fund, Understanding John MacMicking, Kenneth Rainin Foundation, Bifunctional Antibodies for Melanoma Therapy, nificance, 4 years, $1,665,000 • Marina Picciotto, the Pricing Dynamics in the U.S. Health Care Immunity-Related gtpases: A New Network Hub 5 years, $2,230,305; nih, Hypoxia, dna Repair, and nih, Nicotine and Food Intake, 4.7 years, Industry: An Analysis Using hcci Data, 2 years, Model for ibd, 1 year, $100,000 • Mark Mamula, Gene Silencing, 5 years, $1,873,125 • Charles Greer, $2,081,250 • Katerina Politi, DoD, Cellular Plastic- $384,845 • Chris Cotsapas, Mayo Clinic College of Juvenile Diabetes Research Foundation Interna- nih, Piriform Cortex: Sequential Developmental ity and Heterogeneity of egfr Mutant Lung Medicine (nih), Uncovering Genetic Determi- tional, Protein BioMarkers of Beta Cells in T1D, Events, 5 years, $1,769,065 • Daniel Greif, nih, Cancer, 1 year, $166,500 • Neil Romberg, nih, nants of Influenza Vaccine Response in Humans – 1 year, $100,000 • Praveen Mannam, American Pathological Arterial Muscularization and the Blocking Autoantibody Secretion in cvid Patients A hipc Project, 10 months, $162,657 • Robin Thoracic Society, Mitochondrial Quality Control Role of Integrins, 4 years, $1,665,000 • Elena with itp by IL-2 Restored Tregs, 5 years, $897,350 de Graaf, University of Minnesota (nih), Imaging as a Therapeutic Target in Sepsis, 1 year, $40,000 Grigorenko, Department of Education, Founda- Carla Rothlin, nih, tam Receptor Tyrosine Brain Function in Real World Environments & Ruslan Medzhitov, The Leona M. and Harry B. tion for Alliance for Education, 1 year, $399,963 Kinases in Inflammatory Bowel Disease, 5 years, Populations with Portable mri, 9 months, Helmsley Charitable Trust, Exploring the Vulnera- Cary Gross, nih, Impact of Social Contagion on $2,081,250 • James Rothman, nih, Mechanism of $39,884 • Francesco D’Errico, University of Michi- bilities of the Developing Intestinal System and its Physician Use of Unproven Cancer Interventions, Membrane Fusion by snare Proteins, 4 years, gan (Dept. of Energy), Consortium for Verifica- Role in veo ibd, 3 years, $627,000 • Ruth Mont- 4 years, $2,222,343 • Jaime Grutzendler, nih, $2,630,700 • Nenad Sestan, nih, Functional tion Technology, 1 year, $160,000 • James Farrell, gomery, Mayo Clinic of Rochester (nih), Novel Angiophagy a Mechanism Linking Microvascular Genomics of Human Brain Development, Cook Medical, Inc., Comparing a 25G eus-fna Technologies to Define Functional Attributes of and Alzheimer’s Pathologies, 1.7 years, $457,875; 4.9 years, $215,803 • Matthew Simon, nih, Inte- with a 20G eus ProCore fnb Device, 1 year, $5,000 T Cells in West Nile Virus, 10 months, $50,033 nih, Postnatal Development of the Neuro-Glio- grating rnas into Signaling Pathways by Engi- Richard Formica, Icahn School of Medicine at Don Nguyen, Astra Zeneca AB, Role of AZD9291 Vascular Unit, 5 years, $1,821,095 • Michelle neering Covalent rna Modifications, 4.7 years, Mount Sinai (ismms) (nih), Effects of Inhibiting in Treating Brain and Leptomeningeal Metastasis, Hampson, nih, Biofeedback of Activity in the $2,497,500 • Megan Smith, nih, sch:int Harness- Early Inflammation in Kidney Transplant Patients, 1 year, $83,000 • Michael Nitabach, John B. Orbitofrontal Cortex for ocd, 4.8 years, $2,521,700 ing the Power of Technology: momba for 1 year, $76,240 • Alison Galvani, University of Pierce Laboratory Inc. (nih), Development of

6 www.medicineatyale.org Protein-Based Voltage Probes, 11 months, $609,151 • Lajos Pusztai, University of Michi- Shareable Opioid Clinical Decision Support for 1 year, $6,882 • Alda Tufro, Georgia Regents $32,804 • John Pachankis, Hunter College, City gan, Financial Support for the Breast Cancer Electronic Health Records, 1 years, $146,436 University (nih), S-Nitrosylation of Extracellular University of New York (nih), Building Mobile Intergroup Correlative Science Studies, 1 year, Wendy Silverman, Florida International Univer- Matrix Proteins in Diabetic Nephropathy, 1 year, Health hiv-Prevention Capacity for msm in $50,000 • David Rimm, Breast Cancer Research sity (nih), Attention Bias Modification Training $100,000 • Benjamin Turk, University of Min- Romania, 8 months, $37,028 • A. Paltiel, Foundation, Targeted and Immune Therapies in in Youth with Subthreshold Impairing Anxiety, nesota (nih), Multiplexed Kinase Biosensor Tech- Harvard School of Public Health (dhhs), Pre- Breast Cancer, 1 year, $250,000 • Carla Rothlin, 9 months, $55,638 • Satinder Singh, U.S.-Israel nology to Detect Leukemia Signaling with Mass vention Policy Modeling Lab, 1 year, $187,218 Kolltan Pharmaceuticals, Inc., Specificity of Binational Science Foundation, Bacterial Homo- Spectrometry, 11 months, $20,723 • Christopher In-Hyun Park, University of Texas at Dallas tam rtk Immune Function, 3 years, $742,250 logues of Vesicular Neurotransmitter Transport- Van Dyck, Medical University of South Carolina (nih), Analysis of Higher Order Chromatin Struc- Alessandro Santin, The Honorable Tina ers: Tools for Understanding Mechanism, (nih), Apathy in Alzheimer’s Disease Methylphe- tures in Normal and Cancer Epigenomes, 1 year, Brozman Foundation, Brozman Consortium 4 years, $84,698 • Michael Skonieczny, South nidate Trial (admet II), 9 months, $86,780 $56,478 • Godfrey Pearlson, Mount Sinai Planning Grant, 1 year, $15,000; The Honorable Essex Partnership nhs Foundation Trust, Train- Stuart Weinzimer, Nemours Children’s Clinic, Medical Center (nih), Deconstructing Psychoses Tina Brozman Foundation, Brozman Consor- ing and Development, 1 year, $160,000 • Serena Jacksonville (nih), T1D and the Brain in Children: Based on Patterns of Abnormal Brain Activity, tium Sample Collection Grant, 1 year, $30,000 Spudich, Henry M. Jackson Foundation (DoD), Metabolic Interventions, 9 months, $186,920; 11 months, $97,319; Hartford Hospital (nih), Jennifer Sherr, The Leona M. and Harry B. Study of Neurohiv Cure Consortium (Protocols: Stanford University, Outpatient Closed-Loop Neural Architecture of Emotion Regulation, Helmsley Charitable Trust, Effect of LX4211 on RV217, RV254, RV397, RV398 RV412), 1 year, Studies - epid Controller, 1 year, $227,248 • Adam Adolescent Development & Depression, 4 years, Control to Target Automated Insulin Delivery, $182,654; Brigham and Women’s Hospital Wisnewski, American Chemistry Council, Iden- $19,764 • Kitt Petersen, Atara Biotherapeutics, 2 years, $479,900 • Robert Sherwin, Raimund (nih), aids Clinical Trials Group (actg) Leader- tification of Primary Reaction Products of Hexa- Inc., ata 842 Preclinical Mouse Study, 9 months, Herzog, Juvenile Diabetes Research Foundation ship and Operations Center, 1 year, $59,532 methylene Diisocyanate (hdi) in the Respiratory $402,930 • Virginia Pitzer, Bill and Melinda International, Development of Agents to Dimin- Tami Sullivan, University of New Mexico, Tract, 1 year, $65,608 • Wendell Yarbrough, Gates Foundation, Typhoid Modeling Studies for ish the Risk of Hypoglycemia-Induced Brain Financial, Therapeutic, Health and Deterrence Adenoid Cystic Carcinoma Research Founda- Typhoid Conjugate Vaccine Cost Effectiveness Injury in T1DM, 2 years, $491,784 • Richard Outcomes for Domestic Violence Tort Plaintiffs: tion, Targeting Cancer Stem Cells in Salivary and for Typhoid Delivery Strategy, 3 years, Shiffman, norc (dhhs), Standardized and Interdisciplinary Study in Law & Psychology, Adenoid Cystic Carcinoma, 1 year, $27,500

// Stem Cell (from page 1) founded in // Scholars (from page 5) delivery of health 1950, into the Cheung Kong Group, care across the health continuum,” now a multinational conglomerate. says Margaret Grey, dr.ph., r.n., the He established the Li Ka Shing Foun- Annie Goodrich Professor of Nurs- dation in 1980 in part to help spur ing and former dean of the School education reforms and medical innova- of Nursing. “The more we educate tion. His new gift to Yale builds on a people in silos—whether for clinical gift of $1.56 million made in 2011. practice or clinical research, or health “Training side-by-side with leading services research—the less likely it is scientists in stem cell research will be a they will work collaboratively when transformative experience for the stu- they get out in the real world.” dents and faculty at Shantou University Also, Grey says, post-doctoral train- Medical College, and I want to express ing slots for nurses are limited, and my heartfelt appreciation to Professor the Ncsp will provide a much-needed

Haifan Lin and the yscc for this amaz- courtesy of the li ka shing foundation avenue for nurses who seek to combine ing opportunity,” Li said. In addition to independent research, Li Ka-shing (left) and Haifan Lin attend a clinical work with research. “Continued support from Li Ka- scientists in these core labs work with commencement ceremony at Shantou Univer- The new two-year program will shing allows us to accelerate the pace researchers across the university who sity (stu), in China. A new gift from the Li Ka select approximately five physi- and broaden the scope of our work,” need assistance in any of these areas. Shing Foundation to the Yale Stem Cell Center cian- and nurse-scholars per year supports research and a continued interna- says Lin, also professor of cell biology; Since its founding in 2006, yscc tional collaboration between Yale and stu. to complete coursework together at of genetics; and of obstetrics, gynecol- resources have contributed to hundreds Yale, sharing mentors from across the ogy, and reproductive sciences. “We of research projects at Yale. Just this “Yale is enormously grateful to professions. ncsp scholars will lead are extremely grateful to Mr. Li for his year, researchers showed how stem cells the Li Ka Shing Foundation for its their own policy-relevant research generosity,” Lin says. could be used to create miniature hu- continued support of basic science, projects, guided by faculty and com- As yscc’s founding director, Lin man brain models to better understand translational research, and scholarly ex- munity partners. created four core facilities for basic stem autism. Another group tracked stem change,” said Carolyn Slayman, ph.d., Says Gross, “We place a great cell research and has supported more cell development in mouse hair follicles Sterling Professor of Genetics, profes- emphasis on teaching scholars not than 80 research labs at Yale on projects and found that the cells’ development sor of cellular and molecular physiol- just how to do research, but how to covering a range of critical topics. The appeared to be influenced extrinsically ogy, and deputy dean for academic and instill change. And we’re applying the yscc’s core facilities focus on research by the surrounding microenvironment. scientific affairs. “This grant will help same principles to the design of the in human embryonic stem cells and in- Yet another Yale team found that a expedite the development of therapeu- program itself, changing it to reflect duced pluripotent stem cells, cell imag- variant of the gene ccne1 appears criti- tic treatments for some of the world’s the needs of today’s communities and ing, genomics, and cell manipulation. cal for reprogramming mature cells. most debilitating diseases.” tomorrow’s health care system.”

// Chair (from page 1) “The world made to buy into working with the ycec, the possibility of very early treatment when she was a year old. Now that no sense to her,” Mark says. Mark says: “Meghan really trusts for human patients to change the she’s seizure-free, there is finally a That day in Houston, Meghan Hal.” With a thorough review of course of the disease. window to work on the behavioral ran from the hospital. She led Mark her long and complicated history, Blumenfeld is director of the issues that have presented such chal- and Michele down a the team came up with a strategy to Yale Clinical Neuroscience Imaging lenges to Meghan and her family. freeway, running the bring the seizures under control. Center and a member of the Kavli Mark Loughridge is the former wrong way in traffic. Meghan’s family offered annual Institute for Neuroscience. A gradu- chief financial officer of ibm, and is They eventually con- support to Blumenfeld’s epilepsy ate of Harvard University, Blumen- currently lead director of Vanguard vinced her to return. research for several years before en- feld earned his m.d. and ph.d. from and independent director at the Mark sat in a room at dowing the professorship. Says Mark, Columbia University. He completed Dow Chemical Co. He serves on the a psychiatric facility “This was an opportunity for us to his internship in internal medicine Council on Chicago Booth for the alone with Meghan pay back to the community ... and to at Columbia Presbyterian Medical University of Chicago Booth School and attempted to Hal Blumenfeld a facility that had done so much for Center and his neurology residency of Business, where he earned an mba. soothe her. Michele our family.” at Massachusetts General Hospital. Michele serves on the board of sat outside and warned a police of- In addition to his research on loss He then served as a fellow in epilepsy Mercy Learning, a group that pro- ficer that she should not enter the of consciousness during seizures, at Yale School of Medicine (ysm). vides literacy and life skills training room until Mark had more time with Blumenfeld, also professor of neuro- Blumenfeld’s research draws to low-income women. One day one Meghan. But the officer entered, and science and neurosurgery, has delved on such varied areas as imaging, of the women Michele was tutoring Meghan punched her in the face. into the prevention of epilepsy. In bioengineering, and neurochemistry. had a seizure. Although almost 30, Years later, the storm has calmed: 2008 he reported in Epilepsia that Excellence across disciplines and a she had never been under a doctor’s the family began a new chapter when giving the anti-seizure medication culture of collaboration keep him at care for her epilepsy. Meghan visited the Yale Comprehen- ethosuximide to animals with ab- ysm, he says: “It’s really a team effort Michele’s first call was to Blumen- sive Epilepsy Center (ycec). She’s sence epilepsy before onset of seizures that brings us happy stories such feld, and the woman was referred to been seizure-free for nearly two years markedly reduced seizures and con- as Meghan’s.” the ycec for care. Says Michele, “She under Blumenfeld’s care. His gentle tinued to do so for months after the Meghan has neurological impair- got exactly the same treatment that demeanor made it easy for Meghan treatment. He continues to explore ment from the epilepsy that began Meghan did.”

Medicine@Yale October/November 2015 7 Physiologist joins National Academy of Sciences Awards & Honors Pietro De Camilli, Nancy Carrasco, m.d., professor of Autonomous Uni- things about science is that it’s an m.d., chair and cellular and molecular physiology, has versity of Mexico, international pursuit,” she said. the John Klingen- been named to the National Academy and completed a The nas is a private, non-profit stein Professor of of Sciences (nas) as a foreign associ- postdoctoral fellow- institution established under Presi- Neuroscience and ate. She is among 84 new members ship at the Roche dent Abraham Lincoln at the height professor of cell biol- and 21 foreign associates selected for Institute of Mo- of the Civil War to serve as an ogy, has been named membership this year in recognition lecular Biology. She advisory group. With the National president-elect of of their achievements in original scien- joined the School of Academy of Engineering, National the American Society of Cell Biology. His term will begin in 2017. De Camilli tific research. The new cohort includes Medicine’s faculty Academy of Medicine, and National Nancy Carrasco is also director of the Kavli Institute three other Yale faculty members. for Neuroscience at Yale and a Howard Carrasco’s work explores the Hughes Medical Institute investigator. mechanisms of transport across the “I think that one of the most beautiful things about cell membrane. Her research on the Na+/I- symporter (nis), the key plas- science is that it’s an international pursuit.” ma membrane protein that mediates —Nancy Carrasco, m.d. Benjamin A. Fontes, active iodide transport in the thyroid, m.p.h., biologi- lactating breast, and other tissues, cal safety officer, ranges from biochemical, biophysical, in 2011 following an appointment at Research Council, today it provides has received the and physiological investigations to the Albert Einstein College of Medi- science, technology, and health policy American Biological translational studies, including de- cine in New York City. advice to the federal government and Safety Association’s velopment of new cancer treatments. “My election stands as a counterar- other organizations. Arnold G. Wedum Distinguished Her research group was the first to gument to some of the claims we hear Carrasco and the other newly elect- Achievement Award for his “outstand- discover the mechanism for cellular every now and then regarding the ed members will be formally inducted ing contributions to biological safety uptake of iodide, after cloning nis. contribution that immigrants—those at the NAS annual meeting next year, accomplished through teaching, re- A native of Mexico, Carrasco from Mexico, like myself—are making bringing the total number of active search, service, or leadership.” In 2014 received her m.d. and an m.s. in in the U.S. and around the world. I members to 2,250 and the total number he was Yale’s Environmental Health biochemistry from the National think that one of the most beautiful of foreign associates to 452. and Safety Employee of the Year.

Dennis D. Spencer, Yale immunologist named HHMI investigator m.d., the Harvey and Kate Cushing Profes- John D. MacMicking, ph.d., associ- cells that play a critical role in this Investigator in the sor of Neurosurgery, ate professor of microbial pathogen- unusual form of host defense. pathogenesis of has received an Am- esis, is one of 26 scientists named in An hhmi announcement about infectious disease. In bassador for Epilepsy May as investigators of the Howard MacMicking’s selection noted that his 2014 he was named Award from the Hughes Medical Institute (hhmi). “discoveries about how individual cells both an American International League Against Epilepsy. The award recognizes MacMicking is a leading expert protect themselves against viruses, Asthma Foundation Spencer’s outstanding contributions in the emerging field of cell-auton- bacteria, and other pathogens is forc- Scholar and the Ken- to activities advancing the cause of omous immunity—the ability of ing scientists to reconsider what con- neth Rainin Foun- epilepsy internationally. He has helped most nucleated cells, not just those stitutes the boundaries and breadth of John MacMicking dation Innovator. develop epilepsy surgery programs in of the immune system—to defend the traditional immune system.” A non-profit Asia, Africa, and Latin America. against infection via sophisticated MacMicking earned his b.sc. at medical research organization with antimicrobial strategies evolved to the Australian National University an endowment of more than $16 bil- deal with a wide array of microbial in Canberra and his ph.d. at the lion, hhmi was founded by busi- Joan A. Steitz, ph.d., pathogens. Many of these strategies Sloan-Kettering Institute-Cornell nessman Howard Hughes in 1953. Sterling Professor of are orchestrated through interferon University Medical College in New The hhmi’s grants to scientists from Molecular Biophys- (ifn) signaling pathways essential York City. He was a hhmi Life Sci- 19 institutions across the United ics and Biochemis- for host resistance to major infec- ence Research Foundation Fellow States for basic biomedical research try and a Howard tious diseases such as tuberculosis, and adjunct assistant professor at are worth $153 million over the next Hughes Medical aids, and malaria. In work begun The Rockefeller University before five years. The new investigators— Institute investiga- tor, received the 2015 at The Rockefeller University and being recruited to ysm. who include four current hhmi early Connecticut Medal of Science for her continued at Yale School of Medicine MacMicking has been recog- career scientists—were selected for seminal research on the structure and (ysm), he and his lab members iden- nized as a Searle Scholar, an Edward their individual scientific excellence function of rna. The medal is Con- tified a new superfamily of enzymes Mallinckrodt Jr. Foundation Fellow, a from 894 eligible applicants, and necticut’s highest honor for scientific termed ifn-inducible gtpases in Cancer Research Institute Investiga- are expected to begin their appoint- achievement in fields crucial to the both immune and non-immune tor, and a Burroughs-Wellcome Fund ments this fall. state’s economic competitiveness.

// Dyslexia (from page 1) loci on human can have additional disabilities that second grade, some students will also Sometime in the future, Gruen says chromosomes that appear to play a span more than one domain, and participate in an intense intervention he hopes district-wide screening can role in the development of language, hence the need to gather more infor- with specially trained teachers. be implemented to identify children at expression, and reading. mation. Gruen’s aim is to know as By mid-October the nhlp had high risk for learning disabilities, and In recent years Gruen has worked much as possible about how genes enrolled 87 families. The researchers then to match them to a precisely-de- to hone an approach he calls “preci- and the type of learning intervention are focused on recruitment and testing signed curriculum effective for a child’s sion education.” In 2009, with the a child receives interact with each in first grade classes. The target for the unique genomic sequence. support of a $5 million grant from other. Whereas the GRaD Study study’s conclusion and results is 2021. “We know that dyslexia can re- the Manton Foundation, he was the focused on presymptomatic screen- “The School of Medicine is deeply spond to intervention programs that principal investigator of a multicenter ing, the goal of the nhlp is to use appreciative of this further encourage- address multiple learning modalities genetic study of dyslexia in minori- genetics to predict response-to- ment and support from the Manton and are offered in early grades,” Gruen ties, focusing on Hispanic-American intervention, and to inform the Foundation, an institution that has a says. However, “often the diagnosis and and African-American children, optimal intervention for each stu- strong record in the advancement of intervention come too late after a child called the Yale Genes, Reading, and dent with learning disabilities. important work on behalf of under- has experienced repeated academic fail- Dyslexia (GRaD) Study. Its goal was The team will selectively enroll served, urban communities,” said ures, and when the child is less likely to to find genetic markers that can iden- qualified students for individual Dean Robert J. Alpern, m.d., Ensign respond,” he says. tify children at risk for dyslexia well cognitive assessments, classroom and Professor of Medicine. “This new The Manton Foundation was before the children begin to fail in testing performance, family life and grant allows the school to continue established in New York City in 1991 school, so that intervention could be background, culture, serial magnetic its ground-breaking genetics research by Sir Edwin and Lady Manton to started early, when it’s most effective. resonance imaging of brain structure and, equally important, to apply dis- support the arts, education, health The nhlp takes this research a and function, and comprehensive ge- coveries and progress toward improv- care, cultural preservation, and step further. Children with dyslexia nomic analyses. Once they reach the ing human lives.” medical research.

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