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One Park Avenue, 5th Floor MAGAZINE Chemicals vs. Kids New York, NY 10016 When a Transplant

Surgeon Becomes a Transplant Patient

The Science of Conversation

SPRING 2019

SEE A PATTERN HERE?

“ A single MRI can have 65 million pixels of information, and our research involves tens of thousands of imaging studies, so you can see how the data add up.” SEE P. 14

AI does, and it’s transforming medicine SPRING 2019 VIRTUAL URGENT CARE

OUR FUTURE It’s Easier Than Our Physicians, Your Schedule Appointments are available every day of the week: DEPENDS ON Ever to See an Monday through Friday 7AM–11PM Saturday to Sunday 8AM–8PM YOUR PRESENT NYU Langone Doctor. Conditions We Treat Virtual Urgent Care is ideal for non-emergency With Virtual Urgent Care, anyone five health issues such as: cold/flu, mild fever, allergies, Bequests and other planned gifts to NYU School of Medicine, both large and small, Whether you want to give back to support years of age or older can easily receive headaches, rashes, and urinary tract infections. have a resounding impact on our mission. scholarships or educational and research programs, our planned giving specialists will care and treatment from our doctors, help you make a meaningful gift that is right for you. We deeply appreciate the generosity Insurance is Accepted right from a mobile device, for a range of all who support our future. Aetna, UnitedHealthcare, Blue Cross Blue Shield, of non-emergency health issues. (800) 422-4483 or [email protected] or Cigna customers could be covered for the cost Contact us at of a co-pay. Get started today with the NYU Langone Heath app. nyulangone.org/virtualurgentcare A Pattern of Trailblazing

Message from the Dean and CEO

ten years ago, NYU Langone Health became the first healthcare insti- tution in New York City to implement “digital medicine” throughout its en- terprise when it rolled out Epic, a state-of-the-art electronic medical record system that has eliminated paper and enhanced vigilance. Nationwide, one in five medical professionals report that their own system has saved the life of one or more patients. But there’s certainly room for improvement. Each year in the US, an estimated 10 million medical errors occur, and as many as 12 million outpatients are misdiagnosed. As you’ll read in this issue, artificial intelligence, or AI, promises to rev- olutionize medicine by elevating the quality and safety of patient care. The more than 1 million medical records stored in NYU Langone’s database, when stripped of any identifying patient information, provide a rich trove for our clinicians and researchers, and a host of them are mining this data to make better, safer decisions (page 14). You’ll also learn about two impressive trailblazers. Robert Montgomery, MD, DPhil, director of NYU Langone’s Transplant Institute, has long been a pioneering surgeon, but recently he became a pioneering patient as well. Having established a protocol that enables transplant patients to accept organs from hepatitis C–positive donors, he became a recipient himself when he un- derwent a heart transplant last fall (page 26). Leonardo Trasande, MD, a pedi- atrician and epidemiologist, is spearheading several ambitious clinical studies to better understand the link between chronic exposure to everyday chemicals and childhood development (page 44). To borrow a phrase from the cover story, “See a pattern here?” I do. These articles and others in this issue remind us that our community is fortunate to have many innovative, exceptional people. In different ways, they are making their mark by advancing medicine and improving healthcare.

Robert I. Grossman, MD, Saul J. Farber Dean and CEO JULIANA THOMAS JULIANA

SPRING 2019 NYU LANGONE HEALTH ... 1 Contents

NEW YORK UNIVERSITY

William R. Berkley Chair, Board of Trustees

Andrew D. Hamilton, PhD President

NYU LANGONE HEALTH Kenneth G. Langone Chair, Board of Trustees

Robert I. Grossman, MD Saul J. Farber Dean and CEO Kathy Lewis Senior Vice President, Communications and Marketing

NYU LANGONE HEALTH MAGAZINE Steven B. Abramson, MD 10 Dafna Bar-Sagi, PhD Andrew W. Brotman, MD Synthetic biologists Editorial Advisors at GenomeFoundry@ISG seek to build a Nicole Dyer multicellular organism Director of Publications from the ground up, starting with baker’s yeast chromosomes. Thomas A. Ranieri David Sparrow Senior Editors

Larisa Manouilovitch Print Production Coordinator

Modus Operandi Design Art Direction Departments

01 Dean’s Letter 54 Post 64 Anatomy of a Leader A Pattern of Trailblazing NEW PEOPLE, PLACES, Life Lessons from Dafna AND PROJECTS Bar-Sagi, PhD, Senior Vice President and Vice Dean 04 Scope Faculty Conversation for Science, Chief Scientific NEWS FROM MEDICINE Benjamin G. Neel, MD, PhD, on Perlmutter Cancer Center Officer The fourth-year nail-biter earning elite comprehensive known as Match Day 04 status from the National A pro hockey player’s game- Cancer Institute 54 changing hip surgery 06 PLUS Singing mice may shed light on human conversation 08 Long Island’s newest medical school has $0 tuition 58 A novel antirejection protocol for face transplants 12 Smilow basement houses two unique research facilities 60

$75 million gift establishes CHRIS PAYNE TRENT BRAD Center for Blood Cancers 62

2 ... NYU LANGONE HEALTH SPRING 2019 Illustration by tktktktk 14 SEE A PATTERN HERE? Neither can your doctor. But artificially intelligent machines can, and their supervision is poised to radically transform medicine. BY DAVID FREEDMAN 36 Features IMMUNOTHERAPY FOR HIV At NYU School of Medicine, researchers are closing in on 26 a therapeutic vaccine that could one day yield a THE LIFE AND functional cure for a global DEATH AND LIFE epidemic. OF DR. ROBERT BY KAREN HOPKIN MONTGOMERY A pioneering transplant surgeon becomes a pioneering transplant patient. 44 BY KENNETH MILLER A PEDIATRICIAN’S CRUSADE AGAINST CHEMICAL SABOTEURS Dr. Leonardo Trasande is exposing the everyday chemicals that may cause children a lifetime of harm. BY BRYN NELSON CHRIS PAYNE TRENT BRAD

SPRING 2019 NYU LANGONE HEALTH ... 3 PHOTO CREDIT PHOTO

4 ... NYU LANGONE HEALTH SPRING 2019 NEWS@NYULANGONE a SPRING 2019

EMBRACING A FUTURE IN MEDICINE

FOR NYU SCHOOL OF MEDICINE student Kimberly Khouri, this year’s Match Day event on March 15—when fourth-year medical students nation- wide learn their residency placements—was doubly gratifying. She matched not only to the specialty of her choice, but also to a program she describes as “a dream come true.” This fall, she’ll assume one of three coveted res- idency spots in plastic surgery at Harvard Medical School, which serves Boston’s finest teaching hospitals. Khouri, who spent last July at Harvard for a subinternship, looks forward to the diversity of cases that makes the program “a mecca of medicine.” A first-generation American, she is a second-generation physician: her father, a plastic surgeon, is from Lebanon, and her mother, a dermatologist, is from Cuba. “I am extremely grateful to my parents, siblings, mentors, and friends who have supported me along the way,” says Khouri. “This is their dream come true, as well.” PHOTO CREDIT PHOTO

Photograph by Joshua Bright SPRING 2019 NYU LANGONE HEALTH ... 5 Scope

A Game-Changing Surgery Scores Big Stat When a hip injury jeopardized Madison Packer’s career as a pro hockey player, her team physician got her back on the ice and performing like a champion.

By Thomas Ranieri

Madison Packer has never been one important part of their identity, and to let obstacles get in her way. A for- they should stop playing on their own ward on the Metropolitan Riveters, terms, not because they’re forced out one of the four founding franchises of by an injury. “I felt that because Madi- the National Women’s Hockey League son was very fit and tremendously mo- (nwhl), she started playing hockey at tivated,” he says, “it was just a matter of age three, joining boys’ teams on which fixing a fixable problem.” she played until her freshman year of In June 2017, Dr. Gonzalez-Lomas high school. In her senior year, the performed arthroscopic surgery on Detroit native blew out her right knee. Packer’s right hip. Through two small Nevertheless, a year after reconstruc- incisions, he inserted pencil-size in- Number of surgeries tive surgery, as a freshman at the Uni- struments into the joint, reattached performed annually at NYU Langone versity of Wisconsin, she helped the the torn labrum to the pelvic socket, Health’s Sports Medicine Center. Badgers win the 2011 ncaa Women’s contoured the rim of the femur, and Ice Hockey Tournament. restored the seal around the joint. Packer started with the Riveters in “High-level athletes are able to play 2015, their first season. The following through a lot of pain,” he says, “so by season, an opponent caught Packer the time you operate on them, the re- from behind, causing her to fall awk- pairs are a little more complex. This wardly to her knees and tear the labrum was the case with Madison because she in her right hip. She finished the year, had played through her injury.” but when a cortisone shot failed to The day after surgery, Packer says ease her pain, Packer announced her she felt like a new person, and she retirement. The team’s head physician, began riding a stationary bike for two Guillem Gonzalez-Lomas, md, assis- hours a day—instead of the 30 min- tant professor of orthopedic surgery, utes her surgeon had prescribed. By reassured her, however, that her play- December, she was competing again. ing days might well continue. “The fixed hip feels better than the Dr. Gonzalez-Lomas is one of sever- other one,” she says. “I have a phenom- al physicians at NYU Langone Health’s enal surgeon.” Hockey Center in the Department of Dr. Gonzalez-Lomas told Packer Orthopedic Surgery. As part of NYU that, once again, she could play her Langone’s bustling Sports Medicine heart out. She did just that. In 2018, Center, the practice treats not only the Riveters won their first nwhl professional athletes, but also those championship, defeating the Buffa- who play recreationally, in youth lo Beauts in a dramatic 1–0 victory. leagues, and on college teams. Dr. Packer led the league in goals and was Gonzalez-Lomas was a hockey player named an MVP finalist. The Riveters himself during his school days. “He ap- tweeted a photo of her holding the preciates the mental side of the game,” Isobel Cup aloft, with the words: “Re- says Packer. Dr. Gonzalez-Lomas be- tirement is the last thing on Madison

lieves that for elite athletes, sport is an Packer’s mind.” (RIGHT); ISTOCK.COM/FEELLIFE MICHELLE JAY

6 ... NYU LANGONE HEALTH SPRING 2019 PHOTO CREDIT Illustration by tktktktk SPRING 2019

NYU HEALTH LANGONE surgeon at NYU Lan- A championonboth power andtenacity. gone, describes her professional levels, as “a bornleader— on andoff theice.” the collegiate and zalez-Lomas, her Dr. GuillemGon- Madison Packer is known for her

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7 Scope

Getting a Word in Edgewise An NYU School of Medicine study of duetting Alston’s singing mice reveals brain centers that can coordinate conversations with split-second precision.

By Bahar Gholipour

Waiting your turn in a conversation is Dr. Long says. Another area, called the not just polite—it’s an extreme exer- orofacial motor cortex, or omc, is the cise in timekeeping. It typically takes maestro orchestrating the mice’s con- only a fifth of a second, or about half as versational duets. When the research- long as a blink, for people to respond to ers slowed neural activity by mildly another speaker. Anything shorter, you cooling the omc, the mice produced are talking over someone. Anything a longer song. When the omc was longer, you risk creating an awkward turned off entirely, the animals started pause. “If you ever want to experience to sing over each other. it for yourself, try waiting a full second “This is the first demonstration in between conversational turns. It is of the brain mechanisms behind co- extremely painful,” says Michael Long, ordinated vocal turn-taking in any phd, associate professor of neurosci- mammal,” says Dr. Long, who is now ence and physiology at NYU Langone looking for similar mechanisms in Health’s Neuroscience Institute. humans. What he finds may offer a new However, awkward silences rarely happen, and in fact, we have often formulated our response before the other speaker finishes. Given the tight window for switching turns, it’s a wonder that people don’t interrupt each other more often. To find out what enables such precise turn-taking, Dr. Long has spent a long time listening to loud chirps of Alston’s singing mice. These musical creatures, native to Costa Rica’s cloud forest, sing to each other to announce themselves, entice mates, and negotiate territories. Bar- ring occasional blunders, the mice are greatly skilled at waiting for each other to finish before immediately respond- ing with their own song. “They’re quite considerate,” Dr. Long says. In a new study published in Science, Dr. Long and colleagues found that the mice divide the task load between two brain regions. One area produces the songs unique to each mouse. “It’s what allows them to get up on their hind legs and sing out who they are to the world: ‘I am Ralph the mouse,’ ”

8 ... NYU LANGONE HEALTH SPRING 2019 Illustration by Harry Campbell PHOTO CREDIT Photograph by each other for a while,” Dr. Longsays. much better when they have known “Even these mice can get in sync thing humanshonethrough practice. sational turn-taking isprobably some- is involved,” Dr. Longsays. step backandseejusthow muchskill tionally impressive act when we take a conversation every day, “it’s anexcep- an orchestra. Although we practice violin andperforming with others in another player, or learningto play the over the net and competing against between learningto hitatennis ball sophisticated clockwork. It’s theleap another layer complexity of to this ‘Mooondaaaay,’ ”Dr. Longsays. saying ‘Monday,’stead of they’d say ing brain surgery, slows speech.“In that, when cooledinpeopleundergo- have aninternal metronome: anarea 2016, Dr. Longfound humans,too, neurosurgeons that was publishedin slow motion.Inacollaboration with the area iscooled,the birds singin on asmallarea intheir brains; when thebirds’that thepaceof songsrelies Dr. Long and his colleagues showed cal prodigy, the zebra finch. In 2008, ratory hadfocused onanother musi tion in singing mice, Dr. Long’s labo muscles ona 20-millisecond timescale. trate over a hundred speech-involved one word, the brain needs to orches- just inconversations. To produce just central componentto speech,andnot language deficits. Precise timing is a problems inautismor stroke-related way understanding communication of Before studying social communica Just like any complex skill,conver Carrying onaconversation adds Devin Jarvis - - - - - medical school for all historic news: NYU Schoolof Medicinewould become, from that point on,atuition-free start of theirown journey to become physicians. Heshared theirjoy asthey heard some personal story to 102 incoming medical students whohadgathered to marktheformal whelming debt.” At last year’s White Coat Ceremony onAugust herecounted 16, his help aspiringdoctors fulfilltheirdesire to serve humanity, unencumbered by over impression, butalso shapedhisview that amedical school has“a moral obligation to Dean Grossman’s experience asanimpoverished student not onlyleft himwithalasting school, andultimately become theSaul J. Farber Dean and him assistance, enablinghimto complete hisundergraduate education, enroll inmedical in February, after obtaining employment oncampus. Inresponse, theuniversity granted had set himbackfinancially. Heexpressed hopethat hewould beableto repay thedebt “I donot think thiswillbepossible,” citinganumberof extenuating circumstances that semester. Writing to thedirector of financialaidinaletter shown here, heexplained that sum of hisdebt for tuition,anduntil itwas paidoff, he would not beable to begin the fall University inNew Orleans, theonlyamount that really mattered was $446.That was the a new home, $25,000. Butfor Robert I.Grossman, thenanundergraduate at Tulane In August theaverage 1968, cost of aloaf of bread was 22¢; anew car, $3,407; and in another’s life journey.” their careers orother aspects of theirlives. One person can make adramatic difference members looked on.“Everyone isconnected insome way to individualswhohave aided “No oneistrulyaself-made person,” hereminded thestudents, astheirfamily md students. In Debt andIndebted ARTIFACT SPRING 2019

NYU HEALTH LANGONE ceo of NYU Langone Health.

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9 Scope

Stat

The number of genetic experiments that can be run daily—with 100% accuracy—in the GenomeFoundry@ISG thanks to robots. That’s 10 times the number humans can handle.

Jef Boeke, PhD, (above) and Andrew Martin

10 ... NYU LANGONE HEALTH SPRING 2019 ã Modern Jobs By Nicole Dyer

Inside a DNA Factory At GenomeFoundry@ISG, researchers employ robots, computers, and their own brain power to reengineer genes.

We love to quiz kids on what they want to be when they grow up, but these days, it’s not exactly a fair question. By some estimates, up to 65% of grade-schoolers will ultimately have jobs that don’t exist today. How do young people prepare for a constantly evolving marketplace? “That’s a tough one,” says Jef Boeke, phd, director of the Institute for Systems Genetics at NYU Langone Health. Dr. Boeke himself is a pioneer in a field that barely existed two decades ago: synthetic biology, an emerging disci- pline employing industrial robots and computers (like the ones seen here) to reengineer dna in living organisms. The potential applications are vast—everything from manufacturing new medicine and producing biofuels to cleaning up hazardous waste and advancing our under- standing of genetics. But as a kid, Dr. Boeke had his heart set on becoming a scuba diver. “I read all the magazines, memorized the decompression tables, and even bought all the gear,” he recalls. So he was crushed when, in high school, he flunked an open-water certification exam because of a “tooth squeeze,” an excruciating toothache induced by pressure changes. “It was one of the great disappoint- ments of my life,” he says. He reoriented and, in college, gravitated toward bio- chemistry, where he began experimenting with chemical approaches to manipulating dna. Fast-forward to the present, and Dr. Boeke now belongs to an elite interna- tional corps of synthetic biologists (“engineers trapped in the bodies of geneticists,” as he says) working together to build a multicellular organism from the ground up, starting with the 16 chromosomes in baker’s yeast. In 2017, Dr. Boeke’s team graced the cover of Science with a historic package of papers documenting their progress: six fully reengineered yeast chromosomes so far. His state-of-the-art laboratory, called the Genome- Foundry@isg, wouldn’t run without Andrew Martin, a scientific technologist. Part lab manager, part MacGyver, Martin not only specs out all the rarified equipment need- ed to splice, dice, and analyze dna with factory-like effi- ciency, but he also serves as the resident troubleshooter. “People come to me all the time and ask, ‘Hey, can you fix this or that?’ ” says Martin. “I love it.” Beyond that, he finds the lab’s fast-paced progress thrilling. “Researchers used to be able to manipulate 1, 2, maybe 10 genes at a time,” Martin explains. “At the GenomeFoundry, they can work on thousands of genes at once. The robots free up scientists to use more of their brains and less of their hands.”

Photograph by Chris Payne SPRING 2019 NYU LANGONE HEALTH ... 11 Scope

The Mystery of the Missing Rejection Of the 40 face transplants performed worldwide since the procedure debuted in 2005, only two patients—both at NYU Langone Health— have yet to experience an acute rejection episode.

By Thomas Ranieri

In the months after 24-year-old Cam- “A light bulb went on,” says Dr. Gelb. eron Underwood of Yuba City, Cali- “We suspect that rituximab removes fornia, became the second person to some of the immunogenic cells from receive a face transplant at NYU Lan- the donor’s tissue. Adding that drug, gone Health early last year, something while slowly reducing the immuno- unexpected happened: nothing. Trans- suppressants used for maintenance, plant patients are at greatest risk for an may well account for our results.” acute rejection episode during the first Drs. Gelb and Rodriguez decided few months after surgery because the on the same protocol for Underwood, immune system may attack the donor’s but with a different rationale. “For Pat- tissue. The skin is highly immunogen- rick, our aim was to reduce the risk of ic—that is, likely to elicit an immune rejection,” notes Dr. Gelb, “but for response—so face transplant recipi- Cameron, it was to prevent rejection ents are believed to be even more sus- entirely. Our initial results were un- ceptible to acute rejection than recip- expected, but they drove our plan the ients of solid organs. But nearly a year second time around.” and a half after Underwood’s surgery, Dr. Gelb cautions that two success- he has yet to experience this problem. thymocyte globulin, a T cell–depleting The fates—and ful outcomes do not constitute proof The same is true for NYU Langone’s agent, prior to surgery to tamp down faces—of Cam- that rituximab is a game changer. But first face transplant patient, Patrick the immune system. Surprisingly, the eron Underwood “given that the previous rate of rejec- (above right) and Hardison, a firefighter from Mississip- regimen had failed to prevent acute re- his donor, Will tion was 100%,” he notes, “it’s excep- pi, whose surgery was performed four jection in even a single patient. So, in Fisher (above tionally promising.” years ago when he was 41 years old. 2015, when Patrick Hardison was pre- left), merged on The lifelong regimen of immu- A definitive explanation for why paring for surgery, Dr. Gelb, assistant January 5, 2018. nosuppressants prescribed for face both men have escaped the threat of professor of surgery, knew he had to try At right, portraits transplant patients is known to have tissue rejection is still unclear, but something different. Seeking a way to spanning from life-threatening risks, including ma- March 2017 to Eduardo D. Rodriguez, md, dds, chair delay rejection for at least one year, Dr. November 2018 lignancies, organ damage, and virulent of the Hansjörg Wyss Department of Gelb turned to another immunosup- chronicle Under- infections. The first recipient of a face Plastic Surgery, who led the surgi- pressant, rituximab, which is common- wood’s trans- transplant lived for 10 years, but Dr. cal teams for both face transplants, ly used in high-risk kidney transplants. formation after Gelb acknowledges that with so few and Bruce Gelb, md, director of the Unlike the T cell–killing agent, ritux- a self-inflicted cases performed, life expectancy can’t gunshot wound. transplant unit, who devised the an- imab also kills B cells, some of which really be estimated. What is known, tirejection protocol, have an intrigu- linger in the transplanted skin. “There however, is that preventing an acute ing hypothesis. If it’s confirmed, their was little downside to trying it,” Dr. rejection episode avoids high doses of novel approach to heading off acute Gelb recalls, “so we administered a the drugs needed to treat it. rejections could change the standard single dose to Patrick Hardison the day “We now know that face trans- of care for face transplant recipients after surgery.” plants are technologically possible,” everywhere and greatly improve these When Hardison went more than says Dr. Rodriguez, the Helen L. patients’ quality of life. two years without an acute rejection Kimmel Professor of Reconstructive Most face transplant recipients prior episode or even a spike in antibody Plastic Surgery. “What we hope for to Patrick Hardison had received a stan- levels, the doctors began to rethink at this point is that these patients can

dard combination of steroids and anti- what had happened—or didn’t happen. have longevity with their new faces.” (RIGHT) FAMILY OF THE UNDERWOOD (LEFT); COURTESY OF THE FISHER FAMILY COURTESY

12 ... NYU LANGONE HEALTH SPRING 2019 Photographs (right) by Mary Spano PHOTO CREDIT Illustration by tktktktk SPRING 2019

NYU HEALTH LANGONE

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13 An inside look at NYU Langone’s latest efforts to harness the pattern-seeking power of AI.

WHAT ARTIFICIAL INTELLIGENCE CAN SEE THAT WE CAN’T—AND HOW IT’S IMPROVING MEDICINE BY DAVID FREEDMAN ILLUSTRATIONS BY ANDY MARTIN

14 ... NYU LANGONE HEALTH SPRING 2019

“Delaying the start of cancer treatment is never good. Using AI, we will soon be able to instantly determine cancer subtypes and possibly the mutational profile to start targeted therapies sooner.”

ARISTOTELIS TSIRIGOS, PHD, ASSOCIATE PROFESSOR OF PATHOLOGY AT NYU LANGONE’S LAURA AND ISAAC PERLMUTTER CANCER CENTER

Even more remarkable, the Radiology and director of the Among the many reasons ai One day in 2017, computation- system has taught itself to iden- Center for Advanced Imaging projects are booming at NYU al biologist Aristotelis Tsirigos, tify specific genetic mutations Innovation and Research. Langone is that researchers ben- phd, strolled into the kitchen associated with lung cancer by ai is already helping gastroen- efit from the medical center’s near his office in NYU Langone analyzing pathology images terologists to spot hidden polyps trove of medical records stored Health’s molecular pathology lab alone—a process that ordinarily during colonoscopies, ophthal- in Epic, its electronic health re- to grab a cup of coffee, and met relies on expensive genetic tests mologists to diagnose retinal cords database. Stripped of any a new faculty member. When and can take weeks. “Delaying pathologies from eye scans, information that might reveal Dr. Tsirigos introduced himself the start of cancer treatment is and psychiatrists to identify patients’ identities, these re- as director of clinical informat- never good,” says Dr. Tsirigos, post-traumatic stress disorder cords, along with medical scans, ics, his new colleague, Narges associate professor of pathology from voice recordings. Some ex- pathology reports, and even Razavian, phd, perked up. She at NYU Langone’s Laura and perimental ai systems are scan- voice recordings, are now pow- was also a computer scientist, Isaac Perlmutter Cancer Center. ning electronic medical records ering numerous projects intend- albeit one with a slightly differ- “Using ai, we will soon be able and flagging undiagnosed con- ed to leverage neural networks ent focus. While Dr. Tsirigos was to instantly determine cancer ditions like heart failure and dia- for clinical good. Some look to applying genomic data to uncov- subtypes and possibly the mu- betes. Indeed, machine-learning be especially useful for diagnos- er some of the complex cellular tational profile to start targeted algorithms are now 150 times as tic screening, for prompting a processes underlying disease, therapies sooner.” fast as humans in finding signs closer look at cases when a sys- Dr. Razavian, assistant professor Last September, Dr. Tsirigos of stroke and other neurological tem’s decision is at odds with a of population health and of ra- and Dr. Razavian published their events in ct scans. clinician’s, and for flagging risks diology, was experimenting with work online in Nature Medi- What’s more, the machines and problems that sometimes ways to use artificial intelligence, cine. Their paper, along with will only get faster as developers fly under the radar. With com- or ai, in the clinic as a diagnos- hundreds of others published gain access to more clinical data. puters backing up clinicians tic tool. But like most research- in recent years chronicling the The so-called “neural networks” rather than replacing them, pa- ers at the intersection of ai and rapid ascent of ai in medicine, that power ai learn to make de- tients are likely to end up with medicine, her big challenge was signals a looming paradigm shift cisions autonomously by search- better diagnoses and treatment finding enough patient data to in which intelligent machines ing for patterns in vast pools of decisions, potentially at lower properly train her software to are poised to make healthcare data—the more data, the better. cost. “The system can support recognize the telltale markers safer and more efficient. It’s a Indeed, last February, the feder- what we do or help us pay more of pathology. As it happened, prospect that could dramatically al government launched a pro- attention to something we may pulling together large databases reduce the estimated 10 million gram called the American ai Ini- have overlooked,” says Leora of patient data was one of Dr. medical errors that occur every tiative to facilitate data sharing Horwitz, md, associate profes- Tsirigos’s specialties—and so a year in the us, all while mitigat- among federal agencies and uni- sor of population health and of fruitful partnership was born. ing harmful delays and unnec- versities. The hope is to spur the medicine, and director of the The result of that serendip- essary testing. “The partner- development of machine-learn- Center for Healthcare Innova- itous encounter is an exper- ship between human clinician ing software in the us to keep tion and Delivery Science, who imental ai program that can and machine can potentially be pace with ai advances in China, is helping to develop several ma- automatically diagnose two of remarkably richer than either where the absence of privacy chine-learning systems at NYU the most common types of lung one alone,” says Daniel K. Sod- laws gives the government un- Langone. “But we still have to cancer with 97% accuracy, a rate ickson, MD, phd, vice chair for hindered access to hundreds of rely on our experience and what that bests human pathologists. research in the Department of millions of medical records. we see in the patient.”

16 ... NYU LANGONE HEALTH SPRING 2019 THE MUSCLE BEHIND AI’S BRAINY INSIGHTS Meet NYU Langone’s New High-Performance Computers, Big Purple and Skynet.

rtificial intelligence is all well and good until it melts the computers. Just ask Daniel K. Sodickson, MD, PhD, vice chair for re- search in the Department of Radiology. He recalls the day one of his radiology projects churned through so many X-rays that it burned out multiple hard drives on NYU Langone Health’s old high-performance computer system. “We overworked it so much that the circuits actually started smoking,” Dr. Sodickson says. That problem is long gone. Last year, NYU Langone invested in two new, more powerful high-perfor- mance computing systems: Big Purple, which fuels AI projects like the lung cancer diagnosis algorithm of Aristotelis Tsirigos, PhD (see page 22); and Skynet for image-intensive radiology projects like Dr. Sodickson’s fastMRI collaboration with Facebook (see page 24). The two systems share physical space in a secure 5,500-square-foot data center with backup power and cooling systems in Piscataway, New Jersey. Both are configured to protect confidential patient data while crunching millions of data-hogging graphics. “A single MRI can have 65 million pixels of informa- tion, and our research involves tens of thousands of imaging studies, so you can see how the data add up,” says Yvonne Lui, MD, associate chair for artificial intelligence in the Department of Radiology. Big Purple is capable of 18 quadrillion floating point operations per second, or petaflops, and Skynet is close behind at 17 petaflops. While these numbers can’t compete with the 200-petaflop speed of Summit, the Department of Energy’s top-ranked supercomputer, both high- performance computers are among the fastest at any academic medical center, says Martin Ossowski, PhD, director of high-performance computing at NYU Langone. Skynet (a tongue-in-cheek nod to the humanity- hating AI in The Terminator) has already reduced the time required to train a typical neural network to per- form a complex task from days or weeks to hours. Big Purple, meanwhile, runs AI algorithms at roughly twice the speed of its predecessor while also supporting the non-AI work of more than 700 researchers across the institution. “Big Purple and Skynet are a quantum leap forward for NYU Langone,” says Dr. Sodickson. “Many AI projects we are doing now simply wouldn’t be pos- sible without them.”

SPRING 2019 NYU LANGONE HEALTH ... 17 3 BRAIN INJURIES

What happens to the brain after a concussion? AI may be the only way to find the answer.

oncussions are an ever- of Radiology. “But self-reporting that connect different parts of growing concern to those by concussion victims is almost the brain and nervous system, who suffer head trauma. by definition incomplete. Some- stands out in scans and, in many They’re also a concern to doc- times, all they can tell you is that cases, shows signs of alteration tors trying to determine if a hit they don’t remember what hap- after head trauma. By allowing to the head has actually resulted pened, but their head hurts.” the software to study the results in a concussion. Making a cor- What physicians need is a of some 200 research mri brain rect diagnosis is critical to keep- more quantitative measurement scans of patients who experi- ing the patient out of harm’s way of physical and metabolic chang- enced head trauma, along with long enough for them to recov- es in the brain after an impact, physicians’ determinations of er. “If the impact isn’t caught on explains Dr. Lui. It’s easy enough whether or not a concussion oc- camera or closely witnessed, we to scan the brain with a ct or curred, the software learned to have to rely on the patient’s own mri, but physicians don’t really find patterns in the white matter report and memory of the inci- know what to look for in the re- that seem to be associated with dent,” says YVONNE W. LUI, MD, sulting images. “Sometimes, the concussion. associate professor of radiology scan looks completely normal, When the program analyzed and associate chair for artificial even after someone’s head has the scans without the benefit of a intelligence in the Department bounced on the ground hard,” corresponding clinician diagno- she says. “If it’s a football player, sis, it arrived at the correct diag- he may end up back in the game nosis 87% of the time. “Because in the fourth quarter. But it’s of the uncertainties of diagnos- hard to believe nothing has hap- ing concussion, that’s as high pened to his brain.” More than 1.7 a rate of accuracy as we could individual scans into hundreds million Americans are diagnosed expect,” says Dr. Lui. of pieces, with each patch serv- with a concussion each year, but Beyond the potential clinical ing as a unique sample of white Dr. Lui suspects that many of benefits of her system, Dr. Lui matter. In this way, she could these traumas go undiagnosed, has applied an ingenious solution feed the system what equated leaving patients at risk for more to the perennial data shortage to more than 100,000 samples. serious damage. that hampers many ai projects. The approach seemed to work To provide a more quanti- Her project was limited to some well for concussions and may tative diagnostic technique, 200 scans of suspected concus- prove a useful strategy for other Dr. Lui collaborated with sions. That may sound like a lot, ai systems in medicine. “A lot of Yao Wang, phd, of the NYU but ai systems often require tens cutting-edge ai research in med- Tandon School of Engineer- of thousands of cases to build re- icine lacks access to, say, 50,000 ing, and they’ve developed liable accuracy. To get the most samples,” says Dr. Lui. “This an ai program that has out of the low number of sam- approach may be a way to get learned to detect changes ples, Dr. Lui took advantage of meaningful results from smaller in patches of white matter the fact that concussion damage data sets in some other imaging throughout the brain. to white matter is typically applications.” White matter, which is scattered throughout different Of course, any ai system is composed of nerve fibers parts of the brain. She divided only as good as the data it churns,

18 ... NYU LANGONE HEALTH SPRING 2019 3 BIOMEDICAL RESEARCH

What happens to the brain after Can a computer have a a concussion? AI may be the only “Eureka!” moment? way to find the answer.

nderstanding how “It’s become central to med- don’t know yet if it can actual- genes behave in dif- icine, even if you can’t see it ly make novel discoveries.” ferent cells and tissue walking through the hospital For now, basic-research types throughout the body corridors.” discoveries will have to be is breathtakingly complex, Whereas researchers were made the old-fashioned way, but it’s critically important to previously limited to investi- but programs like Moana can advancing our basic under- gating the impact of a single at least crunch through the standing of human biology. gene at a time on disease or mountains of data that those While basic-science re- development, Dr. Yanai’s work new discoveries will undoubt- searchers have become adept has allowed sifting through edly spawn. at identifying gene activity whole strings of genes to among large clusters of cells, pick out the most important pinpointing activity within in- patterns. “Not only can we dividual cells has always been look at all the genes,” he says, elusive. That is, until Moana “but we can track them to an tackled the challenge. individual cell to see which Moana is a machine-learn- particular genes are the most ing program that can infer the important.” gene behavior of a lone cell Machine learning is by churning through massive increasingly important to databases of gene-related advancing the field, insists Dr. data extracted from larger cell Yanai. “It’s becoming one of and Dr. Lui recognizes that her clusters. The system (named the keys to doing some of the own program must evolve as after the favorite movie most complex types of analy- quickly as the science. “I hope character of the daughter of sis on a ton of data,” he says. and expect that within five years one of the program’s devel- But he’s also quick to point or so, we’ll have a wholly differ- opers) recently emerged from out that the biggest promise ent way of diagnosing concus- NYU Langone’s Institute for of AI in basic research sion,” says Dr. Lui. When the Computational Medicine. The is still floating out field gets to that point, she adds, institute’s goal is to focus the there in the future. the next generation of ai systems power of advanced computing “What we’d like to like hers will be ready to step in on basic medical research do is integrate AI into and learn from more and better that’s becoming ever more the discovery pro- case examples. “I think these sys- dependent on enormous sets cess, but we don’t tems will be able to recognize not of gene and other data. “There know how to do only structural changes in the are amazing discoveries to be that yet,” he says. brain, but also metabolic chang- made in new large-scale data “Can it figure out es that are harder to detect,” she sets,” says ITAI YANAI, PHD, the something new says. “That could help take the institute’s inaugural director that we didn’t uncertainty out of diagnosing and professor of biochemistry even know to concussions.” and molecular pharmacology. look for? We 3 PTSD Hearing the signs of trauma in a patient’s voice

n the 1980s, as speech-rec- a way to apply machine learning ognition software began hit- to one of the thorniest diagnos- ting the market, psychiatrist tic challenges in modern psy- CHARLES R. MARMAR, MD, was chiatry: post-traumatic stress quick to adopt the technolo- disorder, or PTSD, a potentially gy. “I used one of the earliest debilitating psychiatric condi- consumer versions,” says Dr. tion affecting one in 13 adults Marmar, the Lucius N. Littauer in the US. In spite of its impact, Professor of Psychiatry and PTSD remains an elusive diag- chair of the Department of nosis. “Normally, it’s done by in- Psychiatry. terviewing patients and asking It’s no wonder, then, that Dr. about nightmares, flashbacks, Marmar would think of enlisting startle reactions, perceiving the voice-processing technology as world as dangerous, risk-taking behaviors, and being fearful of the future, among other indi- interviews. But seeing that niques to study a large number cations,” says Dr. Marmar. “But machine learning was making of features in samples from a because of the stigma of mental inroads into all sorts of diag- small number of subjects. In illness in much of the popula- nostic challenges, Dr. Marmar the end, their machine-learn- tion, many patients underre- considered the possibility that ing software highlighted 18 port symptoms. In a minority a machine-learning program vocal characteristics that of cases, they may dramatize could do the detection. helped distinguish between or fabricate them. Reliance on Dr. Marmar started re- people with or without PTSD, self-reported symptoms leaves searching the question and im- coming to the same diagnostic us prone to error.” mediately ran into a statistical conclusion as a clinician 89% Dr. Marmar knew that as dilemma. “Classically, you need of the time. far back as the 1800s, psychi- 10 subjects for each variable Eventually, a voice sample atrists had established that you examine,” he explains. “But as short as five minutes will patients suffering from depres- there are 40,000 variables in be needed to make a determi- sion tend to have recognizable speech, which means I’d need nation, and the sample could voice qualities. Since then, 400,000 speech samples.” be recorded on a smartphone. research has suggested that For his research, Dr. Marmar “Right now, a patient has to other psychiatric conditions, only had access to 150 voice spend 90 minutes with a psy- including PTSD, may carry samples from the US military chiatrist just for an initial intake with them unique vocal veterans who were serving as interview,” Dr. Marmar says. characteristics. De- research subjects. But help “This software could make tecting those traits came from the nonprofit re- the process less burdensome has always been a search group SRI International, to those patients.” While it matter of the cli- makers of the iPhone’s per- wouldn’t provide the final word nician’s subjective sonal assistant, Siri, which had on who does or doesn’t have perception in patient developed new analysis tech- PTSD, it could suggest which

20 ... NYU LANGONE HEALTH SPRING 2019 3 COLORECTAL CANCER Hearing the signs of A second set of eyes trauma in a patient’s voice for scoping out precancerous lesions

olonoscopies prevent thou- monitor image that Dr. Gross spot precancerous tissues in the sands of cancer deaths sees and draws boxes around stomach and esophagus, such as every year, but even the any parts of the image it deems those associated with Barrett’s most skilled gastroenterologists a potential lesion. “That focuses esophagus, a condition related can miss a potentially deadly my attention on a specific part of to reflux disease. “The software polyp growing flush against the the image, so I can take a closer will continue to improve and colon wall or nestled within its look,” he says. He also provides get better at dealing with nuanc- nooks and crannies. In fact, ac- feedback to help the company es in the appearance of lesions cording to one large study pub- improve its software. on different tissue surfaces,” he lished in 2017, one in eight suspi- Is the system spotting polyps says. “I think we’re just seeing cious growths are missed during that Dr. Gross might not have the tip of the iceberg in what ai the procedure. SETH GROSS, found himself, or that a differ- systems like this can do for us in MD, director of clinical care and ent practitioner might have this field.” quality in the Division of Gas- missed? To answer that ques- troenterology and Hepatology at tion, in June he will kick off the patients may be most in need NYU Langone, believes artificial first multicenter clinical trial of of a full diagnostic interview. intelligence may soon deliver a the system to compare the rate “It’s not meant to replace a powerful solution. “Some of at which precancerous polyps clinical interview,” explains Dr. these polyps can be very subtle are found with and without the Marmar. “But it could become in appearance,” notes Dr. Gross, ai software. Anything that leads an important element of the associate professor of medicine. to even a small improvement in diagnostic process.” In particu- “If ai can help us with a second polyp detection is well worth lar, he says, the program could set of eyes when we’re looking pursuing, he notes. “When we be ideal for screening large for them, that could save lives.” find and remove a precancerous populations that might be at Dr. Gross has long embraced polyp, we’ve just interrupted higher risk for PTSD, including new technology in his clinical one pathway to colon military personnel and first practice. He was among the cancer,” Dr. Gross responders. first gastroenterologists in the says. Dr. Marmar says that it’s country to use a 360-degree If the system possible his system or anoth- endoscope in clinical practice. proves helpful, says er one like it might eventually Recognizing the vast potential Dr. Gross, it will be expanded and modified to of ai to improve outcomes for likely be made screen for other psychiatric his patients, last year, he began available widely to disorders, including depres- using an experimental ma- the field in a com- sion, schizophrenia, and bipolar chine-learning program from a mercial version disorder. That could lead to Chinese company that’s trained within two years. an important improvement in on thousands of colonoscopy Along the way, he medicine’s ability to ensure images to distinguish between adds, it will proba- that patients who most need healthy and diseased colons. bly be extended to psychiatric help are seen by a During a colonoscopy, the soft- assist with endos- clinician. ware scans the same real-time copies intended to

SPRING 2019 NYU LANGONE HEALTH ... 21 3 LUNG CANCER

Giving pathologists supervision to diagnose lung cancer faster and more precisely

hen they decided to col- diagnosis often want reassur- common form of lung cancer, laborate on an ai project ance that their clinician has adenocarcinoma. That’s some- to diagnose lung cancer, made the right call. “A patient thing human pathologists could DR. ARISTOTELIS TSIRIGOS and may think their doctor is the never do from images. Identify- DR. NARGES RAZAVIAN both best in the world,” he says. “But ing these mutations is critical for understood it was impor- they know cancer is complex, determining the best course of tant to let physicians tell them and they often have some doubts treatment for this rapidly metas- where they needed help from ai, about what they’re hearing from tasizing cancer, but normally it not the other way around. “We the doctor.” The apprehension can be done only through dna needed to hear about the big is well founded. The National sequencing of a biopsy, a costly questions they want answered, Academy of Medicine estimates process that can take weeks. and what matters most to pa- that as many as 10% of patient What’s more, no one really tients,” says Dr. Tsirigos, asso- deaths can be attributed to mis- knows how the machine learned ciate professor of pathology at diagnosis, and false positives can this skill. “From our findings, it NYU Langone’s Laura and Isaac suggest that cancer is present seems the machine may be flag- Perlmutter Cancer Center. when it isn’t. ging subtle changes in a tumor’s What they heard back was The researchers thought that appearance,” says Dr. Tsirigos. that patients who get a cancer machine learning could provide “But, really, we have no idea physicians with another set of how it’s recognizing the muta- eyes, so to speak, to wring cor- tions.” Right now, the software rect diagnoses out of images. So isn’t always accurate in labeling they “trained” their ai system by the mutations, but if the accu- feeding it images to which pa- racy can be pushed to 90%, the thologists had already attached researchers plan to seek fda their diagnoses. This allowed approval to use the technology the system to determine which clinically and eventually adapt it sort of visual data in the image, to other types of cancer, such as such as texture, color, density, melanoma. and the distance between cells, Dr. Tsirigos estimates a three- tended to be associated with year time frame before some which diagnosis. version of the software rolls out Not only could their system in clinical use at NYU Langone distinguish between two of the and perhaps elsewhere, but he most common types of lung stresses that it will never serve cancer with 97% accuracy, but it as the sole source of diagnosis. was also able to correctly classify “The goal is to at least help the 83% of the tumors that patholo- doctors by providing a quick gists had misclassified. second opinion,” says Dr. Tsi- There was also a surprise: the rigos. “We can’t even imagine system taught itself to identify that the doctor would ever be out six mutations linked to the most of the loop.”

22 ... NYU LANGONE HEALTH SPRING 2019 3 MEDICAL RECORDS

Giving pathologists supervision Spotting hospital patients to diagnose lung cancer who require an extra faster and more precisely level of vigilance

ore than 90% of hospi- medical records and flag pa- fistula, they are at higher risk of tals in the US now rely tients who are at higher risk infection and clotting. With the on electronic medical for a range of conditions. One AI system, an alert could help records. Digitization offers system looks for the telltale clinicians decide to schedule a huge benefits: different care signs of potential heart failure, patient for dialysis before the providers within a system such as rapid heart rate and need becomes urgent, allowing can access the same patient weight gain from accumulating enough time to place a fistula. record, creating opportunities fluid. Then, it analyzes a list of Dr. Horwitz emphasizes to streamline care, and pa- the patient’s health challenges. that the unit’s efforts are not tients can review their medi- If heart failure isn’t on the list, intended to offload any re- cations and care plan. Indeed, the software flags that risk on sponsibilities from clinicians, electronic medical records the patient’s electronic medical but rather to augment their de- have been shown to reduce record. “Normally, heart failure cision making. “In the torrent costs and save lives. The is on the problem list for pa- of data that clinicians are ex- downside, however, for both tients who are at high risk for posed to today, it’s so easy for doctor and patient alike, is that the disease,” says Dr. Horwitz. something to be overlooked,” care providers increasingly find “But if the patient is new to our she explains. “We’re building themselves spending more system, the records may not systems that bring some of time facing their computer yet have transferred in, and that data to the top, so that cli- screen than their patients. clinicians may be focusing on nicians can do what they think LEORA HORWITZ, MD, and other, more immediate medical is appropriate with it.” her colleagues in the predic- issues.” Almost all patients at tive analytics unit at the Cen- risk for heart failure are eventu- ter for Healthcare Innovation ally identified by clinicians, she and Delivery Science see AI as notes, but the software pro- the perfect tool to help allevi- vides a second line of defense. ate that burden. At the same Another system scrutinizes time, it can perform tasks the medications, lab results, that are beyond the reach of and clinical history of hospi- human cognition, like find- talized patients with kidney ing hidden patterns in a sea disease to predict which ones of clinical records. “Patients are most likely to suffer kidney can have problems, whether failure and require immediate diagnosed or undiagnosed, dialysis. Under ordinary cir- that may seem small but cumstances, dialysis patients aren’t,” says Dr. Horwitz. “Our undergo a surgical procedure to AI system can help clinicians interconnect an artery and vein prioritize those problems.” in their arm, forming a strong The predictive analytics unit section of blood vessel, called a has already rolled out systems fistula, that can safely connect designed to comb through to a dialysis machine. Without a 3 IMAGING

Tapping Facebook’s burgeoning AI expertise to make MRIs speedier and more comfortable

few years ago, DANIEL Research (fair) unit. The result and associate chair for artificial SODICKSON, MD, PHD, is “fastmri,” an initiative that intelligence in the Department A received a message from promises to make mris far more of Radiology, envisioned a way to a colleague who suggested a convenient and accessible to apply ai to achieve those higher partnership with Facebook. His patients worldwide, and benefit speeds: capture less raw data associate was familiar with the NYU Langone patients before and use ai to fill in the gaps by research of FLORIAN KNOLL, the end of this year. inferring what’s missing. The ai PHD, assistant professor in the An mri machine transforms program knows how to flesh out Department of Radiology, who raw radio-signals generated the image in the same way you was using machine-learning by a magnetic field into sharp, might know how to fill in gaps in systems to dramatically reduce detailed images of water-filled an image of a traffic sign partial- the time it takes to capture an tissue and cartilage, includ- ly obscured by tree branches: by mri image. He said Facebook ing organs, that may not come relying on extensive familiarity was looking to support ai-relat- through clearly in an x-ray. The with the complete object. ed projects that would do some downside is that it requires a pa- To familiarize the program good in the world and thought tient to lie still inside a narrow with mri images, researchers it might be a good match, tube for 15 minutes to an hour. from NYU Langone and Face- recalls Dr. Sodickson, vice chair For many patients, especially book’s fair team fed the soft- for research in the Department children, the elderly, and people ware the images from the fully of Radiology. who are claustrophobic, anx- anonymized knee scans from That call led to an ongoing ious, or in discomfort, remaining 1,000 patient exams. Since each collaboration between NYU still for that long can be nearly scan generates multiple images, Langone’s Department of Ra- impossible. Some may require the total number of images pro- diology and the Facebook ai sedation, while others simply vided to the system topped 1.5 refuse to get an mri. The long million. Along with the images, imaging time also raises costs the program was also given by limiting the number of pa- snippets of the radio-signal tients who can be scanned in a data that generated them. The day—one reason many rural re- system then “learned” how the some truly top-notch experts gions can’t make mris broadly sharp, detailed images could be here at NYU Langone, but it’s available to patients. “Speeding derived from the fast-scan data. very difficult to stay on top of up mris can open them up Achieving the current speed-up every aspect of the burgeon- to new populations,” says Dr. of a factor of five involves taking ing ai field,” he says. “Besides Sodickson. only one-fifth as much raw signal helping to design and run the Early on, he and his col- data, yet the software fills in the process of ‘training’ the system leagues, including Michael P. gaps so well that radiologists to fill in the missing data in the Recht, md, the Louis Marx can’t tell the results apart from images, Facebook’s experts also Professor of Radiology and chair those of full scans. hunted down advances in ai al- of the Department of Radiol- Facebook’s fair group has gorithms for other applications ogy, and Yvonne W. Lui, md, been essential to the effort, that helped improve the results.” associate professor of radiology notes Dr. Sodickson. “We have (Facebook provided assistance 3 HEARING

Tapping Facebook’s burgeoning Making things clear AI expertise to make MRIs with cochlear implants speedier and more comfortable

n 2015, SUSAN WALTZMAN, a standardized, objective getting a new implant, the new PHD, and colleagues invit- method, and patients may approach has cut the number ed a physician-scientist not always end up with the of required readjustment from Belgium to speak at an desired result,” Dr. Waltzman visits in the first year by more NYU Langone conference says. In addition, patients who than half. on programming cochlear receive an implant can return Dr. Waltzman expects the implants. Dr. Waltzman, 10 times or more in the first new process to become widely codirector of the Cochlear year for adjustments. available late this year, adding Implant Center, wanted to To reduce that burden, Dr. that the NYU Cochlear Im- hear more about AI-based Waltzman and colleagues em- plant Center is already making software the Belgian group barked on a multicenter clin- it available to cochlear im- had developed to make the ical trial of the new AI-based plant patients outside the trial devices easier to tune. technique. In this study of 100 who have not done as well as The researchers were patients, an AI program ties expected with their implants. struck by what they heard. into the implant to monitor “We’ve been using the same “We were all impressed by the signals received by the au- approach for more than 30 the potential for this technol- ditory nerve. Based on a large years,” she says. “It’s very ex- ogy to dramatically improve database of information from citing to be able to offer better programming methods,” says previous cochlear implant outcomes, a better patient Dr. Waltzman, the Marica F. patients, the software knows experience, and fewer visits to Vilcek Professor of Otolar- what the optimal received the center.” yngology–Head and Neck signals should be to Surgery. produce the ideal result More than 40,000 adults for a given patient. The and 25,000 children in the AI software autoadjusts US have cochlear implants. the way the implant The device picks up sounds converts sounds to and transmits them as elec- signals until it achieves with no expectation that the trical signals to implanted the best match. company would benefit, or that electrodes that stimulate the The trial started in NYU Langone would share any auditory nerve in the inner early 2018 and will end identifiable patient data.) ear. Because the damage this September. Dr. The ai-enhanced mris Dr. to the auditory nerve varies Waltzman points out Sodickson and his colleagues from person to person, every that among patients in hope to roll out this year are five cochlear implant must be the trial who previously times faster than current con- individually programmed to experienced the con- ventional mris, but he says the provide the best outcome. To ventional implant-tun- fastmri team hopes to eventually do that, an audiologist usually ing procedure, more improve the scanning speed by tries different settings on the than three-quarters a factor of 10. “Our progress has implant, noting the patient’s reported preferring the been steady,” he says. response. “There hasn’t been technique. For patients

SPRING 2019 NYU LANGONE HEALTH ... 25 Life of Dr. Robert Montgomery

A pioneering transplant surgeon becomes a pioneering transplant patient.

BY KENNETH MILLER PHOTOGRAPHS BY BRAD TRENT

26 ... NYU LANGONE HEALTH SPRING 2019 PHOTO CREDIT Illustration by tktktktk SPRING 2019

NYU HEALTH LANGONE fatal withoutaheart a rare, progressive in hisfielddespite Montgomery, MD, became a pioneer became apioneer cardiac condition that would prove surgeon Robert transplant. Transplant

...

27 One night in September 2018, transplant surgeon worried Italian ER doctors. In New York, Dr. Montgomery met with the heads of Dr. Robert NYU Langone’s heart transplant team: Nader Moazami, md, surgical director of heart transplantation and mechanical circulatory support, and professor of cardiothoracic surgery; Montgomery and Alex Reyentovich, md, medical director of the Heart Transplant Program and associate professor of medicine. Until recently, neither had known that their boss had a disor- der that might make him their patient. Dr. Montgomery suf- died. fered from familial dilated cardiomyopathy, a rare, progres- sive disease of the heart muscle that weakens its pumping ability and causes dangerous arrhythmias. He’d managed to become a renowned kidney transplant surgeon nonetheless, keeping his illness at bay with medications, electronic im- plants, and sheer willpower. Yet, over the past year, a string of terrifying incidents, of which this was only the latest, had shown that he would need more to survive. “We all agreed he was in serious trouble,” Dr. Moazami recalls. Again. Although his life-threatening symptoms qualified him for priority status on the transplant list, Dr. Montgomery knew He was sitting on a hotel bed in Matera, Italy, where he had how difficult it could be to get a new heart. His uncommon traveled for a medical conference, and was about to get un- size (six feet one) and in-demand blood type (O) made him dressed when the palpitations hit. He shouted to his wife, a tough match. Moreover, as with every other organ, there who ran in from the bathroom just as his face hit the stone simply weren’t enough to go around. In 2018, some 114,000 floor, blood spraying from a gash in his cheek. His heart Americans needed an organ transplant, but only 36,500 re- stopped. Then, after 60 long seconds, the cardiac defibrilla- ceived one; each day, an average of 20 patients died while tor implanted in his chest delivered the shock that brought waiting. About 4,000 people were desperate for a heart, but him back to life. fewer than half that many hearts became available. Dr. Montgomery’s wife, Denyce Graves, struggled to Under Dr. Montgomery’s leadership, however, the keep her own heart rate in check as she helped him back Transplant Institute has been pioneering innovative proto- to bed and pressed a washcloth to his wound. This was cols aimed at improving those numbers. Among the most not the first time the 58-year-old professor of surgery and promising is the use of organs infected with hepatitis C director of NYU Langone Health’s Transplant Institute had (hcv). The deadly virus, carried by an estimated 3.2 million died and been revived; he’d endured several such episodes Americans, attacks the liver, typically causing no symptoms during the past three decades. But it happened again as until the damage is severe. New antiviral medications, in- the couple waited for an ambulance, and twice more at troduced over the past five years, have made hcv curable the tiny local hospital. The staff there, he quickly realized, in up to 98% of cases, without the grueling side effects of were ill equipped to treat his condition. The next morn- older, less effective drugs. If the virus is detected early, ing—against medical advice—he signed himself out and these newer therapies can often eliminate the need for a flew home with his wife and a physician friend, who carried liver transplant. A growing body of research suggests that syringes full of resuscitation medications supplied by the they can also make it safe to transplant organs of all types

28 ... NYU LANGONE HEALTH SPRING 2019 PHOTO CREDIT Illustration by tktktktk SPRING 2019

NYU HEALTH LANGONE transplant surgeon surgeon Dr. Nader with hisboss and Heart transplantHeart Moazami (right) patient, fellow Montgomery.

Dr. Robert ...

29

As a young boy growing up in Philadelphia, slow to read and wildly energetic, Montgomery’s heedless behavior got him kicked out of parochial school. “The nuns used to say, ‘Bobby doesn’t believe the rules apply to him,’ ” he recalls.

obert montgomery’s comfort with risk emerged early, but it took a tragedy to harness it for a larger pur- pose. As a young boy growing up in Philadel- phia, slow to read and wildly energetic, his heedless behavior got him kicked out of pa- rochial school. “The nuns used to say, ‘Bobby doesn’t believe the rules apply to him,’ ” he recalls. Then, when he was 13, his father, a mechanical engineer in the aerospace indus- try, was diagnosed with cardiomyopathy, which doctors mistakenly attributed to a viral infection. His condition deteriorated rapidly, and he suffered three cardiac arrests over the next two years. The last one left him in a chronic vegetative state for several months before his death, at 52. A progressive cardiac condition affected three of the four Montgomery brothers. With his three older brothers away at col- From left to right: Lawrence had a heart transplant in 1996 at age 39; Richard suc- lege and his mother reeling from the loss, cumbed to the disease in 1987 at age 35; Robert, now 59, received a heart transplant in January; and John, now 69, is unaffected. Far right: Dr. Montgomery, age 8. 16-year-old Bobby had to grow up quickly. He discovered a passion for medical science, particularly organ transplantation—fueled, in from hcv+ donors. part, by frustration over his father’s inability to obtain a new Because hcv is most commonly transmitted through heart. (At the time, 50 was considered too old to qualify.) shared needles, using these organs may be one way for During his premed studies at St. Lawrence University, he some good to come out of America’s devastating opioid spent a summer doing aid work in Africa. After graduation, epidemic, which killed more than 49,000 overdose victims he returned to the continent on a fellowship to study the in 2017. Almost 1,500 hcv+ organs were transplanted last interface between Western and traditional medicine. The year—triple the number for 2013. Still, they constituted close personal bonds between African healers and their pa- just 4% of total transplants, and most were implanted in tients would inform his own approach to doctoring. “He’s people who were already hcv+. (Overdose-death donors as incredibly caring toward his patients,” says Brigitte Sulli- a whole now account for over 13% of solid organ transplants, van, executive director of the Transplant Institute. up from 1% in 2000.) Only a handful of transplant programs He went on to medical school at the University of Roch- have adopted them, and many potential recipients remain ester, and then to Johns Hopkins for his residency. One unwilling to accept them. As a result, more than 40% of night during his internship, he received a call from his sis- donated hcv+ organs are discarded. ter-in-law: one of his older brothers had died of cardiac Dr. Montgomery, for his part, had no hesitation. As he arrest at 35 while waterskiing. Suspecting that an inherit- often told his patients, any transplant requires weighing the ed disorder was the culprit, Dr. Montgomery sent tissue risks against the potential rewards. “I’ll take any heart you samples from his brother’s and father’s hearts to his old can find,” he told his team. “I don’t care if the donor has a pathology professor, who confirmed his fears. He decided

needle in their arm.” to undergo tests himself. On the treadmill, his heartbeat FAMILY OF THE MONTGOMERY COURTESY IMAGES VIA GETTY SUN/MCT PERNA/BALTIMORE ALGERINA

30 ... NYU LANGONE HEALTH SPRING 2019 In 24 Hours, One Life Lost, Another Saved SEPTEMBER 20-21, 2018

THURSDAY 3:35 am 4:00 am 7:45 am 9:57 am 11:12 am 12:35 pm

Transplant surgeon Dr. Moazami notifies Dr. Montgomery is Dr. Moazami and Dr. Kon removes the donor Dr. Nader Moazami his patient, Dr. Robert prepped in OR #8 in fellow surgeon Deane heart and places it in a sterile receives word that a Montgomery, that a the Kimmel Pavilion, Smith, MD, make the plastic bag containing a preser- donor heart is available compatible donor has just across from the first incision and start vative solution that will keep it from an overdose victim been found for him. Transplant surgeon Zachary Kon, MD, OR in which he himself removing the tangle of viable for the next six hours. in their 20s. takes a chartered plane from Teterboro performs surgery. wires and capacitors Airport in New Jersey to a neighboring from Dr. Montgomery’s state to procure the donor heart. old implants.

went wild, and he almost passed out. So, in 1989, Dr. Montgomery became the first practicing surgeon in the world to re- ceive an implantable cardiac defibrillator—a device that had just been developed at Johns Hopkins. In those days, the procedure re- quired open-heart surgery. A generator the size of a soda can was placed in his abdomen, powering a pair of large capacitors attached to the outside of his heart. The apparatus made it painful to wear a belt—but worse, it threatened to dash his dreams of becoming a transplant surgeon. (He’d decided to focus on abdominal organs, because heart sur- geons of that era typically performed trans- plants only as a sideline.) “We’d like you to take a few years off and do some research,” his chair of surgery told him. “Let’s see how Dr. Montgomery, in 2009, speaking with family members of a patient who this thing progresses.” underwent kidney surgery at the Johns Hopkins Transplant Center in Baltimore, Maryland. As the center’s director, he gained a reputation for With his pregnant first wife, Dr. Mont- his trailblazing efforts to get more organs to people who needed them. gomery set off for the University of Oxford to pursue a doctorate in molecular immu- nology. Soon after arriving, he heard a crash outside his the first laparoscopic kidney procurement technique. The apartment. Running to the street, he found a car turned innovation made recovery easier for donors, facilitating do- upside-down with a baby strapped inside and a woman nations of live-donor kidneys, which last much longer than screaming on the pavement. He climbed in through the those from cadavers. By 2003, he’d become director of the window and extricated the baby. Then, he felt a blow like transplant program at Johns Hopkins, where he gained a a baseball bat slamming against his chest as his defibrillator reputation as a trailblazer in efforts to get more organs to discharged, triggered by his racing heartbeat. people who needed them. At that moment, he realized that he could never resume One of his innovations was the “domino” kidney trans- his surgical career, in which steadiness under pressure was plant, which occurs when several people who need trans- the most basic job requirement, unless he learned to con- plants have friends or relatives who are willing to donate trol his response to stress. “I had to completely remodel my but aren’t compatible; a chain of surgeries is arranged in brain and not allow my body to react,” he explains. Like a which each would-be donor is matched with a compatible self-taught Zen master, he began to monitor his emotions recipient, with “altruistic” donors, who are willing to give and his flow of adrenaline, forcing himself to grow calmer a kidney to anyone, filling in the gaps. An eight-way swap as a situation grew more challenging. in 2010 landed Dr. Montgomery in the Guinness Book of In 1992, having earned his doctorate, Dr. Montgomery World Records. He also helped develop a protocol combin- returned to Johns Hopkins and was cleared to finish his ing kidney and bone marrow transplants to prevent rejec- training in general surgery and later in multiorgan transplan- tion of donor organs in immune-incompatible patients and

COURTESY OF THE MONTGOMERY FAMILY OF THE MONTGOMERY COURTESY IMAGES VIA GETTY SUN/MCT PERNA/BALTIMORE ALGERINA tation. During his surgical fellowship, he helped develop eliminate the need for immunosuppressive therapy. He was

SPRING 2019 NYU LANGONE HEALTH ... 31 FRIDAY 2:00 pm 2:08 pm 2:26 pm 2:46 pm 4:01 pm 6:27 pm 2:30 pm

Dr. Kon returns to Teterboro Airport, and Dr. Kon delivers Dr. Moazami shocks the new heart Dr. Montgomery Dr. Montgomery leaves his then takes an ambulance to NYU Langone. the donor heart to make it start beating again. recovers in the cardiac hospital bed, assisted by his to the OR. intensive care unit. wife Denyce Graves. He becomes one of 35 patients at NYU Langone—and one of The surgeons place Dr. Montgomery on Dr. Moazami places 3,408 people a heart-lung bypass machine and begin the donor heart in in the US—to receive a removing his diseased heart. Dr. Montgomery’s chest heart transplant and starts connecting it in 2018. to his circulatory system.

also among the first transplant surgeons to promote the day he was diagnosed, he’d been determined to prove that idea of using hcv+ organs, after the new generation of an- his illness could not defeat him. Yet, he’d never known tivirals proved capable of quickly clearing the virus. when the next crisis would hit. His antiarrhythmia medica- Recruited to NYU Langone in March 2016 to found the tion had ruined his thyroid. His defibrillator’s batteries Transplant Institute, Dr. Montgomery (along with Brigitte needed replacing every few years, requiring major surgery. Sullivan, who accompanied him from Johns Hopkins as ex- When the leads wore out, they began triggering shocks ecutive director) brought together transplant specialists from whenever he lifted his kids. He’d eventually gotten a small- all disciplines under one roof, enabling them to pool skills er, more modern device installed, but much of the old hard- and insights without the territorial barriers found at many ware remained in his chest. institutions. A slew of new hires from across the country To defy his disease, Dr. Montgomery had taken up stren- enhanced the institute’s capabilities. The kidney transplant uous pastimes in exotic places—bow hunting in Argentina, program soon added a pediatric group. Dr. Moazami, who fly-fishing in Tanzania. Even there, however, escape was only formerly headed the heart transplant program at the Cleve- provisional. In 2012, researchers supported by his family’s land Clinic, where he helped develop a range of novel sur- charitable foundation had isolated the genetic mutation re- gical and device-based approaches to heart failure, led NYU sponsible for his type of cardiomyopathy. Dr. Montgomery’s Langone’s first heart transplant procedure in January 2018. older son and daughter, as well as his late brother’s two daugh- The institute’s first lung transplant followed just weeks later, ters, proved to have it, and all were implanted with defibril- and its first pancreas transplant some months after that. lators. (Another brother had already undergone a heart trans- Dr. Montgomery also launched several initiatives to plant and is still healthy at 62; the remaining brother is not identify potential donors more swiftly and to ensure that affected.) Later that year, Dr. Montgomery was on a mountain potentially viable organs often rejected for transplantation in the Andes when his defibrillator went off, knocking him didn’t go to waste (including those infected with hcv or facedown in the snow. His son helped him hike to safety. hiv). Within two years of his arrival, NYU Langone had From that point on, he rode in the jeep instead of climbing, increased the number of organ transplants from fewer than but he refused to give up his adventurous trips. “I had to set 50 to more than 280. Its heart transplant rate, or the number an example for the rest of the family,” he says. “I wanted them of transplants each year divided by the number of patients to know you could have this and still live a full life.” on the waiting list, was five times the average for the New But his resistance had begun to fail. In 2017, back in Ar- York region. Its wait times for all organs was the shortest— gentina, he contracted a drug-resistant strain of pneumonia. an average of 36.3 days for a heart, versus 66.1 across the Near death, he was placed on a ventilator. Luis Angel, md, metropolitan area. professor of medicine and of cardiothoracic surgery, and However, when Dr. Montgomery went on the waiting medical director of the Lung Transplant Program, flew down list in September 2018, those statistics were scant comfort. and rushed him to NYU Langone, where he spent weeks No one could say whether he would survive long enough to recovering. That October, he went into cardiac arrest while benefit from his own breakthroughs. watching a Broadway show with his family. This time, his implanted device initially failed, and he needed prolonged cpr before he came back to life. Afterward, his defibrillator s dr. montgomery waited in a patient room at was modified to administer a stronger shock, and he was the Helen L. and Martin S. Kimmel Pavilion, teth- fitted with a pacemaker. Then came the incident in Italy. ered to vital signs monitors, he had time to reflect on Now, here he was, yearning for a reprieve like so many his vulnerability—something he had largely avoided doing of his patients over the decades. In the future, he thought, during the course of his extraordinarily active life. From the he could tell them truthfully that he knew how they felt.

32 ... NYU LANGONE HEALTH SPRING 2019 “Every patient is a VIP in my mind. They’re all someone’s father, mother, husband, wife, son, daughter.”

nader moazami, md

SPRING 2019 NYU LANGONE HEALTH ... 33 “To me, it’s a thrill to do research that can have an impact around the world. Anything I can contribute, as a doctor or a patient, I’m all in.”

ROBERT MONTGOMERY, MD, DPHIL

he hoped-for call came at 4:00 a.m. on Sep- tember 20, just five days after he was admitted to NYU Langone. “We have a donor,” said Dr. Moa- zami. “Heroin overdose, in their 20s, hepatitis C+.” Dr. Montgomery didn’t pause. “Let’s go,” he said. Within a few hours, Zachary Kon, md, assistant pro- fessor of cardiothoracic surgery and surgical director of the Lung Transplant Program, was in a neighboring state, procuring the donor’s heart and preparing it for transport. Meanwhile, Dr. Moazami was in an or at NYU Langone with Deane Smith, md, assistant professor of cardiotho- racic surgery and associate director of heart transplant and mechanical circulatory support, opening Dr. Mont- gomery’s chest. It took an hour to remove the tangle of wires and capacitors that remained from his old implants. Around 2:00 p.m., when Dr. Kon’s chartered plane landed at Teterboro Airport, the two surgeons placed their patient on a heart-lung bypass machine and began to carefully remove his heart. By the time Dr. Kon walked in, with the donor organ in a wheeled cooler, his colleagues were ready to begin the transplant. For Dr. Moazami, the fact that the man under his knife was not only his boss but also his friend was not a particular cause for anxiety. “Every patient is a vip in Dr. Montgomery my mind,” he says. “They’re all someone’s father, mother, receives a visit from husband, wife, son, daughter. And I was confident in our his son, John, and daughter, Elizabeth. team.” It also helped that he had smuggled himself out Both children inher- of Iran as a teenager, made it through college and medi- ited their father’s heart condition and cal training on his own, and held the hearts of hundreds rely on implantable of other men and women in his hands. Like Dr. Mont- defibrillators to gomery, he had trained himself to respond to stress with safeguard against sudden cardiac intense calm. arrest. Bottom: At 2:46 p.m., Dr. Moazami lifted the new heart—healthy Dr. Montgomery with Drs. Alex and strong, despite the virus that lurked in its cells—and Reyentovich (left) placed it in the recipient’s thoracic cavity. At 6:09 p.m., and Nader Moazami. nearly seven hours after the surgery began, he and Dr. Smith were closing up the incision. “Good job, everyone,” Dr. Moazami said. “Thanks for everything you’ve done.” Afterward, one of the nurses approached him with tears in her eyes. “Dr. Montgomery did my daughter’s kidney

transplant,” she said. “I hope he’ll be all right.” OCHS CAITLIN BOTTOM: FAMILY; OF THE MONTGOMERY COURTESY TOP: OCHS CAITLIN

34 ... NYU LANGONE HEALTH SPRING 2019 e was all right. Although his new heart had ed heart is at least 12 years.) One of the immunosuppres- Dr. Montgomery some rhythm problems at first, they were resolved sants causes a hand tremor—a minor annoyance for most visits a transplant patient recovering with medication. Dr. Montgomery went home 10 patients, but not for a surgeon. The effect typically wears from surgery just days later. By then, he’d tested positive for hcv, as expect- off after a few months, but if it doesn’t, he plans to switch a few months after his own transplant ed, and a course of medication had cleared the virus. Less to a different drug. surgery. than a week after his discharge, he returned to work half- Still, Dr. Montgomery is eager to pick up the scalpel time. “You can’t slow him down,” says Dr. Reyentovich, again as soon as safety allows. He’s grateful for the gift in who had suggested that he wait longer. Soon, Dr. Mont- his chest, provided by a grieving family, and he’s glad for gomery was back to his usual long hours at the office. He the chance to prove that the risk he took in accepting it even began doing cardio exercises as part of his recovery can benefit many people other than himself. Everyone who program at Rusk Rehabilitation. “For the first time in years, receives an hcv+ organ at NYU Langone (about half of I can get on a treadmill and run,” he marvels. all heart recipients) does so as part of a clinical trial—one However, eight months after his surgery, Dr. Montgom- that, so far, has shown striking results. “No transplant pa- ery’s life has not quite returned to normal. Like most trans- tient has failed to respond to the hepatitis C therapy we’ve plant recipients, he takes a triple-drug immunosuppressant given,” says Ira Jacobson, md, professor of medicine and cocktail to ward off rejection; a dozen more medications director of hepatology, who led pivotal early studies of the each day to prevent infections, to which the immunosup- new antivirals and helped design the Transplant Institute’s pressants make him vulnerable; and pills to prevent coro- treatment protocols. “The virus is suppressed very quickly.” nary artery disease in his new heart. He’ll be on some ver- “To me, it’s a thrill to do research that can have an impact sion of this regimen, with periodic biopsies to make sure around the world,” Dr. Montgomery says. “Anything I can

TOP: COURTESY OF THE MONTGOMERY FAMILY; BOTTOM: CAITLIN OCHS CAITLIN BOTTOM: FAMILY; OF THE MONTGOMERY COURTESY TOP: OCHS CAITLIN it’s working, forever. (The median survival for a transplant- contribute, as a doctor or a patient, I’m all in.”

SPRING 2019 NYU LANGONE HEALTH ... 35 IMMUNOTHERAPY FOR HIV

BY KAREN HOPKIN

PHOTOGRAPHS BY JONATHAN KOZOWYK ISTOCK.COM/FPM

36 ... NYU LANGONE HEALTH SPRING 2019 IMMUNOTHERAPY FOR HIV

At NYU School of Medicine, researchers are closing in on a therapeutic vaccine that could one day yield a functional cure for a global epidemic.

SPRING 2019 NYU LANGONE HEALTH ... 37 In the mid 1990s, as the first wave of life-extending therapies for hiv began to reach the clinic, microbiologist Nathaniel “Ned” Landau, phd, was puzzling over why some people infected with the virus never fell ill, even without medications, while others seemed immune to infection altogether. As a young scientist at the Aaron Diamond aids Research Center in New York City, he’d been studying how hiv slips into cd4 helper T cells—immune cells whose job is to rally other immune cells to fight off infections. It was clear that hiv grabs onto cd4 cells by attaching to a receptor protein on their surface, but that recognition was not enough. The virus needed another trick to fully infiltrate the cell. The mystery went unsolved until 1996 when, in an un- precedented episode of academic confluence, Dr. Landau and his research partner, Dan Littman, md, phd, now the Helen L. and Martin S. Kimmel Professor of Molecular Immunology at NYU School of Medicine, announced the discovery of a second cd4 receptor, called ccr5, that also mediates hiv entry. The scientists tied five other labs in a nationwide race to publish their findings first, collectively confirming an ingenious two-step locking mechanism that permits hiv to ease its way inside the immune cells. The discovery ignited a wave of excitement in the research world, but its clinical implications were even more stunning. Within months, Dr. Landau and another Aaron Diamond colleague, Richard Koup, md, revealed that a mutation in the gene encoding the ccr5 coreceptor could confer immunity to hiv infection. Some of the pa- tients who appeared immune to hiv, they found, were in fact missing the gene responsible for the ccr5 coreceptor. Remarkably, even people with only one copy of the defec- tive gene had an edge over hiv: while they were still vulner- able to infection, they tended to stay healthier longer than those who did not have the mutation. Disabling ccr5, it turns out, is not the only ticket to For the past two decades, taking advantage of basic biological mechanisms to thwart Nathaniel “Ned” Landau, PhD, has hiv. “That discovery led to lots of research to try to sought to understand the immuno- understand whether other things can make people resistant logical secrets of people infected to hiv infection and how the body fights against hiv in with HIV who naturally suppress the virus without the aid of general,” Dr. Landau says. medications. Nearly three decades later, Dr. Landau, now a profes-

38 ... NYU LANGONE HEALTH SPRING 2019 PHOTO CREDIT Illustration by tktktktk SPRING 2019

NYU HEALTH LANGONE

...

39 Dr. Landau sor of microbiology at NYU School of Medicine, is zeroing ing of their therapeutic vaccine to nonhuman primates over examines a plate in on a therapeutic vaccine he hopes will supercharge the the next couple of years. of “Vero cells,” a immune system’s fighting force: the killer T cells that, once lineage isolated from an African activated, can take down the virus. Indeed, a small number green monkey in of people infected with hiv—fewer than 1%—do just that. 1962 and com- For reasons still unclear, these so-called elite controllers are monly used able to naturally suppress hiv replication. A vaccine that Although the basis of a therapeutic vaccine involves mim- to study viral replication. mimics this ability to hold hiv in check could effectively icking the virus-suppressing skills of elite controllers, it’s transform the 37 million people worldwide currently living not entirely clear how most elite suppressors themselves with hiv into elite controllers. “If we can develop a vaccine manage to keep hiv down. “That’s been one of the impor- that will program an infected person’s immune system to tant questions in aids research for many years,” says Dr. act like that of an elite controller, so that they have a strong Landau. Elite suppressors don’t harbor a weaker strain of T cell response and suppress the virus, we might enable hiv. “Their cd4 T cells are vulnerable to infection, as far as patients to come off their lifelong medications and be func- we can tell,” explains Dr. Landau. “They’re not intrinsically tionally cured,” says Dr. Landau. resistant, like people who lack ccr5.” Last year, in support of his innovative efforts, Dr. Landau Instead, the killer T cells of elite suppressors—the received an Avant-Garde Award for hiv/aids research from immune cells that take cues from T cells to kill off infec- the National Institute on Drug Abuse, part of the National tions—show a naturally vigorous response to hiv. “Perhaps Institutes of Health. The five-year grant, which provides they were previously exposed to something that caused a $4.2 million in funding, will allow his team to expand test- similar T cell response,” says Dr. Landau. “Or maybe it’s

40 ... NYU LANGONE HEALTH SPRING 2019 “If we can develop a vaccine that will program an infected person’s immune system to act like that of an elite controller, we might enable patients to come off their lifelong medications and be functionally cured.”

Nathaniel Landau, PhD, professor of microbiology at NYU School of Medicine

something in their genes. It’s not really understood. But An estimated 66% what we do know is that these people exist. The virus never of adults in East fully clears in these patients, but it remains controlled.” and Southern By hindering viral replication, antiretroviral medications Africa take anti- HIV medications essentially do the same thing, and they have improved over every day. the years. In the early days, “you had to take something like 15 pills a day, and they made you nauseated, depleted your bone marrow, and were very toxic,” Dr. Landau says. “Now, there are combination therapies that are as simple as one pill once a day, and overall, they are much better tolerated.” Even so, each drug component comes with its own tox- icity: some affect the kidneys; others, the bones. It’s not uncommon for patients to switch drug regimens due to side effects. Furthermore, taking one pill a day is not as foolproof as it sounds. If you miss a dose, the virus could develop resistance, which could then render a whole class of medications ineffective. Globally, access to care remains a major challenge. “In the us, we’re fortunate,” Dr. Landau says, “but there are many places throughout the world where medications and clinics aren’t readily available.” A therapeutic vaccine wouldn’t eliminate every single copy of the virus hidden in the body, but it would represent a functional cure. “It would be so much better than having to take a daily regimen of medications for the rest of your life and dealing with all of the side effects that can come with it,” says Dr. Landau. A vaccine that prevents hiv infection continues to be a goal, albeit an elusive one. “There’s been a tremendous effort,” says Dr. Landau, “but it hasn’t worked so far.” A 2007 trial for a vaccine developed by the pharmaceutical company Merck, for example, was halted prematurely when volunteers who received the experimental treatment proved more susceptible to hiv infection than those who did not. “Whether a preventative vaccine will be possible remains to be seen,” says Dr. Landau.

The Landau Lab’s approach to a therapeutic vaccine centers

TINA STALLARD/GETTY IMAGES (TOP) IMAGES TINA STALLARD/GETTY on dendritic cells—a frontline player in the battle against in-

SPRING 2019 NYU LANGONE HEALTH ... 41 fection, and the “brains” of the immune system. These cells patrol the body and, when they encounter a marauding virus or bacterium, ingest the invader, chop it up, and then display these fragments like flyers that allow other immune cells to The Great Vaccine Boom recognize the infection. “Dendritic cells educate T cells,” explains Dr. Landau, “saying, in effect, ‘This is whathiv Flu, malaria, HIV—NYU Langone’s new Vaccine Center builds looks like. Your job is to kill any cells infected with hiv.’ ” on a groundswell of research to eradicate deadly infectious diseases. The insidious trick of hiv is to compromise the abil- ity of helper T cells to call the killer T cells to action. Most children in the US receive 35 vaccination shots by their fifth birthday. (Cue It’s like disabling the body’s 911. To get around this im- the crying.) That may sound like a lot, but public health experts believe we need pairment, Dr. Landau is targeting the dendritic cells, even more—a lot more. The current roster of routine childhood vaccines in the artificially arming them with fragments of hiv to present to US protects against 16 infectious diseases, and the World Health Organization killer T cells and equipping them with some of the stimula- estimates that overall, vaccines save 2.5 million lives each year. Yet an even larger tory chemicals that would normally be provided by helper number of people die annually from malaria, tuberculosis, and hiv/aids combined. T cells. Vaccination with such engineered dendritic cells The good news is that there are a historic number of experimental vaccines in should allow those infected with hiv to activate their killer the pipeline—270 and counting—aimed at preventing these three global killers, T cells and produce a targeted immune response. “The idea along with 51 other infectious diseases. The new Vaccine Center at NYU Langone is to reinforce the immune system so that it can control Health, launched this year by Mark Mulligan, md, a nationally renowned infectious replication of the virus,” says Dr. Landau. disease investigator recently recruited from Emory University, will build on this ex- Preliminary attempts by other labs to produce dendrit- traordinary momentum through a combination of basic research and clinical trials. ic-based therapeutic vaccines have met with some suc- “Vaccine research is of the highest importance to humankind,” says Dr. Mulli- cess. “Two published clinical trials did show a short-term gan, the Jeffrey P. Bergstein Professor of Medicine and director of the Division of immune response,” notes Dr. Landau. “But then the virus Infectious Diseases and Immunology. “We still lack vaccines for many long-stand- ing diseases, and new threats like Zika and Ebola continue to emerge. The center’s rebounded.” That may be because these studies mixed syn- mission is to discover new vaccines to protect and restore human health.” thetic preparations of viral fragments with dendritic cells Dr. Mulligan’s own lab will focus on developing a universal influenza vaccine, before injecting these cells into patients. In such a prepara- a national priority to contain one of the deadliest infectious diseases in the us, tion, the dendritic cells may present antigen fragments for accounting for 80,000 deaths last season alone. The Holy Grail, he says, is a single a short time, but ultimately, the antigens get lost. shot, perhaps with a booster every 5 to 10 years, that inoculates against all influ- In the approach adopted by the Landau Lab, the dendrit- enza strains and eliminates the annual hit-or-miss scramble to predict dominant ic cells are engineered with a gene that encodes a segment strains for each flu season. of hiv protein. These engineered dendritic cells are thus The center will also investigate therapeutic vaccines—like the one Nathaniel armed with a blueprint that allows them to continually pro- Landau, phd, professor of microbiology, is developing against hiv—that train the duce the viral antigen they need to alert killer T cells to be body’s immune system to fight existing infections. It’s a fast-growing strategy now on the lookout for hiv. being explored to treat everything from Alzheimer’s disease to diabetes, but cancer So far, the approach has worked well in a test tube. There, tops the list: currently nearly half of the vaccines in clinical trials target cancer—a the engineered dendritic cells were able to stimulate human trend that Dr. Mulligan, professor of medicine and microbiology, believes will only killer T cells and instruct them to recognize hiv, doing an grow. “Cancer vaccines are an exciting field, reinvigorated in the new era of immu- end run around hobbled helper T cells. What’s more, the notherapy, and we will recruit researchers and collaborate with investigators and vaccine was able to coax dormant hiv hidden inside helper clinicians to develop them,” says Dr. Mulligan. T cells to reveal itself. That observation was particularly

promising, says Dr. Landau, because “if you can wake up ISTOCK.COM/LPETTET BSIP/GETTYIMAGES

42 ... NYU LANGONE HEALTH SPRING 2019 “Their approach takes advantage of how the body naturally detects retroviruses like HIV. It’s absolutely essential.”

Dan Littman, MD, PhD, the Helen L. and Martin S. Kimmel Professor of Molecular Immunology and a Howard Hughes Medical Institute investigator

latently infected cells and allow them to be recognized by A young HIV T cells, the immune system can clear them.” Eliminating patient in Togo, a small country in these latent hiv-infected cells depletes the viral reservoir, West Africa. More lessening the likelihood that one of these stowaway viruses than 90% of the can reawaken later, when the immune system may be un- world’s HIV-posi- prepared, and ignite an explosion of replication that could tive children live in Africa, and globally lead to aids. 120,000 children “Their approach takes advantage of how the body nat- die each year from urally detects retroviruses like hiv,” says Dr. Littman, a AIDS-related Howard Hughes Medical Institute investigator. You need illnesses. to have this hard-wired, innate mechanism, he explains, to mount a strong adaptive response, which includes the activation of both helper and killer T cells, as well as the production of antibodies that recognize the virus. “That’s the part that a lot of people working on hiv had ignored for the first couple of decades of research in the field,” he adds, “but it’s absolutely essential. This project bridges that gap.”

Dr. Landau recently began collaborating with a team at the University of California, Los Angeles, to hone their vaccine in mice. In preliminary tests, he and his collaborators found that their dendritic cells restrained viral replication. “But the suppression lasted only about two months before the virus came back,” says Dr. Landau. “We think the T cells were getting exhausted”—activating the natural “checkpoint” mechanisms they use to shut themselves down once an in- fection has been eliminated, thereby preventing a runaway of the Department of Microbiology, who is involved in immune reaction. “But if you have a chronic infection, you the launch of NYU Langone’s new Vaccine Center (see don’t want those T cells to get turned off,” he explains. “You page 42). “You can reprogram dendritic cells for a lot of want to keep them active.” Now, the researchers are arming different immune responses—to other infectious diseases their dendritic cells with proteins that inhibit those check- and even to cancer.” points to keep killer T cells on their toes—the same strategy Indeed, Dr. Landau has found that reprogrammed den- that’s used in a number of cancer immunotherapies. dritic cells can protect mice injected with melanoma cells While the current focus of this collaborative research from developing cancer. “We hope this is going to be a nice is hiv, its promise extends beyond this one disease. “The addition to the story,” he says. “It’s definitely going to be a cool thing about the research is that it has a number of big focus in our lab. At the end of the day, if you really want potential applications,” notes Jeffrey Weiser, md, the Jan to make a breakthrough in hiv/aids, or any disease, you

ISTOCK.COM/LPETTET BSIP/GETTYIMAGES T. Vilcek Professor of Molecular Pathogenesis and chair need bold new ideas.”

SPRING 2019 NYU LANGONE HEALTH ... 43 A Pediatrician’s Crusade against Chemical Saboteurs

Dr. Leonardo Trasande is exposing the everyday chemicals that may cause children a lifetime of harm.

BY BRYN NELSON

ILLUSTRATIONS BY CHAD HAGEN PHOTOGRAPHS BY TONY LUONG

44 ... NYU LANGONE HEALTH SPRING 2019 SPRING 2019 NYU LANGONE HEALTH ... 45 KNOW YOUR CHEMICAL HAZARDS Phthalates, aka Plasticizers

WHY THEY EXIST Phthalates belong to a class of chemicals that make plastics more elsewhere have since begun to tease out the an- flexible and act as industrial swers. Harsh conditions during a critical early solvents. window of human development, evidence sug- gests, may trigger a survival mechanism called WHERE THEY’RE FOUND a thrifty phenotype. The hypothesis posits that In many plastics that are soft and hormonal changes in the developing fetus can squeezable, including detergent help it adapt to unfavorable conditions, such as bottles, raincoats, plastic bags and packaging, inflatable toys, by converting calories into fat instead of protein food-grade plastic tubing, medical or sugar to maximize energy when food is scarce. tubing, and blood-storage con- Later in life, though, the adaptation can become tainers. They’re also common in a threat: continuing to readily convert calories soaps, shampoos, cosmetics, and nail polish. Look for the recycling into fat, even when food is abundant, can predis- code 3 on plastic containers or the pose someone to obesity and diabetes. ingredient “fragrance” on labels of As it turns out, starvation isn’t the only con- hygiene products. dition that can reconfigure the body’s metabol- ic and hormonal wiring early in life. Leonardo WHY THEY’RE SUSPECT Trasande, md, mpp, vice chair for research in Phthalates cause genital birth defects and impaired reproductive the Department of Pediatrics at NYU Langone function in male mice, and they Health, is among a growing cadre of scientists alter the function of protein re- the winter of 1944, at the tail end of World War who believe that chronic exposure to the chem- ceptors involved in sugar and fat II, Nazi troops cut off food supplies to the west- icals found in numerous everyday sources, such metabolism. The CDC has found detectable levels of phthalate ern provinces of the Netherlands, creating a as plastics, flame retardants, pesticides, and air metabolites in the general popu- widespread famine that killed nearly 20,000 pollution, can trigger the same phenomenon and lation, with higher levels in those people. Conditions improved dramatically when may be fueling the rising rates of diseases like who use more personal care the war ended a year later, but the health impli- obesity and diabetes. “We suspect the thrifty products such as cosmetics, body washes, and shampoos. More than cations of the humanitarian crisis would be felt phenotype can occur in a subtler fashion and 1,000 population-wide studies for generations. In what is considered one of the impact children through early chemical expo- have linked exposures in humans most startling paradoxes in medicine, children sures,” says Dr. Trasande, director of the Divi- to neurodevelopmental issues, low born to women who survived on meager rations sion of Environmental Pediatrics, and professor IQ, infertility, and asthma, among other health problems. during the Dutch Hunger Winter, as the period of pediatrics, environmental medicine, and pop- is now known, tended to be the same weight at ulation health. birth as those born to unaffected mothers, but Equal parts physician, researcher, and policy they became heavier as adults. They were also expert, Dr. Trasande has spent the past two more prone to heart disease, obesity, diabetes, decades painstakingly documenting the threat and early death. and burden of environmental toxins on human The phenomenon raised a profound and per- health, and the economic cost of failing to pre- plexing question: How could the environment vent related diseases, all while advocating for in the womb leave such a dramatic and lasting reforms to mitigate their damage. His concerns mark on human health and longevity? Studies about the health hazards of hormone-disrupting of the Dutch children, as well as other major chemicals have been echoed by the World Health investigations from Japan, Scandinavia, and Organization, the International Federation of

46 ... NYU LANGONE HEALTH SPRING 2019 PHOTO CREDIT Illustration by tktktktk SPRING 2019

NYU HEALTH LANGONE Trasande hasearned burgeoning field of pediatric environ - his expertise and leadership inthe an international mental health. reputation for Dr. Leonardo

...

47 KNOW YOUR CHEMICAL HAZARDS Bisphenols, aka BPA, BPS, BPF, BPP

WHY THEY EXIST This class of chemicals is used to harden plastics and prevent corro- sion in aluminum cans. Gynecology and Obstetrics, the Endocrine So- ciety, and the American Academy of Pediatrics. WHERE THEY’RE FOUND Even as the evidence mounts, however, the Canned foods, beverage contain- challenge of protecting society from a perva- ers, toys, dental sealants, thermal sive threat hiding in plain sight can seem insur- paper receipts, and pipes. Products mountable. Synthetic chemicals lurk just about marketed as “BPA-free” are often replaced with other bisphenols everywhere: in our soil and food supply, in cos- within the same class. metics and hygiene products, in furniture and clothing, and even in medical equipment (think WHY THEY’RE SUSPECT iv bags, tubing, and pill bottles). Since 2004, the BPA exposure causes infertility world has produced more than 4 billion metric and hormonal dysfunction in tons of plastic alone. research animals. In women, higher BPA levels have been linked to Dr. Trasande, for his part, is undaunted by the fewer egg follicles. Population- scope and scale of the task before him. Supported wide studies have linked BPA to by more than $40 million in federal funding, he early puberty, breast cancer, and and his colleagues at NYU School of Medicine are clinical care provided by Hassenfeld Children’s childhood obesity and neurological disorders. In addition, the chemical leading some of the most ambitious clinical stud- Hospital, advances tools and technologies to help makes fat cells bigger and ies yet to clarify the link between chemical expo- measure the effects of environmental exposure disrupts a protein that protects sure and childhood development. Beyond more and translates research findings for the public. against heart disease. research, his antidote turns on a public awareness “I think he’s a towering intellect—and a practi- campaign whose message is as persistent as the cal person,” says Catherine Manno, md, the Pat chemicals it seeks to oust. Dr. Trasande recently and John Rosenwald Professor of Pediatrics and published a book to alert the public to the hazards chair of the Department of Pediatrics. “And those of hormone-disrupting chemicals, which he con- things together augur for a great contribution to siders an environmental challenge second only to public health.” climate change. “We can do a lot to protect ev- eryone from ‘lifestyle’ diseases caused by things other than lifestyle,” he says. “Our choices and r. trasande was first drawn to health habits matter.” policy during medical school at Harvard In the relatively young field of pediatric en- University in the 1990s. After complet- vironmental health, Dr. Trasande has rapidly ing his pediatric residency at Boston earned an international reputation for his ex- Children’s Hospital and Boston Medical Center, pertise and leadership. In 2014, he organized the he completed a legislative fellowship in then-Sen- Endocrine Disrupting Chemical Disease Burden ator Hillary Rodham Clinton’s office. Working on Working Group, a cohort of nearly 30 interna- both child and environmental health policy, he tional scientists who advise policymakers about realized that formulating sound medical guidance the economic burden of medical conditions could fundamentally impact the health of not linked to these chemicals. Earlier this year, he only individuals but entire populations. Since was appointed director of NYU Langone’s new then, Dr. Trasande has increasingly focused on Center for the Investigation of Environmental building the public health case against a group of

Hazards. The center, which complements the chemicals known as endocrine disruptors, which ISTOCK.COM/RAPIDEYE

48 ... NYU LANGONE HEALTH SPRING 2019 Seven Ways to Reduce Your Exposure to Everyday Chemicals Beyond building a case for major policy changes in how chemicals are used and regulated, Dr. Trasande is educating consumers about how to reduce their own risk. Here, he offers some practical tips for protecting yourself and your loved ones from the downstream effects of environmental chemicals.

1. Don’t microwave plastic containers, even those labeled “microwave safe,” or put them in the dishwater. Discard plastic containers that are etched or scratched since heat and physical damage can cause chemicals to leach into food and liquids.

2. Avoid plastic containers labeled with the recycling numerals 3, 6, and 7, which pose the greatest health risk.

3. Eat organic produce, especially leafy greens and vegetables, to avoid pesticide exposure.

4. Limit exposure to canned foods and drinks, and thermal-paper receipts, all of which can shed bisphenols.

5. Avoid using synthetic pesticides on your own garden.

6. Limit the use of fragrances, cosmetics, and hygiene products made with synthetic chemicals. Phthalates commonly found in these products can be absorbed through the skin or inhaled.

7. Open windows for air circulation. ISTOCK.COM/RAPIDEYE

SPRING 2019 NYU LANGONE HEALTH ... 49 KNOW YOUR CHEMICAL HAZARDS Organophosphate Pesticides

WHY THEY EXIST These nerve agents are widely used to kill insect and other animal pests in agricultural fields and homes. interfere with the function of hormones such as estrogen, androgen, and thyroid. “We know that WHERE THEY’RE FOUND hormones, in addition to performing important Pesticides sprayed on crops and physiological functions, are crucial for shaping plants leach into the soil and water body mass,” he says. supply and can make their way to Dr. Trasande’s work has been driven by the your kitchen. Pesticides used in homes have shown up in the cord central hypothesis that early-life exposure to blood of infants. environmental chemicals, especially endocrine disruptors, alters our hormones in harmful WHY THEY’RE SUSPECT ways, contributing to birth defects, develop- Organophosphates cause tumors mental delays, obesity, diabetes, infertility, and and severe brain damage in re- cardiovascular and immunological diseases. search animals and have been linked to lymphoma and leukemia He notes that while these chemicals have been in humans. High exposure can shown to have long-lasting health implications cause nausea, vomiting, neuropa- for everyone, babies and young children are par- thy, and seizures. ticularly vulnerable. “Pound for pound,” says heart disease, potentially contributing to cardio- Dr. Trasande, “children are breathing more air, vascular risks. Phthalates can alter the function eating more food, and drinking more water, so of protein receptors involved in sugar and fat me- they have greater exposure, and their organ sys- tabolism, meaning that—like the thrifty pheno- tems are still developing.” type—they may fundamentally reset the body’s For much of their research, Dr. Trasande and response to calories in food. his investigators have zeroed in on four kinds of Given the pervasiveness of these chemicals, chemicals for which there is the strongest evi- they often end up in household air and dust. Our dence of health effects: bisphenols, phthalates, reliance on products made from them could be organophosphate pesticides, and polycyclic ar- coming at a steep cost. Evidence of the harm omatic hydrocarbons (pahs). Bisphenols make they pose has accrued primarily through epide- plastics hard, and because they are used to pre- miological studies of hormone-deficient moth- vent corrosion in aluminum cans, they are often ers or children and through toxicology studies present in canned foods. Phthalates increase the of lab animals. flexibility and durability of plastics and are often Epidemiological studies are notoriously chal- added to lotions, cosmetics, soaps, fragrances, lenging due to the near-impossibility of finding food packaging, and other consumer products. control populations that haven’t been exposed to Organophosphate pesticides are widely used to the ubiquitous chemicals and the sheer variety of kill insect pests in agricultural fields and homes. other contributing factors that must be consid- pahs are air pollutants found in everything from ered. Uncertainty remains over the cumulative vehicle exhaust to charred meat. effects of exposure to intermingling chemicals Research in humans and lab animals has and over how best to assess the risks from chronic linked these endocrine disruptors to other po- low-level exposures. Some skeptics have likewise tential consequences, as well. Bisphenol A (bpa), questioned the validity of extending the results for example, makes fat cells bigger and disrupts of toxicology experiments on animals to people,

the function of a protein that protects against particularly as the scientific basis for new policies. ISTOCK.COM/FOTOKOSTIC

50 ... NYU LANGONE HEALTH SPRING 2019 “Pound for pound, children are breathing more air, eating more food, and drinking more water, so they have greater exposure, and their organ systems are still developing.”

LEONARDO TRASANDE, MD, MPP, VICE CHAIR FOR RESEARCH IN THE DEPARTMENT OF PEDIATRICS AT NYU LANGONE HEALTH

Pediatrician Leonardo Trasande, MD, in Children’s Hall at Hassenfeld Children’s Hospital. ISTOCK.COM/FOTOKOSTIC ISTOCK.COM/FOTOKOSTIC

SPRING 2019 NYU LANGONE HEALTH ... 51 KNOW YOUR CHEMICAL HAZARDS Polycyclic Aromatic Hydrocarbons, aka PAHs

WHY THEY EXIST Although correlations between exposures and keep doing research,” says Dr. Trasande. “There They appear whenever we burn things. PAHs, a group of more than impairments don’t prove that such chemicals are are substantial gaps.” 100 chemicals, are the ubiquitous toxic, Dr. Trasande argues that most human and by-products of combustion. lab animal studies have consistently pointed in the same direction, strengthening the case for t’s one thing to study chemical expo- WHERE THEY’RE FOUND causation. In a 2015 study that measured chil- sures in mice or to comb existing data sets PAHs are released everywhere dren’s and adolescents’ exposure to phthalates for associations. But how do we really know there’s vehicle exhaust, charred meat from high-temperature cook- found in processed foods, Dr. Trasande and his what’s happening in humans? A few re- ing, cigarette smoke, fumes from colleagues discovered that higher concentrations views of observational studies have yielded con- asphalt roads, or smoke from burn- of phthalate in urine samples were associated tradictory results, and experts agree that the ing coal, gasoline, trash, or wood. with higher blood pressure. In a related study, field may never find a true “smoking gun” be- WHY THEY’RE SUSPECT his group linked some of the same chemicals to cause of the impossibility of ethically testing the Direct exposure to PAHs can increased insulin resistance, which causes sugar effects of potential toxins on people. “Causation irritate your eyes and lungs. Higher to build up in the blood and can lead to diabetes. is never certain,” Dr. Trasande acknowledges. exposures among children have Among multiple studies that have sought “The best we can do as scientists is to lay out the been linked to neurodevelopment to estimate the public health burden of endo- information, along with all the uncertainties, problems like ADHD. Grilled, charred, and smoked meats have crine-disrupting chemicals, Dr. Trasande and and interpret the probability of a scientific phe- long been linked to cancer. his colleagues have suggested that reproduc- nomenon.” tive disorders account for billions of dollars in To drill deeper, Dr. Trasande is spearheading expenditures. In men, these chemicals were as- some of the largest clinical investigations of en- sociated with major costs for disorders such as docrine disruptors to date. In 2016, he and his infertility, testicular cancer, and undescended colleagues began tracking chemical exposures testicles, while in women, they were linked to in women early in their pregnancy through a reproductive disorders such as fibroids and en- clinical study called ches, for NYU Children’s dometriosis. Health and Environment Study. ches has since In a major 2016 study, Dr. Trasande and his received substantial funding through a larger Na- team conservatively estimated that exposure to tional Institutes of Health (nih) program called endocrine disruptors accounted for total annual Environmental influences on Child Health Out- healthcare costs of $340 billion in the us (2.3% comes, or echo. This research initiative is ex- of the nation’s gross domestic product) and $217 amining how maternal and pediatric exposure billion in Europe. They linked the lion’s share of to a wide range of environmental factors prior these costs to the effects of organophosphates to conception through early childhood can affect on children’s brain development. Even these the health and development of children and ado- huge expenditures are likely to be underesti- lescents. echo aims to enroll more than 50,000 mated, Dr. Trasande explains, given that the children from dozens of study sites nationwide, researchers focused on only a small fraction of providing a scale that Dr. Trasande says will rep- the chemicals sold commercially and their asso- resent the best opportunity yet to understand ciated medical conditions. There are more than the effects of endocrine disruptors and other 85,000 such chemicals on the market, but limit- environmental exposures. ed screening efforts have identified about 1,000 By the end of last year, Dr. Trasande’s team as endocrine disruptors. “That’s why we need to had recruited more than 2,000 women and 1,100 ISTOCK.COM/MILEHIGHTRAVELER

52 ... NYU LANGONE HEALTH SPRING 2019 “Causation is never certain. The best we can do as scientists is to lay out the information, along with all the uncertainties, and interpret the probability of a scientific phenomenon.”

DR. LEONARDO TRASANDE

will be one of only three in the world to contain prospective data from preconception through early childhood, and the only one to contain pre- conception semen samples from male partners.

ne of dr. trasande’s overarching goals is to establish the threats posed by certain chemicals with enough evi- dence to guide people on how to better protect themselves and their children. But he acknowledges that personal choices can only go so far, given the pervasiveness of these chemicals in consumer products and the environment. Even if you can control what’s in your home, you infants from Tisch Hospital, NYC Health + Hos- can’t necessarily control what’s in your school, pitals/Bellevue, and NYU Langone Hospital– workplace, or surrounding environment. For this Brooklyn. Based on their success, they subse- reason, he and other researchers stress that quently received a $40 million five-yearnih grant change must also take place at the institutional to ramp up their efforts. Some of that funding has level. “We have much more power as a society gone toward amplifying existing collaborations through our pocketbooks and wallets,” Dr. with other institutions in the US and the Nether- Trasande says. “The ban on bpa in sippy cups and lands that are examining the effects of chemicals baby bottles occurred because consumers cried on infant development. Another portion of the out to companies asking whether bpa was in grant has allowed Dr. Trasande and his colleagues these products.” to extend their ches study window to include Dr. Trasande hopes that his studies will help childhood exposures through age two and track drive broader changes in public policy, as well, by some maternal exposures prior to pregnancy. Dr. characterizing and confirming the risks of specific Trasande and his colleagues are calling the new chemicals and by identifying the most vulnerable preconception phase Factors Influencing Repro- populations, notably children. The key, he says, ductive Success and Time to pregnancy, or first. is to imagine childhood health and disease as a “While pregnancy matters, it may be expo- three-legged stool supported by environment, sures even before pregnancy that impact how behavior, and genetics: any leg can affect another, the baby does,” Dr. Trasande explains. The first and all three must be examined together. “If we phase enrolls women who come in for regular gy- incorporate better information about these influ- necologic or well visits. If they become pregnant, ences into our studies,” says Dr. Trasande, “we they move on to the second phase, ches prena- can unlock diseases and their origins.” tal. Researchers follow the women through their As the lessons of the Dutch Hunger Winter prenatal care and collect samples at 18 weeks suggest, revealing the true agents of disease and or less, at 18 to 25 weeks, and again in the third devising early ways to overcome them may help

ISTOCK.COM/MILEHIGHTRAVELER ISTOCK.COM/MILEHIGHTRAVELER trimester. The combined first-ches data bank prevent a lifetime of avoidable illness.

SPRING 2019 NYU LANGONE HEALTH ... 53 POST

New People, Places, and Projects at NYU Langone Health

Faculty Conversation REINVENTING A CANCER CENTER Benjamin G. Neel, MD, PhD, guides Perlmutter Cancer Center to the top tier—and aims higher.

When Benjamin Neel, md, phd, joined NYU Langone Health in 2015 to lead the Laura and Isaac Perlmutter Cancer Center, he was tasked with propelling the center into the elite echelons of cancer research. It was a lofty mandate tailor-made for Dr. Neel, a renowned cancer biologist who had just spent the past eight years at the helm of the largest cancer research center in Canada, the Ontario Cancer Institute at Princess Margaret Cancer Centre. In his new role, he quickly set in motion a trifold strategy, bolstered by a $50 million gift from Laura and Isaac Perlmutter, to reinvigorate basic research, expand the center’s clinical trials, and recruit a new wave of top- notch physician-scientists focused on cancer. Just four years later, these investments are paying off. In February, Perlmutter Cancer Center earned com- prehensive status from the National Cancer Institute 3

54 ... NYU LANGONE HEALTH SPRING 2019 Benjamin G. Neel, MD, PhD, director of Perlmutter Cancer Center, first trained his talents on cancer research 40 years ago after he lost his grand- mother to the disease.

Photograph by Jonathan Kozowyk SPRING 2019 NYU LANGONE HEALTH ... 55 POST

(nci), a prestigious designation shared top physicians and scientists has mark- donor to fund a new Center for Blood by only 49 other cancer centers nation- edly improved our collaborations with Cancers, announced in February? wide and accompanied by $20 million pharmaceutical companies, providing in funding over the next five years. our patients with access to more cut- I’m sure it helped. The Center for Blood We sat down with Dr. Neel to discuss ting-edge clinical trials. When I arrived, Cancers (see page 62) will also have a this recent milestone, its implications it could take up to 250 days to launch a new focus on advancing treatments for patients, and the most important new clinical trial. Today, on average, it for multiple myeloma, a blood cancer actions you can take to mitigate your takes less than 95 days. Thanks to the originating in the bone marrow that cancer risk. leadership of Dan Cho, md, who di- kills nearly 13,000 Americans each year. rects our Phase 1 Drug Development We’ve recruited two top experts in the The NCI describes its Cancer Centers Program, we’ve gone from having two field and plan to expand our multiple Program as the anchor of the nation’s phase 1 clinical trials in 2015 to over 100 myeloma clinical trial efforts. cancer research efforts. What does its this year. Overall, the size of our clinical “comprehensive” designation mean trials office has tripled since 2014. Perlmutter Cancer Center is now the for patients? Another huge benefit is enhanced third NCI-designated comprehensive clinical services. For example, with cancer center in New York City. How Comprehensive cancer centers are the recruitment of renowned hema- does that concentration of expertise unique in that they offer full-service tologist-oncologist Ahmad Samer motivate you? teams that can bridge the gap between Al-Homsi, md, director of the Blood basic science and clinical care. Ulti- and Bone Marrow Transplant Program, Scientific research has always been, in Perlmutter Cancer mately, that means scientific insights we’ve now built an elite team capable Center–Sunset my opinion, the most collaborative en- and discoveries reach patients faster. of tackling the most complex cases of Park in Brooklyn, terprise in the us. That said, NYU Lan- Not only do patients benefit from a full blood cancer. This year, we’re on track slated to open gone also competes with other research complement of clinical services in one to perform more than 100 bone marrow next month, is part institutions. It’s that tension between of NYU Langone place—medical oncology, surgical on- transplants, most of them allogeneic, Health’s broader collaboration and competition that cology, radiation oncology—but they meaning that a patient receives stem effort to bring com- drives progress in research. The reali- also have access to the latest experi- cells from a donor instead of himself. prehensive cancer ty is that people in my lab work harder mental therapies. Unfortunately, for too care to more New knowing that somebody else might be Yorkers. “Cancer many cancers, the best medicine is still Did that shift help attract the $75 knows no boundar- working on the same thing. I do, too. It’s a clinical trial. million donation from an anonymous ies,” says Dr. Neel. a good thing, a healthy thing. Humans

How are Perlmutter and its patients benefiting from NYU Langone’s con- tinued growth?

NYU Langone’s dramatic expansion in recent years into Brooklyn, Queens, and Long Island means that Perlmut- ter Cancer Center now reaches more people than ever before. We’ve seen pa- tient volume increase 110% over the past five years. What’s more, our enlarged footprint enables us to provide the high- est-quality care to many patients who live in traditionally underserved areas. Sadly, minority groups have much poorer outcomes for almost every dis- ease, including cancer. Among our pri- orities at Perlmutter is addressing these unacceptable health disparities.

You’ve recruited 30 distinguished cancer researchers and clinicians, many in leadership positions, since you joined NYU Langone. What’s been the impact?

One benefit is that our growing roster of

56 ... NYU LANGONE HEALTH SPRING 2019 incredible testament to public policy, and we need similar policies for obesity. As a community, I think we need to do a better job of communicating relative risk. We’re unwilling to say, “Smoking is the single worst thing you can do for your health. It’s like playing in traffic.” Or, “Tanning beds are like cigarette smoking through your skin.” That’s pretty easy to communicate, but we don’t lay it out that bluntly. The truth is there are certain things that are just really, really bad for you be- cause they substantially increase your cancer risk—smoking, obesity, exces- sive sun exposure, excessive drinking, a sedentary lifestyle. We know that up to 60% of all cancers are preventable. It’s mind-boggling. Of course, I’m very sympathetic to the challenges of behavioral change. I was a fat kid. I was fat all the way to med- ical school. There’s no question that genes play a role in appetite control and obesity. But the rate of obesity is climb- ing too fast to attribute it to genetics alone. Environmental influences play a thrive on competition. But as scientists In the lab, Dr. Neel with cancer, you’d insist that they major role, and many of those variables we also thrive on the exchange of infor- studies signaling are treated at an academic medical can be controlled. mation. So our researchers will always pathways in cancer. center. Why? He recently began collaborate with their counterparts here a clinical trial Do you have to work at keeping your in New York City and beyond. investigating the I’d pretty much insist on that if they weight down? impact of vitamin needed to be treated for anything more Do you see personalized medicine as C on a form of serious than a broken bone. In general, Constantly. I walk to work. I try to get to preleukemia linked the future of cancer therapy? to mutations in an academic medical centers are better po- the gym four or five days a week. That’s enzyme that regu- sitioned to deliver state-of-the-art care. my goal. And I’m hungry all the time. No two cancers are the same. In some lates blood cells. Part of that is because they encourage It’s hard. types of cancer, no two cancer cells are a culture of competitive exploration, the same. But it’s also true that no two so there’s never really time to rest on What’s the most common question humans are the same, even identical your laurels. The day after we received laypeople ask you about cancer? twins, and yet they still share common an overall “outstanding” rating on the traits. Similarly, there are generally de- renewal of the nci Cancer Center Sup- “When is there going to be a cure for scribable principles about cancers that port Grant, I was on to the next grant. cancer?” Of course, that question under- apply to genetics and even the host There’s a coterie of people whose raison scores a pervasive misperception about response, which means you don’t nec- d’etre is to push the boundaries of cancer, because cancer isn’t one dis- essarily need individualized therapy for knowledge, and I think everyone ben- ease but many diseases. It’s like asking, every patient. The truth is that we’ve efits from that mind-set. “When is there going to be a cure for made great progress in our understand- infectious disease?” Everyone realizes ing of cancer genetics. We know most What can people do to reduce their that what we need to treat pneumonia is of the genes that contribute to various cancer risk? not what we need to treat a urinary tract types of tumors at the research level. infection. What we haven’t fully figured out is Obesity has surpassed cigarette smok- Unfortunately, we’re never going how to apply that knowledge clinically ing as the leading cause of cancer in the to wake up to the headline “Cancer to best treat most cancers. That remains us. The number of people who smoke cured!” The boring answer is that over a very active area of our research. cigarettes, which used to be about 35% the next decade, we’ll continue to make of the population, has been cut in half steady, and occasionally, major, prog- You’ve said that if any of your family over the last 30 years to around 17%. ress against many different forms of members or friends were diagnosed That’s an amazing success story. It’s an cancer. And that’s our focus.

SPRING 2019 NYU LANGONE HEALTH ... 57 POST

HEADING NEW FUNDING EAST

THE SCIENCE Seeking to Stem Pancreatic Cancer’s FIVE THINGS TO KNOW Relentless Growth ABOUT LONG ISLAND’S NEWEST HOW MUCH $6.7 million MEDICAL SCHOOL

HOW LONG Seven years

SOURCE National Cancer Institute

LEAD INVESTIGATOR 3 Alec Kimmelman, MD, PhD, the Anita Steckler and Joseph Steckler Chair of Ra- diation Oncology and professor of radiation oncology, Perlmutter Cancer Center

WHY IT MATTERS Pancreatic ductal adenocarcinoma (PDAC) kills more than 40,000 Americans annually, and just 20% of patients diagnosed with the disease live beyond a year. The cancer’s signature oncogene, KRAS, endows it with a supernatural ability to proliferate in environ- ments devoid of nutrients and oxygen, giving it a clear edge over cancer treatments. “It’s one of the most metabolically plastic tumors, because it adapts to stress and rewires its metabolic pathways,” says Dr. Kimmelman. “That’s why even when you catch it early, patients still tend not to do very well.”

WHAT IT FUNDS This NCI Outstanding Investigator Award en- ables Dr. Kimmelman to build on his decade’s worth of research on the adaptive metabolic processes of pancreatic cancer. These in- clude PDAC’s ability to derive nutrients from damaged or nonessential parts of its own cells (a scavenging phenomenon known as autophagy) and to induce stromal cells in the tumor microenvironment to secrete nutri- ents, such as amino acids, that can provide fuel. Dr. Kimmelman and his team plan to identify the metabolic dependencies of PDAC tumors by performing sophisticated screens in cell lines and mice. “We need to understand how these adaptive processes integrate with each other and how to target them,” says Dr. Kimmelman. Although the main objective is to identify potential therapeutics that might stem PDAC’s growth, Dr. Kimmelman adds that if his research uncovers a metabolite from the tumor that is secreted into the blood stream, “it could lead to an early detection test for pancreatic cancer.”

58 ... NYU LANGONE HEALTH SPRING 2019 New Leaders TUITION COSTS $0. A year after 1 NYU School of Medicine launched the first top-ranked MD program to award full-tuition scholarships to all stu- dents, NYU Long Island School of Med- icine launches this July on the campus of NYU Winthrop Hospital, in Mineola, New York, with the same full-scholarship model. Of the dozen medical programs nationwide specializing in primary care medicine, it’s the only one that spares students the annual burden of tuition. PRIMARY CARE IS THE FOCUS. 2 With a national shortage of prima- ry care physicians, the School is training future doctors who are committed to careers in internal and community med- icine, pediatrics, ob/gyn, and general surgery. It received more than 2,400 applicants for 24 spots. The class size will grow to 40 by 2021. SCHOOL’S OUT IN THREE YEARS, 3 NOT FOUR. NYU Long Island School of Medicine will be the first medical school in the nation to offer an exclusive three-year md program. Fac- toring in the tuition benefit, savings on cost-of-living expenses and the oppor- tunity to begin practicing one year earli- er, students stand to save $417,000. TALENT STAYS LOCAL. Matricu- 4 lated students receive conditional acceptance to an NYU Winthrop resi- dency slot in primary care through the Eric Sulman, MD, PhD Vamsidhar Velcheti, MD National Resident Matching Program. “There’s a high correlation between An international leader in malignan- Vamsidhar Velcheti, md, a nationally where primary care doctors do their cies of the central nervous system, renowned clinician and researcher, residency and where they wind up Erik Sulman, md, phd, was recently has been appointed director of thorac- practicing,” says founding dean Steven appointed codirector of the Brain ic medical oncology at NYU Langone Shelov, md. Tumor Center at NYU Langone Health’s Perlmutter Cancer Center. Health’s Perlmutter Cancer Center Dr. Velcheti broadens the depth and NYU LANGONE HEALTH IS FAMILY. and vice chair for research in the breadth of cutting-edge clinical trials 5 After the merger of NYU Langone Department of Radiation Oncology. for lung cancer patients at Perlmutter Hospitals and NYU Winthrop Hospital Dr. Sulman, professor of radiation Cancer Center through his research this September, the new school will be oncology, treats patients with brain on biomarkers to predict response affiliated with NYU Langone Health, a and spinal cord tumors using Gamma to immunotherapy. He also serves as relationship that offers clinical experi- Knife® radiosurgery and external principal investigator of a multisite, ences and future professional oppor- beam radiation therapy. He also National Institutes of Health–funded tunities for its graduates. “NYU Long serves as the translational chair on translational research project on Island School of Medicine will serve a many large clinical trials for develop- early-stage lung cancer. Previously, special role in the history of our institu- ing and validating biomarkers, molec- Dr. Velcheti was associate director tion as it prepares the next generation ular predictors of treatment response, of the Center of Immuno-Oncology of physicians to meet the needs of our in patients with malignant tumors. Dr. Research at Cleveland Clinic’s Taussig evolving healthcare system,” says Robert Sulman joined NYU Langone Health Cancer Institute. After earning an md I. Grossman, md, Saul J. Farber Dean and from the University of Texas MD An- at the Armed Forces Medical College ceo, NYU Langone Health. derson Cancer Center. He had worked in India, Dr. Velcheti completed a resi- there since his residency and research dency in internal medicine at Ochsner fellowship, and recently served as sec- Medical Center in Louisiana and a tion chief of central nervous system fellowship in hematology and oncolo- and pediatric radiation oncology. gy at Yale University.

SPRING 2019 NYU LANGONE HEALTH ... 59 POST

Reinvented Spaces Grounded in Science A once-flooded basement is reborn as the home of two high-tech facilities that advance biomedical research and surgical training.

When Superstorm Sandy un- procedures and techniques used leashed its devastation on NYU in some of the most complex, Langone Health’s main campus in pioneering operations attempted October 2012, more than 15 million anywhere. The facility features a gallons of water surged through procedure room, complete with vents and other openings, filling eight prosection stations, and an basements and subbasements—all adjacent seminar room that can in about 30 minutes. In the depths accommodate up to 140 visitors. of the Joan and Joel Smilow Re- “To be a trailblazer for surgical search Center, located near the procedures, NYU Langone must FDR Drive, a mix of water and fuel be an epicenter for training,” says oil rose to a height of some seven Eduardo D. Rodriguez, md, dds, feet, reaching the tops of doorways. the Helen L. Kimmel Professor of The damage was so shocking that Reconstructive Plastic Surgery and an administrator of the Federal chair of NYU Langone’s Hansjörg Emergency Management Agency, Wyss Department of Plastic Sur- upon surveying the damage, re- gery. “This model facility enables us marked to NYU Langone officials, to groom champions.” “Don’t look at this,” he told them. Its next-door neighbor, the “Think about what’s next.” Cryo-Electron Microscopy Lab, Robert I. Grossman, md, the Saul houses two massive microscopes J. Farber Dean and ceo, needed that use subzero temperatures to no encouragement to see light at capture proteins in a natural state the end of the submerged tunnels. and preserve features down to the “Even as the torrent of water was atomic level. A suite of cameras can pouring into our campus,” he told capture up to 1,000 high-resolution the class of 2013 at graduation, “I images within 24 hours, while NYU just knew we’d come out stronger.” Langone’s new supercomputer, To ensure that the entire base- Big Purple (see page 17) combines ment would be impervious to future them into a single 3-D image. flooding, it was essentially reengi- “Setting up the facility was no neered to function like a vault. NYU small feat,” says David Stokes, Langone’s office of Real Estate phd, professor of cell biology, who Development and Facilities devised launched the core facility. The a comprehensive flood mitigation larger scope weighs 7,220 pounds system designed to withstand a while the smaller one tips the 14-foot storm surge. Newly forti- scales at 5,264 pounds. The com- fied and gut renovated, the Smilow ponents were transported from the basement is now home to two new Netherlands on a 747 cargo plane, state-of-the-art facilities that are and then painstakingly assembled advancing the frontiers of science on vibration-control platforms, all and medicine—and fulfilling the in temperature-controlled rooms most optimistic vision of NYU Lan- shielded by aluminum-lined walls gone’s leadership. to eliminate electromagnetic inter- The Surgical Education Train- ference. ing Center, made possible in part “Both spaces were meticulously thanks to a gift from Swiss philan- designed to provide distinct, spe- thropist and international busi- cialized environments,” says Vicki nessman Hansjörg Wyss, provides Match Suna, aia, senior vice pres- a high-tech rehearsal studio for ident and vice dean for Real Estate surgeons, enabling them to master Development and Facilities.

60 ... NYU LANGONE HEALTH SPRING 2019 Photograph by Rene Perez SPRING 2019 NYU LANGONE HEALTH ... 61 POST

NEW FUNDING

THE SCIENCE Can an Epilepsy Drug Curb Alcohol Cravings in People with PTSD?

HOW MUCH $6 million

SOURCE National Institute on Alcohol Abuse and Alcoholism

PRINCIPAL INVESTIGATOR Transformational Gift 3 Charles R. Marmar, MD, the Lucius N. Littauer Professor of Psychiatry, chair of Creates Dedicated Center the Department of Psychiatry, and director of the Steven and Alexandra Cohen for Blood Cancers Veterans Center

WHY IT MATTERS Thanks to a transformational philanthropic gift, NYU Langone Health’s Laura and People who abuse alcohol are more likely to Isaac Perlmutter Cancer Center has established a new Center for Blood Cancers. develop PTSD after experiencing a traumatic event, and those with PTSD are more likely The $75 million gift, made by an anonymous donor, supports the center’s ongoing to abuse alcohol. Each syndrome tends to campaign to enhance its state-of-the-art research and clinical space. The center magnify the other, complicating treatment significantly expands patient services, bolsters new and existing research efforts, options. The urgent need for medications that and enriches educational resources for students and faculty at NYU School of Med- address both conditions has led Dr. Marmar and his colleague Michael Bogenschutz, MD, icine. “There is a pressing need for more research in the areas of early diagnosis and professor of psychiatry, to topiramate, an prevention of blood cancers,” says Benjamin G. Neel, md, phd, director of Perlmutter anticonvulsant drug used to treat epilepsy Cancer Center. “This gift will help us as attract new talent, leaders, and added exper- and migraines. In early studies, the drug has tise to further our mission to prevent and treat these deadly diseases.” shown promise as a remedy for alcohol abuse. Now, Dr. Marmar’s team is among the first to Unlike solid organ tumors, blood cancers originate in the bone marrow, where blood study topiramate’s effect on both disorders. is produced, or in the lymphatic system, which protects us from infection. The most common forms—leukemia, lymphoma, and multiple myeloma—prevent the blood WHAT IT FUNDS from fighting off infection or containing serious bleeding. Leukemia, found in the blood NYU Langone Health is the exclusive location and bone marrow, is caused by the rapid production of abnormal white blood cells. for the 12-week clinical trial, which will recruit Lymphoma strikes the lymphatic system, which removes excess fluids from the body 150 volunteers diagnosed with both PTSD and produces immune cells. Multiple myeloma, which affects antibody-producing and alcohol abuse. “Our goal is to find out who plasma cells, prevents the normal production of cells in the bone marrow. topiramate works for and at what dosage, so we can take a personalized approach to To advance Perlmutter Cancer Center’s clinical and research programs in mul- treatment,” says Dr. Marmar. Participants will tiple myeloma—a disease for which there has been major progress during the past begin with a minimal daily dose that is 15 years but still no cure—NYU Langone has recruited two nationally renowned he- increased incrementally. At weekly visits, matology experts. Gareth Morgan, md, phd, has been appointed director of multiple their blood will be tested to measure levels of two brain chemicals that regulate stress myeloma research. He previously served as director of the Myeloma Institute and and anxiety: glutamate, which is increased in deputy director of the Winthrop P. Rockefeller Cancer Institute at the University of patients with alcohol dependency, and gam- Arkansas for Medical Sciences (uams). While low-risk cases of multiple myeloma ma-aminobutyric acid, which is decreased. are largely treatable, Dr. Morgan focuses on developing targeted treatments for high- Aside from tracking self-reported patient progress, the trial will use functional MRIs to risk variants of the disease. His wife, Faith Davies, md, has been named director of the measure changes in the brain as volunteers Clinical Myeloma Program. At uams, she served as medical director of the Myeloma respond to alcohol cues, such as images Institute. Dr. Davies directs a new inpatient facility in the Kimmel Pavilion for myelo- of a glass of wine or a bottle of beer, before ma transplants. Her research focuses on genetic, biological, and radiological markers and after treatment. “We hope topiramate helps patients achieve better emotional and to improve patient outcomes through new drugs and technologies. cognitive control, a reduced urge to drink, and Blood cancers account for nearly 10% of all new cancer cases in the us each fewer PTSD symptoms,” says Dr. Marmar. year, according to the National Foundation for Cancer Research. In 2018, more than 170,000 Americans were diagnosed with a form of blood cancer, and these diseases collectively claimed the lives of more than 58,000 people. More than 1,345,000

Americans are either living with blood cancer or in remission. ISTOCK.COM/VIRUSOWY

62 ... NYU LANGONE HEALTH SPRING 2019 In Memoriam Frank C. Spencer, MD 1925–2018

Frank C. Spencer, md, a pioneering cardiac surgeon who served as chair of the Department of Surgery at NYU Lan- gone Health for more than 30 years, died on July 23, 2018. He was 92. Dr. Spencer joined NYU Langone’s faculty in 1966, when he was appointed the George David Stewart Professor of Surgery and chair of the Department of Surgery at the age of 41. Over the next three decades until his retirement in 1998, he pioneered techniques, such as coronary artery bypass grafting, that served as the basis for what is now modern car- diac surgery. Advances in the surgical treatment of coronary artery disease, valvular heart disease, myocardial preserva- tion, mitral valve repair, and safe cardiopulmonary bypass have been attributed, in large part, to his efforts or those of surgeons he trained and mentored. Born in 1925, Dr. Spencer grew up on a farm outside Has- kell, Texas, a tiny town in the Panhandle. As a child who was educated at home and later in a two-room schoolhouse until he entered high school, he dreamed of becoming a physician like his paternal grandfather. At 15, he became the youngest freshman at North Texas State College, graduating in two and a half years. After being rejected by both medical schools in Texas due to his age, he applied to the one at Van- derbilt University in Nashville, Tennessee, which accepted him. He enrolled just before his 18th birthday and earned his md in 1947. Elected to Alpha Omega Alpha, he was also honored as class valedictorian. After completing his internship at Johns Hopkins Hos- pital in 1948, Dr. Spencer began his residency in the just- formed Department of Surgery at the University of Califor- nia, Los Angeles, but his training was interrupted by service in the US Navy during the Korean War. Having learned how to perform arterial repairs during his surgical training, Dr. Spencer was dismayed to see soldiers with arterial injuries scheduled for amputation, as protocol dictated, rather than repair. Because rescue helicopters could swiftly transport the wounded to a mobile surgical hospital, Dr. Spencer saw an opportunity for more timely repairs. He sought permission to repair arteries, but when three weeks went by without a response, he assembled surgical teams in two medical units behind the combat zone. At the risk of being court-martialed for not following protocol, he spent the After military service, Dr. Spencer completed his sur- next nine months performing more than 150 arterial repairs, gical training at Johns Hopkins, where he remained on the with a success rate of nearly 90%. faculty for several years. Subsequently, he launched the car- When a reporter interviewed Dr. Spencer about his diac surgery program at the University of Kentucky’s School unsanctioned limb-saving technique, news of his efforts of Medicine. Dr. Spencer was one of only a handful of sur- traveled across the wire services, earning the 26-year-old geons to be elected president of the American Association surgeon widespread acclaim, as well as the navy’s Legion of of Thoracic Surgery, the American College of Surgeons, and Merit Award for exemplary service. “Arterial repair in Korea the American Surgical Association. benefited more people than anything I’ve ever done,” Dr. Dr. Spencer is survived by his daughters, Dr. Elizabeth Spencer recalled many years later. “Why did I do this? It was Kay Spencer Crabb and Patricia Spencer, and grandchil-

ISTOCK.COM/VIRUSOWY simply a reflex—do what’s best for the patient.” dren, Elizabeth and Adelaide Crabb.

SPRING 2019 NYU LANGONE HEALTH ... 63 Anatomy of a Leader Dafna Bar-Sagi, PhD

“Running a lab involves guiding people through good times and not so good times. And it requires being curious, listening, trying to understand, and finding creative solutions.”

Last spring, NYU Langone Health leader Dafna Bar-Sagi, done myself or lived through with the people in my WHO: PhD, spoke to first-year medical students about what she’s lab has taken longer than expected. We might think learned during her career as a pioneering cancer researcher a certain project will take three months, and it ends Dafna Bar-Sagi, PhD and executive leader at NYU Langone Health. The conver- up taking three years. But that’s part of the beauty of Senior Vice President sation was part of NYU School of Medicine’s Leaders and what we’re doing. We let the science guide us through and Vice Dean for Teams lecture series. Here, a few highlights. the journey of finding an answer to the question that Science, Chief Scientific we’re pursuing. Officer • • • Professor, Department Gratitude will take you far. My parents were Holocaust Transparency is key to inspiring a team. It’s wonder- of Biochemistry and survivors, and their stories taught me never to take any- ful when people have a clear-cut idea of the landscape Molecular Pharmacology thing for granted. Human life is so, so precious. Be grateful and the motives behind how things are being done. Professor, Department for everything that comes your way and determined to do I’ve always been a firm believer in disclosing whatever of Medicine the most you can with it. is possible so that everyone understands where they’re coming from and where they’re going to. No secrets. Think of everybody around you as a potential role model. All of us interact daily with people who are either colleagues Don’t just talk the talk; walk the walk. To energize or supervisors, who are so capable, so intelligent, so cre- people to achieve your vision, you need to be positive, ative that it’s a huge privilege to be around them. have a can-do attitude, and empower them by giving Every day I hear something that causes me to them the tools to succeed. Only then you can hold pause, consider how I think about things, and them accountable. ask myself whether I need to recalibrate. Live your career by these three principles. Women shouldn’t feel obligated to take on Work hard, no matter how smart or privileged everything. Because a minority of women you are. Seize the opportunity—there are so hold leadership positions, we’re asked to do a many amazing things you can learn from and lot of things. That can detract from our abil- take advantage of, so don’t let them pass you ity to accomplish our goals. It’s important to by. Finally, look for someone you can relate be gracious about the trust and the respect to, either as a role model or a friend. To nav- your peers are paying you by asking you to igate through your professional career, you do certain things, but also to guard need a compass, someone you can your own interest and make sure always come to and count on. that you prioritize things in a way that allows you to proceed Keep striving to improve. It’s with your own career. very easy to become comfort- able when things are going Good science requires lead- well. But leaders don’t get ership. Running a lab involves any particular points for that motivating people, guiding success because it’s expect- them through good times ed of them. That’s why they and not so good times. And it were picked in the first place. requires being curious about Where you’re really being things, listening, trying to tested is when things aren’t understand, and finding cre- going well—what you learn ative solutions. from these situations and how you correct them. It takes perseverance, too. Every research project I have

64 ... NYU LANGONE HEALTH SPRING 2019 VIRTUAL URGENT CARE

OUR FUTURE It’s Easier Than Our Physicians, Your Schedule Appointments are available every day of the week: DEPENDS ON Ever to See an Monday through Friday 7AM–11PM Saturday to Sunday 8AM–8PM YOUR PRESENT NYU Langone Doctor. Conditions We Treat Virtual Urgent Care is ideal for non-emergency With Virtual Urgent Care, anyone five health issues such as: cold/flu, mild fever, allergies, Bequests and other planned gifts to NYU School of Medicine, both large and small, Whether you want to give back to support years of age or older can easily receive headaches, rashes, and urinary tract infections. have a resounding impact on our mission. scholarships or educational and research programs, our planned giving specialists will care and treatment from our doctors, help you make a meaningful gift that is right for you. We deeply appreciate the generosity Insurance is Accepted right from a mobile device, for a range of all who support our future. Aetna, UnitedHealthcare, Blue Cross Blue Shield, of non-emergency health issues. (800) 422-4483 or [email protected] or Cigna customers could be covered for the cost Contact us at of a co-pay. Get started today with the NYU Langone Heath app. nyulangone.org/virtualurgentcare NYU HEALTH LANGONE

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One Park Avenue, 5th Floor MAGAZINE Chemicals vs. Kids New York, NY 10016 When a Transplant

Surgeon Becomes a Transplant Patient

The Science of Conversation

SPRING 2019

SEE A PATTERN HERE?

“ A single MRI can have 65 million pixels of information, and our research involves tens of thousands of imaging studies, so you can see how the data add up.” SEE P. 14

AI does, and it’s transforming medicine SPRING 2019