NYUTHE MAGAZINE OF NEW YORK UNIVERSITYPHYSICIAN SCHOOL OF MEDICINE SPRING 2015

DANGEROUS RHYTHMS For children with dangerous cardiac arrhythmias, implantable defibrillators can be lifesaving. Yet for active children, these devices pose special challenges.

PLUS TRACKING HOSPITAL-ACQUIRED INFECTIONS • SLOWING BRCA TUMORS • NEW TARGET FOR CHILDHOOD EPILEPSIES Help Us Make Dreams Come True

EVERY ASPIRING PHYSICIAN DREAMS OF THE DAY SOMEONE WILL MAKE A GIFT ONLINE CALL HIM OR HER “DOCTOR” FOR THE FIRST TIME. But getting there Please visit www.nyu.edu/alumni. takes a lot more than hard work and dedication—it takes resources. By contributing to the NYU School of Medicine Alumni Campaign, you help To discuss special ensure that our next generation of physicians will have access to the best giving opportunities, teaching and research, along with a competitive financial assistance package. call Anthony J. Grieco, MD, Associate Dean for Alumni Relations, When you make a gift, you help us guarantee that all of our students will at 212.263.5390. have the means to complete our rigorous education. One day, you may even have the privilege of addressing them yourself as “Doctor.”

Thank you for your generosity. THE MAGAZINE OF NEW YORK UNIVERSITY SCHOOL OF MEDICINE SPRING 2015 NYUPHYSICIAN

New York University A new center will explore Martin Lipton, Esq. Chairman, how the microbiome Board of Trustees may provoke the body’s John Sexton President immune system to turn Robert Berne Executive Vice President against itself. for Health • NYU Langone Medical Center Kenneth G. Langone Chairman, Board of Trustees

Robert I. Grossman, MD COVER STORIES The Saul J. Farber Dean and CEO Dangerous Rhythms Kathy Lewis For children with dangerous Senior Vice President 10 cardiac arrhythmias, implantable Communications defibrillators can be lifesaving. and Marketing Yet for active children, these devices DEPARTMENTS • pose special challenges. NYU PHYSICIAN By Kenneth Miller 02 Dean’s Letter Steven B. Abramson, MD  The Versatile Heart Anthony J. Grieco, MD Confronting an Ever-Present Editors, Science Threat in Hospitals 03 News from Medicine and Medicine 18 A new surveillance system at NYU • Slowing BRCA Tumors

Marjorie Shaffer Langone Medical Center aims to track • Unprecedented Microbial Diversity Editor healthcare-associated infections in Reported in Remote Amazonian Tribe real time. • Newer Stents, Less Risk Thomas A. Ranieri By Bryn Nelson • Linking Dirty Air and Stroke Nicole Dyer Contributing Editors • A New Treatment Target Emerges for A Window onto the Brain Severe Childhood Epilepsies Sherry Zucker The tiny roundworm is yielding Print Production 22 surprising insights into 26 Around Campus Coordinator psychiatric disorders and a rare At the Colton Center for Autoimmunity, genetic condition among children. the Microbiome Is Key Segal Savad Design By Nicole Dyer Art Direction 28 Faculty Conversation • ON THE COVER: Q&A with Dr. Bernard Dreyer, President-Elect ILLUSTRATION BY of the American Academy of Pediatrics STUART BRIERS 30 Faculty News • Dr. Danny Reinberg Is Elected to the NAS • Time Magazine Honors Dr. Martin Blaser

31 Obituary Joseph Herbert, MD

32 End Page Preparing for Ebola in Ghana By Sari Soghoian, MD ILLUSTRATION BY ANDREA ROSSI BY ILLUSTRATION

NYU PHYSICIAN SPRING 2015 1 MESSAGE FROM THE DEAN & CEO

The Versatile Heart

I’ve always been amazed by the heart. This mighty muscle works continuously to send oxygen-rich blood to cells. Every minute about 11 pints of blood are sent through the lungs and around the body. In the course of a lifetime, the heart beats over 3 billion times. When the beat goes awry, the consequences, of course, can be life threatening. Today, due to the revolution in genetic testing, it is possible to identify in infants and children congenital mutations that dramatically raise the risk of fatal cardiac arrhythmias. To prevent sudden death, they can be fitted with an implanted cardioverter-defibrillator (ICD). In this issue of NYU Physician magazine, the stories of some of these young patients and their families are brought to light. Under the care of Dr. Frank Cecchin, a remarkable physician who is director of pediatric and congenital electrophysiology, these young patients learn to adapt to life with an ICD and to appreciate the lifesaving technology that enables them to lead normal lives. I hope you enjoy reading about him and his patients. Other stories highlight discoveries from our laboratories that will one day affect children’s health, from epilepsy to familial dysautonomia. Finally, our faculty conversation with Dr. Bernard Dreyer, president-elect of the American Academy of Pediatrics, underscores our unswerving commitment to children’s health and well-being. I’d like to end this letter with a note about the newest member of our family—Lutheran Medical Center, an acute care teaching hospital in southwest Brooklyn, now known as NYU Lutheran Medical Center. Our unprecedented alliance creates a clinically integrated healthcare network that provides access to our vast array of specialty and surgical care. In turn, NYU Lutheran gives us the opportunity to extend our expertise to a larger number and broader spectrum of patients. This is an exciting chapter in our history.

DEAN & CEO ROBERT I. GROSSMAN, MD

NYU PHYSICIAN PHOTOGRAPH BY 2 SPRING 2015 JOHN CARNETT NEWS FROM MEDICINE SPRING 2015

ADVANCES IN BREAST CANCER RESEARCH, THE MICROBIOME, EPILEPSY AND MORE

ILLUSTRATION BY STUART BRIERS NEWS FROM MEDICINE

This much less reliable mending kit In healthy cells, the employs an error-prone enzyme called polymerase theta, encoded by the POLQ BRCA genes encode gene, which may fuel cancerous growth. proteins that reliably But a cancerous cell is still a living cell. From the cell’s vantage, this backup repair damaged DNA. polymerase strategy is potentially In mouse and human lifesaving as it helps stave off full-blown cells with BRCA1 or genetic havoc. Agnel Sfeir, PhD, an investigator at the Skirball Institute of BRCA2 mutations, Biomolecular Medicine and a member of a backup repair the Laura and Isaac Perlmutter Cancer Center, says this observation suggests strategy takes over. an entirely new way to target BRCA cancers. “One way to kill cells with BRCA mutations is to block this enzymatic fuse together, sometimes leading to AGNEL SFEIR, PHD pathway and deplete POLQ,” she says. massive DNA rearrangements like those The finding stems from what Dr. seen in cancer. Which DNA letter, Dr. SLOWING Sfeir describes as a “simple” question Sfeir wondered, appears at the precise BRCA TUMORS about basic biology. The tips of our junction between two abnormally fused chromosomes, called telomeres, contain telomeres? “You answer the question, A glitch in a molecular repair multiple repeats of the DNA letters and you don’t know where the science tool may offer a way to halt TTAGGG and are normally protected will take you,” she says. some breast cancers. by protein caps that act like the plastic When the researchers sequenced the nibs on shoelaces. If left unprotected, DNA at multiple telomere fusions, they however, the telomeres can decay or unexpectedly found that many of the

WOMAN’S LIFETIME risk of developing breast cancer in the U.S. is A about 12 percent. But if she carries inherited mutations in the BRCA1 and BRCA2 genes, which account for 5 to 10 percent of all breast cancer cases, her risk is dramatically higher—anywhere from 40 to 90 percent, depending on individual risk factors. In a recent study published in Nature, and funded partly by the Breast Cancer Alliance, researchers at NYU Langone Medical Center describe a new way to potentially slow or halt the growth of cancers linked to BRCA1 and BRCA2 mutations. In healthy cells, the BRCA genes encode proteins that reliably repair damaged DNA. In mouse and human cells with BRCA1 or BRCA2 mutations, however, the researchers discovered

that a backup repair strategy takes over. BRIERS BY STUART ILLUSTRATION THEA BRINE. BY PORTRAITS

NYU PHYSICIAN 4 SPRING 2015 junctions contained randomly inserted Austin, Dr. Sfeir’s lab found that blocking DNA letters instead of the TTAGGG the activity of POLQ in cells lacking the repeats. The random insertions suggested BRCA genes, meaning those deprived the activity of an error-prone polymerase. of both DNA repair mechanisms, led After testing several kinds of polymerase, to chromosomal chaos and markedly the collaborators found that knocking reduced survival. Her lab is now testing out the POLQ gene for polymerase theta whether the same POLQ-targeting significantly reduced the propensity of strategy can inhibit tumor formation in dysfunctional telomeres to stick together, mouse models of breast cancer. suggesting that the enzyme might actually A simple question and observation, promote the phenomenon. In particular, Dr. Sfeir says, has since opened the the data suggested that this polymerase door to an entirely new line of scientific plays a key role in the highly unreliable inquiry. “There are many types of cancers DNA patching service that may that have altered DNA repair, and trigger both chromosomal fusions and this polymerase theta seems to be up- The tips, or telomeres, of these mouse chromosomes have become wholesale rearrangements in cells with regulated in many tumor cells,” Dr. Sfeir dysfunctional, causing individual BRCA mutations. says. “So why? What is it doing? Why is it chromosomes to fuse together in long Together with collaborators from The up-regulated? All of these are important tangled strands of DNA. Scripps Research Institute in La Jolla, questions. We’re going to be busy for the California, and the University of Texas at next 10 years or so.” • —BRYN NELSON

N 2008, a helicopter spotted percent less diverse, the scientists estimate. an uncharted village of “We have found unprecedented Yanomami Indians in the diversity in fecal, skin, and oral samples I remote Amazonian jungles of collected from the Yanomami villagers,” southern Venezuela. The clan says senior author Maria Dominguez- had subsisted for hundreds of generations Bello, PhD, associate professor of by hunting and gathering, and up until medicine at NYU Langone. Science is that moment, its members had lived in only just beginning to understand the total seclusion from the outside world, as significance of diversity in the human a medical expedition would later learn. microbiome. But the results bolster a For biologists, the unbroken isolation growing body of data suggesting a link MARIA DOMINGUEZ-BELLO, PHD of the tribe offered a rare window on a between, on the one hand, decreased seemingly ancient human microbiome, bacterial diversity, industrialized UNPRECEDENTED the trillions of bacteria that live in and diets, and modern antibiotics, and on the body and that are increasingly on the other, immunological and MICROBIAL seen as vital to our health. Most human metabolic diseases such as obesity, DIVERSITY REPORTED microbiome studies have focused on asthma, allergies, and diabetes, which Western populations. Now, a multicenter have dramatically increased since the IN REMOTE team of U.S. and Venezuelan scientists, 1970s. “We believe there is something AMAZONIAN TRIBE led by researchers from NYU Langone environmental occurring in the past Medical Center, report in the journal 30 years that is driving these diseases,” New findings shed light on Science Advances that the villagers possess adds Dr. Dominguez-Bello. “We think the the human microbiome. the most diverse collection of bodily microbiome could be involved.” bacteria ever documented. By comparison, In the study, the researchers analyzed the microbiome of people living in bacterial samples collected and preserved

SCIENCE IMAGE: AGNEL SFEIR AGNEL SCIENCE IMAGE: industrialized countries is about 40 from 34 of the 54 Yanomami villagers.

NYU PHYSICIAN SPRING 2015 5 6 NEWS FROM MEDICINE electron photomicrograph. U.S. skinsamples,includingPropriobacterium , shownhere in a colorized By contrast,relatively higherproportions ofsomemicrobes dominated No singlegroup ofbacteriadominatedtheYanomami’s skinsamples. showed lower diversity andrelatively contrast totheU.S. skin samples, which dominant taxonomic group ofbacteria, in the researchers foundnosingle from ourmicrobiome.” removes potentially beneficialbacteria exposure greatly decreases diversity and Medicine at Mount Sinai.“Even minimal Clemente, PhD, oftheIcahn School of and processedfoods,”says coauthor Jose proportional toexposure toantibiotics There isagradient ofdiversity in fecesandskin that isinversely the outside world thantheYanomami. tribal populations withmoreexposure to Africa. The latter communities represent Malawian communities insoutheast in Venezuela andresidents ofrural from theAmazonian Guahibo Indians in theUnited States, aswell assamples compared tosamples frompopulations samples. Their bacterial DNA was then oral swab samples, while 11gave fecal Among thevolunteers, gave 28 skin and Among theY “ anomami skin samples, Propionibacterium. , Neisseriaceae,Corynebacterium and within thehuman microbiome. rehabilitate disease-causing imbalances he researchers hopetheirinsights will lead tonew therapies that will resistant genes,” says Dr. Dominguez-Bello. modern antibiotics topossessantibiotic- shows that you don’t needexposure to to new classes ofantibiotics. “This rate at which bacteria develop resistance antibiotics may helpexplaintherapid in microbiota unexposed tomodern well. The presenceofresistance genes surprisingly, tosynthetic antibiotics as formillennia,but found inthesoil only tonaturally occurringantibiotics bacterial genes conferresistance not code forantibiotic resistance. The had bacteria containing genes that revealed that theYanomami villagers n anotherintriguing finding, a genetic analysis ofgutandoralbacteria high proportionsof SPRING 2015 NYU PHYSICIAN T I

Staphylococcus, —NICOLE DYER •

causing vessels toconstrict again. inflammation andscar tissue growth, hold bloodvessels open—can promote arteries, stents—the scaffolds usedto SRIPAL BANGALORE, MD hese observations stem fromstudies years following. chance ofheartattack anddeath—in the they aremorerisky—with agreater first month or so after theprocedure, stents arelessrisky forpatients inthe less likely totrigger strokes. Though recoverywith faster times,andismuch traditional open-heart bypass surgery, a much shorter hospital stay than intervention, orPCI—however, requires he technique forinsertinga stent—called percutaneouscoronary C bypass surgery. stents are compared to The latestgenerationof LESS RISK NEWER STENTS, T T attacks andnarrowed used totreat acute heart Although commonly or bypass surgery? ORONARY STENTS

PORTRAITS BY THEA BRINE. KWANGSHIN KIM / SCIENCE SOURCE BSIP / SCIENCE SOURCE he study isbasedonobservational data fromtheNew York State cardiac n a clots, inflammation, andtissue growth. living tissue andlesslikely tocause are designed to bemorecompatible with Center, who points outthat newer stents medicine at NYULangone Medical Bangalore, MD of older-generation stents, says Sripal inflammation andtissuegrowth. are coatedwithdrugsthatinhibit clogged bloodvessels.Newerstents Stents are that prop tinyscaffolds open between stents andbypass surgery.” their physicians tochoose morewisely should make iteasierfor“patients and the findings about comparable mortality bypass surgery. Dr. Bangaloresays that cause greater longer-term mortalitythan inflammation andtissue growth, didn’t everolimus,with thedrug aninhibitorof surgery. They foundthat stents coated of thenewer-generation stents to bypass Bangalore andcolleagues compared some The New EnglandofMedicine Journal , Dr. T I study published recently in , associate professorof the market. two everolimus-coated stents now on he study was funded by Abbott Laboratories, which makes oneofthe with stenting.” long-term needforrepeat procedures stroke withbypass surgery, withthe weighing theup-front risk ofdeath and bypass surgery should bebased on “the decision between stenting and blind clinical trial,Dr. Bangaloresays h thislatest study does not not onthegold standard ofadouble- it isbasedonobservational data and settle thequestion definitively because significant increase inheart attacks. of theirdiseasedarteries,therewas no whose stents successfully openedall the bypass group, butforthosepatients attacks during theperiodcompared to group had about 50percent moreheart significantly different. Patients inthe stent of deaths inthetwo groups were not for death. Inthenumbers thelongrun, group didn’t worse fare inthelonger term to earlier studies ofolder stents, thestent risk ofdeath andstroke, butincontrast betterinthefirst 30daysfared withlower implanted. The stent group, asexpected, those who had everolimus-coated stents patients who had bypass surgery with registries. It compared outcomesof bypass surgery.” between stents and choose more wisely their physicians to for “patients and make iteasier The analysis should T Althoug •

—JIM SCHNABEL JEFFREY S.BERGER, MD A he the brain. thearteriesfeeding affect Air pollutionappearsto AND STROKE LINKING DIRTY AIR MD stroke,” says coauthor Jeffrey S. Berger, the riskstenosis ofcarotidartery and from combustion engines,would reduce fine particulates, which originate mostly the possibilitythat lowering levels of carotids. “Findings like thesepoint to a greater chance ofnarrowing inthe microns indiameter, isassociated with fine particulate matter smallerthan2.5 form ofairpollutioncalledPM2.5, or study that long-term exposure to a the risk ofstroke. They reportinanew relationship—air pollutionmay increase Center researchers foundaworrisome to thebrain,NYULangone Medical T , assistant professor ofmedicine. study, published inarecent issue which supply blood the carotidarteries, of ultrasoundtests of from tensofthousands NALYZING DATA

NEWS FROM MEDICINE

of the Journal of the American Academy the elderly, and people with other health of Cardiology, is based on ultrasounds problems like diabetes, air pollution performed on over 300,000 New York, might be a very important source of risk,” New Jersey, and Connecticut residents says NYU Langone cardiologist Jonathan from 2003 to 2008. Segregating the D. Newman, MD, MPH, the lead author data by patients’ zip codes and adjusting of the study. • —JIM SCHNABEL for demographic and socioeconomic factors, the researchers found that those people in the quartile of zip codes with the highest average PM 2.5 levels during the testing period were about 24 percent more likely to have stenosis—defined as a narrowing by at least half—in either of the two internal carotid arteries that NYU Langone supply the brain. The analysis also showed that even Medical Center a modest increase in the average PM researchers found 2.5 level, by just 10 micrograms per a worrisome cubic meter, was associated with a near doubling of carotid stenosis risk. relationship—air “If you’re in very good health, the pollution may levels of air pollution that we see in most of the U.S. probably don’t pose a increase the risk significant risk, but for the very young, of stroke.

HE SYNAPSE, a mere consortium. Some 2 to 3 million people wisp of a structure at the in the U.S. have epilepsy. Severe forms junction where neurons of the disorder, such as West syndrome, T communicate, may which affects some 2,000 to 2,500 infants hold the key to novel each year in the U.S., are less common. therapies for a group of debilitating and Children with epileptic encephalopathies sometimes fatal childhood epilepsies. have frequent seizures and experience

RUBEN I. KUZNIECKY, MD New research by an international progressive cognitive impairment, consortium of investigators has, for the leading to lifelong disability. Pre- A NEW TREATMENT first time, uncovered distinct anomalies and perinatal infections and other in genes that help regulate synapses complications, and inherited gene TARGET EMERGES FOR among children with these epilepsies. mutations are among the known causes. SEVERE CHILDHOOD “I think this finding is oingg to offer In recent years, teams of epilepsy a new view of the kinds of interventions researchers have been investigating EPILEPSIES that could help patients with these another culprit: de novo (new) mutations disorders,” says Ruben Kuzniecky, that are found in children’s genomes but not Researchers are focusing MD, professor of neurology, codirector in their parents’ genomes. Such mutations on the synapse. of the NYU Comprehensive Epilepsy typically arise from spontaneous mutations

Center, and a member of the research in sperm or egg cells. BRIERS BY STUART ILLUSTRATION THEA BRINE. BY PORTRAIT

NYU PHYSICIAN 8 SPRING 2015 The new findings, based on DNA excitability of nerve cells—the readiness Mutations in samples gathered worldwide from to fire bursts of neurotransmitter 356 patients and their parents, were molecules to other neurons. A mutation synaptic genes published recently in The American may leave an ion channel stuck open appear to be Journal of Human Genetics. By comparing or closed in a way that makes cortical children’s DNA with that of their neurons too excitable and thus prone to another major parents, the researchers found evidence seizure activity. underlying that a substantial proportion—some 12 The new study indicates that mutations cause of seizure percent—of the children with no known in synaptic genes are another major cause of epilepsy harbored de novo underlying cause of seizure disorders. disorders. mutations. Surprisingly, 75 percent of The DNM1 gene and its protein are likely these mutations were in genes encoding to come under particular scrutiny as proteins believed to help regulate potential drug targets. “Reversing or synapses, the communication ports used circumventing this DNM1 deficiency by neurons to send chemical messages will be an interesting challenge,” Dr. to one another. Most previous genetic Kuzniecky says. studies have implicated a different The new study was a collaborative nerve-cell process. effort by the Epi4K Consortium, the The de novo mutations occurred EuroEPINOMICS-RES Consortium, and most frequently in a synaptic gene the Epilepsy Phenome/Genome Project, called DNM1, which codes for a protein which Dr. Kuzniecky codirected. • named dynamin 1 that allows neurons —JIM SCHNABEL to recycle some of the tiny capsules, or vesicles, used to send neurotransmitters across synapses to other neurons. This recycling process, called endocytosis, is essential for proper neuronal signaling. “The DNM1 mutations that we’ve detected appear to impair endocytosis,” says Dr. Kuzniecky. The research, he says, also suggests that the gene defects mainly impair activity in inhibitory circuits that ordinarily restrain neuronal firing. Thus, such defects remove the breaks that prevent the excessive firing associated with seizures. Other researchers reported in 2010 that a mutation in DNM1 leaves mice with a severe epilepsy-like syndrome, but until now, DNM1 mutations haven’t been implicated in human forms of epilepsy. Nearly all previously reported mutations that cause childhood epilepsies were in genes coding for ion-channel proteins. These pipelike proteins, which form tiny channels in the outer membranes of neurons, allow Computer artwork of a nerve cell, showing passage of sodium, calcium, chloride, long branches of dendrites emanating and potassium ions. The movement of from the nerve cell body. Dendrites collect

PASIEKA / SCIENCE SOURCE PASIEKA the ions, in turn, regulates the general information from other cells.

NYU PHYSICIAN SPRING 2015 9 BY KENNETH MILLER • ILLUSTRATION BY JAMES STEINBERG

For children with dangerous cardiac arrhythmias, implantable defibrillators can be lifesaving. Yet for active children, these devices pose special challenges. Dr. Frank Cecchin has developed a nuanced approach to the problem of risk in his young patients—one informed by clinical studies showing that safety and flexibility are not always incompatible.

NYU PHYSICIAN 10 SPRING 2015

A few months ago, Jake Baxter decided to get rid of the device that had protected him for a decade from the cardiac disorder that killed his sister. Jake was born with a genetic mutation that could send his heart into a rapid arrhythmia—ending in cardiac arrest—at any time. As a teenager, he was surgically fitted with an implantable cardioverter-defibrillator (ICD), designed to detect dangerously irregular heartbeats and deliver a shock to set the rhythm back on course. However, he’d never actually experienced a cardiac event, and the business card–size gadget had never been activated. Now he was 24, and he wanted it out of his chest.

THE REASON WAS PURELY PRACTICAL: He’d set computing allowed them to be made small enough to fit his sights on a career as an electrical lineman, and after inside a child’s chest. The basic version consists of a titanium passing a series of grueling exams, he’d been accepted box, or generator (containing computer circuitry, a capacitor, into the union. Then he learned that anyone with an ICD and a battery), and a wire known as the lead. In most patients, was disqualified from working with power lines, because the generator is implanted in the left side of the chest, under electrical interference could cause the device to malfunction. the skin or muscle, and the lead is threaded through a vein For a worker 50 feet up a utility pole, a jolt from a misfiring into the chambers on the right side of the heart. Sensors relay defibrillator could have disastrous consequences. heart rhythms to the ICD’s microprocessors. If potentially Frustrated, Jake went to see Frank Cecchin, MD, director life-threatening tachycardia or fibrillation persists for of pediatric and congenital electrophysiology at NYU too long, the generator interrupts these very chaotic, fast Langone Medical Center, who had overseen his ICD’s rhythms by sending a surge of energy to an electrode in the maintenance since implanting it in 2005. From previous right ventricle. conversations with the doctor, the young man knew that for ICDs are used for two broad purposes: primary patients with his condition, the risk of cardiac arrest may prevention, which means warding off sudden cardiac decline after age 20. “I don’t really need this thing anymore,” arrest in high-risk patients, and secondary prevention, he pleaded. “Can’t we just chuck it?” which means avoiding a recurrence in those who’ve already “Maybe we can,” Dr. Cecchin (pronounced “check-een”) endured such an episode. Newer ICDs can also double as told him. “But before we move ahead, let me do a little pacemakers, delivering pulses of low-voltage electricity to more research.” keep the heart from beating too slowly. The device can be implanted in infants as soon as a few weeks after birth. In • • • these patients, the generator is implanted in the abdomen, where there’s enough space to accommodate it, and the leads For children at risk of fatal cardiac arrhythmias, an ICD are routed to the outside of the heart. In patients like Jake, can greatly improve the odds of long-term survival. First who may experience sporadic arrhythmias, an ICD can introduced in 1980, the devices were used almost exclusively function like a sprinkler system, kicking in if a biochemical in adults until the 1990s, when advances in electronics and glitch ignites a cardiac inferno.

An ICD has never prevented Jake Baxter from pursuing his passion—mountain biking. He has been racing since 2006. PHOTO BY PAULETTE MERTES BY PAULETTE PHOTO

NYU PHYSICIAN 12 SPRING 2015

Yet ICDs are difficult to live with. Batteries run out every five years or so, requiring surgery to replace the device. Leads can wear out or fracture, sometimes triggering a painful and terrifying storm of shocks. Even when an ICD does what it’s designed to do, zapping a runaway heartbeat into submission, the sensation is scary—a kick in the chest that can leave even a strong man reeling. For children, there are additional challenges. Their higher activity levels and growing bodies put more stress on the hardware, necessitating more frequent equipment changes and posing a An ICD and a cast of an infant’s heart. greater potential for complications. If a lead creates scarring in a vein, for example, it must be rerouted. After several such operations, a child can run out of viable pathways.

• • • 20 percent of pediatric ICD patients experience inappropriate shocks, whether due to a broken lead or to misidentification The most daunting downside for pediatric ICD patients of a harmless arrhythmia. Many cardiologists add to may be psychological. “You’re completely dependent on young patients’ angst by forbidding activities that could that device functioning properly,” observes Dr. Cecchin. hypothetically damage the implant, such as sports in which “That knowledge affects all age groups, but it can have a collisions or falls are common. They may retain the ICD’s huge impact on kids.” Several studies show that children factory settings, which program it to fire the moment a with ICDs have far higher rates of anxiety than healthy kids. ventricular tachycardia (an arrhythmia originating in the According to a paper he coauthored in the journal Pediatrics, heart’s lower chambers) reaches 160 beats per minute. incidence rises with children’s age at implantation and the Better to suffer an unnecessary shock, goes the thinking, severity of the disorder under treatment. “It’s enormously than to risk ventricular fibrillation, in which the rhythm stressful for the parents as well,” notes nurse practitioner becomes so rapid and disorganized that the heart stops Sharda McGuire, who often recommends counseling for pumping altogether. both patients and family members. Over his 20 years as a pediatric cardiac electrophysiologist, The devices and the doctors who prescribe them can Dr. Cecchin has developed a more nuanced approach to the sometimes reinforce recipients’ sense of insecurity. More than problem of risk in his young patients—one informed by

HUNZA MIRZA says Hunza’s mother, Katherine. to keep his heart from beating too AGE 14/BROOKLYN, NY As a kindergartner, he tired easily slowly. His mother and three of his and was often short of breath, and four brothers also tested positive for his condition worsened with each the disorder, and though only one Hunza was three years old when he passing year. By sixth grade, he could sibling shows signs of illness, the others was diagnosed with hypertrophic barely climb a flight of stairs. Because are being carefully monitored. Amid cardiomyopathy, a genetic disorder the disease can trigger a sudden, these worries, Hunza’s ICD allows that causes part of the cardiac fatal arrhythmia, his doctor referred him and his family some precious muscle to thicken. At first, his only him to Dr. Cecchin at NYU Langone peace of mind. “Sometimes it feels symptom was a heart murmur. “I Medical Center. weird, but I’m really glad I have it,” kept praying that it would go away, At age 11, Hunza received an he says. “I might not be here today but that’s not how it worked out,” ICD, which doubles as a pacemaker if I didn’t.”

NYU PHYSICIAN 14 SPRING 2015 PHOTOS BY BÉATRICE DE GÉA ell children “ things safely.” to enable you to do anything. It’s there you from doing not there to stop that this device is I t  individual. “If Isay, ‘You can’t do this,’theyget angry, andthey discusses thepossibledangers, andleaves thedecision up tothe Dr. Cecchin carefullyconsiders each patient’s condition, needed.truly least two years. Nor have theirdevices tofire when failed patients shock hasexperiencedanunnecessary inat improved computer algorithms, hereports,noneofhis possible todeliver ashock.” Thanks tothat strategy and and resolve themselves. We wait forthemaximum time lot ofarrhythmias areshort-lived to betooaggressive. In children, a ICDs, hesays, “we’ve learnednot incompatible. In programming and flexibility arenot always clinical studies showing that safety Rather thanissue blanket bansonstrenuous exertion, arrived. At a local hospital, she was arrived. Atalocalhospital,she was revived bythetimeparamedics frantically, andthetwo-year-old Her parents pumpedherchest breathing,” recalls herfather, Dhruv. “I pickedherup,andshewasnot she crumpledtothelivingroom floor. playing withhertwinbrother when in2008,Dishitawas One morning AGE DISHITA AGARWAL

9 /SYRACUSE, NY from the brain to the sympathetic from thebraintosympathetic nerves inthechestthatrelay impulses stresses, acardiac alsosevered surgeon mute herheart’sresponse toemotional who implantedherwithanICD.(To for allknowngeneticmarkers. sequencing, Dishitatestednegative bygene be confirmed can and Although mostcasesare inherited about1in5,000 people. affecting a commondisorder rhythm cardiac diagnosed withlongQTsyndrome— Dishita wasreferred toDr. Cecchin, willing toconsider it. we’ll deal withit.The bottomlineisthat you have toenjoy life.” there toenable you todo things safely. If somethinghappens, that thisdevice isnottheretostop you fromdoinganything. It’s encourages patients tobeasactive astheycan.“Itellchildren sports seldom cause damage toICDs.Except inrarecases,he door, theyusually make theright choice.” usually do itanyway,” heexplains.“But ifIgive themanopen If, insomecases,that might meanremoving anICD, he’s In hepoints out,recent fact, studies show that even rough

become apartofallourlives.” mother, Ruchi.“Butthe uncertaintyhas ‘The ICDisprotecting you,’”saysher to allayheranxieties.“We tellher, is buzzing.”Herparents trytheirbest “Myheadhurts.Everything tearfully. scary whenIgetshocked,”Dishitasays she climbedstairsathome. lesson. Itrescued heragainrecently, as duringaswimming out ofanarrhythmia her lifeatagefour, shockingherheart nervous system.)Thedevicefirstsaved Yet theemotionaltollisheavy.“It’s • • •

Jake Baxter is fair-haired and athletic, and the name of his late sister is tattooed over his heart. Rebecca was 13 in July 2000, the second of three children born to a pair of science teachers. She’d just finished eighth grade at Mansfield Middle School in Storrs, Connecticut, where she’d played basketball, softball, and soccer. She was a strong swimmer, too. So when she drowned in the shallow end of a public pool, her family’s grief was accompanied by bafflement. The autopsy revealed that the cause of death was sudden cardiac arrest. “It was a mystery,” recalls Jake, who was nine at the time. “We were all just blindsided.” There was one clue, however: Rebecca’s father, Ed, had lost two brothers to drowning, both before they turned 18. A physician friend, suspecting that an inherited electrophysiological disorder might be the culprit, referred the Baxters to Dr. Cecchin, who was then practicing at Boston Children’s Hospital and whose own family had been touched tragically by cardiac disease. The son of Italian immigrants, Frank Cecchin grew up An illustration of an ICD implanted in The Bronx and Long Island, where his father worked as in an infant’s abdomen. a tile setter. His parents never made it past sixth grade, and they were fiercely proud of their high-achieving son. But his dad died of a heart attack during Frank’s first year of medical school. That event influenced his choice of specialties and helped shape his attitude toward his patients. “Dr. Cecchin then 21, traveled to Boston for countless stress tests meant is very warm and welcoming,” says Jake. “He makes you to spur a telltale arrhythmia. None of them yielded an feel like he has all the time in the world for you.” Adds Jake’s abnormal graph line. Dr. Cecchin even immersed the mother, Judith: “He’s incredibly persistent. He wouldn’t give siblings’ faces in ice water (which Jake recalls enjoying), but up until he figured out how to help us.” the electrocardiogram remained unperturbed. Then, at a Over the next two years, Jake and his sister Sarabeth, professional conference, he met a Mayo Clinic scientist who

CAMERON KNOWLES found their way to Dr. Cecchin. Recently, Cameron enjoyed his AGE 14/ROCHESTER, NY “He was the first doctor who talked first roller coaster ride. He joined an to us about the course of treatment Explorer Scout troop that teaches all the way to adulthood,” recalls firefighting skills, and though he may When Cameron was seven years Rebecca. Dr. Cecchin also never be able to run into burning old, his parents went to wake him exchanged Cameron’s original buildings, he plans to major in fire for school and found him in cardiac ICD for one with a safer and more prevention in college. “At first, I arrest. Rebecca, a nurse, and Mark, effective design. Genetic tests was a little angry about needing a firefighter, saved his life using CPR. showed that Mark was at risk, as an ICD,” he says. “I thought my Diagnosed with long QT syndrome, well, and after his brother died life was over. But when you look Cameron was implanted with an of an arrhythmia at 45, he, too, past the limitations, you see all the ICD. A few months later, the family received an implant. opportunities that are out there.”

NYU PHYSICIAN 16 SPRING 2015 ILLUSTRATION BY SCOTT LEIGHTON. PHOTO BY BÉATRICE DE GÉA electrophysiologists inthecountry, maybe theworld.” Dr. Ludomirsky. “Iconsider him oneofthebest pediatric Hospital. “I’d himforages,” torecruit beentrying says who’d beenhisfellowship adviser at Texas Children’s and directoroftheDivision ofPediatric Cardiology, Pearsonthe AndrallE. ProfessorofPediatric Cardiology NYU Langone, luredthereby Achiau Ludomirsky, MD Then, hebeganstudying tobecomeanelectricallineman. college, earningacertification in sustainable energy. tracks fromCanada toCalifornia.He went ontojunior the timehefinished high school, he’d competed onsingle mountain-bike teamandbeganracing every weekend. By his otherrugged pursuits. At 15, adownhill hejoined he agreed togive up swimming, hesoonreturnedto aunts andcousinsafter theytested positive forCPVT. the device. SodidSarabeth, andso didseveral oftheir Jake—an avid mountain biker andsnowboarder—chose the heartrate. Jake’s optedforthemedication. father and beta-blockers, which prevent tachycardia by blunting two choices: anICDoralifetimeofexercise restriction first symptom iscardiac arrest. exercise oremotionalstress. In somecases,however, the may include inresponse dizzinessorfainting tointense sudden cardiac deaths inyoungsters. Warning signs and toberesponsible for15percent ofunexplained channels.) It’s believed toaffect about 1in10,000 people, involve different typesof ion QT orshort QT syndrome, rhythm disorders, such aslong ions—between cells.(Other signals—carried by calcium of certainelectrochemical proteins that control thepassage the body’s calcium channels, ventricular tachycardia (CPVT). catecholaminergic polymorphic causes arhythm disorder called specimens showed amutation that the results cameback. Allthe and theirfather. In June 2004, samples fromJake, Sarabeth, from Rebecca’s autopsy, andblood Cecchin sent himatissue sample genes governing cardiac cells.Dr. was researching raremutations in After Jake visitedhisofficelast winter, Dr. Cecchin Meanwhile, in2013, Dr. Cecchin moved fromBoston to Jake was 13when hereceived theimplant. Although To prevent that fromhappening, Dr. Cecchin offered CPVT stems fromadefect in , someday, itjust might save my life.” I love todo,” Jake says, “and it’s good toknow that developing prostheses forbike riders withdisabilities. founded withafriend.The startup aimstospecialize in project, asmallindustrial-prototype businessthat he’d the status quo. Instead, heturnedhisenergy toanother department ofpublic works. But hedidn’t surrender to out. He would keep hiscurrent job, driving trucks forthe the implant would stay in;working onpower lineswas of cardiac arrest intheir30s. Some ofthosepatients, Dr. Cecchin discovered, had died just ortwo arung away ontheryanodine receptorgene. there were afew casesofmutations onDNA basepairs mutation shared by Jake andhisrelatives. literature insearch ofotherpatients withtheprecise follow different courses.He begancombing through the he knew that different variants of thedisorder could sudden death sharply inadulthood, fromCPVTfall remove theyoung man’s ICD. Although theoddsof set towork todetermine trying whether itwas safe to with ayoungpatient. practitioner Sharda McGuire Dr. FrankCecchinandnurse “My defibrillator hasnever heldmeback from what When Jake got thenews, hecametoanew decision: No oneelseturnedup withthat particularglitch, but • Dr. Bo Shopsin (left) and Dr. Michael Phillips are working to find an effective solution to hospital-acquired infections.

NYU PHYSICIAN 18 SPRING 2015 Confronting an Ever-Present Threat in Hospitals A new surveillance system at NYU Langone Medical Center aims to track healthcare- associated infections in real time, providing an early warning for potential outbreaks. BY BRYN NELSON • PHOTOGRAPH BY BÉATRICE DE GÉA

NYU PHYSICIAN SPRING 2015 19 AN UNWASHED HAND, an uncovered Now he’s partnering with Bo Shopsin, patient before symptoms emerge, and cough, inadequately sterilized instruments. MD, PhD, assistant professor of medicine asymptomatic patients can still pass on In a hospital, any breach, small or large, can and microbiology, on a faster, more disease-causing microbes to others, the set off a chain reaction of deadly infections. effective solution for fighting nosocomial Medical Center screens certain high- The margin for error is so small that 1 in infections. “Traditionally, infection risk patients for infectious disease. 25 patients in the United States battles at control in hospitals has been done really The problem is that this screening least one infection acquired during hospital ad hoc,” says Dr. Shopsin. “We’re creating process generates a daily avalanche of care, known as a nosocomial infection. a more systematic way of identifying laboratory data. The task of scouring Because hospitals care for the nation’s clusters and outbreaks.” it for telltale patterns and suspicious most gravely ill patients, they regularly In late 2013, the doctors introduced clusters traditionally falls to a handful encounter a range of tenacious bacterial, a new infection-surveillance system at of infection-control practitioners, viral, fungal, and parasitic infections that NYU Langone Medical Center’s Tisch typically nurses with advanced degrees can readily incubate and spread among Hospital and the Hospital for Joint in public health. It’s painstaking, other patients if not aggressively countered. Diseases that leverages the booming time-consuming work that diverts Consequently, nosocomial infections are fields of big data and genomics. The resources away from other important among the nation’s leading causes of death, system combines classic shoe-leather tasks such as education, observation, killing an estimated 75,000 every year. epidemiology with advanced data mining and prevention planning, says Tania Simple measures such as improved and biomolecular analysis, allowing Bubb, RN, PhD, a researcher in sanitation can help, but the more complex scientists to source hospital pathogens infection control and prevention. In challenge is tracking infections in real at unprecedented speed. With the fact, one study found that nonelectronic time and tipping off healthcare providers ability to slice and dice vast amounts surveillance and analysis accounts for before pathogens spread. Most hospital of information culled from electronic an average of 45 percent of the total surveillance systems are geared toward medical records and hospital databases, time in infection prevention. identifying past infections. To flag potential and then interrogate pathogen samples in Under the new surveillance system, hospital outbreaks, they rely on human the lab with painstaking detail, scientists computers do the tedious work, beings to identify patterns in complex data at the Medical Center are challenging analyzing data in a fraction of the sets and on cumbersome rules. One such common assumptions about how time that it would take a human. At rule calls for a follow-up investigation only pathogens spread. NYU Langone, electronic surveillance after three infections appear within two Dr. Phillips recalls a case of two pivots around an open-source weeks on the same unit. “By the time you patients sharing a room who both tested software program called WHONET, figure out that the cluster has occurred, positive for the superbug methicillin- which was originally designed by weeks and months have gone by and your resistant Staphylococcus aureus, or researchers at Harvard University to opportunity for action has vanished,” says MRSA. On the surface, the infections help the World Health Organization Michael Phillips, MD, medical director looked like a simple instance of cross- track antibiotic-resistant microbes of Medical Epidemiology and Infection contamination, likely due to a lapse in in developing nations. WHONET’s Control at NYU Langone. hand washing. But a deeper look at the chief value is its ability to merge and Dr. Phillips has devoted his career to molecular profile of the MRSA samples manage large volumes of disparate studying the transmission of infectious indicated two unrelated bugs. Such data, from laboratory results to patient diseases, ranging from multidrug- information, revealed only through information. Researchers at NYU resistant bacteria to hepatitis C, and he savvy biomolecular sleuthing, radically Langone work closely with the Harvard is the Medical Center’s leading expert in redirected the investigation as well as developers to continually customize tracking the international stew of viruses hospital efforts to contain the infections. the software for the Medical Center’s and bacteria swirling around New evolving needs. York. He also assisted with the complex • • • WHONET alone cannot spot logistics of safeguarding staff and potential outbreaks, so the researchers patients from possible exposure to the The first step in any hospital surveillance rely on a second, complementary Ebola virus during Bellevue Hospital’s effort is to determine who might be software tool called SaTScan. “WHONET successful treatment of a physician carrying infectious pathogens on structures the data, SaTScan analyzes who had contracted the disease while their skin or in their gastrointestinal it,” explains Dr. Phillips, who first volunteering in Africa. tract. Since microbes can colonize a encountered the electronic tracking

NYU PHYSICIAN 20 SPRING 2015 system in 2004 during a Centers genetic differences within a single At a recent infectious diseases for Disease Control and Prevention gene or among a defined set of them, conference, Dr. Cloonan offered an early fellowship at the New York City Health allowing researchers to differentiate glimpse of strain typing’s potential at Department, where it was being used pathogenic microbes and determine NYU Langone. He described a case to flag signs of bioterrorism at city whether a bacterial strain in one patient study in which the Medical Center’s hospitals. “It really opened my eyes likely originated in another or in a electronic surveillance system had to newer, electronic ways of tracking source beyond the Medical Center. For identified a cluster of three infections infection,” he adds. more difficult cases, Dr. Shopsin’s team that would have been overlooked Together, the software systems may sequence and compare the entire otherwise. Dr. Shopsin’s team followed automatically comb through and set of genes, or the genome, of similar up by sequencing the genomes of all compare hundreds of electronic strains in collaboration with NYU’s three bacterial isolates, which were medical records, pharmacy records, Genome Technology Center. multidrug-resistant versions of an lab results, and other data, flagging potential clusters of infections that would be unlikely to occur by chance alone, such as three similar infections in the same unit within a few days, instead of a few weeks. “ The key is to get all of these data Churning through the neatly organized and automated so that the packaged WHONET data, SaTScan can track 15 kinds of nosocomial analysis and interpretation can be bacterial infections at lightning done by anyone. ” speed, grouping potential clusters of infection into low-, medium-, and high-risk categories. Sean Cloonan, MD, an instructor in the Division of Infectious Diseases and Immunology, Strain typing is a particularly important hospital pathogen called oversees this data analysis, then powerful technique in the fight against Pseudomonas aeruginosa. Fortunately, reviews the results. In high-density nosocomial infections. In 2011, a highly the results showed that all three strains cities like New York, where visitors virulent strain of KPC spread from one were unrelated. It was a false alarm. have introduced microbes from around patient to 17 others over a six-month As NYU Langone’s electronic the world, multiple strains of resistant period at the National Institutes of surveillance system becomes more superbugs like MRSA and Klebsiella Health Clinical Center in Bethesda, sensitive, Dr. Cloonan says, it will pneumoniae Carbapenemase, or KPC, Maryland, a premier research hospital. help inform critical decisions can appear nearly identical at first Strain typing eventually revealed that about whether and how to step up blush. So whenever the software and a lung transplant patient had passed containment precautions, such Dr. Cloonan’s analysis point out a the same KPC strain on to three other as isolating infected patients and suspicious cluster of cases, Dr. Shopsin patients, initiating a transmission chain requiring anyone who enters their and his team step in to determine if the that eventually killed six patients. The room to wear gown, gloves, and infections may be linked. vital information showing that the other personal protective equipment. Researchers rely on several tools and infections were linked finally helped Eventually, Dr. Shopsin adds, the techniques to do this job. One, known as the hospital contain the outbreak. As team hopes to set up a more highly an antibiogram, assesses the sensitivity part of its counteroffensive, the hospital automated process that can quickly of the swabbed microbes to a range physically separated infected patients and cheaply collect and analyze the of antibiotics. Identical sensitivity from others, tested every patient in the most relevant clinical data culled patterns between two bacteria of the hospital, and set up a strict protocol from patients’ lab tests and electronic same species might suggest a high that barred the sharing of most hospital medical records. “The key is to get all degree of relatedness and point to a equipment and staff between infected of these data organized and automated common source. Another tool is strain and noninfected patients to prevent the so that the analysis and interpretation typing. This technique identifies further spread of the microbe. can be done by anyone,” he says. • A WINDOW ONTO THE BRAIN

The unassuming roundworm captivates cell biologist Niels Ringstad, PhD, whose studies of the tiny worm are yielding surprising insights into psychiatric disorders and familial dysautonomia, a rare genetic condition among children.

BY NICOLE DYER PHOTOGRAPH BY JOHN CARNETT

NYU PHYSICIAN 22 SPRING 2015 Dr. Niels Ringstad uses fluorescence microscopy to illuminate genetically altered pathways in roundworms.

NYU PHYSICIAN SPRING 2015 23 HE DIRT-DWELLING ROUNDWORM is hardly the pinnacle of animal “A lot of people wonder evolution. A grain of sand could crush what the connection is between T its boneless body like a boulder. Its a little worm laying eggs and brain—if you can call it that—consists of a mere 302 neurons, about 100 billion shy of depressed humans.” the number in a human brain. It has neither heart nor lungs, and its lifespan is only nine days. Yet, after a decade of studying this modest creature— known formally as Caenorhabditis elegans, or C. elegans— Niels Ringstad, PhD, assistant professor of cell biology at NYU Langone Medical Center, believes he has only Much of Dr. Ringstad’s current work focuses on just begun to scratch the surface of its biochemical signals that govern serotonin, known for its salubrious complexity. For scientists, the worm’s outward effect on mood. In worms, however, the brain chemical simplicity is its greatest asset. Its translucency offers is better understood for its role in reproduction. “A lot a convenient window onto a compact nervous system, of people wonder what the connection is between a which functions, cell to cell, in much the same way little worm laying eggs and depressed humans,” says that ours does. Only instead of a chaotic universe of Dr. Ringstad, whose laboratory houses hundreds of 100 trillion cellular junctions, or synapses, it has just millions of roundworms. “It’s serotonin. It turns out 8,000, all of which have been neatly mapped. Perhaps that a lot of serotonin signaling in the human brain no organism has been more examined than C. elegans, is conserved over a billion years of evolution.” and yet there is so much more we can learn from it. Serotonin became a household word in the 1990s, This simple fact is the engine that propels Dr. when doctors began writing more than 2.5 million Ringstad’s research. Since opening his laboratory at annual prescriptions for Prozac, which boosts the Skirball Institute of Biomolecular Medicine in serotonin levels in the brain. It’s a remarkable 2009, when he joined NYU Langone, the scientist phenomenon, considering that so little is understood has spent countless hours peering into a microscope, about how serotonin actually influences mood. “For examining the neurons of C. elegans for clues to the more than 50 years, we’ve known that levels of cellular underpinnings of psychiatric disorders serotonin in the brain are correlated to mood,” says like depression and schizophrenia, for which there Dr. Ringstad. “But we still don’t know a lot about how are desperately few treatment options. His latest the brain regulates serotonin signaling. That’s what discoveries, including genetic mutations that disrupt motivates us to look at this very tiny organism.” the brain chemicals serotonin and dopamine, build on That simple question—How does serotonin work?— a body of work conducted as a postdoctoral researcher led Dr. Ringstad to an unexpected discovery that has at the Massachusetts Institute of Technology. There, taken his research in a new direction. In trying to he studied under the tutelage of H. Robert Horvitz, understand the tangle of signals that regulate serotonin PhD, a leading authority on C. elegans, who shared the and underlie so many psychiatric problems, he set Nobel Prize in Physiology or Medicine in 2002 for his upon a mysterious neuropeptide that binds to serotonin discovery of programmed cell death in C. elegans. neurons and shuts them down. The finding raised two Dr. Ringstad helped discover a new family of important questions: Where did the protein come from, chloride channels that open and close quickly, serving and what’s the purpose of an on/off switch for serotonin? as an express route to the nervous system. Such In a paper published in November 2013 in The Journal channels, if they exist in humans, could point to of Biological Chemistry, Dr. Ringstad and his colleagues novel treatments for neuropsychiatric conditions like describe a series of genetic experiments in which they addiction and mood disorders. “Dr. Ringstad is an trace the source of the protein to a set of novel sensory unusually impressive scientist,” says Dr. Horvitz. “He neurons, dubbed “BAG cells” because they have is hungry for knowledge, reads the literature avidly and structures that resemble big, floppy bags dangling off broadly, and is fearless, yet practical, in defining his the end of a long stalk. The cells cluster near the worm’s scientific vision and in incorporating new approaches nose, where they function as carbon dioxide detectors. and technologies into his experimental efforts.” Dr. Ringstad believes BAG cells may let worms sense

NYU PHYSICIAN 24 SPRING 2015 the carbon dioxide emissions of pathogenic bacteria. For the worm, carbon dioxide sensing is a lifesaving Too much carbon dioxide triggers the release of the adaptation. The question is whether a similar mechanism serotonin-blocking neuropeptide and shuts down egg could be at play in humans. Surprisingly, little is production. From an evolutionary perspective, the understood about how brain cells monitor carbon mechanism makes good sense. Why would a worm lay dioxide levels in the blood and help regulate breathing. eggs only to watch its offspring be killed by pathogens? “We think that this simple worm model can help us “As soon as our studies of simple behaviors in the understand how the nervous system monitors carbon worm led us to carbon dioxide–sensing neurons, we got dioxide and transduces it into a signal that the rest of completely captivated with the problem of how a neuron the nervous system can interpret,” says Dr. Ringstad. detects carbon dioxide,” Dr. Ringstad explains. “No one Lucy Norcliffe-Kaufmann, PhD, and her colleagues knows how this happens in mammals on a molecular at NYU Langone’s Dysautonomia Center confront this level, and we didn’t know how it happened in worms.” problem daily. The center is one of only two clinics in the The finding challenges the prevailing theory of world that treat familial dysautonomia, a rare genetic how brain cells detect carbon dioxide. When carbon condition that afflicts children. The disease impairs the dioxide reacts with water, it generates carbonic acid. body’s autonomic nervous system, including sensory The long-held belief is that neurons indirectly detect neurons that monitor carbon dioxide in the blood. “These carbon dioxide by detecting this acid. “People say, ‘Well, kids lose their ability to control blood-gas homeostasis,” neurons are acid sensitive. So the way that carbon explains Dr. Norcliffe-Kaufmann, assistant professor dioxide regulates any cell is by generating acid, ’” Dr. of neuroscience and physiology. “Many times, they lack Ringstad notes. “But what we found violates that dogma.” the drive to breathe, so carbon dioxide levels in their blood can get very high, and they can die in their sleep.” Dr. Ringstad and Dr. Norcliffe-Kaufmann are eager to learn whether any of the molecules and mechanisms that Dr. Ringstad’s laboratory uncovers might inform the work of the Dysautonomia Center. “Dr. Ringstad’s research is “ We think that this simple extremely important because for people with rare diseases, worm model can help us there aren’t many therapies,” says Dr. Norcliffe-Kaufmann. understand how the nervous “A discovery like this, which enables you to understand the properties of the nerve cells, gives you a chance to system monitors carbon think about new therapies that can enhance breathing.” dioxide and transduces it into Among the books that sparked Dr. Ringstad’s interest in biology were The Lives of a Cell and The Medusa and a signal that the rest of the the Snail by Lewis Thomas, MD, who served as dean of nervous system can interpret.” NYU School of Medicine from 1966 to 1969. Dr. Thomas’s award-winning books discussed basic biology through the lens of his clinical experiences. “I didn’t appreciate it at the time,” Dr. Ringstad acknowledges, “but when I think about those books now, I see the trajectory Dr. Ringstad’s research shows that BAG cells detect of basic knowledge turning into an understanding carbon dioxide directly. Again, this makes sense of how the world works, of changing the way people evolutionarily: If you huff and puff and generate a lot experience the world, and making the world better.” of carbon dioxide, at some point you will generate too Dr. Ringstad recalls that back then, he thought much acid, your blood pH will drop, and your entire cells were “cool little machines,” and he wanted to body will suffer. So the sooner your brain detects rising understand how they worked. That hasn’t changed carbon dioxide levels, the better. “It would be stupid much. He’s still captivated by the mysteries of the cell, to design a system that monitors the buildup of carbon and grateful for a tool as powerful as the roundworm dioxide but only sounds the alarm when levels become to explore them. “You realize that there are simple so catastrophically high that your blood pH starts to questions for which there are no satisfying answers,” fall,” explains Dr. Ringstad. “At that point, the house he says. “As basic scientists embedded in the medical is on fire, and you’re already in a world of pain.” community, our job is to run with those questions.” • AROUND CAMPUS

AT THE COLTON CENTER FOR AUTOIMMUNITY, THE MICROBIOME IS KEY The new center will explore how the vast collection of microbes living on and in us may trigger autoimmune disease. BY BRYN NELSON

BY SOME ESTIMATES, 50 million Americans suffer from lupus, rheumatoid arthritis, or one of the more than 80 other kinds of autoimmune disease identified so far. Although scientists have linked many of these diseases to genetic mutations, emerging research suggests that environmental factors may trigger much of the dysfunction that turns the body’s immune system against itself. A $10 million gift by philanthropists Judy and Stewart Colton to establish the Colton Center for Autoimmunity will allow researchers at NYU Langone Medical Center to explore whether a major culprit lies hidden within the human microbiome, the vast collection of microbes living on and in us. “The microbiome has opened a whole these largely unknown bacteria in and preventive strategies. new opportunity for discovery and for unprecedented numbers. The Colton family’s ties to the Medical addressing this question in ways that NYU Langone is a leader in Center date back to the 1960s. Judy’s we were never able to do,” says Steven microbiome research, and the uncle was eminent NYU Langone Abramson, MD, senior vice president Colton Center will bring together its surgeon Lester Breidenbach, MD, in and vice dean for education, faculty, immunologists, microbiologists, and whose honor they established a loan and academic affairs; chair of the rheumatologists to investigate how the fund for medical students, and Stewart Department of Medicine; and director microbiome interacts with specialized has been a long-time patient of Philip of the new center. T and B immune cells to provoke Moskowitz, MD, the Mamdouha S. Bobst Our gut-dwelling microbial residents autoimmunity. During its first phase, the Associate Professor of Internal Medicine. supply nutrients, help us digest food, Colton Center’s researchers will identify Previously, the Coltons also donated and regulate our metabolism. More and characterize the gut microbiome $1.5 million to support an asthma unexpectedly, some have been linked to in patients with rheumatoid arthritis, research program led by Joan Reibman, the maintenance of a healthy immune lupus, and antiphospholipid syndrome MD, director of the NYU-Bellevue system and to immune dysfunction (APS). During its second phase, the Asthma Clinic, in honor of a daughter-in- when disrupted. Faster, cheaper, and center’s scientists and physicians will law. Their latest gift again holds special more sophisticated molecular tools are focus on translating the new discoveries meaning because one of their sons has now allowing researchers to identify into badly needed diagnostics, therapies, battled a range of autoimmune diseases.

NYU PHYSICIAN 26 SPRING 2015 researchers better understand a concept called preautoimmunity. “In other words, “The microbiome when does the process start?” says Jill has opened a whole Buyon, MD, one of the Colton Center’s investigators and director of the Division new opportunity of Rheumatology and the Lupus Center for discovery and at NYU Langone. Some people, she says, have self-targeting antibodies circulating for addressing this in their blood that are characteristic of question in ways lupus or rheumatoid arthritis, yet they remain symptom free. that we were never “Our question is, can you find an able to do.” environmental factor in the microbiome that explains why people have circulating antibodies but no disease?” and Dr. Scher, his lab also found that a says Jose Scher, MD, assistant professor bacterial species called Prevotella copri is of medicine and director of the NYU disproportionately common in patients Microbiome Center for Rheumatology with newly acquired rheumatoid arthritis. and Autoimmunity. Dr. Scher will Could Prevotella and other microbes coordinate the Colton Center’s research activate specific T cells that promote with NYU Langone’s rheumatoid inflammation and provoke autoimmune arthritis patient population. disease? The Colton Center’s researchers One of the center’s main projects plan to look for them among a larger will be led by Dan Littman, MD, PhD, group of rheumatoid arthritis the Helen L. and Martin S. Kimmel patients using Dr. Buyon’s SAMPLE Professor of Molecular Immunology (Specimen and Matched Phenotype- “We’re pleased to be doing this, and and a Howard Hughes Medical Institute Linked Evaluation) biorepository we would love for it to nudge the field, investigator. Dr. Littman’s lab found for all patients with autoimmune or hopefully sooner rather than later,” that a gut microbe known as segmented rheumatologic diseases. Stewart Colton says. filamentous bacteria, or SFB, might shape Gregg Silverman, MD, professor As part of their donation to establish the immune system by influencing the of medicine and pathology, will lead the new Center for Autoimmunity, the development of specialized T cells. another main project. His team will Coltons have funded a professorship that In collaboration with Dr. Abramson examine how gut microbes might trigger will allow the recruitment of another autoimmunity in lupus and APS patients expert in autoimmunity and will through an abnormal activation of the continue the Colton Scholars program, immune system’s B cells. “We want to established three years ago to support characterize the fecal microbiome in the research of early career physician- at least 30 patients who have clinically scientists. “This gift not only allows defined lupus and APS, and compare very targeted, focused discovery, but it them to controls,” Dr. Buyon says. also creates a hub that people studying The researchers plan to compare the other diseases can interact with,” Dr. microbiome patterns in patients with Abramson says. Research at the center, differing disease severities and levels he explains, will help inform parallel of antibody production. Their findings investigations probing the potential links may identify the warning signs of a between the microbiome and diseases disease flare-up. Eventually, such such as inflammatory bowel disease microbiome-associated biomarkers and diabetes. of disease could let doctors intervene At its core, though, the autoimmunity before a troubled immune system

ILLUSTRATIONS BY ANDREA ROSSI BY ILLUSTRATIONS center will help NYU Langone becomes its own worst enemy. •

NYU PHYSICIAN SPRING 2015 27 FACULTY CONVERSATION

“Love Your Children” An Interview with Benard Dreyer, MD, President-Elect of the American Academy of Pediatrics By Anastasia Toufexis

FOR MORE THAN FOUR DECADES, of childhood,” recalls Dr. Dreyer. Now, as the earliest years, the figure is one in four. Benard Dreyer, MD, professor of pediatrics president-elect of the 63,000-member This has an impact not only on children, at NYU Langone Medical Center and American Academy of Pediatrics, he is set but on their families and the nation.” Dr. director of the Department of Pediatrics to become an ardent advocate for changes Dreyer recently shared his hopes for his at Bellevue Hospital Center, has tirelessly to policies that affect children’s health and tenure, as well as what he’s learned from tended to children. “At an early age, I just well-being. “One in five children in the U.S. his years of practice. fell in love with children and the magic lives in poverty,” he notes, “and for those in Why did you become a pediatrician? I remember when I was 12 or 13 visiting one of my cousins, a 4-year-old girl, and being amazed and intrigued by how her mind worked—her imagination and language, and the way she viewed the world around her. I suppose that is when I began to view childhood as the “magic years” and wanted to be part of it.

Some physicians start out wanting to be pediatricians, but they can’t bear to see children suffer. How do you deal with seeing children in distress? I know that I can ease their suffering and help their family, as well, because a pediatrician is not only a child’s doctor, but a family’s. I find that very fulfilling. You know, people tend to view pediatricians as soft and mushy. But in fact, in my opinion, we’re actually stronger and more rational than many other physicians. Pediatricians are very loving, but we also understand that children suffer and sometimes die.

It’s often said that children are not small adults. In what ways do children need a special kind of care? Well, there’s the size difference, so the same concentration of toxins—say, from breathing polluted air—is just more toxic to them. The diseases that afflict them are also different. For example, children tend

to have type 1 diabetes and adults type 2. BY SASHA NIALLA PHOTO

NYU PHYSICIAN 28 SPRING 2015 Pediatricians must To what extent are many childhood When your term as president of the American illnesses the product of poverty? Academy of Pediatrics begins, what do you “speak out in unison Almost all childhood problems, including hope to accomplish as your unique and lasting and declare that infant mortality, low birth weight, contribution? prematurity, and obesity, are related to My big focus will be trying to do something childhood poverty poverty. Moreover, many chronic diseases in early childhood to help poor kids. There is unacceptable.” are more frequent and more severe in are good studies that show that we know poor children. If you look at kids who get what to do. We’re just not doing it. The War admitted to the hospital with asthma, for on Poverty really worked. In the 1960s, But childhood is a stage of continual example, they’re almost never middle- childhood poverty dropped from 27 percent change, which, of course, complicates class children. Poor children often live to 14 percent. We just didn’t continue it. care. There’s this whole developmental in environments that are more toxic, and trajectory on top of whatever the problem their families are less educated, have Do you have specific goals you hope to meet is. Managing a child with diabetes is less access to healthcare, and have fewer while leading the academy? very different from an adult doing self- resources to manage chronic diseases. Yes, I’ve laid out five. First, to mobilize management. You’re working with a These children also have problems with pediatricians to speak out in unison family that has to manage the child. academic achievement. By the time low- and declare that childhood poverty is But as the child gets older, his or her income children get to school, they’re two unacceptable. Second, to form coalitions needs change. You involve the child to three years behind their middle-class with child advocacy organizations to more and more. Ultimately, the child is peers, on average. The first two years of promote change. Third, to advocate for the an adolescent who has to be taught to life are the most critical in terms of brain federal and state governments to better manage the disease herself. development—700 synapses form every fund programs, such as food stamps second, and the brain triples in size. and early childhood programs, which Which health issues affecting children Children reared in poverty are more likely have been shown to help. Without these concern you most? to drop out of high school and get into resources, instead of 20 percent of children One of the problems right now is parents trouble with drugs, alcohol, and crime. living in poverty, it would be 33 percent. choosing not to immunize their children. It’s I’d also love to see an expansion of tax the result of a number of things. The success As the birthplace of modern pediatrics, credits that affect children. A fourth goal is of vaccines means that today’s parents how does Bellevue enrich pediatrics there to enrich the education of medical students, don’t see many diseases. When I was a and at NYU Langone? residents, and fellows so that they gain a child, people were eager to get their kids These days we talk a lot about the more in-depth understanding of the social immunized for polio or measles or anything “medical home.” That’s a pediatric determinants of childhood health. Finally, because they saw the diseases. Now, we’ve concept invented in the early 1970s I’d like to see changes in the pediatrician’s pretty much eradicated those diseases, so that has now become very important in office, which is a great place to educate parents are not afraid of them. They’re more healthcare reform. It means you don’t people on becoming better parents. One afraid of the vaccines. Most of that is due to just see patients for specific complaints, national program I’d like to see expanded science illiteracy. Parents don’t understand you take care of all their problems— is Reach Out and Read. We give books to science enough to understand what science medical, educational, and social. It’s parents at every well child visit up to five shows us. We live in a society where there’s particularly important in managing years of age. Four million children are access to a lot of information, so parents feel chronic disease. We’ve employed that now getting books from pediatricians, empowered to make their own decisions. holistic model at Bellevue for many years, and studies show that it advances language That isn’t bad, but you can’t just pick and and NYU Langone will be expanding it development. choose what you want to believe. You have with the construction of the Hassenfeld to be able to tease out facts from emotions to Children's Hospital within the new After so many years in practice, what is your make sound decisions. The recent measles Kimmel Pavilion. The idea is to provide best advice? outbreak in Disneyland is a lesson we need access to medical staff virtually 24/7 for That’s simple! Love your children every day, to learn from. all the needs of the child and family. in every way. • FACULTY NEWS

unobstructed by histones, the proteins Dr. Danny Reinberg that help DNA spool into a tight coil. Is Elected to the He and his collaborators were also the first to sequence the complete National Academy genomes of two ant species as part of Sciences of a broader effort to understand the molecular machinery that turns genes on and off, and influences protein DANNY REINBERG, PHD, the Terry and expression. These so-called epigenetic Mel Karmazin Professor of Biochemistry changes, Dr. Reinberg’s lab has found, and Molecular Pharmacology and a account for many of the striking member of the Laura and Isaac Perlmutter differences in longevity and behavior Cancer Center, has been elected to the among different castes of ants. A queen prestigious National Academy of Sciences. ant, for example, can live for 25 years, Dr. Reinberg, who also is a Howard depending on its species, while Hughes Medical Institute investigator, a worker ant might die within 2 years. Sciences class of fellows in 2012. He has spent three decades studying how the Dr. Reinberg’s insights into was also elected into the Institute of constituents of chromatin—DNA, RNA, epigenetics hold promise for Medicine and has received an NIH Merit and protein—impact gene expression. therapeutics that could potentially Award and a Faculty Research Award Among his notable achievements, Dr. silence disease-causing genes from the American Cancer Society. He Reinberg has isolated the mechanism that and proteins. has authored or coauthored more than allows RNA polymerase II, the enzyme Dr. Reinberg was inducted into the 230 scientific papers and coedited an that transcribes genes, to move along DNA American Academy of Arts and authoritative textbook on epigenetics.

FEW RESEARCHERS HAVE DONE has tirelessly advocated for better Dr. Martin Blaser more to expose the dangers of antibiotic bacterial stewardship, bringing to light Makes Time overuse than Martin J. Blaser, MD, the the hidden ecosystem of bacteria that Muriel and George Singer Professor of maintains the health and balance of our Magazine’s List of Medicine and director of NYU Langone bodies. At a time when scientists were Most Influential Medical Center’s Human Microbiome calling for the eradication of Helicobacter Program. This year, in tribute to his pylori, a gut bacterium that causes peptic People pioneering research on the role of ulcers and gastric cancer, Dr. Blaser’s bacteria in human health and disease, research suggested that H. pylori prevents Time has named Dr. Blaser among its disease as well as causes it. Children top 100 most influential people. without H. pylori, he found, were more “Blaser’s work is a stunning dose likely to develop asthma, hay fever, or of reality in an environment flooded skin allergies. More recently, Dr. Blaser with corporate-agenda-fulfilling has shown how excessive antibiotic use in pseudoscience,” Congresswoman Louise childhood increases the risk of obesity and Slaughter, the lone microbiologist on type 2 diabetes, as well as inflammatory Capitol Hill, wrote in Time. Slaughter disorders such as type 1 diabetes, asthma, calls Dr. Blaser “an incredibly important psoriasis, and skin infections. voice” on the alarming rise of bacterial Dr. Blaser is a member of the Institute superbugs and the link between of Medicine, a fellow of the American antibiotics and modern plagues such as Academy of Arts and Sciences, and author obesity, asthma, allergies, and diabetes. of Missing Microbes: How the Overuse of

In the past three decades, Dr. Blaser Antibiotics Is Fueling Our Modern Plagues. • ANDREW NEARY BY PHOTO WEYMOUTH; BY MIKE PHOTO

NYU PHYSICIAN 30 SPRING 2015 OBITUARY

Joseph Herbert, MD

JOSEPH HERBERT, MD, 65, professor using whatever he thought would work. of neurology and founder and “He was very interested in patients and director of the Multiple Sclerosis (MS) their stories, very empathetic, and they Comprehensive Care Center at NYU responded to that,” says Dr. Kister. “He was Langone Medical Center, died January just very level with patients, and that’s how 2, at home surrounded by family, after a he was with colleagues and trainees.” 10-year battle with cancer. Born in South Africa, Dr. Herbert Beloved for his kindness and gentle immigrated with his family to Israel, manner, Dr. Herbert built the MS center where he graduated from the Hebrew over two decades. A model of patient- University Hadassah Medical School centered care, today the center provides in Jerusalem and served as a physician medical, nursing, physical therapy, and in the Israel Defense Forces. He psychosocial support for 2,500 MS moved to the United States to pursue a patients annually while maintaining an neuropathology fellowship at Harvard active and vigorous research program. Medical School and then took a research “He had a dream of a multidisciplinary position at Columbia University. His Joseph Herbert, MD MS center with everything under work on transthyretin, a transport one roof,” recalls Lisa Laing, RN, the protein produced in small amounts in center’s nurse coordinator. She began the brain’s choroid plexus, won him the working for Dr. Herbert 20 years 1986 S. Weir Mitchell Award for young ago, after he established an inpatient researchers from the American Academy neurorehabilitation unit at the Hospital of Neurology. for Joint Diseases, before it became part Even after becoming a full-time a member of the MSBase Scientific of NYU Langone Medical Center. clinician, Dr. Herbert never lost interest Leadership Group in 2012. Always interested in the social and in research. He received the Research Clinically, he focused on refining the emotional well-being of his patients, Dr. Award of the National Association use of FDA-approved MS treatments, Herbert asked how they spent their days of Rehabilitation Facilities for the and under his leadership, the center and taught staff to ask, says Laing. “I once study of desmopressin, or DDAVP, in participated in a wide variety of national had a patient tell me she watched TV or the management of nocturia in MS. and international multicenter clinical counted the tiles on the ceiling. When (DDAVP is the synthetic replacement trials of experimental treatments. you hear someone say that, you realize for vasopressin, the hormone that Only a handful of his colleagues and you need to do more than just take care of reduces urine production.) Recently, patients knew he was ill. Ten years ago, the immediate needs of MS—you need to he was engaged in implementing the he underwent successful treatment make referrals and get that patient out of MS Severity Score as a clinical tool, for colon cancer, but it returned at the the house.” investigating ethnic variability among five-year mark. “It meant that he was on Ilya Kister, MD, assistant professor of people with MS, and developing a new chemo almost all of the last five years,” neurology, who started with the center bedside disability scoring system for MS, Laing says. “He came to work with a port in 2006 as a fellow of Dr. Herbert’s, says, among other projects. and a chemo bag in an inside pocket. The “MS was not part of his initial focus, but A founding member of the New York patients never knew.” He continued to see he was encountering a lot of MS patients State MS Consortium in 1994, Dr. Herbert patients up until last July. on the wards. It’s one of the leading served on its executive finance and Dr. Herbert is survived by his wife, causes of disability in young people.” scientific review committees. In 2006, he Bette; their children, David, Shira, Always an innovator, Dr. Herbert tried joined the International MSBase Registry, Adina, Adam, Joshua, and Elana; and six various strategies, combining treatments, maintained in Australia, and became grandchildren. • —AUBIN TYLER END PAGE

Center for Technology and Economic Development convened a roundtable Preparing for at the NYU Accra campus last October. Our purpose was to identify what is needed to protect healthcare workers Ebola in Ghana and the public in Ghana, a nation BY SARI SOGHOIAN, MD without Ebola cases but where the risk is high. Since then, we have made progress. Donations of personal “EBOLA SHOULDN’T COME,” they stigma was his chief complaint. protective equipment from NYU, said. “If it comes, we will run away.” As I asked our head nurse how the staff Henry Schein, Inc., and the mining the clinical coordinator for emergency was doing. “We’re embarrassed,” company Newmont, for example, medicine at Korle Bu Teaching Hospital she replied. The fear was still there, have provided a measure of security in Accra, Ghana, a major hospital in but now also a deep sense of failure. and allowed us to conduct training West Africa, it was my job to mobilize I learned that day that emergency in donning and doffing procedures. our departmental response in advance preparedness with limited resources Innovations have appeared. We of a potential Ebola outbreak here. involves not only the technical wrap cloth blood-pressure cuffs in The task was overwhelming. We challenge of identifying and washable plastic covers, create hand- lacked space for individual patient managing potential cases, but also— washing stations out of garbage cans, isolation, equipment for personal and just as important—building mixing stronger bleach solutions. protection, reliable systems to support for staff to maintain their Staff volunteer to manage cases and investigate and monitor suspects, and professional ethics in the face of fear, give input on protocol design. staff who were willing to participate uncertainty, and personal risk. Of course, even with the crisis in training or the effort to organize. Many of our team members are waning, there is much work yet to The situation made everyone fearful, the sole breadwinners or primary be done. Staff needs more practical and for many, it was unthinkable caretakers for their families. None have training and oversight to solidify that we should manage a case. disability or life insurance. No hazard changes in infection-control practice. In the last week of July 2014, pay or facilities for self-quarantine Supply chains and financing for gloves, just after Nigeria reported its first were being offered. “I am a widow. I masks, and other materials must be Ebola case, we heard that a much- have two young children. What will developed. Interruptions in power and loved physician who recently happen to them if I get Ebola?” asked water are still routine, and 70 percent finished training at our hospital one nurse. Others expressed concerns of Accra’s population still has no access had died of the disease in Sierra about receiving care if they were to plumbing. We still have our fear. Leone. Suddenly the epidemic felt exposed. “Our experience is that we It will take considerable and very close to home, geographically come to work every day, but when long-term commitment to raise and emotionally. That evening, we we get sick, hospital management standards of hygiene in healthcare admitted a man for hematemesis doesn’t make any provision for us.” facilities and communities, build [vomiting blood] after several days These fears and a widespread sense mechanisms for better collaboration, of fever, diarrhea, and abdominal of demoralization were compounded and engage stakeholders in creating pain. The team on duty panicked. by an ongoing cholera epidemic that the needed local solutions. The Ebola Staff fled the male ward, abandoning overwhelmed the health system and epidemic crystallizes and provides all 10 patients there overnight. affected more than 20,000 patients an unprecedented opportunity to The next day, I asked the patient in the capital, Accra, alone from June support progress on these long- how he was doing. “I’m embarrassed,” to October 2014. “If we can’t handle standing issues of critical importance he said. We had isolated him in the cholera, how can we be prepared for to local and global health. • male ward pending Ebola test results, Ebola?” staff members asked. and no one wanted to enter the room. To address the epidemic, faculty from Sari Soghoian, MD, assistant professor of (The results turned out to be negative.) NYU’s Global Institute of Public Health, emergency medicine at NYU School of Medicine, He was still sick and in pain, but NYU School of Medicine, and NYU’s has been working in Ghana for three years.

NYU PHYSICIAN 32 SPRING 2015 he attended medical school, Dr. school, dedicated is also medical Harris attended he when student tutorial.Ascholarship surgical student to asecond-year teach now retired, continues he Though oncologist. surgical and professor SOM) (NYU Medicine of School NYU respected Dr. ahighly became Harris to me return to my residency.”convinced Dr. moment. a serendipitous Mulholland It was General. a U.S. Inspector Army was arrived—he of Surgery partment Langone’s of chair NYU De legendary MD, the Mulholland, H. John then “but mying residency,” says Dr. Harris, continu about doubts having was “I “home.”surgeon ended up bringing the talented young MD, also it but Harris, cy of Matthew interrupted the NYU/Bellevue residen C in a postwar Korea M.A.S.H. unit unit Korea M.A.S.H. in apostwar governmentompulsory service Changing - - - MATTHEW N. HARRIS, MD HARRIS, N. MATTHEW www.NYULMC.org

[email protected]. or 212-404-3653 at Affairs, Alumni and Development director, Van senior Marilyn Houten, of contact Office For of information, Medicine. more School NYU at programs other or scholarships to support gift planned to a with they physicians the be were meant become You, today’s help also too, students young can bright the World have earned.” they sure they have opportunities the it’s and to up of to funds, us make by lack are hampered students ified Says Dr. well-qual many “So Harris, Fund SOM. MD, NYU at Scholarship Harris, N. Matthew the to fund estate in their abequest rollover made and Frances, have contributed an IRA his wife, of six and grandfather This their educations. today’s complete to helping students Dr. Harriswithsome of histutorial students. -

Jon Simon Office of Communications and Marketing 550 First Avenue, New York, NY 10016