december 2010 volume 6, issue 5 Advancing Biomedical Science, Education, and Health Care

Alumna supports doctors who join her on a road less traveled Medicine offers satisfying careers in Hudson Valley and Catskills region. challenges faced Grand Rounds at Yale, often trans- both science and patient care, and at But she also boasts a curriculum vitae by physicians who porting a patient with an unusual the School of Medicine, students and that bristles with honors, including are as dedicated to or difficult illness. “Though she will faculty are encouraged to creatively the Master Dermatologist Award advancing medi- be quite hard for anyone to emulate, combine these two vocations as physician from the American Academy of cine as they are to this gift will help future generations –scientists. But Marie-Louise T. Dermatology and membership in the well-being of of potential Marie-Louise Johnsons Johnson, m.d., ph.d., has forged a the National Academy of Sciences’ their patients. To reach for that bar.” career path that is “utterly unique in Institute of Medicine. What makes help others attain Johnson graduated from the med- Marie-Louise our field, and an exceptionally lofty Johnson special, says Edelson, Aaron Johnson this uncommon ical school in 1956, having already model,” says Richard L. Edelson, m.d., B. and Marguerite Lerner Professor of balance, Johnson earned her ph.d. in microbiology at chair of the Department of Dermatol- Dermatology, is that she blends clini- has recently made a gift of $1 million Yale in 1954. Since her medical school ogy, who calls Johnson “a physician, cal care with biomedical insight and to the School of Medicine, creating training preceded the arrival of Yale’s scientist, humanist.” inspirational teaching. “She sees every an endowment to support “clinical first chair of dermatology, she became At age 83, Johnson maintains a medical problem as a mystery inviting scholars” at Yale. troubled during her internship at busy dermatology practice in Kings- a solution, a teaching opportunity, “As a role model, she presents Grace-New Haven Community Hos- ton, N.Y., a city of 23,000 on the Hud- and a very personal challenge.” a very high bar,” Edelson says of pital (now Yale-New Haven Hospital) son River about 100 miles north of The rarity of the particular Johnson, who on many Wednesday by her lack of comprehension of the New York City, which draws patients constellation of qualities possessed mornings drives over 90 miles from many skin lesions and rashes she saw from a wide swath of the surrounding by Johnson is a testament to the her home to attend Dermatology in patients admitted // Gift (page 7)

Built from scratch, Yale’s picks to beat cancer: a pair of aces lungs are a big leap An illustrious new chief of medical oncology, in bioengineering a leader for the Yale Cancer Biology Institute Laura Niklason, boost efforts to develop better drugs for cancer m.d., ph.d., has spent the past 15 It has been an eventful December for the advancement of years in the lab basic and translational cancer research at Yale. On the 13th, developing ways Yale University announced that Joseph Schlessinger, ph.d., a to build new world-renowned scientist with an unparalleled track record of arteries using identifying molecular targets for novel anticancer drugs, was tissue engineer- Laura Niklason named the first director of the University’s new Cancer Biol- ing techniques, ogy Institute (cbi), one of five major interdisciplinary research but as an anesthesiologist who initiatives located on Yale’s West Campus. terry dagradi works in the intensive care unit, Just a week before, Thomas J. Lynch Jr., m.d., director Joseph Schlessinger (above) will direct the Yale she always had another idea roll- of Yale Cancer Center (ycc), broke the news that ycc has Cancer Biology Institute, a major research initia- ing around in the back of her head. appointed Roy S. Herbst, M.D., Ph.D., who has also had a dis- tive that will bring as many as 11 new principal Niklason, professor of anesthe- tinguished career in the development of new cancer therapies, investigators and 150 research scientists to West siology and biomedical engineering, Campus over the next few years. Roy Herbst (left) as chief of medical oncology at Smilow Cancer Hospital and has led several clinical trials of the latest anti- was troubled that a large number associate director for translational research. cancer compounds at the MD Anderson Cancer of her patients suffered damage Schlessinger, whose appointment is effective immediately, Center in Houston, Texas. to the lungs, organs that simply will retain his positions as chair and William H. Prusoff Pro- don’t fix themselves very well after fessor of Pharmacology at the School of Medicine, dividing his “Dr. Schlessinger has significantly expanded the footprint injury or serious illness. Hundreds time between the medical campus and West Campus. Herbst and faculty roster of the Department of Pharmacology, which of thousands of Americans die from comes to Yale in March 2011 from MD Anderson Cancer Cen- was ranked in the top three departments this year by the Na- lung disease each year, and the only ter at the University of Texas in Houston, where he is professor tional Research Council,” says Robert J. Alpern, m.d., dean of effective treatment for severe cases of medicine, chief of the section of thoracic medical oncology, the School of Medicine. “His taste for excellence has resulted is transplantation. Unfortunately, and Barnhart Family Distinguished Professor in Targeted in outstanding faculty recruitments, and we look forward this expensive procedure is associ- Therapies. His appointment marks Herbst’s return to Yale, to the application of his talents in building an outstanding ated with high mortality and is where he received his undergraduate and master’s degrees. Cancer Biology Institute.” // Cancer (page 7) also limited by an // Lungs (page 7)

Non-Profit Org. inside this issue 1 Church St., Suite 300, New Haven, CT 06510-3330 U. S. Postage www.medicineatyale.org 2 Lifelines paid For Drosophila expert Lynn Cooley, New Haven, CT curiosity is key. Permit No. 526 3 Paying it forward School of Medicine mentors put students and postdocs on a productive path. 5 The inside story Endoscope with a tiny, powerful microscope gives doctors a new view of GI diseases. also Advances, pp. 3, 5 Out & About, p. 4 Grants and Contracts, p. 6 lifelines Associate dean wins top honor in medical education

In an age of increasing em- Rosemarie L. phasis on research explicitly Fisher, m.d., directed toward treatments professor of for human diseases, Lynn medicine and Cooley is a passionate advocate of basic, “curiosity- pediatrics and driven” research, which often associate dean provides insights that later for gradu- prove useful in the clinic. Re- ate medical cent studies of ovarian muscle Rosemarie Fisher education, has in the fruit flyDrosophila melanogaster in Cooley’s lab received the have shown that the fly could Dema Daley Founders Award, the provide an important new highest honor bestowed on medi- model of human diseases cal educators by the Association such as muscular dystrophy. of Program Directors of Internal Medicine. The award honors a member of the internal medicine community recognized interna- Lynn Cooley tionally as an educator, innovator, michael marsland and leader. Fisher has spent 35 years on the School of Medicine faculty, includ- ing 12 as director of graduate medi- Putting eggs in a new basket cal education at Yale-New Haven Science for its own sake professor of genetics, cell biology, and of developing egg chambers through the Hospital (ynhh), a role in which molecular, cellular, and developmental Drosophila ovary. she oversees all residency pro- can also hatch payoffs, biology, studied proteins in the cyto- In a 2008 study reported in Develop- grams, and seven as associate dean. says a Yale geneticist skeleton, the “scaffolding” of cells. After mental Biology, Cooley and colleagues She is the former program direc- earning her master’s degree, she left used a technique known as protein tor for the Department of Internal The laboratory of Lynn Cooley, ph.d., is graduate school for a time and worked trapping to selectively tag specific com- Medicine’s residency program. As abuzz, not only with thousands of vials in the Yale lab of Dieter G. Söll, ph.d., ponents of ovarian muscle in Drosophila a member of the ynhh Nutrition of live fruit flies, but with the excite- Sterling Professor of Molecular Biophys- with fluorescent molecules, revealing Support Team, Fisher’s research ment scientists experience when their ics and Biochemistry and professor of surprising details of these structures has focused on the role of nutri- research may cross a new threshold. chemistry, “probably the most impor- that had previously received little atten- tional support such as intravenous Cooley, an authority on oogenesis tant influence in my career,” she says. tion from scientists. feeding in gastrointestinal diseases. (egg development) in the fruit fly Dro- Though Cooley eventually received “Then a student started trying to She received her medical degree sophila melanogaster, says that until her doctorate from Texas, she con- use the ovarian muscles as a model from Tufts University School of recently she would have characterized ducted her dissertation research in Söll’s for studying mutations in proteins Medicine in 1971 and completed a her work as “one hundred percent basic lab, studying the formation of histidine that cause muscular dystrophies,” says residency in internal medicine at science.” But Cooley believes that recent transfer rna, a molecule involved in Cooley. “So now I feel at least I have a Montefiore Hospital and Medical findings in her lab have great potential protein synthesis, in both yeast and toe in the door for developing what we Center in New York City. She com- for important new insights into human Drosophila. During a postdoctoral fel- love about Drosophila oogenesis as a pleted fellowships in gastroenterol- diseases such as muscular dystrophy. lowship with Allan C. Spradling, ph.d., more translationally oriented model.” ogy at both the Royal Free Hospital Fruit flies are an all-too-common nui- at the Carnegie Institution for Science in But Cooley, who also directs the in London and at Yale. Fisher is sance in kitchens around the world. But Baltimore, Md., Cooley began her explo- cross-campus ph.d. program known board-certified in gastroenterology the ubiquity of these tiny flies belies their rations of oogenesis, working exclusively as the Combined Program for Biologi- and internal medicine. tremendous importance to biology. More with Drosophila, and settled on the cal and Biomedical Sciences, empha- In 2006, Fisher was one of two than a century of work on Drosophila — a research niche and the model species sizes that the potential of Drosophila people to win the first Parker J. species that is unusually amenable to that have defined her work ever since. ovarian muscle as a model for human Palmer Courage to Lead Award genetic manipulation and that repro- Cooley and those in her lab study disease was revealed by basic research, from the Accreditation Council duces and matures rapidly — has helped not only the formation of eggs but the which is in danger of being “down- for Graduate Medical Education, to unravel the molecular basis of core chambers in which eggs form, the flow graded” by society’s increased demand which honors excellence in over- biological functions; over 60 percent of of information and nutrients from so- for translational work. It’s essential, seeing residency programs. Drosophila genes have counterparts in called nurse cells to oocytes (develop- Cooley believes, “for curiosity-driven the human genome. ing eggs), changes in the cytoskeleton science to continue, since you never As a graduate student at the Uni- during egg development, and the role know where efforts to figure out how versity of Texas–Austin, Cooley, now of muscle tissue in the progression of biology works will lead.”

Managing Editor Peter Farley Assistant Editor Charles Gershman Contributors John Curtis, Michael Fitzsousa, Kathy Annual auction nets more than $25,000 for New Haven charities Katella, Karen Peart, Janelle Weaver Design Jennifer Stockwell The annual student-run Hunger At an evening live auction, first- Medicine@Yale is published five times each year by the Office of Institutional Planning and and Homelessness Auction, held on year students Alex Kula and Conor Communications, Yale School of Medicine, November 18, garnered more than Brady served as auctioneers and led 1 Church St., Suite 300, New Haven, CT 06510-3330 Telephone: (203) 785-5824 Fax: (203) 785-4327 $25,000 for New Haven charities. the bidding on items that included a E-mail [email protected] The event started with a silent faculty vs. medical student softball Website medicineatyale.org auction featuring California wines, game; a dinner and wine tasting at Copyright ©2010 by Yale University. All rights reserved. fencing lessons, movie tickets, and the home of Dean Robert J. Alpern, If you have a change of address or do not wish to receive future issues of Medicine@Yale, please write to us at the an incomparable evening of watch- m.d., Ensign Professor of Medicine; above address or via e-mail at [email protected]. ing sports or action movies on tickets to a Red Sox baseball game; Postal permit held by Yale University, 155 Whitney Avenue, New Haven, CT 06520 TV (plus dinner of corn dogs and and a four-hour cruise on the sailboat turkey burgers). of James D. Jamieson, m.d., ph.d., Robert J. Alpern, m.d. Some off-beat services were professor of cell biology. Dean and Ensign Professor of Medicine offered by students to bidders: This year’s proceeds will ben- Jancy L. Houck Associate Vice President for Development and Director of “I will be your running buddy for efit Loaves and Fishes, Columbus Medical Development (203) 436-8560 any distance and any speed”; “I will House, New Haven Home Recovery, Mary Hu john curtis make a breakup phone call for you Downtown Evening Soup Kitchen, Director of Institutional Planning and Communications First-year medical students Alexandra Adler and explain to your significant other Community Health Care Van, and (left) and Eileen Harder (right) make bids at the why the relationship is over.” the Community Soup Kitchen. student-run Hunger and Homelessness Auction. Printed on recycled paper ♻

2 www.medicineatyale.org advances Health & Science News Medical school’s mentors ‘pay it forward’ It all adds up: diabetes Seasoned pros are vital and oxidative stress in preparing students to succeed on their own

Though few of the hundreds of busy people who pass through the doors of Sterling Hall of Medicine each day notice the Greek inscription on a plaque over- head, the language there says much about

corbis images life at the School of Medicine. In transla- We need oxygen, but it comes with a tion it reads, “Those having torches will catch. Aerobic metabolism produces re- pass them on to one another.” active oxygen species (ros), which are Some torches are passed straightfor- toxic to mitochondria (one is pictured wardly. During their training, medical above), the “power plants” of cells. students, doctoral students, and even Gerald I. Shulman, m.d., ph.d., postdoctoral associates learn facts, many the George R. Cowgill Professor of thousands of them. But as in all fields,

Physiological Chemistry, has proposed from the law to violin-making, to ulti- harold shapiro that type 2 diabetes mostly affects mately succeed in medicine or science there is no substitute Pediatric surgeon and scientist Christopher Breuer (left) is “a very easy older people because cumulative ros- for learning the ropes from a seasoned mentor. Throughout person to talk to,” says Daniel “Pete” Duncan (right), a student spending induced damage reduces mitochondrial its 200-year history, mentorship has been integral to the mis- an additional year of medical school doing research in Breuer’s lab. Breuer sion of Yale School of Medicine, where it plays a part today in and colleague Toshiharu Shinoka are pioneers in the use of tissue engineer- activity, which predisposes older indi- ing techniques to build new blood vessels for children with heart disease. viduals to intracellular fat accumulation nearly every sphere. and insulin resistance — the major fac- tor in the development of the disorder. A hand up in medicine earning the ph.d. Graduate students study at the medical Shulman and colleagues engi- Until recently, Associate Dean for Student Affairs Nancy school via the Medical Scientist Training Program (mstp; neered mice to express high levels of R. Angoff, m.p.h., m.d., served as advisor to every mem- known more commonly on campus as the m.d./ph.d. Pro- the antioxidant enzyme catalase in ber of every medical class at Yale, providing counseling in gram), which is devoted to educating physician–scientists, mitochondria to tamp down ros. As every realm from the academic to the personal. In 2009 the and the Combined Program in Biomedical and Biological Sci- reported in the December issue of Cell advising duties were split among four faculty, each of whom ences (bbs), which gives ph.d. students experience in several Metabolism, the mice were protected guides one quarter of each class. While they are not mentors labs at both the university and the medical school before they from age-related declines in energy in the strictest sense of the word, the new advisors—John S. settle into a bbs-affiliated department, many of which are at metabolism, intracellular fat accumu- Francis, m.d., ph.d., assistant professor of medicine; Karen the School of Medicine. lation, and insulin resistance. J. Jubanyik-Barber, m.d., assistant professor of emergency Daniel Okin, a member of the medical school’s Class of “It is estimated that 40 percent medicine; Michael K. O’Brien, m.d., ph.d., assistant professor 2014 in the m.d./ph.d. Program, and Noah Palm, a doctoral of the U.S. population over 65 has of surgery; and Patrick G. O’Connor, m.d., m.p.h., professor candidate in the bbs program, both work in the laboratory im­paired glucose tolerance or type 2 of medicine—meet with students individually during stu- of Ruslan Medzhitov, ph.d., the David W. Wallace Professor diabetes. Targeting ros in mitochon- dents’ first year, and in groups thereafter. Angoff still stands of Immunobiology and a Howard Hughes Medical Institute dria may prevent and treat diabetes in by to lend a hand with personal or social challenges, but the investigator. Medzhitov is world-renowned for his work on these individuals,” Shulman says. new advisors concentrate on “any kind of academic problems, the innate immune system, the body’s first line of defense struggles, issues,” Angoff says. against infection. The School of Medicine requires that medical students “When I heard about him and read some of his papers, How the brain may find complete a thesis based on original research. Students are I was immediately drawn to working with him,” Okin says encouraged to independently seek out and contact research- of Medzhitov. “Ruslan is probably one of the most creative a way around autism ers they’d like to work with, but many begin their research thinkers that I’ve ever encountered.” Research at the medical school’s Child after their first year, before they are familiar with the many After doing a rotation in Medzhitov’s lab, Okin decided Study Center (csc) has shown that research options available to them. One role of the advising to join the research team during his second year of medical autism spectrum disorder (asd) can team is to help pair up students with mentors who can best school. Okin, who is conducting research on the innate immune disrupt children’s ability to recognize guide medical students through the projects that will ulti- system’s response to nonpathogenic stressors such as obesity, “biological motion,” the distinctive mately form the basis for their theses. describes Medzhitov’s approach to mentorship as “very col- repertoire of movements made by Medical student Daniel “Pete” Duncan, who is spending laborative. It’s very much that you work with him, together, living things, including other people. an extra year at Yale devoted to research, chose to work with to define an area that you’re both interested in, and to define In a study reported in the De- Christopher K. Breuer, m.d., assistant professor of surgery a project that would be interesting both intellectually and cember 7 issue of Proceedings of the and pediatrics, who uses tissue engineering techniques to scientifically.” Having spent more than // Mentors (page 6) National Academy of Sciences, Kevin build new blood vessels for children with congenital heart Pelphrey, ph.d., Harris Associate Profes- disease. With colleague Toshiharu Shinoka, m.d., ph.d., sor in the csc, first author Martha associate professor of surgery, Breuer has pioneered the use of D. Kaiser, ph.d., and colleagues used tissue-engineered vascular grafts (tevgs). Created by seeding To honor your own mentor . . . functional magnetic resonance imaging a biodegradable scaffold with a patient’s bone marrow cells, Ask any successful person about their road to achievement and (fmri) to scan the brains of children tevgs are living vessels that live and grow with the patient you’re likely to hear the story of a valued mentor or advisor who with autism, their unaffected siblings, and are not prone to the immunological problems that affect played a key role. Your gift can help faculty members at the and typically developing children as transplanted tissue. School of Medicine to provide guidance and inspiration to the the children watched animations of Despite Breuer’s busy schedule, which also includes clini- next generation of physicians and scientists. biological movement. The team identi- cal work as a pediatric surgeon, “somehow he is always keep- • Support student research: Every medical student at Yale com- fied three distinct “neural signatures”: ing track of what we’re doing,” Duncan says. “When he’s in pletes a thesis based on original research; access to research trait markers — reduced regions of his office, he is always available. I’m interested in pediatrics, funds gives students the opportunity for meaningful participa- activity in both children with asd and and he is very excited about that, very supportive, and willing tion in the laboratories of top faculty researchers. their unaffected siblings; state mark- to help in any way. He’s a very easy person to talk to.” • Endow an advisor: The Yale System of medical education encour- ers — reduced activity seen only in For his part, Breuer stresses that mentoring students is a ages students to explore their individual interests and to advance children with asd; and compensatory two-way street, with great benefits for his lab. “It’s a wonder- at their own pace within the curriculum. In this individualized activity — enhanced activity seen only ful give-and-take relationship,” he says. “I’ve got incredibly program, each student needs an advisor to get all they want and in unaffected siblings of asd patients. enthusiastic and accomplished people that come and help me need from their education. This enhanced compensatory brain with my project. I’m a huge beneficiary of working with these Who helped you along the road to success? Honor them today activity is of particular interest, say bright, hard-working people.” with a gift to help others “pay it forward.” For more information, the researchers, because it may reflect contact Jancy Houck, assistant vice president for development a developmental process by which Faculty and graduate students and director of medical development, at (203) 436-8560. unaffected children overcome a genetic In addition to future doctors, future scientists also train in predisposition to develop asd. many departments at the School of Medicine, ultimately

Medicine@Yale December 2010 3 out & about

September 30 Faculty and staff of the School of Medicine and Yale Cancer Center October 16 At the Discovery to Cure Gala, held at the Stamford Marriott Hotel & joined employees of Tucker Mechanical, of Meriden, Conn. (an emcor Company) to Spa in Stamford, Conn., over $200,000 was raised for cancer screening for women form a Human Pink Ribbon in support of Breast Cancer Awareness Month. More than at high risk, the training of high school students for careers in biomedical research, 160 people participated in the event. and the translation of basic research in gynecological oncology into practical treat- ments. 1. News analyst and political commentator Cokie Roberts delivered the evening’s keynote speech. 2. (Seated, from left) Discovery to Cure committee members Michelle Mills, Gladys O’Neil, Stephanie Ercegovic, Arlene Schwartz, and Judi Egbert. Top: Gil Mor, m.d., ph.d., professor of obstetrics, gynecology, and reproductive sciences and creator of 1 the Discovery to Cure program; Peter E. Schwartz, m.d., the John Slade Ely Professor of Obstetrics, Gynecology, and Reproductive Sciences; Thomas J. Rutherford, ph.d., m.d., associate professor of obstetrics, gynecology, and reproductive sciences; Jacques Dickinson, and Charles J. Lockwood, m.d., the Anita O’Keeffe Young Professor of Women’s Health and chair of the Department of Obstet- rics, Gynecology, and Reproductive Sciences. 3. (From left) Melissa Sheehan, William B. Sheehan, Discovery to Cure committee member Wendy Long, and James Long.

terry dagradi 2

October 16 At Community Day, part of a series of events celebrating the School of Medicine’s Bicentennial, faculty and staff provided tours, demonstrations, and lectures for members of the New Haven community. 1. New Haven Mayor John DeStefano Jr. made remarks on the steps of Sterling Hall of Medicine. 2. Linda Pellico, ph.d., a.p.r.n., assistant professor at Yale School of Nursing (right), led an educational session for children. 3. John Gallagher, m.l.s., deputy director of public services at the Cushing/Whitney Medical Library, led a tour of the new Cushing Center, which houses brain specimens, photographs, drawings, and memora- bilia collected by famed neurosurgeon and Yale College alumnus Harvey W. Cushing, m.d.

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3 michael marsland (3) harold shapiro (3)

October 28 The Branford, Conn.-based Jack of All Hearts Foundation (joah) made a gift November 4 of $3,000 to support pediatric cardiology programs at Yale-New Haven Children’s Hos- A reception was pital and a fellowship in pediatric cardiology at the School of Medicine. Laura and Mark held in the Medical Hanson, whose son, Jack, was born with a rare congenital heart defect, cofounded the Historical Library organization. In September, the first joah Walkathon netted $10,500. (From left) Clif- honoring John ford W. Bogue, m.d., associate professor of pediatrics; Mark Hanson; Laura Hanson; Alan A. Persing, m.d., H. Friedman, m.d., professor of pediatrics; and joah board member Melissa Thibeault. professor of surgery and neurosurgery, recently named the inaugural Irving and Silik Polayes Professor in Plastic Surgery. The new professorship was established with a $2.5 million gift from the late Mau- rice B. “Moe” Po- layes, and is named terry dagradi in honor of his brother, Irving M. Polayes, m.d., and his late great-uncle, Silik H. Polayes, ph.d. Irving is a retired New Haven surgeon and dentist who was a voluntary faculty member in the Department of Surgery’s Section of Plastic Surgery from 1965 to 1997. Silik earned his graduate degree from Yale in 1921 and worked as a pathologist in New York. From

courtesy of joy carrigan left: Persing with Maurice Polayes’s children, Amy Polayes Margolis and Roy Polayes.

4 www.medicineatyale.org advances Tiny scope is a big advance for GI cancers Health & Science News Stomach acid zapped New confocal laser endomicroscopes by a single dose of zinc offer doctors an unprecedented view Gastroesopha- geal reflux disease to diagnose early malignancies (gerd, or “heart- burn”) and related Last year, when Harry Aslanian, m.d., associate professor of diseases caused medicine, first looked at images produced by a new diagnos- by excess stomach tic device known as a confocal laser endomicroscope, he saw acid affect more what no one had seen before: stunning, high-resolution im- than a quarter of ages of cells, individual red blood cells within vessels, and scar istockphoto.com/ceneri

Americans, but © tissue within a pancreatic tumor, all magnified 1,000 times. existing therapies often don’t work. For the first time, a miniaturized prototype microscope About 60 percent of patients still experi- was passed into a pancreatic mass via a small needle that trav- ence symptoms while taking commonly eled through the stomach wall, obtaining amazing real-time prescribed proton-pump inhibitors (ppis) pictures of an organ that is notoriously difficult to reach, and such as omeprazole (e.g., Prilosec). tricky to evaluate even by ct scans or mri. These drugs have been linked to “The quality was very good,” recalls Aslanian, associ- robert a. lisak the depletion of zinc, an essential ate director of endoscopy for Yale Medical Group (ymg), (From left) Yale Medical Group’s Harry Aslanian, Priya Jamidar, and Uzma Sid- nutrient that protects the stomach who was taking part in the world’s first visualization of the diqui are using powerful new high-resolution microscopes to peer deep into lining and heals ulcers. In a new study interior of a pancreatic mass using confocal laser endomi- the digestive tract, making it possible to detect cancers at early stages when they can be successfully treated. led by John P. Geibel, m.d., d.sc., croscopy (cle). professor of surgery and of cellular Aslanian and Uzma Siddiqui, m.d., specialize in com- and molecular physiology, a team of bining ultrasound and endoscopy to evaluate and perform Doctors at ymg are also using cle to gain new views of Yale and Swiss researchers found that biopsies in pancreas disorders. Previously, endosonograph- the colon, bile duct, and esophagus. Siddiqui, ymg’s director zinc itself is significantly better than ic views of the pancreas showed only its overall texture, of endoscopic ultrasound, has used the technique to examine omeprazole at combating stomach and needle biopsies were required to examine and stain patients with Barrett’s esophagus, a disorder associated with acid. As reported online August 24 in individual cells outside of the body. Aslanian and Siddiqui long-term esophageal reflux disease that can be a precursor to the American Journal of Gastroenterol- are participating in an international trial using cle to esophageal cancer. Siddiqui says the microscopic probe helps ogy, adding zinc to sections of stomach diagnose precancerous pancreatic cysts, which can be sur- her target the most suspicious regions of dysplasia, or precan- tissue immediately abolished acid gically removed. “Now we’re in the process of fine-tuning cerous tissue changes. Meanwhile, gastroenterologist Priya secretion triggered by the compound this, making a road map to identify precancerous change,” Jamidar, m.d., director of endoscopy at ymg, is using cle histamine, and oral zinc treatment in Aslanian says. to diagnose bile duct tumors, where current tissue sampling rats prevented acid secretion. High-resolution confocal microscopes are a mainstay in techniques are only reliable about half the time. The researchers also found that zinc biomedical research, but they have evolved from what Asla- “It’s an impressive technology that is much less inva- treatment in healthy humans is faster nian calls “tabletop versions” to scopes that measure only 2.5 sive for our patients, providing on-the-spot information and more effective at lowering gastric millimeters in diameter. Yale Cancer Center and Smilow Can- that can guide the endoscopic evaluation, and, in some acid levels than omeprazole: a single cer Hospital at Yale-New Haven are among only a handful of cases, treatment,” says Aslanian. In cases of early esopha- dose works within seconds and lasts institutions in the world and the only centers in Connecticut geal and colon cancer, he says, the earliest tumors can be for about three hours. “This opens a using the technology. The microscopes fit through the biopsy removed through the scope during the same procedure promising new avenue of treatment for channels of many endoscopes, the lighted optical instruments with the specialized techniques of endoscopic mucosal suffering patients,” says Geibel, “espe- gastroenterologists use, to look deep inside the body to spot resection. “The potential for the microscope is that we can cially the many who continue to have cancer and precancerous tissue at their earliest stages of devel- look at the cells in real time and identify the ones that are symptoms of acid-related illness even opment, when many conditions are curable with surgery. likely to progress to cancer.” after a standard dose of ppis.”

Connections that stick: Yale cell biologist is honored with two awards Syn 1 and synapses cam James E. Rothman, ph.d., the Fergus in the nervous and High-Throughput Cell Biology at Yale’s Synapses, the junctions where signals F. Wallace Professor of Biomedical endocrine systems. West Campus, came to Yale from Co- pass between nerve cells, are crucial Sciences and chair of the Department In neurons, vesicles lumbia University in 2008. A 1971 Yale to thought and behavior. Plasticity, of Cell Biology, has been awarded carrying neu- College graduate, he is the recipient of synaptic reorganization throughout life, both the E.B. Wilson Medal and the rotransmitters pass some of the top honors for biomedical underlies learning and memory. School Massry Prize for his seminal contribu- on chemical mes- research, including the Louisa Gross of Medicine scientists have discovered tions to the field of cell biology. sages that govern Horwitz Prize and the Albert Lasker that Syncam 1, an “adhesion molecule” The Wilson Medal, the highest movement, percep- Basic Medical Research Award. In June that spans synapses, is essential for honor for science presented by the James Rothman tion, cognition, of this year, Rothman shared the Kavli synapse formation during development American Society for Cell Biology memory, and mood. Prize in Neuroscience with Thomas and maintenance in adulthood. (ascb), is awarded “for far-reaching In hormone-producing endocrine Sudhöf, ph.d., of Stanford School of In the December 9 issue of Neuron, contributions to cell biology over a cells, substances such as insulin enter Medicine, and Richard H. Scheller, Thomas Biederer, ph.d., associate lifetime in science.” The Massry Prize, the extracellular space or the blood- ph.d., executive vice president of Ge- professor of molecular biophysics and established in 1996 and awarded stream via exocytosis. nentech, for his work on exocytosis. biochemistry, and colleagues describe by the Meira and Shaul G. Massry For three decades, Rothman has The ascb, founded in 1960, aims mice in which the Syncam 1 gene could Foundation, honors individuals who performed elegant, focused experi- to promote and develop the field of be switched on and off at will. More have made “outstanding contributions ments that have revealed the molecular cell biology, and to ensure the future synapses formed during development to the biomedical sciences and to the machinery of membrane trafficking of basic scientific research by provid- when Syncam 1 was overexpressed, and advancement of health.” in fine detail. Much of this work was ing opportunities for scientists and the molecule was required to maintain Rothman is widely recognized as done using an innovative “cell-free” ap- keeping Congress and the American synapses in adults. But mice lacking a pioneering researcher in membrane proach, in which Rothman sidestepped public informed about the importance Syncam 1 showed enhanced plasticity, trafficking, the means by which pro- the complexities of working with com- of biological research. performing better on spatial learning teins and other materials are trans- plete cells by isolating the intracellular The Massry Foundation was cre- tests than mice overexpressing it. ported within and between cells. components crucial to membrane traf- ated by Shaul Massry, m.d., professor “Some Syncam 1 is needed to Rothman has made particu- ficking. This strategy allowed him to emeritus of medicine, physiology, promote contact,” Biederer says, “but larly important contributions to our propose that complexes of membrane- and biophysics at the University of too much glues down the synapse and understanding of exocytosis, a form associated proteins which he named Southern California’s Keck School of inhibits its function. These findings of trafficking in which spherical sacs snares are required for vesicles to fuse Medicine. The non-profit organiza- provide new molecular insight into syn- called vesicles fuse with cell mem- with membranes. tion is dedicated to the promotion of aptic aberrations underlying develop- branes to deliver their contents outside Rothman, who has spearheaded education and research in nephrology, mental brain disorders such as autism.” the cell. Exocytosis plays a crucial role the creation of a new Center for physiology, and related fields.

Medicine@Yale December 2010 5 Grants and contracts awarded Development, 3 years, $1,198,036 • Tami P. Group: A Pilot Project Using Mobile Technol- Sullivan, Department of Justice, Achieving Suc- ogy to Increase Social Support for hiv-Positive cessful Researcher–Practitioner Partnerships that Women, 1 year, $2,010 • Gerald Friedland, to Yale School of Medicine Strengthen Practice and Policy: Lessons Learned Albert Einstein College of Medicine, Molecular from the Field, 2 years, $343,565 • Yulia Surovt- Epidemiology of hiv-Associated Extensively Drug March/April, 2010 seva, nih, Analysis of Mammalian Mitochon- Resistant Tuberculosis in Rural South Africa, drial Transcription Machinery, 2 years, $99,316 1 year, $43,813 • David C. Glahn, Southwest Federal Benjamin A. Toll, nih, Advancing Tobacco Foundation for Biomedical Research, Identi- Steven L. Bernstein, nih, Treating Low-Income Michelle Hampson, nih, Biofeedback of Real- and Cancer Control: Reducing Alcohol Use to fication of Novel Micrornas Associated with Smokers in the Hospital Emergency Department, Time fmri to Control Activity in the Orbitofrontal Promote Smoking Cessation, 2 years, $798,162 Brain Structure and Function, 6 years, $19,264 5 years, $3,343,594 • Linda K. Bockenstedt, nih, Cortex, 2 years, $496,500 • Kazue Hashimoto- Benjamin E. Turk, nih, Global Peptide Microar- Jeffrey R. Gruen, University of California–San Real-Time Imaging Analysis of Vector-Borne Torii, nih, Mechanisms Leading to Cortical ray Profiling of Tyrosine Kinase Deregulated in Diego, Creating a Pediatric Imaging–Genom- Lyme Borreliosis Pathogenesis and Persistence, Dysplasia in Fetal Alcohol Spectrum Diseases, Cancer, 2 years, $359,962 • Anthony N. Van ics Data Resource, 6 months, $221,639 • Yiyun 5 years, $2,068,750 • Sonia Caprio, nih, Neural 2 years, $176,874 • William H. Konigsberg, nih, den Pol, nih, Arcuate Nucleus Glutamatergic H. Huang, University of Montana, Positron Functioning of Feeding Centers in Obese Youth, Molecular Biology and Structure of dna Rep- Neurons Modulate Energy Homeostasis, 4 years, Emission Tomography Imaging for als Therapy, 5 years, $2,726,025 • Jessica A. Cardin, nih, licase, 4 years, $1,456,400 • Gary Kupfer, nih, $1,455,158 • Andrea H. Weinberger, nih, Gender 10 months, $72,000 • Leonard K. Kaczmarek, Impact of Local Network Dynamics on Visual htlv-I Tax1 Protein Chemosensitization of p53 Differences in the Association of Depression to fraxa Research Foundation, Development of Cortex Function, 3 years, $607,988 • Katarzyna Mutant Tumors, 2 years, $395,959 • Janghoo Transitions in Smoking, 2 years, $70,750 • John J. Pharmacological Activators for fmrp-Regulated Chawarska, nih, Development of Face Process- Lim, nih, The Role of Nemo-Like Kinase in Wysolmerski, Department of Defense, Effects Potassium Channels, 1 year, 45,000 • Jason ing in Infants with Autism Spectrum Disorders, Neuro­degeneration, 3 years, $249,000 • Steven of Nuclear Parathyroid Hormone-Related Protein W. Mastaitis, Juvenile Diabetes Research 5 years, $2,068,750 • Jersey Chen, Agency for Marans, Substance Abuse and Mental Signaling in Breast Cancer, 2 years, $620,626 Foundation International, Investigation of the Healthcare Research and Quality/dhhs, Geo- Health Services Administration, Childhood Andrew Xiao, nih, A Novel Enzymatic Activity Role of Hypothalamic map Kinase in Counter­ graphic Variation in Use of Imaging with Cardiac Violent Trauma Center, 3 years, $1,799,997 of wstf and its Role in Tumorigenesis, 3 months, regulation, 2 years, $47,704 • Linda C. Mayes, Stress Testing, 5 years, $723,060 • Nihal C. James C. McPartland, nih, The Developmental $72,040 • Jiansong Xu, nih, fMRI and DTI Study Baylor College of Medicine, Maternal Brain and deLan­erolle, Office of Naval Research, Under- Neuroscience of Social Perception in Infants on Neural Predictor of Treatment Outcome Behavioral Responses to Infant Cues in Cocaine- standing the Biomechanical, Biochemical, At Risk for Autism, 4 years, $728,429 • Peter T. in Cocaine Dependence, 5 years, $801,726 Exposed Mothers, 5 years, $377,281 • Michael J. Physiological and Functional Consequences of Morgan, nih, Modafinil, Sleep Architecture, and Hongyu Zhao, nih, Statistical Methods to Map Paidas, CerviLenz Inc., Establishing the Utility Explosive Blast Injury to the Human Brain— Cocaine Relapse, 5 years, $2,558,685 • Walther Genes for Complex Traits, 4 years, $1,406,752 of Cervi­lenz as a Predictor of Short Cervical prevent Phase II, 2 years, $1,409,700 • Gary H. Mothes, nih, A Novel trim Protein Involved in Length and Preterm Delivery in the Mid–Second V. Desir, nih, Renalase Deficiency and Car- Innate Immunity, 2 years, $496,500 • Michael Non-Federal Trimester of Pregnancy (CL-1003), 20 months, diovascular Complications of Chronic Kidney H. Nathanson, nih, A Confocal Endomicroscope Marcus W. Bosenberg, Pennsylvania State $200,005 • Lubna Pal, Virginia Commonwealth Disease, 1 year, $500,000 • Sabrina Diano, nih, for Clinical Research, 1 year, $159,900 • Kitt Falk University, Targeted Chemoprevention for University, Pharmacogenetics of Metformin A Carboxypeptidase in the Regulation of Hypo- Petersen, nih, Mechanisms of Insulin Resis- Melanoma, 5 years, $311,414 • Igor E. Brodsky, Action in pcos, 1 year, $34,126 • Robert S. thalamic Circuitry, 4 years, $1,443,989 • Robert tance in the Aged, 5 years, $1,696,375 • Marc I. Harvard Medical School, Inflammasome Acti- Sherwin, The John B. Pierce Laboratory Inc., Dubrow, nih, Patterns of Care and Outcomes for Rosen, nih, Benefits Management for People vation by Yersinia Virulence Factors, 2 years, The Role of the Amygdala in Weight-Gain Sus- Glioblastoma Patients, 2 years, $165,500 with Psychiatric Disabilities, 3 years, $480,324 $291,085 • R. Todd Constable, The John B. Pierce ceptibility, 5 years, $62,844 • Rajita Sinha, The Veraragavan P. Eswarakumar, nih, Mechanisms Joseph Santos-Sacchi, nih, Membrane Proper- Laboratory Inc., The role of the amygdala in John B. Pierce Laboratory Inc., The Role of the of fgfr2 Signaling in Craniofacial Development, ties of Cells Comprising the ohc System, 5 years, weight gain susceptibility, 5 years, $67,057 Amygdala in Weight-Gain Susceptibility, 5 years, 5 years, $2,079,310 • Adrienne S. Ettinger, nih, $2,294,887 • William C. Sessa, nih, Microrna Lynn Cooley, Howard Hughes Medical Institute, $776,061 • Barbara Szepietowska, Juvenile Dia- Genetic and Epigenetic Modifiers of Mater- Regulation of Endothelial Functions, 4 years, Yale Medical Research Scholars Program, 4 years, betes Research Foundation International, Role nal–Fetal Transfer of Toxicants & Outcomes, $1,904,610 • Gerald I. Shulman, nih, Cellular $700,000 • Michael P. DiGiovanna, Connecti- of EphA5 in Hypoglycemia, 2 years, $51,004 20 months, $256,017 • Carlos A.V. Fragoso , nih, Mechanisms of Insulin Resistance in Humans, cut Breast Health Initiative Inc., Combination Hugh S. Taylor, Brigham and Women’s Hospi- Defining Chronic Obstructive Pulmonary Disease 5 years, $764,317 • Stefan Somlo, nih, A Forward Targeting of igf-1 Receptor and her2 in Breast tal, The Kronos Early Estrogen Prevention Study in Older Persons, 2 years, $135,710 • Patrick G. Genetic Screen for pkd Pathways in Mice Using Cancer, 1 year, 50,000 • Marie E. Egan, Cystic (keeps) Mammographic Density and Breast Gallagher, nih, Molecular Biology of Human the PiggyBac Transposon, 1 year, $500,000 Fibrosis Foundation, A Model of Chronic Airway Health Ancillary Study, 10 months, $8,250 Erythrocyte Alpha Spectrin, 4 years, $1,655,000 Bing Su, Department of the Army, The Role of Inflammation in cftr-/- mice, 1 year, $43,200 Wang-Jing Xiao, Alfred P. Sloan Foundation, Peter M. Glazer, nih, Epigenetic Regulation in mtor Signaling in the Regulation of rag Expres- Brian W. Forsyth, American Medical Associa- Sloan–Swartz Annual Meeting 2010 on Compu- Hypoxic Cancer Cells, 5 years, $1,682,723 sion and Genomic Stability during B Lymphocyte tion Foundation, An sms-Based Peer Support tational Neuroscience, 7 months, $25,047

// Mentors (from page 3) six years in problem is important and interesting, own careers by helping Medzhitov’s lab, Palm has learned to be able to define important and them to think strategi- and grown, he says, and has himself interesting questions, and to see where cally about their futures, become a sort of mentor to new lab that line of investigation will go and providing extensive members. “There is a real feeling of how it fits into the broader picture,” feedback on their grant responsibility in the lab of helping out Medzhitov explains. proposals and par- the new students and postdoctoral fel- ticipating in mock job lows to become used to the lab, to feel A continuing cycle interviews as they pre- welcomed, but also to get up to speed,” Mentorship continues to play an im- pare for real interviews; Palm, who plans to begin a postdoc- portant role even after a person finishes and, not least, he strives toral fellowship at Yale next year, says. medical or graduate school. Scientists to maintain a “family- “When I came in, the people who are holding a doctorate still need the guid- friendly” climate in his now long gone helped me, so it’s kind ance of mentors before they strike out lab that acknowledges of a ‘pay-it-forward’ scheme,” he says. on their own. and accommodates the Last April, Medzhitov became one Michael J. Caplan, m.d., ph.d., challenges of balancing of the youngest members ever to join knows this well. As a graduate student a scientific career with the elite National Academy of Scienc- at Yale School of Medicine, Caplan, family life. es. But despite his accomplishments, now chair and c.n.h. Long Professor of Mentorship is cycli- Medzhitov is extraordinarily dedi- Cellular and Molecular Physiology and cal: mentees become cated to those under his wing. “He has professor of cell biology, gained vital mentors, and knowl- an amazing track record of producing experience working jointly with Profes- edge is continually really top-notch scientists,” says Palm. sor of Cell Biology James D. Jamieson, passed on. As with par- “As far as I know, there’s no better lab m.d., ph.d. (now director of the m.d./ ents and children, one in the world to have been in during ph.d. Program) and George E. Palade, generation of scientists the past five to 10 years, in terms of m.d., the late Romanian-American cell raises the next, “just like going on to really great positions at biologist and Nobel laureate. we hear our parents’ great universities and continuing to Last April, Caplan received the voices in our heads

publish really great papers.” first annual Yale University Post- when we’re talking to harold shapiro Medzhitov sees developing a doctoral Fellows Mentoring Award. our children,” Caplan Michael O’Brien (left), one of a new team of student’s individual interest as vital The fellows who nominated Caplan says. In the laboratory, as in parenting, four advisors to medical students, works with to the role of an advisor. “The chal- described three ways in which he is maturity and confidence come with Jorge Ramallo (right) of the Class of 2013. lenge is to nurture that interest and to an exceptional mentor: he checks in time—and when they do, the rewards develop a certain set of skills that are with his lab members daily to talk are unparalleled, he says. tremendous intuition for the wood, and necessary to do research, which are about experimental data and to chal- Caplan likens scientific training to there are people who don’t.” And with beyond just technical skills.” Among lenge them to think creatively about an apprenticeship in carpentry: “There the latter, “the great pleasure comes these skills, he says, are “the ability interpreting their results; he helps are people who come in knowing from watching as, either suddenly or to see the big picture, to see why the postdoctoral scholars advance their how to use all the tools and having a gradually, they acquire that intuition.”

6 www.medicineatyale.org // Gift (from page 1) through the emer- bombs dropped on Japan at the close // Lungs (from page 1) extreme shortage of environment in which lungs develop gency room. And she was struck by of World War II. Her experiences donor organs. An alternative solution in the fetus, such as the flow of liquid the myriad cutaneous ways in which there led Johnson to become an active is to create synthetic lungs, but past at- through the growing vasculature. To a disease could manifest itself in dif- member of International Physicians tempts to do so have failed because the provide ventilation, the researchers ferent patients. Skin problems, she for the Prevention of Nuclear War. lungs, with networks of branching air- used a syringe pump to withdraw air, says, “looked different, even when She vividly remembers the polio ways and vasculature, are so spatially which caused the lungs to inhale liquid they were the ‘same diagnosis.’ ” epidemic and “life before penicillin,” complex, says Niklason. from the windpipe. At that time, the medical school when people routinely died of what She and her research team took a In the reverse process, the pump offered electives in microbiology and would now be considered minor infec- leap forward recently, when they engi- returned air to the bioreactor, causing electrocardiology to interns. Having tions, and she believes that physicians, neered the first lungs that are capable of the lungs to exhale liquid. Inside the already earned a doctorate in the and dermatologists in particular, have exchanging oxygen and carbon dioxide, bioreactor, the lungs even produced former, “I could find my way around a vital role to play in ensuring the con- an achievement that was reported in the proteins that allowed the organs to a microbiology lab,” Johnson says, tinuation of the advances in medicine journal Science this past July. inflate normally. and the cardiology elective held little she has witnessed since her youth. The key to the Niklason group’s By imitating natural conditions, the interest. She petitioned the medi- “The skin is the body’s largest success was finding a suitable scaf- researchers improved the clearance of cal school to allow her to pursue her organ, and it gives protection to the fold for supporting lung tissue, and secretions in the airway, enhanced cell budding interest in dermatology as body in its interactions with every- they did so by adapting a tissue survival, and fostered the growth of the an elective, and got a green light. thing that’s outside,” Johnson says. engineering technique that has been major cell types found in the lung. Af- As it happens, Aaron B. Lerner, “It’s pretty important!” Nonetheless, applied to the heart, liver, and kidney. ter culturing the tissue inside the biore- m.d., ph.d., had joined the Yale fac- she adds, medical dermatology is be- By using detergent solutions to wash actor for about a week, the researchers ulty in 1955 to head the Department ing absorbed into other specialties, as cells out of lung tissue from rats, the implanted it into rats and observed of Internal Medicine’s Section of Der- in the case of lupus, which is general- researchers removed all cellular com- that the lungs exchanged gas for a few matology. Lerner, who would go on ly treated by rheumatologists despite ponents that could cause an immune hours—a major accomplishment. to make medical history as discoverer the disease’s significant effects on the reaction after transplantation. The team saw similar results with of the hormones a-msh and melato- skin. “This is a disservice to derma- What remained was a hollowed-out human cells, suggesting that the same nin, was an ideal mentor to immerse tology,” Johnson says, “because there matrix with the right three-dimensional approach, perhaps using stem cells, Johnson in the scientific life; she still is something to knowing the skin shape, mechanical properties, and vas- could help to treat diseases in humans. recalls him tinkering with the chemi- and to knowing what these serious culature. Unexpectedly, molecular cues Niklason cautions that “it will take cal models he kept on the ledge of his diagnoses do in the skin.” that could guide cells to appropriate us another 10 or 20 years of work to office blackboard, deciphering the Her gift, she says, is “to encour- regions had been preserved in the ma- develop reliable and robust means of structure of a-msh “click-by-click.” age the young, able, innovative trix as well; when the scientists placed differentiating primitive stem cells into Before long, Johnson was direct- derma­tologist to pursue new avenues various neonatal lung cells inside the the lung cell types we’re looking for ing the Section of Dermatology’s opened by his or her inquisitive mind scaffold, the cells positioned themselves and keeping them stable over time.” inpatient and outpatient services. and give funding so he or she not be in the correct locations. But the wait will be worthwhile, She held that post until 1964, when compelled to work in the clinic at the “I was surprised by how much Niklason says. “The potential ad- she and her husband, cardiologist expense of time to think. You have to information is in the matrix,” Niklason vantage in the long run is that we Kenneth G. Johnson, m.d., were have support to do that.” says. “I expected the different cell types could take a biopsy from a patient dispatched to Hiroshima, Japan, Edelson says he can think of no to go helter-skelter, but by and large, who needs a lung replacement, where Marie-Louise served as chief better person than Johnson to inspire the cells landed in their correct ana- generate stem cells from that biopsy, of dermatology on the Atomic Bomb young physicians in the field. “She is tomic locations. This tells me that the and from those cells regenerate a Casualty Commission (abcc), which precisely the physician any of us would matrix has ‘zip codes,’ or information whole lung that we could implant was conducting rigorous long-term want for ourselves, and she is precisely about who should go where.” without it being rejected,” she says. studies of the medical effects of the teacher any of us would want to The next challenge was to develop “It could really be a new era for radiation released by the atomic have—or to be.” a bioreactor—a system to mimic the organ transplantation.”

// Cancer (from page 1) Under Schless- proliferation, differentiation, and He is a member of the National He will work to help integrate Yale’s inger’s direction, the cbi plans to hire 150 survival. Certain mutations in rtks can Academy of Sciences and the Institute strengths in basic science and transla- research scientists, including 11 principal result in faulty signaling, which in turn of Medicine and serves on the editorial tional medicine to have a more direct investigators, over the next three to four can cause aberrant cell proliferation that boards of numerous journals, includ- impact on clinical care. years, with the primary goal of pinpoint- may ultimately lead to cancer. ing Cell and Molecular Cell. He received “Dr. Herbst is nationally recognized ing root molecular causes of cancer, Blocking RTK activation has become the Taylor Prize in 2000, the Dan David for his leadership and expertise in lung identifying new molecular targets, and a major strategy in anticancer drug Prize in 2006, and the Pezcoller Prize cancer treatment and research,” says ycc developing new drug treatments. design. Schlessinger and colleagues have from the American Association for Director Lynch, also physician-in-chief These researchers will work in formed three companies—Sugen Inc. Cancer Research (AACR) in 2010. of Smilow Cancer Hospital at Yale-New concert with scientists at the neigh- in 1991, Plexxikon in 2001, and Kolltan Drugs that target rtks have also Haven. “He is a natural leader and will boring Yale Center for Genome in 2008—and drugs based on insights been of great interest to Herbst, who have a critical role in building our cancer Analysis, using state-of-the-art ge- gained in his laboratory are having a has spearheaded clinical studies of program while mentoring the next gen- nomic sequencing techniques to better major impact in the lives of patients with many such drugs over the last sev- eration of cancer doctors at Yale.” understand and exploit the molecular liver, kidney, stomach, and skin cancers. eral years. His work using erlotinib Herbst is a member of the AACR, profiles of various tumor types. Sugen’s drug Sutent, approved (Tarceva) in combination with bevaci- for which he is senior editor of Clinical The institute will significantly by the fda in 2006 for kidney and zumab (Avastin) was among the first Cancer Research, as well as the American increase the extent of basic research on stomach cancers, was one of the first to combine multiple targeted agents for Society of Clinical Oncology and the cancer at Yale, especially in the areas of in a new generation of targeted cancer non-small cell lung cancer (nsclc). Institute of Medicine’s National Cancer computational biology, cancer genomics, drugs. An experimental compound, Herbst is co-principal investigator Policy Forum. He is a fellow of the American cancer immunology, and drug discovery, plx4032, which was discovered by of the Biomarker-Based Approaches of College of Physicians. He has authored and it will complement Yale’s transla- Plexxikon and is currently in clini- Targeted Therapy for Lung Cancer Elimi- more than 200 peer-reviewed papers tional and clinical research programs, cal development in partnership with nation Program (battle) Trial, which and has current grant funding for his including a major expansion of clinical Roche, has attracted wide media cover- has significantly advanced “personalized” work from numerous sources, including trials planned by ycc. age for its unprecedented success in therapy of nsclc by using molecular the National Cancer Institute, the AACR, Schlessinger, known to colleagues early-stage clinical trials for the treat- analysis of tissue biopsies to determine and multiple charitable foundations. and friends as “Yossi,” is a pioneer in ment of melanoma. The drug is now the best available targeted treatment Herbst received his medical degree the field of signal transduction, the in Phase III trials for melanoma, and is for each patient. He recently developed a from Cornell University Medical means by which receptors in the cell also in Phase I trials for the treatment battle-2 trial to explore novel combi- College and earned a ph.d. in molecu- membrane, when bound to certain of colorectal cancer. nations of agents to target genetically lar cell biology from the Rockefeller molecules, pass signals to the interior of Schlessinger, who was recruited to mutated pathways in lung cancer and to University. He completed his medical the cell that guide basic processes such Yale in 2001, was born in Croatia and overcome drug resistance. Herbst plans oncology fellowship at Dana-Farber as cell division and cell growth. educated at Hebrew University and to open this study at Yale and to bring Cancer Institute and a medical hema- In particular, over several decades, the Weizmann Institute of Science in this approach to other forms of cancer. tology fellowship at Brigham and his group has done fundamental Israel. He was a member of the Weiz- In his new position, Herbst hopes Women’s Hospital in Boston, where he research on signaling by receptor mann Institute from 1978 to 1991, and to bring novel and more personalized additionally received a master’s degree tyrosine kinases (rtks), a set of related moved to New York University School therapies to cancer treatment to im- from Harvard University’s clinical cell-surface proteins that affect cell of Medicine in 1990. prove efficacy and reduce toxicities. investigator training program.

Medicine@Yale December 2010 7 Neurologist is named first Zimmerman and Spinelli Professor David M. Greer, m.d., m.a., a special- coming to Yale earlier this year as clin- ist in the areas of coma, neurocritical ical vice chair and associate professor care, stroke, and neuroimaging, has of neurology. At Yale, he also serves been named the inaugural Dr. Harry as program director of the Neurology M. Zimmerman and Dr. Nicholas Residency Program and director of the and Viola Spinelli Associate Professor Outpatient Neurology Clinic. of Neurology. Greer has also served as a spe- Greer’s research focuses on vascu- cialty consultant to the New England lar neurology and on improving the Patriots, the Boston Bruins, and the ability of doctors to give an accurate Boston Red Sox. His numerous hon- prognosis for patients in coma, par- ors include a 2010 Teacher of the Year ticularly after suffering a cardiac ar- Award from the Partner Neurology rest. He is also interested in the use of Residency at Massachusetts General hypothermia to improve neurological Hospital, where he also received sev- outcomes for various brain injuries. eral Partners in Excellence Awards, After earning his m.d. and a among other distinctions. master’s degree in English Literature The new professorship was estab-

from the University of Florida, Greer lished through the bequest of Nicho- terry dagradi trained in neurology at Massachu- las “Nick” Spinelli, m.d., a beloved David Greer, the inaugural Dr. Harry M. Zimmerman and Dr. Nicholas and Viola Spinelli Associate Profes- setts General Hospital (mgh), where alumnus of Yale College and the sor of Neurology, spoke at a celebratory reception in the Cushing/Whitney Medical Historical Library he underwent specialized fellowship School of Medicine who died in 2007, with a portrait of the late Nicholas Spinelli standing nearby. Spinelli established the chair with his sister, training in stroke and neurocritical and his sister, Viola Spinelli, m.p.h., Viola, in honor of Zimmerman, a neuropathologist on the School of Medicine faculty during Nicholas Spinelli’s student years who later became founding director of Albert Einstein College of Medicine. care. He was an associate neurologist a 1964 graduate of the Yale School of and attending physician in neurology Public Health. It honors Harry M. Nicholas Spinelli, a native of Strat- Army physician in Germany. Spinelli at Brigham and Women’s Hospital in Zimmerman, m.d., a notable neuro- ford, Conn., entered Yale College in practiced medicine in Stratford until Boston, and an attending physician pathologist during Nicholas Spinelli’s 1937 at 16 years old. After graduating 1968, when a heart condition forced and director of Neurology Consul- student days at the medical school in 1941, he entered the School of Medi- him to give up his practice. He was tive Services and the Inpatient Stroke who became the founding director of cine, and, like the rest of his class- able to continue working, however, and Service at mgh, where he was also the Albert Einstein College of Medi- mates, was inducted into the Army as served thereafter as director of medical the program director of the Partners cine in Bronx, New York. In addition part of Yale’s Company C, combining education at Bridgeport Hospital. He Neurology Residency Program. to the professorship, the Spinellis’ his medical studies with military was a familiar face on campus, serving Greer was an associate professor $4.5 million bequest supports a schol- drills on the New Haven Green. After from 1985 to 1990 as alumni director at Harvard Medical School before arship fund for medical students. graduating, Spinelli served as an for Yale School of Medicine.

Expert on genetics of psychiatric disorders Neuropsychiatrist, stem cell researcher is is appointed Foundations’ Fund Professor new Harris Professor of Child Psychiatry Joel Gelernter, m.d., the newly named Yale. He has also conducted research Flora M. Vaccarino, m.d., who studies She recently helped found the Pro- Foundations’ Fund Professor of Psy- in China and Israel. the pathophysiology of neuropsychi- gram in Neurodevelopment and Regen- chiatry, focuses his research on the Gelernter is a 1979 graduate of atric disorders and has elucidated how eration, an interdepartmental initiative genetics of psychi- Yale College. He received his m.d. at neural stem cells that will use induced pluripotent stem atric illness. suny Downstate Medical Center in self-renew, survive, cells as a research tool to understand The director 1983, and fellowship training at the and differentiate, neuronal development in individuals of the Division of National Institute of Mental Health. has been named with specific neuropsychiatric disorders. Human Genetics He has been a full professor at the Harris Professor of Vaccarino earned her medical in the Depart- School of Medicine since 2002, and Child Psychiatry. degree at Padua Medical University ment of Psychiatry, is currently professor of psychiatry, Members of Vac- in Italy and studied neuropharmacol- Gelernter seeks genetics, and neurobiology. carino’s laboratory ogy and cell biology at the National Joel Gelernter to identify genes He also is affiliated with the Flora Vaccarino study the prolifera- Institutes of Health as a research fel- that predispose Molecular Cell Biology, Genetics, and tion and differentia- low before starting her residency in individuals to substance-dependence Development track of the Combined tion of neural stem cells during prenatal psychiatry at Yale School of Medicine. traits—primarily cocaine, opioid, Program in the Biological and Bio- and postnatal development and after After her residency, Vaccarino studied nicotine, and alcohol dependence, medical Sciences. injury, as well as the diversity and func- developmental biology and genetics, as well as to other psychiatric traits, An associate editor of Neuropsy- tion of astroglial cells in neuropsychiat- and joined the Yale faculty in 1994. especially anxiety disorders. In ad- chopharmacology, Gelernter is on the ric disorders. A member of the faculty at Also affiliated with the Yale Stem Cell dition, he explores the genetics of editorial boards of Biological Psychia- the Yale Child Study Center and in the Center, Vaccarino became a full profes- other phenotypes, such as neuroim- try, The American Journal of Medical Department of Neurobiology, Vaccarino sor in 2009. aging measures and basic issues in Genetics Part B, Psychiatric Genetics, was the principal investigator of a 2003 Her honors include a National Alli- population genetics. His laboratory and Asian Biomedicine. study which found that patients with ance for Research in Schizophrenia and is engaged in ongoing research col- The professorship was estab- Tourette’s syndrome have fewer gaba Depression (narsad) Young Investiga- laborations on the genetics of sub- lished with contributions from The interneurons in their brains than those tor Award, a Lustman Award from Yale, stance dependence with colleagues Foundations’ Fund for Research in without the syndrome. She is known in two Tourette’s Syndrome Association at the Chulalongkorn Faculty of Psychiatry, established by philan- the neuroscience community for discov- Awards, a Women in Research and Edu- Medicine in Bangkok, Thailand, and thropist Charles B.G. Murphy, a ering the role of fibroblast growth fac- cation Award from the National Science he helps to train Thai investigators member of the Yale College Class tors in the growth of the cerebral cortex Foundation, and a narsad Indepen- in substance-dependence genetics at of 1928. during mammalian development. dent Investigator Award.

Development and function of the retina are research interests of Marvin Sears Professor Z. Jimmy Zhou, ms.c., ph.d., newly mechanisms underlying the genera- His team also explores the mechanisms at the University of California–Los designated as the Marvin L. Sears tion of spontaneous of visual signal processing in the ma- Angeles, Zhou joined the faculty at Professor of Visual Science, studies rhythmic activities ture retina, particularly the physiology the University of Arkansas. He came the physiology and development of the (retinal waves) in the of the neuronal circuits responsible for to Yale in 2008. He is vice chair and mammalian retina under normal and developing retina detecting image movement and move- director of research in the Department pathological conditions, as well as the and the functional ment direction. of Ophthalmology and Visual Science organization and function of retinal role of such activities Zhou earned his b.s. at Fudan and is affiliated with the Combined synapses and circuits. in the development University in China and his master’s Program in the Biological and Biomedi- Research in his laboratory is of neuronal circuits and doctoral degrees at the University cal Sciences and the Graduate Program focused on the cellular and network Z. Jimmy Zhou in the visual system. of Houston. After postdoctoral studies in Cellular and Molecular Physiology.

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