Winter/Spring 2020

WINTER/SPRING 2020

EINSTEINTHE MAGAZINE FOR ALUMNI AND FRIENDS OF ALBERT EINSTEIN COLLEGE OF MEDICINE

FORGING THE OF Einstein and Montefiore scholars FUTURE meld research with data to improve MEDICINE patient care INSIDE: Mapping a Roundworm’s Nervous System • The Physician Investigators EINSTEIN A Message from the Dean Science at the Heart of Medicine Winter/Spring 2020 The magazine for alumni, faculty, s 2019 came to a close, students, friends, and supporters of we learned that Einstein Albert Einstein College of Medicine and Montefiore researchers had secured $178 million in grants Published by Afrom the National Institutes of Health The Philip and Rita Rosen Department of Communications and Public Affairs (NIH)—our largest annual total ever Gordon Earle, Associate Dean (page 14). The grants included funds Office of Development to study the Ebola virus and HIV, to Rachelle M. Sanders, Vice President and continue research on neuroscience and Chief Development Officer genetics, and to improve health among Director, Science and Research Content minority groups. Larry Katzenstein The year’s end also brought news Senior Director, Strategic Communications and External Relations that Philip O. Ozuah, M.D., Ph.D., Deirdre Branley has become the new chief executive Managing Editor officer of Montefiore Medicine, the Susan Byrne umbrella organization for Montefiore Director, Creative Services Health System and Einstein (page 2). system of the worm C. elegans for the Marie L. Kurtz

Dr. Ozuah has decades of experience better part of two decades. The story of Senior Director of External Relations, in leadership positions at Montefiore his success in completing the first wiring Development Rachel Eddey and a strong commitment to research diagram of an animal’s entire nervous and medical education. He replaces system—a major milestone in biology— Associate Director of External Relations, Development Steven M. Safyer, M.D., who retired begins on page 36. Sean McMahon after 40 years of service to Einstein and For the past 20 years, Einstein’s Art Director Montefiore. Clinical Research Training Program has Lorene Tapellini

Moving medicine forward is the trained dozens of physicians in a variety Associate Art Director focus of our cover story (page 22). The of specialties. Five of those scholars talk Jeneffer Gonçalves Lee article describes a talented group of about their research (page 16). Illustrations Einstein and Montefiore faculty scholars New funding, new leadership, and Tatyana Starikova Harris who epitomize what a learning health new research add up to bright days ahead Digital Imaging Donna Bruno system can do: influence complex health at Einstein. I’m looking forward to them. systems to adapt and change behavior Photography jtorresphoto.com thanks to evidence obtained from rig- Multimedia Communications orous research and data collection. The Sunita Reed, Director scholars are members of a new center of excellence established with a $3.3 Address correspondence to: Editor, Einstein Magazine million NIH grant. It is one of only 11 Jack and Pearl Resnick Campus such centers in the nation and the only 1300 Morris Park Avenue, Belfer 905 one in New York State. Bronx, NY 10461 GORDON F. TOMASELLI, M.D. Another example of outstanding Email: [email protected] The Marilyn and Stanley M. Katz Dean Website: www.einstein.yu.edu research can be found in the work of Albert Einstein College of Medicine Copyright © 2020 Einstein scientist Scott Emmons, Ph.D., Executive Vice President, Chief Academic Officer Albert Einstein College of Medicine who has been mapping the nervous Montefiore Medicine All rights reserved WINTER/SPRING 2020 IN THIS ISSUE COVER STORY 22 FORGING THE FUTURE OF MEDICINE Einstein and Montefiore scholars meld research with data to improve patient care FEATURES 16 THE PHYSICIAN INVESTIGATORS Einstein’s Clinical Research Training Program marks 20 years of giving doctors the right skills for study success 22 32 READY FOR ROTATIONS A new Transition to Clerkship week helps third-year medical students shift from the classroom to the clinic 36 CONNECTING THE DOTS With the help of a tiny worm, Einstein scientists complete the first wiring diagram of an animal’s nervous system 58 SPOTLIGHT: CARING FOR THE LITTLEST HEARTS Expectant mothers find expert resources for congenital heart issues at a new Montefiore center 62 YOUR IMPACT: UNLOCKING A 36 POTENTIALLY DEADLY DISORDER Thanks to one family’s philanthropy, researchers are moving closer to new treatments for Lynch syndrome DEPARTMENTS 2 Campus News 8 Mavens of Medicine: Dr. Jonathan Alpert 10 Research Notes 12 Lab Chat: Dr. Michael Berney 48 Passionate Pursuits: Artist Adele Heib 50 Crossword: Albert’s Puzzler 54 51 Motivations: The Front Line of Philanthropy 54 Continued Connection: Easing Medical Debt 66 Class Notes 69 A Look Back

Visit magazine.einstein.yu.edu or scan code ON THE COVER: A depiction of a learning health system, where research and data collection are used to help change behavior and more quickly benefit patients. Illustration concept by Tatyana Starikova Harris.

MAGAZINE.EINSTEIN.YU.EDU 1 CAMPUS NEWS

Dr. Philip O. Ozuah Named CEO of Montefiore

hilip O. Ozuah, M.D., Ph.D., has been named the chief executive officer (CEO) of Montefiore Medicine, the Pumbrella organization for Montefiore Health System (MHS) and Albert Einstein College of Medicine. He started his new role on Nov. 15, 2019, succeeding Steven M. Safyer, M.D., who retired after 40 years of service to Einstein and Montefiore.

As CEO, Dr. Ozuah will lead organization of exceptionally talented Montefiore’s next phase of growth and and compassionate people. Working evolution as a global healthcare leader, closely with the board, I look forward renowned for its excellent medical to continuing to expand inclusive access school, groundbreaking research and to state-of-the-art care and to furthering technology, and highly specialized, coor- Montefiore’s role as a global leader in dinated care of diverse populations in healthcare and biomedical research.” “I look forward to the New York region, across the country, Dr. Safyer, who has worked alongside continuing to expand and globally. Dr. Ozuah for the past 25 years, says, “I “We are thrilled that Dr. Philip know I am leaving our institution in the inclusive access to state- Ozuah, a proven senior executive best possible hands. I have consistently of-the-art care and to and strong strategic thinker, will lead been impressed by Dr. Ozuah’s strate- Montefiore into the next decade,” says gic vision for the Montefiore Health furthering Montefiore’s Dan Tishman, chair of the Board of System. His appointment as CEO will role as a global leader Trustees of Montefiore Medicine. “What guarantee a smooth transition, and I stood out was his impressive record of know he’ll continue to uphold the stan- in healthcare and success, his intellect and warmth as a dard of excellence on which Montefiore biomedical research.” physician, his strength as a leader and has built its reputation.” manager, and his deep commitment Gordon F. Tomaselli, M.D., the to Montefiore’s mission. I’d also like to Marilyn and Stanley M. Katz Dean at — DR. PHILIP O. OZUAH thank our outgoing CEO, Dr. Steven Einstein, says, “Dr. Ozuah has a long Safyer, for putting our organization on a and storied history at Einstein, and we path of excellence.” could not have hoped for a better choice Dr. Ozuah joined Montefiore in to lead our joint enterprise. His vision, 1989. “It will be a privilege to lead an commitment to excellence, and dedica- organization with a clear purpose— tion to social justice will undoubtedly to heal, to teach, to discover, and to provide the direction and support for advance the health of the commu- Einstein to thrive in the coming years.” nities we serve,” he says. “We are an Dr. Ozuah previously served as

2 EINSTEIN : WINTER/SPRING 2020 Dr. Philip O. Ozuah Named CEO of Montefiore president of Montefiore and physician- in-chief of the Children’s Hospital at Montefiore (CHAM), where he worked to deliver best-in-class clinical care with a commitment to healthcare access for the underserved. U.S. News & World Report has ranked MHS’s medical specialties, under his leadership, in the top 1% of the nation’s hospitals and CHAM as one of “America’s Best Children’s Hospitals.” Dr. Ozuah has a strong commitment to medical education as well as deep academic medical research expertise, including as a National Institutes of Health–funded investigator and as a professor and the university chair of pediatrics at Einstein. In these roles, Dr. Ozuah expanded access for underserved communities, Philip Ozuah, M.D., Ph.D., with a young patient at the Children’s Hospital at Montefiore. recruited and cultivated outstanding Under his leadership, CHAM was named one of “America’s Best Children’s Hospitals” by talent, advanced programs of excellence, U.S. News & World Report magazine. fostered innovations in medical education, and improved financial and oper- Dr. Ozuah earned his medical degree ational performance by integrating care from the University of Ibadan, Nigeria, across a rapidly growing and evolving a master’s degree in education from the Montefiore system that sees more than University of Southern California, Los 6 million patient interactions a year. Angeles, and a Ph.D. in educational He has been recognized regionally leadership and administration from the and nationally for excellence in teach- University of Nebraska, Lincoln. He ing and patient care, including as an completed his pediatric internship and inductee into the Alpha Omega Alpha residency at Einstein and Montefiore, Honor Medical Society and a two-time and his postdoctoral fellowship in recipient of the Academic Pediatric medical education at the University of Association’s prestigious Helfer Award Southern California School of Medicine, for Innovation in Medical Education. Los Angeles. Along with receiving various awards for teaching and clinical excellence, Dr.

Ozuah has been recognized by Modern WATCH THE VIDEO Healthcare magazine as one of the View Dr. Ozuah’s message:

Photo by Jason Torres “Top 25 COOs in Healthcare.” magazine.einstein.yu.edu/ozuah20

MAGAZINE.EINSTEIN.YU.EDU 3 CAMPUS NEWS

Einstein Joins With CUNY to Offer M.D./M.P.H.

second-highest-ranked school in New York State. With the October 2019 announce- ment of its new M.D./M.P.H. program, Einstein joins about 80 medical schools across the nation with similar programs available at a single institution or in collaboration with another. Einstein first offered this opportunity to the Class of 2023 and made it available to all subsequent incoming M.D. students. Physicians with M.P.H. degrees work in a variety of settings, including departments of health, nonprofit organizations, instein and the City University in a doctor of medicine (M.D.) degree and research institutions. of New York Graduate School of from Einstein and a master’s degree in Earning a separate M.P.H. degree typ- EPublic Health & Health Policy public health (M.P.H.) from CUNY. ically takes two years. The new program’s (CUNY SPH) have collaborated to offer In its Best Public Health Schools list, structure will allow Einstein students to Einstein medical students an opportunity U.S. News & World Report ranks CUNY complete both their M.D. and M.P.H. to complete a five-year program resulting SPH 23rd in the nation—making it the degrees in five years.

DoSA Marks 50 Years With Opioid Conference

cientists, clinicians, policymak- Substance Abuse (DoSA), which was ers, and community activists established as an Einstein methadone S discussed opioid-use disorder’s treatment program and—as a part of past, present, and future at a daylong Montefiore—has evolved into a leading conference at Einstein and Montefiore provider of comprehensive outpatient in September 2019 featuring a keynote care at multiple locations for more than address by Michael Botticelli, M.Ed., 3,400 adults in the Bronx. former director of the Office of National Einstein and Montefiore researchers Drug Control Policy under President and clinicians discussed recent discov- Barack Obama. eries, from neuroscientific advances The event, “On the Front Lines of on the brain’s role in reward-seeking the Opioid Epidemic,” highlighted behavior to effective, evidence-based Einstein and Montefiore’s leadership in opioid-use-disorder treatment strategies. the field of opioid-use disorder, from Panel discussions also addressed public basic and clinical research to community policy concerns and the need for reduc- Joyce Lowinson, M.D., was honored for her decades of service to DoSA. With her care and outreach services. It also marked ing the stigma of addiction and struc- are Jonathan Alpert, M.D., Ph.D., left, and the 50th anniversary of the Division of tural barriers to care. Montefiore CEO Philip Ozuah, M.D., Ph.D.

4 EINSTEIN : WINTER/SPRING 2020 3 Physicians Win National Honors Dr. Irene Blanco Named Hispanic Health Leader Dr. Cristina Gonzalez Gets New Investigator Award

Cristina Gonzalez, M.D. ’04, an associate professor of medicine at Einstein, an internist at Montefiore, and an activist in the fight against health disparities, received the 2018 New Investigator Award from the Association of American Medical Colleges in November 2019. The award was given in recognition of the publication of a paper for which she was the lead author, “How to Make or Break Implicit Bias Instruction: Implications for Curriculum Development,” in a November 2018 online supplement to the journal Academic Medicine. Last November, the National Implicit bias refers to subconscious, unintentional assumptions about other peo- Hispanic Health Foundation (NHHF) ple, which can often lead to disparities in healthcare for disadvantaged populations. recognized Irene Blanco, M.D. ’04, Many medical schools offer their students instruction about avoiding bias, and M.S., associate dean for diversity Dr. Gonzalez has made significant contributions to such programming at Einstein. enhancement at Einstein and a Teachers, however, have not been on the receiving end of these educational efforts, rheumatologist at Montefiore, with and in her paper Dr. Gonzalez explores faculty members’ personal challenges, the its Hispanic Health Leadership role of institutions, and strategies for helping educators. Award. Her goals are to see the topic recognized as a faculty-development priority and to The NHHF is part of the National change the culture around implicit bias in medical education and healthcare. Hispanic Medical Association, a nonprofit organization that rep- Mentor Award Goes to Dr. Michal Melamed resents 50,000 licensed Hispanic physicians in the United States and Michal Melamed, M.D., M.H.S., was given the Distin- is a partner organization of the guished Mentor Award by the American Society of National Institutes of Health. Nephrology (ASN) at its annual Kidney Week meeting in Dr. Blanco, associate professor of November 2019. Earlier in the year, Dr. Melamed, associ- medicine at Einstein and director of ate professor of medicine and of epidemiology & popula- the Lupus Clinic at Montefiore, was tion health at Einstein and a nephrologist at Montefiore, chosen for the honor because of also received a mentoring award from Einstein’s depart- her leadership in improving health- ment of medicine. Since joining the faculty at Einstein, care. She works with the American she has mentored multiple junior faculty members, fel- College of Rheumatology’s Lupus lows, residents, and Einstein medical students. Initiative on information sheets dis- Several of Dr. Melamed’s colleagues nominated her for the ASN mentorship tributed to Hispanic patients. With award. They lauded her reputation as a national expert in studying risk factors for the help of a two-year federal grant, chronic kidney disease progression and praised her drive, enthusiasm, patience, and she is recruiting more minority advocacy for her mentees. “I try especially to mentor women and people who may patients for lupus clinical trials. The be underrepresented in medicine because I think that it’s important to get more peo- disease is two to three times more ple with diverse backgrounds into research,” Dr. Melamed says. Her research inter- prevalent among women of color, ests include the epidemiology of, and ethnic and racial disparities in, chronic kidney particularly Hispanics, than among disease, vitamin D deficiency, and the health consequences of metabolic acidosis. Caucasian women.

MAGAZINE.EINSTEIN.YU.EDU 5 CAMPUS NEWS

Enhancing Einstein, Inside and Out

rom new outdoor benches and lighting to completely refurbished lobbies, several projects begun in 2019 are Fmaking Einstein a better place to work and live. “Upgrading and modernizing our grounds and facilities and investing in enhancements to our campus community are a priority,” says Gregg Tarquinio, Einstein’s associate dean for administration and finance. The renovations have included adding new furniture and lighting to student housing, the Belfer Educational Center, and the D. Samuel Gottesman Library study area. Necessary structural improvements have involved upgrading elevators and replacing air conditioners in several buildings. Audiovisual equipment has been replaced in auditoriums, lecture halls, and conference rooms; wireless and wired networking technology is currently being overhauled campus- wide; and additional automated external defibrillator units have been placed in all buildings. In addition to those projects, the Clinical Research Center has moved from the Jack D. Weiler Hospital and the Leo Forchheimer Medical Science Building to space within the Van Etten Building, and the Magnetic Resonance Research Center has received a new 3T magnet and had its infrastructure upgraded.

THIS PAGE, at top: The renovated Belfer lobby welcomes visitors with new Einstein signage and terrazzo flooring. At left: New tables and chairs adorn the lobby at the 1925/1935 Eastchester Road Residence Complex. OPPOSITE PAGE, at top: First-year medical students assem- ble before class in the renovated Belfer basement. Middle left: First-year medical student Christina Pil does some laptop work on a new couch in the Belfer basement. Middle right: Inspiring words from Albert Einstein decorate the Belfer lobby. Two bottom photos: Students convene on new couches in the expansive 1925 student housing lobby. Photos by Jorg Meyer Photos by Jorg

6 EINSTEIN : WINTER/SPRING 2020 Photos by Jorg Meyer MAGAZINE.EINSTEIN.YU.EDU

7 MONTEFIORE AND EINSTEIN MAVENS OF MEDICINE

Ensuring Diversity onathan E. Alpert, M.D., Ph.D., is the in Mental Health Dorothy and Marty Silverman Chair in JPsychiatry and chair of the department Research of psychiatry and behavioral sciences at Einstein and Montefiore. Dr. Alpert arrived in 2017 from Q&A with Massachusetts General Hospital, where he was Dr. Jonathan Alpert associate chief of psychiatry and director of the depression research program. He was also the first incumbent of the Joyce Tedlow Chair in the field of depression studies at Harvard Medical School.

8 EINSTEIN : WINTER/SPRING 2020 Why did you specialize in Was the Einstein and Montefiore Einstein Student Mental Health Center, psychiatry? consolidation an attraction? which provides expert, accessible evalua- It is a remarkable field that spans basic Yes, very much. Among other things it tion and treatment for medical and grad- neuroscience, clinical pharmacology, and created the opportunity for psychiatry uate students on the Einstein campus. social, emotional, and cognitive develop- to partner with Einstein’s exceptional ment. It engages fundamental questions department of neuroscience—one of the Do people in the Bronx face such as what it means to be human and world’s first freestanding neuroscience unique mental health challenges? to live a good life. On a more personal departments. Working with neurosci- Many patients we see have experienced level, I think clinicians are drawn to ence, we’ve launched PRIME (Psychiatry some kind of major trauma. It might be different forms of human suffering. As Research Institute at Montefiore and physical violence, poverty, housing inse- long as I can remember, I’ve been drawn Einstein) in a refurbished research space curity, dislocation from their country of to suffering related to psychiatric condi- on the fourth floor of Van Etten. origin—significant burdens that increase tions and to people traditionally margin- the risk of mental illness and addiction. alized in society and in healthcare due to What does PRIME do? mental illness or addiction. PRIME will allow us to greatly increase Could more be done to prevent clinical and translational research in psy- mental health problems from What influenced you to leave chiatry. Our health-equity research pro- developing? Boston? gram within PRIME will enable us to Certainly. We can do more to impart My wife and I were empty nesters, with study how factors such as socioeconomic practical coping and resilience skills in two young-adult sons off at school, so status, ethnicity, and sexual or gender our school systems and to support good we were at an inflection point when I orientation affect mental health out- parenting skills, particularly for parents was contacted about the department comes. PRIME brings together clinically who’ve experienced early life adversity chair opportunity here. I was grateful focused people like me and outstanding and trauma and aren’t fully equipped for the wonderful career, outstanding basic scientists, many of whom share a to be the parents they want to be. We colleagues, and formative opportunities devotion to unraveling the mysteries of need to enhance access to affordable, I’d had in Boston. But with, I hope, a mental illness. We’re fortunate that our high-quality mental health services to decade or more of active professional clinical programs serve diverse commu- address problems early on before they life ahead, it seemed like an ideal time nities that are exceedingly underrepre- become severe and chronic. to make a meaningful contribution sented in studies on mental illness and elsewhere. addiction. We have the obligation to What has been the main focus of ensure that these diverse voices are better your research? Were you familiar with Einstein represented in psychiatry research. I’ve been interested in mood disorders, and Montefiore? particularly treatment-resistant major I knew of Einstein and Montefiore by What other programs have you depressive disorder. Available therapies reputation and of Montefiore’s lead- started? don’t work well enough for far too many ing national role in behavioral-health We have many new programs, thanks individuals, and those gaps in knowledge integration in primary care and school mainly to strong interdepartmental and treatment continue to motivate me. health. And when I came here for collaborations. We’ve worked with the interviews I was inspired by what I Children’s Hospital at Montefiore emer- Have you read any good books saw: a special place where commit- gency department to develop a special- lately? ments to advancing social justice and ized pediatric psychiatry emergency I’m now reading Sapiens: A Brief History science—two values very important to service to improve the care of children of Humankind, by Yuval Noah Harari. It me—are seamlessly interwoven and fully presenting with psychiatric problems. raises fascinating, provocative questions embraced across campuses. We’ve also joined with the dean’s office about our improbable ascendancy as the

Photo by Jason Torres and Montefiore leadership to create the dominant species on the planet.

MAGAZINE.EINSTEIN.YU.EDU 9 RESEARCH NOTES Firefighter Heart Disease Linked to WTC Exposure

dust was thick- autoimmune rheumatologic diseases est—have a 44% and for a blood-cancer precursor that increased risk of can lead to the cancer multiple myelo- CVD compared ma—“highlights the need to add these with those who health conditions to the list of WTC- arrived later in the related diseases that are coverable under day. The study the James L. Zadroga 9/11 Health and was published in Compensation Act,” Dr. Prezant adds. September 2019 Other studies have linked both acute in JAMA Network and prolonged exposure to air pollution Open. to CVD. The authors noted that the “The increase firefighters’ exposure to dust and prod-

Photo by Neville Elder/CORBIS/Corbis via Getty Images in risk was signif- ucts of combustion could have triggered icant, even taking into account known persistent disease processes involving study of nearly 10,000 New CVD risk factors such as age, hyperten- chronic inflammation that increased York City firefighters has found sion, elevated cholesterol, diabetes, and their risk for CVD years later. A that exposure to 9/11 World smoking,” says study leader David J. “Our results emphasize why it is Trade Center (WTC) dust is associated Prezant, M.D., professor of medicine at crucial to monitor the long-term health with a significantly increased long-term Einstein, a pulmonary disease specialist of anyone exposed to massive environ- risk of cardiovascular disease (CVD). at Montefiore, and chief medical officer mental disasters, even many years after The study was conducted by research- of the FDNY. the event,” says co–lead author Rachel ers at Einstein, Montefiore, and the Fire This study’s finding of an increased Zeig-Owens, Dr.P.H., research assistant Department of the City of New York risk of CVD with WTC exposure—as professor of epidemiology & population (FDNY). Firefighters who arrived first well as the researchers’ earlier stud- health at Einstein and an epidemiologist at the WTC site—when the airborne ies identifying an increased risk for at Montefiore and the FDNY.

Promising Treatment for Cancer-Caused Anemia

n myelodysplastic syndrome (MDS), 2019 in Clinical Cancer Research, come Dr. Verma and colleagues developed a cancer of the bone marrow, anemia from an international phase 2 clinical galunisertib using tumor samples I occurs because the proliferation of trial conducted at 14 centers in Italy, from patients at Montefiore. The drug abnormal blood cells leaves people with Spain, and Germany. The study’s inhibits a molecule called ALK5 that too few normal ones. An experimental principal investigator was Amit K. plays a role in activating defective MDS cancer drug called galunisertib may Verma, M.B.B.S., professor of medicine stem cells. offer a way to treat anemia in low- to and of developmental and molecular The research was co-led by Valeria intermediate-risk MDS patients without biology at Einstein and director of Santini, M.D., associate professor of the need for blood transfusions. the division of hemato-oncology at hematology at the University of Florence The findings, published in September Montefiore. in Italy.

10 EINSTEIN : WINTER/SPRING 2020 Unexpected Origin of Hospital Infections

he intestinal bacterium six months, 38% of those Clostridium difficilecan be lethal carriers progressed to T and is difficult to treat. Each year symptomatic C. diff; by it sickens about half a million Americans contrast, only 2% of ini- and causes about 30,000 deaths. C. diff, tially noninfected patients as it’s called, has long been thought to ended up with symptom- infect people hospitalized or in other atic C. diff. healthcare facilities. But in a study pub- The U.S. Centers lished in December 2019 in Infection for Disease Control and Control and Hospital Epidemiology, Prevention considers the researchers report that nearly one in prospective identification 10 patients admitted to the hospital of C. diff carriers a “sup- is already infected with C. diff, even plemental intervention” though they do not have symptoms. but doesn’t recommend The researchers, led by Sarah Baron, it as a prevention strategy. This study Baron is an assistant professor of medi- M.D., M.S., tested 220 incoming hospi- suggests that prospectively identifying cine at Einstein and director of inpatient tal patients with no symptoms of C. diff and treating carriers could help prevent quality improvement in the department and found that 21 were infected. Within C. diff–related illnesses and deaths. Dr. of medicine at Montefiore.

Growing Retinas in the Lab

t’s not easy to study the retina and resemble human tissues or organs— its diseases—in particular, macular have emerged as powerful models for Idegeneration, the leading cause of studying human development and irreversible vision loss in people over disease. They are derived from stem 60. The retina’s macula, a small spot in cells—in this case, human embryonic the center of the retina where vision is stem cells, which Dr. Liu and his col- the sharpest, is crucial for both central leagues coaxed to develop into retinal vision and visual acuity. It is also rich in organoids. cones, the photoreceptors that enable Cone-rich retinal organoids could color vision. But the macula is unique to be a valuable resource for studying the primates, and nonhuman primates are biology of the human retina and may extremely costly to study. help reveal the molecular glitches that Now, as reported in May 2019 in the Cones (red) and rods (green) in a retinal affect the retina, leading to treatments Proceedings of the National Academy of organoid cultured for about 7 months. for macular degeneration and other Sciences, Einstein scientists have for the blinding retinal diseases. first time successfully produced cone- ophthalmology and visual sciences and WATCH THE VIDEO rich retinal organoids that resemble the of genetics at Einstein. See photoreceptor cells in a human macula. The research was led by Organoids—tiny clumps of retinal organoid come to life in 3-D. Wei Liu, Ph.D., assistant professor of cells grown in tissue culture that magazine.einstein.yu.edu/retina20

MAGAZINE.EINSTEIN.YU.EDU 11 RESEARCH NOTES Lab Chat

ichael Berney, Ph.D., is a microbiologist who studies Mycobacterium tuberculosis (Mtb), the microbe that causes TB. Dr. Berney was M born in Switzerland, where he studied environmental sciences and microbiology at the Swiss Federal Institute of Technology in Zurich, which was also Albert Einstein’s alma mater. After completing a postdoctoral fellowship in bacterial bioenergetics in New Zealand, he came to Einstein to collaborate with TB pioneer William Jacobs, Ph.D. Dr. Berney joined the Einstein faculty in 2016, where he is an assistant professor of microbiology & immunology.

How did you become interested in For TB researchers, what is special microbiology? about Einstein? During my education in Switzerland, I We have world-class infrastructure was a visiting student in environmental for TB research and various groups sciences at the Massachusetts Institute of studying TB from every angle, from Technology, and we studied a polluted bacteriology to immunology to clinical lake outside Boston. Industrial toxic epidemiology. You get to learn about so chemicals were leaking in but, oddly, many aspects of the disease. toxins weren’t flowing out. We learned that bacteria, and not some inorganic What are you studying now? process, were degrading the chemicals. We’ve uncovered vulnerable compo- That opened my eyes to the importance nents of Mtb metabolism: the aspartate of microbes in shaping the environment. pathway and the respiratory chain. In papers published in 2019 in Nature Why did you become a TB Communications and in 2017 in PNAS, researcher? we wrote about finding ways to eradi- I was looking for a postdoc where I cate Mtb persisters—the bacteria that could dive into a bacterium that matters resist conventional treatment. We’re to human health and found a position at now testing combinations of existing the University of Otago in New Zealand and novel enzyme inhibitors in vitro

with Gregory Cook, an expert in myco- and in animal models. Dr. Berney wears a protective Tyvek suit as bacterial bioenergetics. he enters Einstein’s Biosafety Level 3 facility Is there anything about you that to study Mycobacterium tuberculosis. And what led you to Einstein? people would be surprised to A paper we published in 2010 caught know? Have you read anything interesting Dr. Jacobs’ eye, and we started to talk I was a ski instructor in Switzerland lately? about possible collaborations. Two years and then in New Zealand during my Currently, I am reading The ONE Thing: later, I asked Dr. Jacobs if I could work days at university. The Surprisingly Simple Truth Behind in his lab. I didn’t anticipate that I’d end Extraordinary Results [by Gary W. Keller up on the faculty. But that’s what you Do you have any hobbies? and Jay Papasan]. I also like to read get with a scientific career. It takes you I have three children, ages 7, 9, and 11. biographies of great scientists, such as to unexpected places, and if you work They keep me very busy. But when I Albert Einstein and Craig Venter. And I hard and stay focused you can end up in have time, I love running, biking, just read The Remedy [by Thomas Goetz],

a great place to do science. and skiing. about the quest to cure TB. Photo by Jason Torres

12 EINSTEIN : WINTER/SPRING 2020 Bolstering Biopsies: Testing Novel Therapy for Acute Migraine Shows Promise Single Cells in Lupus Patients in Phase 3 Clinical Trial

cientists have used a powerful new cells. With scRNA-seq, we can see drug belonging to a new tool to zero in on individual cells the inner workings of different types generation of acute migraine Sin a patient’s diseased organ and of kidney cells and identify disease- A headache treatments elim- reveal the cells’ underlying abnormalities associated genetic ‘signatures’ within inated pain and reduced symptoms in gene expression—information that those cell types.” in a large-scale trial reported in July may allow for more-precise and more- The researchers found that 2019 in The New England Journal effective treatment. The findings, made scRNA-seq testing of skin cells mir- of Medicine. The drug, rimegep- by scientists at Einstein, Montefiore, rored the results obtained with kid- ant, is awaiting U.S. Food and Drug and other medical institutions, were ney cells—opening up the possibility Administration approval and may offer published in May 2019 in Nature that patients with lupus nephritis advantages over currently available Immunology. may one day be able to avoid kidney migraine medications. The study, The study involved 21 patients with biopsies altogether. led by researchers at Einstein and lupus nephritis (kidney inflammation), “While our study focused on the Montefiore, involved more than 1,000 which affects half of all people who have kidney,” Dr. Putterman says, “we’re men and women with migraine. systemic lupus erythematosus (SLE), optimistic that scRNA-seq can “For the first time in nearly three a chronic autoimmune disease that potentially be similarly employed to decades, people with migraine not inflames and damages tissues and organs improve on results obtained from helped by existing medications may throughout the body. many other types of clinical biopsies, have a new option to find relief during “Lupus inflammation can destroy such as those done on the prostate, attacks,” says Richard B. Lipton, M.D., kidney tissue and is a leading cause of breast, and skin.” the study’s first author and the Edwin death among patients with SLE,” says S. Lowe Chair in Neurology, vice chair Chaim Putterman, M.D., the paper’s of the Saul R. Korey Department of co-corresponding author, professor of Neurology at Einstein, and director of medicine and of microbiology & immu- the Montefiore Headache Center. nology, and chief of rheumatology at Currently, many people with Einstein and Montefiore. migraine take triptan drugs (examples The kidney biopsy has been the gold include sumatriptan, eletriptan, and standard for diagnosing the condition, rizatriptan), which were introduced in assessing its severity, and monitoring the 1990s. People not helped by trip- patients’ response to therapy. But it tans may benefit from the new class of requires interpretation of stained tissue drugs called gepants, which includes sections, which is not always sufficiently rimegepant. accurate for assessing disease severity or Gepants work by targeting the guiding treatment decisions. receptors for the small protein CGRP, By contrast, Dr. Putterman says, long implicated in migraine. During “we used a much more sensitive tool migraine attacks, CGRP is released, called single-cell RNA sequencing, or resulting in pain. Gepants relieve the scRNA-seq, which requires only a tiny pain and other symptoms of migraine amount of clinically obtained tissue to by blocking the CGRP pathway. reveal the gene expression of individual

MAGAZINE.EINSTEIN.YU.EDU 13 RESEARCH NOTES

MAJOR NIH RESEARCH AWARDS

Einstein and Montefiore Detecting Arterial Disease Understanding How Antibodies investigators received in the Legs Protect Against TB Lower extremity arterial disease (LEAD) Tuberculosis (TB) ranks among the 10 $178 million in research is a debilitating but under-recognized leading causes of death worldwide. To funding from the condition usually caused by fatty plaque develop an effective vaccine and new buildup in arteries carrying blood from immunotherapies against TB, research- National Institutes of the heart to the legs. LEAD typically ers need to better understand how the Health (NIH) during isn’t diagnosed until people experi- immune system works to prevent and ence cramping or pain while walking. control Mycobacterium tuberculosis federal fiscal year The National Institutes of Health has (Mtb) infection. The NIH has awarded 2019—the largest annual awarded a five-year, $8 million grant Jacqueline Achkar, M.D., M.S., a five- to Einstein’s Robert Kaplan, Ph.D., year, $3.7 million grant to investigate total in the College of and a Johns Hopkins co-investigator to the role of antibodies in protecting Medicine’s history. identify early symptoms of LEAD so it against TB. can be promptly diagnosed and treated. Dr. Achkar and colleagues are Some 6,000 participants in a community focusing on the surface glycans of health study will first undergo diagnostic Mtb, some of which elicit an antibody testing for LEAD. They’ll then be fitted response. The researchers particularly with wristwatch monitors to measure want to learn where on the glycans the daily activity. Comparing the monitor antibodies attach. Findings could fill a results with the diagnostic-test results critical gap in the current knowledge may reveal telltale patterns of activity about TB immunity and lead to new associated with LEAD. Dr. Kaplan is a strategies for developing both vaccines professor of epidemiology & population and antibody-based immunotherapies health and the Dorothy and William against TB. Dr. Achkar is an associate Manealoff Foundation and Molly Rosen professor of medicine and of micro- Chair in Social Medicine at Einstein. biology & immunology at Einstein.

14 EINSTEIN : WINTER/SPRING 2020 Curbing Heart Disease Preventing Diabetes in Finding an Enzyme’s Role Among Those With HIV Minority Men in Blood Stem-Cell Disorders Antiretroviral therapy has turned For people with prediabetes, a life- Myelodysplastic syndrome (MDS) is HIV into a chronic disease in the style intervention called the Diabetes a bone-marrow disorder arising from United States. Lifelong HIV infection, Prevention Program (DPP) has been defective hematopoietic (blood-forming) however, greatly increases the risk of shown to reduce their risk of developing stem cells (HSCs). The enzyme TET2 age-related diseases, including car- type 2 diabetes by 60% to 70%. Men controls how HSCs produce healthy diovascular disease (CVD). Chronic of color, however, are far less likely to blood cells and is frequently mutated inflammation triggered by the body’s enroll in the 12-month DPP and to in MDS. TET2’s normal catalytic immune response to HIV infection remain engaged if they do enroll. The activity is essential for suppressing contributes to CVD, but it’s not yet NIH has awarded Earle Chambers, MDS. Keisuke Ito, M.D., Ph.D., and known which genes are altered in this Ph.D., and Jeffrey Gonzalez, Ph.D., a Meelad Dawlaty, Ph.D., have found immune response. Robert Kaplan, five-year, $3.1 million grant to evaluate evidence that TET2 also suppresses Ph.D., has received a four-year, $3.3 Power-Up, a version of DPP tailored MDS through noncatalytic means. million grant from the NIH to iden- to black and Latino men. Men with The scientists have received a four-year, tify the genes that are over- or under- prediabetes will be randomly assigned $2.8 million NIH grant to conduct expressed in immune cells of people to a traditional coed DPP program or to further research into how TET2 acts living with HIV. Researchers hope Power-Up. The researchers will evaluate noncatalytically to suppress MDS. to find differences in blood cells that the participants’ engagement, as well Discovering additional ways in which can be targeted by existing medicines as weight loss and levels of hemoglobin TET2 influences MDS could lead to or to identify new targets for which A1c (a blood test indicative of diabetes). new treatments. Dr. Ito is the director drugs can be developed. Dr. Kaplan is Dr. Chambers is an associate professor of scientific resources of the Einstein a professor of epidemiology & pop- of family and social medicine and of Stem Cell Institute and an associate ulation health and the Dorothy and epidemiology & population health at professor of cell biology and of medicine William Manealoff Foundation and Einstein; Dr. Gonzalez is a professor of at Einstein; Dr. Dawlaty is an assistant Molly Rosen Chair in Social Medicine medicine and of epidemiology & popu- professor of genetics and a member of at Einstein. lation health at Einstein. the Einstein Stem Cell Institute.

MAGAZINE.EINSTEIN.YU.EDU 15

Chinazo O. Cunningham, M.D., M.S. CRTP Class of 2009 Professor of medicine (general internal medicine), of family and social medicine, and of psychiatry and behavioral sciences

t was in the mid-2000s when I first started to think critically about how I best to deliver care to people struggling with homelessness, drug use, and HIV. I THE was collecting data but didn’t know how to analyze it. When I look back at my first study, I cannot believe it was published, and I shudder at the thought of my name PHYSICIANon it. I’m proud I was able to do it, but the level of rigor was terrible. I finally realized I had to go back to school. Perhaps the most valuable things I learned in CRTP was how to do statistics, INVESTIGATORSuse statistical software, and write code. For the previous three or four years, I had all these questions about research methods, and all of a sudden they were being answered. It was amazing. Nowadays, I do less and less hands-on work with statistics, only because I work with statisticians who do it for me. What’s important is that I have the ability to discuss things with them. It eliminates any miscommunication between what I’m saying and what they’re hearing. During CRTP, I continued my studies of marginalized populations, publishing Einstein’s Clinicalabout Research ten papers on that Training work. My thesis Program (CRTP) marks project was to write a large, multi-site 20 years of givingNIH doctors grant. It didn’t getthe funded, right mainly skills for study success because I was ahead of curve in terms of BY GARY GOLDENBERG addressing this population. Nonetheless, that effort was a turning point. It was essentially the beginning of my NIH- funded research career. This is what I’ve n 1998 Einstein created its first terminal and Paul Marantz, M.D., M.P.H., the program always wanted to do. I love it. master’s degree program, leading to an has trained dozens of clinical research schol- M.S. in clinical research methods.One of my Atgoals that now is to makears sure in a variety of specialties. I that junior faculty don’t take the same time there were very few pathtraining I did. Ifprograms they’re interested in research,On the following pages five of those schol- for physicians like it acrossI tell the them country. they have to get the rightars skillfrom across the years talk about CRTP In the two decades since set.then, Four under years ago, the we developedand a gen how- it has made all the difference in eral internal medicine research fellow- guidance of director Aileenship, McGinn, and all of ourPh.D., fellows are requiredmaking to their research possible. and former directors Ellieenroll Schoenbaum, in CRTP. M.D.,

It’s a different world now for clinical researchers. Twenty or thirty years

16 EINSTEIN : WINTER/SPRING 2020ago, M.D.s usually didn’t pursue formal “Twenty or 30 years ago, M.D.s usually didn’t pursue formal research training. Programs like CRTP didn’t exist. Today, one might think that one could do research without this training, but there’s no way.”

— DR. CHINAZO CUNNINGHAM

One of my goals now is to make sure that junior faculty don’t take the same path I did. If they’re interested in statistics, use statistical software, and research, I tell them they have to get the CHINAZO O. CUNNINGHAM, write code. For the previous three or right skill set. Four years ago, we devel- M.D., M.S. four years, I had all these questions oped a general internal medicine research CRTP Class of 2009; associate division about research methods, and all of a fellowship, and all of our fellows are chief of general internal medicine at sudden they were being answered. required to enroll in CRTP. Einstein and Montefiore and professor Nowadays, I do less and less It’s a different world now for clini- of medicine, of family and social med- hands-on work with statistics, only cal researchers. Twenty or 30 years ago, icine, and of psychiatry and behavioral because I work with statisticians M.D.s usually didn’t pursue formal sciences at Einstein who do it for me. What’s important research training. Programs like CRTP is that I have the ability to discuss didn’t exist. Today, one might think that t was in the early 2000s when I first things with them. It eliminates any one could do research without this train- started to think critically about how miscommunication. ing, but there’s no way. I best to deliver care to people strug- During CRTP, I continued my gling with homelessness, drug use, and studies of marginalized populations Dr. Cunningham is currently the prin- HIV. I was collecting data but didn’t and published about 10 papers on that cipal or co-principal investigator on four know how to analyze the information. work. My thesis project was to write NIH grants: “Mentoring Researchers on When I look back at my first study, I a large, multisite National Institutes Drug Abuse and HIV,” “Resilience in cannot believe it was published, and I of Health (NIH) grant. It didn’t get HIV-Infected Drug Users,” “Does Medical shudder at the thought of my name on funded, mainly because I was ahead of Cannabis Reduce Opioid Analgesics in it. I’m proud I was able to do it, but the the curve in terms of addressing this HIV+ and HIV- Adults With Pain?” and level of rigor was terrible. I finally real- population. Nonetheless, that effort “The Center of Excellence in Promoting ized I had to go back to school. was a turning point—the beginning of Learning Health System Operations Perhaps the most valuable things my NIH-funded research career. This is and Research at Einstein/Montefiore

Photos by Jason Torres I learned in CRTP were how to do what I’ve always wanted to do. I love it. (EXPLORE)” (see page 22).

MAGAZINE.EINSTEIN.YU.EDU 17 gynecologic care. The award was a major going to be able to support part of M. DIANE McKEE, M.D., M.S. career milestone, and I would have been your salary as a clinician-investigator. CRTP Class of 1999; professor and far less likely to receive it without my Being able to network with more-senior chair, department of family medicine formal research training. The CRTP faculty bolstered my confidence that I and community health, University credential says to grant reviewers, “This could be successful in this career path. of Massachusetts Medical School, person really does have the skills to be Worcester an investigator.” Dr. McKee is the former director of the There was another side effect of New York City Research and Improvement hose who stand to benefit most CRTP as well. By staying here, as Networking Group, sponsored by Einstein’s from CRTP are researchers on opposed to going to an outside mas- department of family and social medicine, T the verge of becoming inde- ter’s degree program, I was exposed to where she oversaw a wide range of pendently funded investigators. That researchers across multiple departments practice-based research and quality- describes me in the late 1990s. I was in the Einstein and Montefiore world. improvement efforts, with the goal of starting to do clinical research, but I It was like becoming part of a family. improving care for the urban underserved. soon realized there were significant gaps There’s a real leap of faith that you’re in my knowledge of research methods, particularly in study design and statistics. CRTP offered a unique opportunity to focus on these and other core competencies—much more so than in a conventional master of public health program. During CRTP, I was able to continue to strengthen my research. It involved seeing how clinicians in community health settings communicate results to patients about mildly abnormal Pap smears and what patients understood about those results. Several papers came out of that work. It was incredibly valuable having not one but several mentors during CRTP. One helped me with statistics, another with qualitative methods. My primary mentor was Michael Mulvihill [then director of the division of research in family medicine, and now professor emeritus], who was, and still is, my most important mentor in terms of my overall career development. Immediately after the program, I received a Robert Wood Johnson Generalist Physician Faculty Scholar Award, which I used to explore barriers that adolescent girls face in starting

18 EINSTEIN : WINTER/SPRING 2020 “That’s the sign of a true mentor: someone who knows what’s good for you and pushes you in directions that you might not otherwise go.”

— DR. THOMAS OW

and molecular characteristics of head and neck squamous-cell cancer and tumor-cell resistance to cisplatin and radiation. writing. That’s the sign of a true mentor: CRTP was instrumental in helping THOMAS J. OW, M.D., M.S. someone who knows what’s good for me develop my research and submit a CRTP Class of 2017; associate profes- you and pushes you in directions that competitive grant application. It has sor of otorhinolaryngology–head & neck you might not otherwise go. truly improved my ability to differenti- surgery and of pathology at Einstein My primary mentors were (and still ate outstanding research from work that and Montefiore are) Evripidis Gavathiotis [professor of has inherent design flaws. I feel like a biochemistry and of medicine], who has true expert when I discuss clinical and was hired at Einstein and Montefiore helped me stay current with experimen- translational research with my peers and in 2012 to be a surgeon-scientist. I’d tal therapeutics and cancer cell signal- leaders in the field. If programs such as I had some experience in basic and ing, and Chandan Guha [professor of CRTP were universally available, I think translational science and wanted to radiation oncology, of pathology, and of science and research would advance continue building our head and neck urology], whose expertise in radiation more quickly. cancer research program, which has a biology, immunology, and stem-cell strong relationship with the department biology has helped me move my research Dr. Ow specializes in the surgical treat- of pathology. into those fields. Having a basic scientist ment of head and neck tumors, including In 2015, I was accepted as a K12 and a translational investigator as my those that occur in the mouth, throat, Paul Calabresi scholar, which required mentors is critical for someone like me, larynx, neck, sinuses, salivary glands, and work in career development. One of my who is balancing a career that combines thyroid gland, and of skin cancers that senior colleagues, Mark Einstein, was a lab work and patient care. occur on the scalp, face, and neck. He is a CRTP graduate, and he strongly sug- At the end of CRTP, I received translational investigator who is focused on gested that I enroll in CRTP. It wasn’t an a National Institutes of Health K23 molecular and genomic alterations in head ultimatum, but he wisely advised that I Mentored Research-Scientist Career and neck squamous-cell cancer that can be needed more experience with statistics, Development Award. My project focuses used to develop important biomarkers and clinical research study design, and grant on the association between key genetic treatment targets.

MAGAZINE.EINSTEIN.YU.EDU 19 “CRTP changed absolutely everything. It would be hard to overstate the effect it had on my life.”

— DR. WILLIAM SOUTHERN

in class to my CRTP research project—a redo of that hospitalist versus nonhospi- talist study, with a new study design, new data analysis, new everything. I ultimately did publish my work in 2007, the year I graduated from the CRTP course. That was only the beginning. I’ve published dozens of papers since then. CRTP changed absolutely everything. It would be hard to overstate the effect it had on my life. I once thought conducting research was inacces- sible to me, but it has turned out to be an extraordinarily rewarding part of my career, personally and professionally. Today, my job entails running the medicine services at Montefiore’s Moses, or even write a paper—and I guess it Weiler, and Wakefield campuses. The WILLIAM SOUTHERN, M.D., showed. Before sending the paper off to skills that I took away from CRTP have M.S. a journal, I gave it to my division chief, allowed that work to flourish. As before, CRTP Class of 2007; chief of the division who gently said, “Maybe you’ll get it I have access to patient data, but now I of hospital medicine at Einstein and published someday, but if you want to have the ability to draw valid conclusions Montefiore and professor of medicine do research, you’ll need additional train- about the type of care we offer and how (hospital medicine) at Einstein ing.” After that humbling experience, I we can do it better. I would never have enrolled in CRTP. been able to do that before CRTP. ’d been working as a hospitalist for 10 It would be hard to single out which years, mostly providing clinical care CRTP course was the most important. In May 2019, Dr. Southern was the senior I and teaching. Then I decided it would The statistics courses were certainly author of a study showing that patient safety be a good idea to study the relative effec- invaluable, where I learned statistical is not compromised by allowing physicians tiveness of hospitalist versus nonhospi- principles and how to use statistical to view multiple electronic patient records talist care, based on data from electronic software, among many other things. So, at the same time—a practice barred at health records. I didn’t know much too, were the courses in epidemiology 40% of the hospitals across the nation. The about how to design a study, collect data and grant writing. Almost immediately, paper was published in the Journal of the in a rigorous way, do statistical analyses, I was able to apply what I was learning American Medical Association.

20 EINSTEIN : WINTER/SPRING 2020 It was fascinating, this idea that CRTP was a real eye-opener. JOE VERGHESE, M.B.B.S., M.S. doing two things can interfere with your Interacting with students and faculty CRTP Class of 2000; professor in the ability to do a third thing. There were a from different disciplines and in dif- Saul R. Korey Department of Neurology, few case reports in the literature about ferent stages of their careers gave me a the Murray D. Gross Memorial Faculty this, showing that those nursing home broader perspective on research life, on Scholar in Gerontology, and director of residents who had to stop walking while the intersection of clinical and research the Jack and Pearl Resnick Gerontology talking were the ones who fell most duties, and on possible career paths. Center often. I decided to create my own walking- Dr. Verghese serves as clinical director of didn’t go to medical school because while-talking divided-attention test. I the NIH-funded Einstein Aging Study, I wanted to become a doctor; I went discovered that elderly people whose a longitudinal study examining both I because I was good at my studies. In walking had slowed down by a third had normal aging and the special challenges time I realized that what I really wanted a huge risk of falling during the next of Alzheimer’s disease and other disorders to be was a researcher. I started doing year. This idea led me in many different involving cognitive decline. He is a three- clinical research during my residency in directions, and I’ve incorporated it into time recipient of the CRTP Mentor of the neurology here at Montefiore, but I was many of my studies. Year Award. a bit worried because my computing and math skills weren’t all that great. As luck would have it, CRTP was just getting started when I was finishing my fellowships [in aging and demen- tia and in neurophysiology]. Since I was already familiar with Einstein and Montefiore, I didn’t want to go elsewhere to learn more about clinical research. Right from the beginning, the program had a practical emphasis. It gave us the tools to succeed as clinical researchers—tools such as statistics and epidemiology and study design—and I could see immediate applications in my studies. One of the best aspects of CRTP is that it can accommodate each student’s needs. For example, I decided to change my thesis when I came up with a better study idea. I was already halfway through the program, but the faculty were supportive. As it happened, one day a colleague told me that he saw two older women walking and talking and they were so engrossed in their conver- sation that, when they came to a door, they didn’t know what to do.

MAGAZINE.EINSTEIN.YU.EDU 21 BY GARY GOLDENBERG

22 EINSTEIN : WINTER/SPRING 2020 FORGING THE FUTURE OF MEDICINE Einstein and Montefiore scholars meld research with data to improve patient care 0 BY TERESA CARR 1

ll too often, cancer cells can break away from breast, prostate, and other tumors and travel through the bloodstream to different parts of the body. For some A 330,000 Americans, that means living with cancer that has metastasized, or spread, to their bones. Metastases can crop up anywhere in the skeleton, most commonly in the spine, where they can weaken bones and lead to fractures. Identifying and treating spinal tumors early—before they can cause severe pain and disability—helps people live longer and better lives. But that’s easier said than done. “Early symptoms, such as back pain or fatigue, caused by bone metastases are so subtle and common that they’re easily overlooked,” says Parsa Mirhaji, M.D., Ph.D., director of clinical research informatics at Einstein and Montefiore and director of the Center for Health Data Informatics. He notes that the tumors themselves are rare and, in the earliest stages, hard to spot on images—even by highly skilled radiologists. “A radiologist may review 50,000 MRIs of patients with back pain and only 10 will have a spine metastasis; it’s like looking for the proverbial needle in a haystack,” Dr. Mirhaji says. “And even when scans reveal a possible tumor, it can take weeks to follow up and get patients to the appropriate specialist for treatment—a critical delay that can allow tumors to progress.”

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EXPLORE grant co-principal investigators, from left, Chinazo Cunningham, M.D., M.S.; Michael Rinke, M.D., Ph.D.; and Paul Marantz, M.D., M.P.H.

Core at the Harold and Muriel Block Institute for Clinical and Translational Research at Einstein and Montefiore. “With an LHS, you’re constantly improving and innovating to achieve best practices, which you incorporate into the healthcare you deliver.” An LHS “epitomizes evidence-based medicine and is the best way to get at complex medical issues like detecting spinal metastases,” says Vijay Yanamadala, M.D., M.B.A., M.S., assistant professor of neurological surgery at Einstein and director of the Center for Surgical Optimization at Montefiore. In fact, he says, the logic behind an LHS is not unique to healthcare. “To devise a game plan, football “In the simplest terms, A STRATEGY FOR coaches use what they learn from try- an LHS is a system COMPLICATED CASES ing different configurations and plays In order to solve complex medical during practice,” Dr. Yanamadala says. where research and problems, a talented group of young “After game day, the team goes over data collection inform researchers at Einstein and Montefiore the films to see what worked and didn’t is harnessing the power of something work, and it then builds on its anal- practice and, in turn, called a learning health system (LHS). ysis of those data to develop a better practice influences Combining research, data, and a cul- strategy.” ture dedicated to continuous improve- But medicine has been reluctant to research.” ment, the LHS educates physicians and let data steer it toward better healthcare. develops ways to more efficiently care “Multiple studies show that when a new — DR. MICHAEL RINKE for people. Not only do patients bene- and better way to treat patients comes fit from state-of-the-art care, but their out, it takes about 17 years to be widely experiences are helping drive the future adopted,” Dr. Rinke says. “The classic of medical research. example we give in quality improvement “In the simplest terms, an LHS is a is that we’ve all tried to change some- system where research and data collec- thing about ourselves—exercise more, tion inform practice and, in turn, prac- for instance, or get more sleep—and it’s tice influences research,” says Michael really challenging. Changing things in a Rinke, M.D., Ph.D., associate professor workplace can be just as hard.” of pediatrics at Einstein and co-director One of the main goals of LHS of the Health Research Implementation research is to greatly shorten that

24 EINSTEIN : WINTER/SPRING 2020 17-year lag time, he says. And Einstein and Montefiore are at the forefront of this approach. “We have incredible researchers who analyze data—primar- ily information from patients’ electronic health records—to continuously generate information aimed at solving problems,” Dr. Rinke says. “But just as important, once a new treatment or tool has been rigorously tested, we have an equally strong operations group to integrate it into our systems to make sure that all patients benefit.” Dr. Yanamadala, in collaboration with Dr. Mirhaji, is using LHS practices to detect and treat spinal tumors. Dr. Mirhaji is creating a machine-learning algorithm to do what no human can: analyze millions of pieces of data— images, lab results, doctors’ notes, and more—to uncover the patterns indicating that a patient’s cancer may have spread. “Physicians are only human, so they can factor only about seven variables— things like blood pressure, pulse rate, Parsa Mirhaji, M.D., Ph.D., processes data generated by the EXPLORE scholars. and body temperature—into their Physicians can factor about seven variables into their decision-making process, he says. decision-making process,” Dr. Mirhaji says. “But the algorithm can look at hundreds of different variables and using what you learn to continually 11 LHS Centers of Excellence in the draw conclusions regarding a patient’s improve—is where medicine is headed,” nation and the only one in the state of condition from that information.” Dr. Yanamadala says. “And Einstein New York. Dr. Yanamadala, for his part, is and Montefiore are at the cutting edge, “This is the first federal grant to train interviewing patients and their providers which is what drew me here.” investigators in the LHS model,” says and collecting other patient-care data to Dr. Rinke, who is also a co–principal uncover roadblocks that cause delays. THE NEW FACES OF MEDICAL investigator for the EXPLORE grant. The goal is to create a center staffed by a RESEARCH Traditionally, promising physician- variety of specialists, including neuro- Dr. Yanamadala is one of four scholars scientists such as Dr. Yanamadala surgeons, radiation oncologists, and who’ve recently joined the new Einstein approach medical institutions with physiatrists. The new center will enable and Montefiore LHS center—known research questions they’d like to pur- patients to receive prompt, appropri- as the Excellence in Promoting LHS sue. EXPLORE turns that model on its ate treatment in one place for spinal Operations and Research at Einstein head, Dr. Rinke says. It first identifies metastases. and Montefiore, or EXPLORE. It was high-priority questions—such as how to “This way of operating—constantly established in November 2018 with a detect bone metastases early—and then

Photos by Jason Torres collecting and analyzing data and $3.3 million federal grant—one of only seeks applicants with the experience and

MAGAZINE.EINSTEIN.YU.EDU 25 FORGING THE FUTURE OF MEDICINE

EXPLORE scholar Vijay Yanamadala, M.D., M.B.A., M.S., uses learning health system practices to detect and treat spinal metastases.

that we can use all those data—not only to figure out the right things to do clinically, but to influence complex health systems to adapt and be willing to implement new evidence.” To that end, he says, EXPLORE brings together professionals from all parts of the healthcare system—from physicians and nurses to data scientists and pharmacists. “Their collaboration is key in a learning health system,” he emphasizes. “There’s great value in having people from different disciplines and different levels of the health system leadership sitting around the same table,” says Chinazo Cunningham, M.D., M.S., a co–principal investigator for the EXPLORE grant. “That takes discussions to another level where we’re able to see beyond our respective roles and consider how best to make changes in a complex system. And by publishing ”This way of operating— the intense curiosity to answer those what we’ve learned about improving constantly collecting questions. clinical practice, we’re helping patients “A major advantage to that approach at other hospitals and health systems and analyzing data and is that we can have all the resources in benefit as well.” using what you learn to place for the scholars to hit the ground The EXPLORE program “reflects the running,” says Paul Marantz, M.D., changing culture of medical research,” continually improve— M.P.H., associate dean for clinical says Shalom Kalnicki, M.D., chair of is where medicine is research education and a co-principal radiation oncology at Einstein and investigator on the grant. He notes Montefiore and one of Dr. Yanamadala’s headed.” that each scholar will have both clin- mentors. “Research done at wet-lab ical and health-systems mentors, plus benches using test tubes and animal — DR. VIJAY YANAMADALA access to expertise in sophisticated data models is vital,” he says. “But research processing. increasingly is being done by computer The abundance of medical data modeling, with results that can be fed now stored digitally “amounts to a into an LHS. I feel that these young treasure trove for an LHS center like investigators we’re training and mento- EXPLORE,” Dr. Marantz says. “At the ring in collaborative research represent heart of the LHS model is the notion the future of medicine.”

26 EINSTEIN : WINTER/SPRING 2020 FOUR SCHOLARS AND THEIR COMPLEX CHALLENGES The four Einstein and Montefiore WHAT IS A EXPLORE scholars (three more will LEARNING HEALTH SYSTEM? be selected next year) take courses and undergo training in three areas essential for a career as an LHS investigator: health-information technology, quality INFOGRAPHIC improvement, and clinical research. LEARNING HEALTH SYSTEM Applying their new skills and their previous experience, the scholars work with mentors to solve thorny healthcare problems. As noted above, Dr. Yanamadala’s EXPLORE project leverages the power of an LHS to research ways to detect Knowledge Practice and treat spinal metastases. “Vijay is a skilled spine neurosurgeon, but he’s dedicated to improving care by reduc- Identify and Apply knowledge ing the need for surgery,” Dr. Kalnicki evaluate evidence gained to improve says. “From the bottom of his physician regarding clinical quality of care for heart, he feels compelled to find ways to challenges patients improve patients’ quality of life, to really PATIENTS make a difference.” The projects of the other three EXPLORE program scholars are described below.

Using Electronic Health Records to Spot Sepsis Sepsis—the body’s overwhelming and potentially fatal response to infection— is the most expensive inpatient problem in American hospitals, costing an estimated $27 billion yearly. Kaitlyn Philips, D.O., M.S., assistant professor Data of pediatrics at Einstein and an attending physician at the Children’s Hospital at Montefiore (CHAM), is pursuing an Assess performance and create a EXPLORE project aimed at improving feedback cycle for continuous the care of sepsis patients. improvement of care Dr. Philips says that her experience treating sepsis in children, who often Source: Adapted from the Agency for Healthcare Research and Quality, display more-subtle symptoms than Journal of Hospital Medicine, May 2019. adults, helps in her effort to recognize

MAGAZINE.EINSTEIN.YU.EDU 27 FORGING THE FUTURE OF MEDICINE

”Being able to predict sepsis at an early, treatable stage. “I’m alerts and make them more usable to which patients are at able to act as a liaison between the help physicians identify patients at pediatric and adult worlds in sepsis high risk for sepsis and treat them,” risk and to prompt research,” she says. Dr. Philips says. “Being able to predict doctors to quickly take One-third of patients who die in which patients are at risk and to prompt hospitals have sepsis. But according to doctors to quickly take preventive action preventive action can Dr. Philips, the challenge is diagnosing can save lives.” save lives.” sepsis early enough to save lives—before the heart weakens and organs start shut- Connecting At-Risk Patients Via ting down. For her project, Dr. Philips Big Data — DR. KAITLYN PHILIPS is sifting through the electronic health After a divorce, Montefiore outpatient records of patients whose organs have Fatoumata Camara lost her apartment, failed due to sepsis. and she and her four children wound Sepsis can progress rapidly, and it’s up living in a homeless shelter for a not known why one patient develops year. Montefiore community health it and another, similar patient doesn’t. worker Janet Gonzalez was determined “Once we can identify early signs and to find the family a place to live—and symptoms that these patients have in succeeded. “Now that we have a home, common we can modify electronic we’re sleeping better, eating better—I’ve even lost weight,” Ms. Camara says. Research confirms that the health of people like Ms. Camara improves when healthcare systems link them with community resources. But what’s the best way to identify those outpatients, like Ms. Camara, most in need of a community health worker’s help? Asking all Montefiore outpatients to fill out a social-needs survey isn’t practical. So for his EXPLORE project, Kevin Fiori, M.D., M.S., M.P.H., assistant professor of pediatrics and of family and social medicine at Einstein and an attending physician at Montefiore Medical Group Pediatric Practice, is using data to identify people most likely to need social services and then developing strategies to alert clinical teams to administer surveys and, when

EXPLORE scholar Kaitlyn Philips, D.O., M.S., uses electronic health records to predict which patients are most at risk of developing sepsis.

28 EINSTEIN : WINTER/SPRING 2020 ”Montefiore already has social-needs data on over 50,000 patients— an impressive amount of information.”

— DR. KEVIN FIORI

EXPLORE scholar Kevin Fiori, M.D., M.S., M.P.H., uses social-needs data on more than 50,000 Montefiore patients to identify people most in need of help from community health workers. warranted, connect those patients to community health workers.” various community health workers in A key aspect of the research is what’s the clinic. known as “implementation science,” he Dr. Fiori recently spent 15 years says. “It involves repeatedly tweaking directing a nongovernmental organi- processes to work out all the details.” zation in Togo that uses community For example, who’s responsible for health workers to address health dispari- inputting data on patients coming in ties and improve care. His insights from for appointments so that doctors can Africa should help with his EXPLORE discover who should be screened? And project. what’s the best way to alert physicians to “Montefiore already has social-needs administer a survey? data on over 50,000 patients—an “Once we have optimized the impressive amount of information,” screening process in our pilot clinic, we Dr. Fiori says. “If the algorithm reveals will be able to incorporate that process which of those patients could benefit throughout the Montefiore system,” Dr. from taking a social-needs survey, the Fiori says. He adds that he hopes the next step is to find the best way to effi- findings from his EXPLORE research ciently integrate into a busy clinic the will eventually benefit patients in the screening and subsequent referrals to larger world.

MAGAZINE.EINSTEIN.YU.EDU 29 HOW A LEARNING SYSTEM CAN SAVE LIVES

Ventilation (APPROVE) score. APPROVE continuously monitors the records of hospitalized patients and can alert doctors, raising red flags up to 48 hours before symptoms become life threatening. In validating APPROVE, the researchers found that 20% of patients with high APPROVE scores at any time during their hospital stays either will develop respiratory failure requiring mechanical ventilation or will die in the hospital, compared with only 1% of patients with low scores. A 2018 study, conducted at multiple medical centers, compared existing early-warning measures with APPROVE. Results showed that APPROVE was the most accurate, with fewer false alarms, in identifying hospitalized patients at risk of death Using data from more than 68,000 patient encounters at Montefiore and the Mayo Clinic, or in need of breathing machines. Michelle Gong, M.D., helped develop the Accurate Prediction of Prolonged Ventilation (APPROVE) score for predicting respiratory failure or death in critically ill patients. “One of the most exciting outcomes of this study is that we were able to demonstrate that APPROVE multidisciplinary group at (NHLBI) to develop and test a pro- works in a variety of complex hospi- Einstein and Montefiore has gram that would (1) provide an early tal settings,” Dr. Gong says. “That A proved that the LHS model warning regarding which hospital- means that patients elsewhere, as can help medical advances reach ized patients were at high risk for well as those at Montefiore, can ben- patients faster—and save lives. respiratory failure and (2) prompt efit from it.” Respiratory failure causes severe providers to administer proven ther- APPROVE scores should help breathing problems and is a leading apies to those patients. even more if doctors are notified cause of death for hospitalized To create their early-warning about the best-possible treatments patients. “Knowing that a patient system, the researchers worked with for their patients. That’s where has a high risk of developing acute artificial-intelligence experts to comb the second fruit of Dr. Gong’s respiratory failure allows doctors through data collected from more NHLBI-funded research comes in: to take steps to address it,” says than 68,000 patient encounters at a patient-specific checklist, called Michelle Ng Gong, M.D., chief of Montefiore and the Mayo Clinic. PROOFCheck (Prevention of Organ the divisions of pulmonary medicine The researchers determined which Failure Checklist), of interventions and of critical care medicine at signs, symptoms, and other factors considered appropriate for that Einstein and Montefiore. could predict risk and then looked patient. Physicians also have the In 2014, Dr. Gong and her LHS for patterns of data indicating that option to call on critical-care spe- colleagues received a five-year, respiratory failure or death was likely. cialists for assistance. APPROVE and $1.9 million grant from the National The result: an algorithm called the PROOFCheck are now both in use at Heart, Lung, and Blood Institute Accurate Prediction of Prolonged Montefiore.

30 EINSTEIN : WINTER/SPRING 2020 FORGING THE FUTURE OF MEDICINE

Using Decision Tools to Prescribe once the prescribing protocol is solid, ”It’s exciting to Pain Medicine she plans to integrate it into Montefiore’s Opioid pain medications can effectively electronic-record system. “Ideally, the pull together a relieve pain after surgery. But opioids provider who is discharging a patient will multidisciplinary team are often started without a clear plan for be prompted with a recommended dose transitioning patients to safer forms of and tapering schedule for opioid pain to work on a project pain relief. As a result, as many as 1.6 medication as well as customized instruc- like this.” million Americans who have surgery tions for patients,” she says. each year wind up taking opioids over Dr. Groeger’s project also involves — DR. JUSTINA GROEGER the long term, increasing the risk of seri- developing a clinical decision tool to ous side effects such as opioid-use dis- help physicians tailor their pain medica- order and overdose. For her EXPLORE tion prescribing to patients’ individual project, Justina Groeger, M.D., assistant needs. Ultimately, she envisions using professor of medicine at Einstein and the clinical decision tool for other pur- data from electronic records accumulate an internist at Montefiore, is trying to poses as well, such as customizing doses and our ability to analyze those data figure out how to prescribe the right of insulin for patients with diabetes. improves, we’ll be relying on a pipe- amount of opioids to surgical patients. line of rigorously trained researchers to “The severity of pain is highly MINING DATA FOR BETTER harness data and take us into the future. dependent on the individual patient,” HEALTH Thanks to the EXPLORE grant, we’re Dr. Groeger says, “so a one-size-fits-all “Having an LHS means recognizing that fortunate to have this crack squad of approach doesn’t work when prescrib- every patient’s experience is an opportu- researchers focused on finding the best ing pain medication.” She is researching nity to learn as much as possible to help possible healthcare strategies and deliv- how to tailor opioid prescribing, starting the next person,” Dr. Rinke says. “As ering them to patients.” with the amount of pain medication a patient was taking before leaving the hospital and tapering the dose over several days at home. Using the LHS approach, Dr. Groeger is working with a team of clinicians, performance-improvement experts, and researchers to develop a protocol, test it in small groups of patients, and refine it based on feedback. “It’s exciting to pull together a multidisciplinary team to work on a project like this,” Dr. Groeger says. Initially, Dr. Groeger is studying people who’ve had knee replacements. But

EXPLORE scholar Justina Groeger, M.D., works with a team of clinicians, performance-improvement experts, and researchers to develop a protocol for prescribing the right amount of opioids to surgical patients.

MAGAZINE.EINSTEIN.YU.EDU 31 READY FOR ROTATIONS Einstein’s new Transition to Clerkship program helps third-year medical students shift from the classroom to the clinic

BY SUE BYRNE

32 EINSTEIN : WINTER/SPRING 2020 10-month-old girl sits in a contribute to the overall picture of their pediatrician’s office with her patients’ health and what they can do to A grandmother. Two days ago help,” says Todd Cassese, M.D., assistant she was in the hospital because a piece dean for clinical sciences at Einstein. of a candy bar was lodged in the air- way leading to her right lung. Doctors FROM SCHOOL TO HOSPITAL removed it successfully and she’s breath- The first two years of medical school are ing comfortably now, but her grand- much like regular college work—lots mother, who speaks limited English, has of studying, memorization, classwork, some questions. and practice exams with volunteers and She doesn’t understand the handout actors. But things change with the start about choking hazards that they were of the third year, when medical students given when they left the hospital or why begin a series of clerkships on hospi- they received it. She also wonders if the tal wards to learn how to take care of mold in their apartment might be con- patients under the supervision of medi- “We want students to tributing to the baby’s wheezing and to cal professionals. start thinking about her other granddaughter’s asthma. “Students have to apply their class- As the baby’s physician, what do you room knowledge in ways they haven’t all the aspects that focus on during this visit? The choking been asked to before,” Dr. Cassese contribute to the overall risks, certainly. But what about address- explains. “Now they will need to go ing what you suspect is food insecurity? on rounds with doctors and residents, picture of their patients’ And what about the mold problem? make oral presentations, and create daily health and what they Cases like the real-life one above hap- progress notes. That can be stressful and pen regularly in medicine. Third-year involve long hours. And as the most can do to help.” Einstein medical students used it as an junior members of the team, they won’t opportunity last summer to learn about have as much say regarding what they — DR. TODD CASSESE what they might face as they began their have to do and when they have to do it clerkships at various clinics and hospi- as they did in years one and two.” tals in the Bronx. “We want students to An increasing number of medical start thinking about all the aspects that schools are recognizing the importance

OPPOSITE PAGE, clockwise from left: Third-year medical students Xavier Quezada, left, and Marouf Hossain use a ventilation device on an adult mannequin as part of basic life-support training; Eden Gelman practices on a baby model; and a student tries out lifesaving compression techniques on an adult model. THIS PAGE: Stephen Baum, M.D., distinguished professor of microbiology & immunology, leads a workshop on

Photos on this and facing page by Lori Adams clinical reasoning.

MAGAZINE.EINSTEIN.YU.EDU 33 READY FOR ROTATIONS

help from more than 150 Einstein and knowledge to human patients,” he Montefiore physicians, nurses, social explains. The session on seeking and workers, respiratory therapists, and receiving feedback was among the most other volunteers. helpful, he says. “We learned to take feedback as constructive criticism and ESSENTIAL EXERCISES not to be defensive about it. You can To third-year student Deborah Schwartz voice your opinion, but you have to be one of the week’s most important exer- open to the idea that you still have a lot cises involved the clinical reasoning ses- to learn.” sion on how to present patient cases to other health professionals on rounds. APPLYING SCIENCE “Learning how to summarize all the TO PATIENTS relevant patient information and con- The Transition to Clerkship week dense it into a short, informal presen- began with a disease-mapping exercise. tation was very helpful to a third-year, Students were presented with a fictional because that is an essential skill on the patient who had acute rhinosinusitis, wards,” Ms. Schwartz says. “Without a common inflammatory condition of Above, Natalie Ramsey practices a phys- that workshop, I would not have under- the upper airways that affects nearly 40 ical exam on fellow third-year medical stood what was expected of me, how million Americans every year. student Nisha Shah in the Clinical Skills to structure my presentations, or what Third-year students were given key Center in the Van Etten Building. content to put in them.” clinical features of the condition, such M.D./Ph.D. candidate Niloy Jafar as congestion, loss of sense of smell, and of better orienting students to the rigors Iqbal says that learning clinical science nasal drainage; then, working in small of the clerkship years. To help students is quite different from learning basic groups, they mapped those features to cope with the demands of their new science. “There is a change in men- their possible causes—for example, a roles, Einstein’s senior associate dean for tality. You’re applying your scientific viral infection, an allergic reaction, or medical education, Joshua Nosanchuk, M.D., asked the offices of medical education and student affairs to develop a plan to expand Einstein’s student training from one day to a full week. “We convened focus groups of third- and fourth-year medical students, and many told us that they faced challenges in the hospital they weren’t prepared to man- age,” Dr. Nosanchuk says. A working group spearheaded by Dr. Cassese asked colleagues nationwide to come up with authentic experiences that would give students the tools needed to succeed once they started their rotations. Introduced last June to 196 third- year students, the Transition to Clerkship program involved five days Alan Engler, M.D., shows third-year medical student Lucy Oh how to conduct a physical of classes and hands-on workshops and exam of “patient” Shayon Mottahed, also a third-year.

34 EINSTEIN : WINTER/SPRING 2020 nasal polyps. Using those maps, the students were asked to list four medications that could potentially be effective in treating the root causes of rhinosinusitis and not just its symptoms. “This session was meant to help students better understand how basic- science principles are linked to clinical reasoning,” Dr. Cassese says. Another exercise focused on the hypothesis-driven physical exam, in which students practiced physical examination maneuvers on their peers in the Clinical Skills Center in the Van A STRESSFUL LEARNING ENVIRONMENT Etten Building. As a leader of one of The hospital environment can be intense for medical students. the small-group sessions, Alan Engler, “Being in an acute-care setting, you will encounter shouting, M.D., a clinical assistant professor in temper tantrums, and rudeness,” Allison Ludwig, M.D., Einstein’s the department of surgery, presented a associate dean for student affairs, told the medical students as- scenario to the third-years: “I’m having sembled in Lubin Dining Hall as part of their Transition to Clerkship trouble breathing. What should you do? training. “It may not be directed at you. But it erodes the learning Examine my abdomen? My neck? What environment,” she said. questions should you ask me?” She cautioned students to not confuse being embarrassed with Students took part in basic life- being mistreated. “On rounds, we go from the lowest up, which support training, also in the Clinical means the student speaks first” when giving a patient assessment, Skills Center, practicing effective com- Dr. Ludwig said. This is meant to be a learning experience—not pression techniques using different an exercise in humiliation. She noted that mistreatment, which ventilation devices on adult and baby can include public belittling, will not be tolerated at Einstein. “We mannequins. Other sessions included have a zero-tolerance policy, and an ‘ombuds’ panel of faculty and work-life balance (see “A Stressful students will confidentially investigate your complaint without risk Learning Environment,” at right), best of retaliation,” she said. practices regarding electronic health Dr. Ludwig offered other advice to the third-years: records, note writing in different special- • Use your time wisely during clerkships. “At the end of the day, ties, clinical informatics at the bedside, ask ‘Is there anything else I can do today?’ If the answer is no, medical interpreters, the student’s role then you should leave. You don’t get bonus points for staying on the interdisciplinary healthcare team, when the work is done, so ask to be dismissed.” developing a professional identity, and • Advocate for yourself. “Part of a strategy for maintaining work- career planning. life balance is being proactive,” she said. “You’re entitled to a Now many weeks into his clerkship, doctor’s appointment or a sick day. And inform people as soon Mr. Iqbal reports that “the days are long as you know that you have an important function you have to but the weeks are short. Medicine is one attend.” of the hardest careers as far as hours per • Seek out Einstein’s mental-health resources if needed. The new week, but it’s one of the most gratifying. Student Mental Health Center in the Van Etten Building is set up So far it has been an amazing experience. with staff trained to help with such issues as stress, anxiety, and Nothing beats learning on the job.” depression. “You can be more effective in caring for others when you attend to your own well-being first,” she said.

MAGAZINE.EINSTEIN.YU.EDU 35 36 EINSTEIN : WINTER/SPRING 2020 CONNECTING the DOTS With the help of a tiny worm, Einstein scientists complete the first wiring diagram of an animal’s entire nervous system

BY GARY GOLDENBERG

ho doesn’t have fond memories of the Dr. Emmons’ magnum opus—featured on childhood puzzle Connect the Dots? the July 4, 2019, cover of the prestigious journal W With the stroke of a pencil, you could Nature—marks a major milestone in the field of create order from disorder by transforming a seem- “connectomics,” the effort to map the myriad ingly random series of numbered points into a line neural connections in a brain, brain region, or drawing of a fish, a rabbit, or a tree. Einstein scien- nervous system, with the goal of finding the spe- tist Scott Emmons, Ph.D., has never outgrown his cific nerve connections responsible for particular fascination with that sort of magic. behaviors. For almost two decades, Dr. Emmons, profes- “Structure is always central in biology,” Dr. sor of genetics and in the Dominick P. Purpura Emmons says. “The structure of DNA revealed Department of Neuroscience and the Siegfried how genes work, and the structure of proteins Ullmann Chair in Molecular Genetics, has been revealed how enzymes function. Now the struc- connecting many thousands of dots—each repre- ture of the nervous system is revealing how senting a neural structure—visible on thousands of animals behave and how neural connections go serial electron micrographs of the tiny roundworm wrong to cause disease.” Caenorhabditis elegans. Dr. Emmons’ painstaking pointillist portraiture NEW FIELD WITH A LONG PAST has culminated in the first complete wiring diagram Although the word connectomics began to be used of the nervous system of any animal—in this case, only some 15 years ago, the field dates back at an animal used by scientists worldwide as a model least to the Renaissance. Fascinated with anatomy, organism for studying the basics of biology and Leonardo da Vinci dissected a variety of organ- disease. isms, from frogs to oxen to humans, seeking to

Sinclair Stammers/Science Photo Library At left: C. elegans adults, colorized and greatly magnified beyond their actual 1 mm length.

MAGAZINE.EINSTEIN.YU.EDU 37 CONNECTING THE DOTS

basic learning, memory, experiencing THE MIND OF A WORM fear, sensing and squirming away from predators, navigating toward food, and mating and reproducing using its sperm and eggs. All those activities occur in one tiny animal containing only about a thousand cells, one-third of them dedicated to the nervous system.

FINDING THE RIGHT MICROSCOPE Although the worm was small, the task ahead loomed large. Details of its nervous system were beyond the resolving power of the light microscope, so Dr. Brenner and his colleagues would need to use electron microscopy (EM). EM works by passing electrons A figure from “The Structure of the Nervous System of the NematodeCaenorhabditis through razor-thin slices of tissue elegans (The Mind of a Worm),” by Dr. Sydney Brenner and colleagues. The 450-page to produce magnified images. Some manuscript mapped a significant portion of theC. elegans nervous system. 20,000 cross-sectional slices—each one-thousandth the width of a human understand how the nervous system’s understanding how that nervous system hair—would be required to cover the interconnected structures give rise to the functions. Or to paraphrase one neu- roundworm’s nervous system from senses and perhaps even the soul. With roscientist: You won’t fully understand “head” to “toe.” his crude tools and razor-sharp mind, he the brain with a wiring diagram, but Further complicating things, each developed an original model of sensory you likely won’t understand the brain slice contained numerous anatomical physiology. (The soul, alas, eluded his without one. details—slivers of chemical and electri- grasp.) Dr. Brenner needed a suitable exper- cal synapses and neuromuscular junc- Connectomics began in earnest in imental organism, one with accessible tions. (A synapse is the junction where the 1960s with Sydney Brenner, a South genetics but relatively advanced behav- a neuron passes an electrical or chemi- African–born molecular biologist based iors. The fruit flyDrosophila met both cal signal to another neuron, or where at the Medical Research Council in criteria, but its 100,000-neuron nervous a neuron connects with another type Cambridge, England. Early in his career, system was too complex. He ultimately of cell. For example, a neuromuscular Dr. Brenner made important discoveries chose C. elegans, a benign, nearly trans- junction is a synapse at which a neuron regarding how genes replicate and con- lucent, millimeter-long roundworm. transmits a signal to a muscle fiber, trig- vey information. In the late 1960s, he It can be found the world over, dining gering muscle contraction.) turned his attention to the genetic and on microbes that live on rotting vegeta- Making a wiring diagram required neural bases of behavior. tion, especially fruit. (“It really should scrutinizing every slice, identifying each Dr. Brenner’s first order of business be called the fruit worm,” Dr. Emmons neural structure, and connecting that was describing the structure of a nervous says.) structure to the corresponding structure system: a network of connected neu- Although C. elegans lacks circula- rons. He realized that figuring out how tory and respiratory systems, its nervous Einstein’s Scott Emmons, Ph.D., and colleagues completed the effort begun by those neurons are connected would be system—which includes a rudimentary Nobel laureate Sydney Brenner to com- essential (although not sufficient) for brain—is capable of several functions: pletely map the C. elegans nervous system. Photos by Jonathan Heisler

38 EINSTEIN : WINTER/SPRING 2020 MAGAZINE.EINSTEIN.YU.EDU 39 CONNECTING THE DOTS

Thousands of in the previous slice—all by hand. Dr. Brenner’s paper has been cited more laboratories around Led by lab member John White, a than 4,000 times—a level of recognition team of half a dozen scientists and artists achieved by just a handful of studies. In the world would adopt worked for 15 years to connect most of 2002, Dr. Brenner was honored with a the roundworm as an the dots. All told, Dr. Brenner and his share of the Nobel Prize in Physiology colleagues produced 132 maps, encom- or Medicine for findings related to his essential animal model. passing about 5,000 chemical synapses, work on C. elegans. He died in 2019 at 600 electrical synapses, and 2,000 age 92. neuromuscular junctions. In 1984, they delivered their Tolstoyan, 450-page BUILDING A BETTER manuscript—subtitled “The Mind of a CONNECTOME Worm”—to Philosophical Transactions of Voluminous though it was, Dr. the Royal Society. It was published two Brenner’s roundworm map was incom- years later as a special one-volume issue plete. It skipped large portions of the of the journal. worm’s body and pertained only to the The scientific community initially hermaphrodite (which can self-fertilize greeted the paper with a collective yawn, and is considered the equivalent of the perhaps because so few researchers knew female of the species), not to the male. what to make of it. One reviewer con- In 1999, Dr. Emmons and his col- fined his comments to the introductory leagues took on the challenge of finish- discussion, writing “after all, few will ing Dr. Brenner’s map. Looking back, read the detail.” But C. elegans research it seems as though Dr. Emmons’ career eventually flourished, largely because of had been designed to lead him to this all those connectome maps. Thousands very task. of laboratories around the world would A native of Sudbury, Massachusetts, adopt the roundworm as an essential Dr. Emmons discovered his love for animal model. “‘The Mind of a Worm’ science and mathematics through his became their bible,” Dr. Emmons wrote. father, a professor of applied engineer- The study of Dr. Brenner’s connec- ing at Harvard University. Dr. Emmons tome has yielded numerous benefits, earned a B.S. in biology at Harvard, including the discoveries of: followed by a Ph.D. in biochemistry at • How the roundworm responds Stanford, where he grew interested in to temperature, chemicals, touch, gene function and regulation and devel- and other stimuli—fundamentals opmental biology. that apply also to the nervous Shortly after earning his doctorate in systems of higher organisms; 1974, he heard a lecture on C. elegans • Netrins, members of a class of and quickly realized that this tiny organ- proteins that guide nerve ism could help him in his research. projections called axons to their Geneticists gain insights into how intended targets. Netrin defects normal genes work by inducing muta- have been linked to human tumors; tions and observing their effects. So they • MicroRNAs; prize animal models that have readily • RNA interference; and manipulable DNA, short life cycles, and • Programmed cell death. quick reproduction—all of which the Since its publication 36 years ago, roundworm offers.

40 EINSTEIN : WINTER/SPRING 2020 C. elegans by the NUMBERS LIFE SPAN

1900 development 2 from a fertilized to YEAR FIRST to egg to a fertile 1 2 adult DESCRIBED DAYS 3 worms able to 3 AS A SPECIES fit on the head WEEKS of a pin NEURONS

in an adult 38% 383 male C. elegans genes with in an adult hermaphrodite human equivalents 302

PROTEIN-CODING GENES SYNAPSES

20,444 in roundworms ~8,000 chemical & electrical ~21,000 in humans connections

ROUNDWORM RESEARCHERS 15,000 WORLDWIDE to 20,000 6 ELECTRON-MICROGRAPH NOBEL PRIZES AWARDED TO C. ELEGANS

SLICES 1970 TODAY NEEDED TO CONSTRUCT RESEARCHERS the complete connectome 10 to 20 4,000 to 5,000 TO DATE

MAGAZINE.EINSTEIN.YU.EDU 41 With perfect timing, the National Institutes of Health (NIH) issued a call for “big field” projects with the potential to affect a wide array of disciplines. To Dr. Emmons, his quest for the male roundworm connectome fit the bill. The NIH The image above is among thousands Dr. Emmons joined the Einstein fac- agreed, awarding him a pilot project of C. elegans cross sections curated by ulty in 1979. Several years later he took grant to develop the necessary software. electron microscopist David Hall, Ph.D. a sabbatical to do a postdoctoral fellow- The project would ultimately be funded ship at the Medical Research Council, for 10 years by the G. Harold and Leila the mecca of C. elegans research, study- Y. Mathers Charitable Foundation. ing under Jonathan Hodgkin, Ph.D., “We thought it could be done with one of Dr. Brenner’s former students. the help of a personal computer, but we Upon returning to Einstein in really didn’t know,” Dr. Emmons recalls. 1986, Dr. Emmons studied how genes “The male is much more complex than encode roundworm morphology (form the female. Also, it was possible that and structure), eventually focusing on some of the neurons ran in the plane of male mating behavior and the neurons the slices rather than across them, which responsible. “It struck me that the male would mean we wouldn’t be able to see connectome was a big missing piece of all the connections using serial electron C. elegans biology. Our field is char- micrographs.” acterized by completeness. We seek to Dr. Brenner by this time had differ- know all the cells in the organism, all ent research priorities and was pleased the genes in the genome, and all the that others were continuing work on the connections in the nervous system,” Dr. C. elegans connectome, according to Dr. Emmons says. Emmons.

42 EINSTEIN : WINTER/SPRING 2020 MEETING THE CHALLENGE gap junctions in animals, including fish eventually include all of Dr. Brenner’s To complete the male connectome, and snails, but eventually switched back original connectome maps and images Dr. Emmons would need an electron to C. elegans. (see “The WormAtlas,” page 44). microscopist with expertise in round- “I returned to a field that was Constructing the male connec- worms. Such specialists were rare at the starving for people to do EM,” Dr. tome was possible, but also arduous. In time, so he was incredibly lucky to find Hall recalls. “When I said I was open 2012, after a dozen years of work, Dr. one at Einstein: David Hall, Ph.D., for business, researchers from all over Emmons and his colleagues published professor in the Dominick P. Purpura started sending me C. elegans mutants in Science the wiring diagram of the part Department of Neuroscience. for imaging.” of the nervous system controlling mat- Dr. Hall began working with Dr. Emmons would come to rely on ing in the male roundworm. Their find- C. elegans while earning his doctorate Dr. Hall’s know-how for his connectome ings revealed that male mating requires at the California Institute of Technology. studies. In addition, Dr. Hall provided 144 neurons—nearly half the worm’s He came to Einstein in the mid-1970s a priceless resource: the WormAtlas, a total number—and described the con- to study the comparative anatomy of trove of roundworm data that would nections among those 144 neurons and

Electron microscopist Dr. Hall sits between a desk featuring a C. elegans electron micrograph cross section and boxes containing many other cross sections of the roundworm.

MAGAZINE.EINSTEIN.YU.EDU 43 The WormAtlas: All Things Anatomical in One Place 64 muscles, involving more than 8,000 synapses. y the 1990s, connectomics Einstein, for further analysis and “Our work [on] the underlying func- pioneer Sydney Brenner had safekeeping. “Dr. Brenner and tion that governs mating behavior in the closed his lab and moved his colleagues agreed, with the B male roundworm is a step toward identi- on to other pursuits, his volumi- stipulation that we devise some fying how an animal controls seemingly nous roundworm research files way to communicate the data to complex movements,” Dr. Emmons left to collect dust on shelves at the roundworm community,” said at the time. In addition to finding the Medical Research Council in Dr. Hall says. out how the neurons and muscles are England. But thanks to an Einstein The data would become the connected, the researchers for the first scientist, this invaluable trove of centerpiece of the WormAtlas time accurately measured the weights of data wouldn’t remain untouched (www.wormatlas.org), a leading those connections—in other words, they for long. resource for C. elegans research- estimated the strength with which one In 1998, David Hall, Ph.D., pro- ers. The open-source (i.e., freely neuron or muscle communicates with fessor in the Dominick P. Purpura available) WormAtlas offers tens another. Department of Neuroscience at of thousands of EMs, wiring Dr. Emmons’ contribution to Einstein and a veteran roundworm diagrams, anatomical illustrations, the roundworm canon was awarded researcher and electron microsco- detailed handbooks on both the 2013 Newcomb Cleveland Prize pist, won a National Institutes of sexes and on worms in every by the American Association for the Health grant to establish a center stage of development, links to Advancement of Science (AAAS), rec- for C. elegans anatomy at Einstein. outside roundworm resources, ognizing the most outstanding paper Among the center’s goals were to a compendium of worm-related published in Science from June 2012 to extend the use of electron micros- publications, a community forum, May 2013. copy (EM) in roundworm research and more. “This one paper emerged as a tour de and to create a clearinghouse for Dr. Hall, a coauthor of Dr. force from amongst many competitive all types of anatomical data for C. Emmons’ groundbreaking Science entries,” Science editor-in-chief Marcia elegans. and Nature papers, is constantly McNutt remarked at the time. “The Dr. Hall asked Dr. Brenner’s expanding the WormAtlas with robust model system will contribute sig- permission to move the round- data from his own studies and nificantly to our further understanding worm files to his fledgling center at from researchers the world over. of the precise mapping between neuron activity and essential behaviors that ensure survival of the species.” Still, there were those who wondered what all the fuss over connectomes was about. At a 2012 debate held at Columbia University just before the publication of the Science paper, New York University neuroscientist Anthony Movshon remarked that the connectome “is a sort of a bed on which we can build experiments—and many people have built many elegant experiments on that bed. But that connectome by itself has The 348-page C. elegans Atlas is derived from the online WormAtlas. (Cover illustration by Chris Crocker.) not explained anything.”

Dr. Emmons to convince doubters that software, which significantly facilitated This image, from the 2019 Nature paper mapping neural connections was worth the process. Yet it took seven more years published by Dr. Emmons and his colleagues, shows the nervous system and the effort. of work before Dr. Emmons and his nerve connectivity of the adult C. elegans colleagues could complete the two con- hermaphrodite. Triangles equal sensory THE MIND OF A WORM 2.0 nectomes and publish their maps in July neurons, ovals or circles equal motor Although the AAAS award would have 2019 in Nature. By diagramming both neurons, hexagons equal interneurons (which connect sensory and motor been a fitting capstone to his career, Dr. the male and female C. elegans nervous neurons), and rectangles equal muscles. Emmons had more dots to connect. systems, the researchers were able to Shades of red equal categories of sensory Using new electron micrographs and make the first comprehensive compari- neurons, shades of yellow and orange Dr. Brenner’s old ones, he and his team son of the wiring of the sexes. equal classes of motor neurons, and shades of blue equal categories of compiled complete wiring diagrams “While the synaptic pathways in interneurons. Sex-specific neurons are of the adult male and the hermaphro- the two sexes are substantially simi- pink or purple. dite roundworm. They found all the lar, a number of the synapses differ in synapses connecting neurons with one strength, providing a basis for under- another, as well as the synapses con- standing sex-specific behaviors,” Dr. necting nerves to muscles and other Emmons says. tissues, such as the gut and skin, and the The primary sex differences per- connections between the muscle cells— tain to reproductive functions: for including estimates of the strength of the hermaphrodite, it’s the vulval and those synapses. uterine muscles and the motor neurons The EM images were digitized and that control them; for the male, it’s the analyzed using the group’s homegrown large number of additional neurons, sex

MAGAZINE.EINSTEIN.YU.EDU 45 The project to map the C. elegans connectome involved the close collaboration of neuroscientist Dr. Hall, left, and geneticist Dr. Emmons.

schematics of simple electronic devices; they look more like the cobwebs that lurk at the back of the broom cup- board,” Dr. Portman added. “Although intriguing patterns can be identified, distinct circuits for specific behavioral responses are not readily apparent. As others have pointed out, the connectome is only a map of possibilities.” But those very possibilities are what drive researchers in connectomics. “These connected networks serve as starting points for deciphering the neural control of C. elegans behavior,” Dr. Emmons says. “Since the roundworm “Since the roundworm muscles, and connections in the tail that nervous system contains many of the nervous system generate the circuits for copulation. But same molecules as the human nervous beyond those reproductive differences, system, what we learn about the former contains many of the a surprising percentage—up to 30%— can help us understand the latter.” same molecules as the of synapses between neurons in cen- Dr. Emmons believes that the com- tral pathways shared by both sexes also bined impact of his two major connec- human nervous system, appear to differ considerably in strength. tome papers—first inScience , then in what we learn about The Nature paper attracted a lot of Nature—has largely persuaded skep- attention in both the lay and scientific tics that plotting neural connections is the former can help us press, including major articles in The worth the effort. “We not only mapped understand the latter.” New York Times, The Washington Post, the connectome, we mapped the first The Telegraph, The Guardian, and New natural neural network,” he says. “Using Scientist. The findings mark “a major graph theory, we were able to separate — DR. SCOTT EMMONS step forward in the attempt to under- the neurons and muscles into groups, stand how a brain’s function emerges and we could say that this group must from its form,” wrote University of be doing this and that one must be Rochester neuroscientist Douglas S. doing that—linking specific parts of the Portman in a “News & Views” article connectome to specific behaviors.” accompanying Dr. Emmons’ paper in Researchers have hypothesized that Nature. some neurological and psychiatric disor- “Depicted graphically, the new ders, such as schizophrenia and autism, connectomes don’t obviously resemble are “connectopathies”—that is, prob- artificial neural networks or the wiring lems caused by “faulty wiring.”

46 EINSTEIN : WINTER/SPRING 2020 “This hypothesis is strengthened by A Sampling of C. elegans Researchers the finding that several mental disorders are associated with mutations in genes at Einstein that are thought to determine connectivity,” Dr. Emmons says. “Connectomics Michael Aschner, Ph.D., professor of molecular phar- has the potential to help us understand macology, in the Dominick P. Purpura Department of the basis of some mental illnesses,” pos- Neuroscience, and of pediatrics, and the Harold & sibly suggesting new treatment strate- Muriel Block Chair in Molecular Pharmacology gies. In concluding his Nature “News Using roundworms, rodents, and tissue cultures as & Views” article, Dr. Portman wrote: experimental models, Dr. Aschner studies how heavy “Once again, Brenner’s tiny worm, metals, such as methylmercury and manganese, are occupying its unique sweet spot between transported in the nervous system and cause neurode- simplicity and complexity, finds itself on generation. the front line of biology’s most challenging problems.” Hannes E. Buelow, Ph.D., professor of genetics and in the Dominick P. Purpura Department of Neuroscience ON TO THE HUMAN Dr. Buelow works with roundworms to understand how CONNECTOME? developing axons and dendrites (which relay signals Dr. Emmons is now studying how the away from and to neurons, respectively) navigate the roundworm’s wiring is encoded in the extracellular space in order to connect to their partner genome, a challenge as complex and neurons. Improper neuronal connections have been laborious as his connectome studies. linked to a range of neurological problems, including Meanwhile, other groups are attempting Alzheimer’s disease, schizophrenia, and autism to draw wiring diagrams of more- spectrum disorders. complex model organisms, including the fruit fly and the mouse. David Hall, Ph.D., professor in the Dominick P. Purpura If these efforts are successful, connec- Department of Neuroscience tomics will become even more relevant Dr. Hall, a pioneer in the use of electron microscopy to to the study of human biology. Whether study the roundworm connectome, currently uses the neuroscientists will ever be able to map technique to map neural connections and neural de- the human nervous system, with its 100 velopment in both younger and older roundworms and billion neurons and quadrillions of con- in mutants—work that may improve our understanding nections, is the stuff of far-off dreams. of early development and aging. As described in “The “My imagination isn’t good enough WormAtlas: All Things Anatomical in One Place” (page to contemplate the implications of 44), Dr. Hall also serves as director of this premier online knowing the whole human con- resource for C. elegans researchers. nectome,” Dr. Emmons says. “It’s a profound thought, though. It could ulti- Peri Kurshan, Ph.D., assistant professor in the mately get to questions about the nature Dominick P. Purpura Department of Neuroscience of consciousness.” A new member of the Einstein faculty, Dr. Kurshan studies synapse formation in C. elegans, with the goal of understanding how defects in the development and WATCH THE VIDEO See Dr. Emmons explain function of synapses lead to neurodevelopmental disor- the worm connectome: ders, such as autism spectrum disorders and intellectual magazine.einstein.yu.edu/worm20 disability.

MAGAZINE.EINSTEIN.YU.EDU 47 PASSIONATE PURSUITS Finding the Body’s Internal Beauty Medical student Adele Heib honors those who donate themselves to science

BY WAYNE COFFEY

striking piece of art, measuring 3½ by 4½ feet, hangs on the A corridor wall connecting the Forchheimer and Belfer basements. It comprises 40 drawings of body parts, ranging from the wispiest air sacs to the chunkiest leg bones, each about 5 inches square and drawn by Adele Heib, a third-year Einstein medical student. Farther down the corridor, near the Belfer elevator, a magazine rack holds copies of Ad Libitum, Einstein’s annual art and literary magazine. Inside its pages are two more of Ms. Heib’s creations, showing a weathered gas station and an inviting arched entryway. “Drawing is a really nice way to escape the rigors of med school and decompress—to kind of lose yourself in the process,” she says. “For me it’s therapeutic.”

THANKING THE DONORS The opportunity to draw the various parts of the body arose when Ms. Heib took the clinical and developmental anatomy course, in which first-year students dissect cadavers to deepen their understanding of the human structure. After completing the class, Einstein students present a gift to their school during the “Convocation of Thanks” ceremony, which celebrates their Four of the 40 sketches of human body parts that third-year medical student Adele Heib achievements and pays homage to the completed include, clockwise from top left: the pelvis (specifically the ilium, ischium, and people whose bodies were donated. acetabulum), the diaphragmatic crus, the sternum (rib cage), and the mandible (jaw).

48 EINSTEIN : WINTER/SPRING 2020 “Drawing is a really nice way to escape the rigors of med school and decompress—to kind of lose yourself in the process. For me it’s therapeutic.”

— ADELE HEIB

The ceremony, one of the first of its the Arthur S. Abramson Department of kind in the country, was begun by Todd Physical Medicine and Rehabilitation Olson, Ph.D., emeritus professor of and current director of the anatomy anatomy and structural biology. Every course, regularly walks through the March, anatomy students decide on Belfer-Forchheimer corridor and says their gift and then present it. New gifts she continues to be impressed by Ms. take their place alongside previous ones Heib’s work. “Adele’s drawings are along the Belfer-Forchheimer corridor, beautiful, but what strikes me the most including a mounted and framed blue about them is the fact that she thought scrub top, signed by every student in to create one to honor each cadaver.” one class, and a surrealistic painting of Albert Einstein wearing headphones. LINKING ART AND SURGERY Ms. Heib’s drawings, selected as the Ms. Heib says she has loved art for as class gift for 2018, took three weeks to long as she can remember. Growing up complete. She worked on the project in Rye Brook, New York, she would day and night while studying, painstak- often draw on her own at home. ingly drawing one body part from each As much as she savors every oppor- of the 40 cadavers dissected that year. tunity to take out her sketch pad, Ms. Her favorite mediums—ink and graph- Heib knows that pursuing a career in ite—captured the nuances and contours medicine was the right choice for her. of structures representing every major And when she recently did a surgical organ system in the body. She found it rotation, she realized that her artistic a powerful way to reinforce many of the sensibility might well make her a better anatomical intricacies she had learned physician, too. about in the course. “I am a very visual learner, a very tac- “The human body is amazing and tile, hands-on person,” Ms. Heib says. fundamentally beautiful, and I wanted “During an operation, you have to visu- Two of Ms. Heib’s ink sketches can be found in recent issues of Einstein’s Ad to represent that,” Ms. Heib says. alize in your brain how it’s going to go. Libitum magazine. At top is “Station #59” “There’s so much fluidity, so many pat- You have to know your anatomy and be and above is “Entryway.” terns and lines. And I like using black very particular about everything. If I go and white to make it cohesive.” into surgery, I think my art background VIEW MORE Sherry Downie, Ph.D., professor of will help with that visualization and Find additional art by Ms. Heib: anatomy and structural biology and in with mapping out what I have to do.” magazine.einstein.yu.edu/art20

MAGAZINE.EINSTEIN.YU.EDU 49 ALBERT’S

1 2

PUZZLER 3 4 5 6 BY DEIRDRE BRANLEY 7 8 9 10

11 12 13 14

Great and Nobel Deeds 15

(in Physiology or Medicine)* 16 17

18 19 20 Across 3 Common model organism, and you 21 22 23 24 can bake with it 25 26 27

8 2000 Nobel research focused on this 28 29 30 31 neurotransmitter 32 33 34 9 Einstein’s student-run free clinic 11 Petechia, or a mark of shame 35 36 14 2018 Nobel research led to creation of

this cancer-treatment strategy 37 38 39 16 Nobel winner who shares name with city 40 41 42 in Maryland 18 Element named for Glenn Seaborg, 43 44 45 46 47 winner of 1951 Nobel in Chemistry 48 49 50 51

19 “Guinea-pig doctor” who won the 52 53 54 55 2005 Nobel 21 Unexpected variant of a gene 24 Short for silicon 56 57 25 Calcium’s atomic symbol 58

26 Genus of the species implicated in 59 stomach ulcers 29 Not cancerous 30 How you pronounce @ in an email address Down 32 Syndrome caused by the MeCP2 gene, found only in girls 1 One of 2012 Nobel winners who spoke at 31 Thinner, longer bone of the forearm Einstein as a Lasker winner 34 Smallest structural and functional unit of 33 Perception of noise or ringing in ear an organism 2 Department of family and ______medicine 34 Sac-like pocket that contains fluid 35 Bronx-born Nobel winner Rosalyn Yalow 4 Disease caused by uncontrolled HIV 36 2015 Nobel honored Chinese discoverer co-developed this lab technique infection, for short of this antimalarial drug 37 Invention made by benefactor of the 5 C. elegans 40 Type of joint at the knee, elbow, and ankle Nobel Prize 6 Country with the most Nobel laureates 41 Bones of head, known collectively 38 A nurse, or abbreviation of radon 7 Common name for ovum 42 These cells are attacked by the body in 39 Main artery from heart 10 Winners of 2019 Nobel found how cells type 1 diabetes 43 They won the Nobel for discovering DNA: “sense and adapt to” this molecule 44 Where Nobel Prize is awarded ______and ______12 A physical injury, or disturbing experience 45 Medical acronym for apnea 46 Married couple awarded 2014 Nobel 13 2003 Nobel was awarded for 47 Nucleic acid essential in regulating the share this last name development of this imaging technique expression of genes 48 Across Manhattan from the UES 15 Frenchman who received 2008 Nobel, 50 Before becoming extinct, a species of 49 Reverse the effects or results of for the discovery of HIV animal slowly ______(2 words) 51 An established standard or average 17 What autophagy rids the cells of 53 Artificial opening made in hollow organ 52 Eric Kandel shared 2000 Nobel for 18 Only deceased recipient of a Nobel 55 Awarded 2016 Nobel for discovery of discovering learning process in this animal 19 Only woman to receive an unshared autophagy 54 Oldest (age 87) Nobel winner (1966) has Nobel, awarded in 1983 56 A soothing ointment a tumor-inducing virus named after him 20 Let sleeping dogs _____ 56 English for être or ser 22 Albert Einstein won the 1921 Nobel “for * Note: All references are to the Nobel Prize in Physiology or Medicine unless otherwise indicated. 57 Bacteria need quorum ______his services to” which area of physics? 58 Condition characterized by low blood 23 NIH’s cancer research funder counts 27 Barium’s symbol See how well you did at: 59 Owed his 1945 Nobel to an uncovered 28 Psychoanalyst nominated 32 times but magazine.einstein.yu.edu/ Petri dish never won a Nobel puzzler2020

50 EINSTEIN : WINTER/SPRING 2020 MOTIVATIONS The Front Line of Philanthropy at Einstein and Montefiore

IN THIS ISSUE 52 From the Co-Presidents of the Women’s Division 53 Remembering Burton Resnick 54 Continued Connection: Dr. Rachel Katz 58 Spotlight: Caring for the Littlest Hearts 62 Your Impact: Targeting Cancer 66 Class Notes 68 In Memoriam To learn more, please visit montefiore.org/supportmontefiore

Photo by Jason Torres and einstein.yu.edu/deans-fund

MAGAZINE.EINSTEIN.YU.EDU 51 MOTIVATIONS

A Message From Co-Presidents of the Women’s Division TERRI GOLDBERG & TRUDY SCHLACHTER

In 1953, a group of New York City women came together to help build an inclusive medical school that would conduct world-changing research. Two years later, these pioneering women—later dubbed the Women’s Division—took part in the groundbreaking on what became Einstein’s campus. Throughout the Women’s Division’s storied past, generations of members have raised more than $100 Terri Goldberg and Trudy Schlachter million to fund investigations into breast cancer, translational medicine, molecular cardiology, and more. Today, we write with pride as co-presidents of the Women’s Division—a group that has since expanded tremendously while staying true to our mission of funding science. Einstein’s history carries a common theme: We can repair the world with enough passion, persistence, and people. We remember one of those leaders with great fondness—Burton P. Resnick, who served on the Einstein Board of Trustees for more than four decades (see opposite page). His clarity of purpose, foresight, and inspiring generosity helped shape Einstein into the research powerhouse it is today. In this edition of Motivations, you’ll read about others who share this mindset. Dr. Rachel Katz’s family scholarship has helped propel aspiring doctors’ careers (page 54) since 2001. The Feinberg family has partnered with Einstein researchers who have made promising strides against an important type of cancer (page 62). And the John H. Gutfreund Fetal Heart Program, launched in 2017 in memory of former Montefiore trustee and father of current trustee J.P. Gutfreund, addresses critical cardiac concerns for hundreds of mothers and infants in the Bronx each year (page 58). From those stories we learn that the path toward a healthier future is possible, and where there is no path, we can forge one. On behalf of the Women’s Division, we appreciate your willingness to join us on this journey.

With gratitude,

Terri Goldberg Trudy Schlachter

52 EINSTEIN : WINTER/SPRING 2020 REMEMBERING BURTON RESNICK, BOARD CHAIR EMERITUS

he Einstein and Montefiore communities lost a devoted and loyal friend on Dec. 14, 2019. Burton (“Burt”) P. Resnick, chair emeritus of Einstein’s Board of Trustees, whose Tfamily legacy includes long-standing support of the College of Medicine dating back to its founding, died peacefully at his home in Rye, New York, at age 83. Burt joined the Einstein board in 1976, serving for more than four decades, including 19 years as chair.

A FAMILY MAN established the Einstein Montefiore Burt graduated from the University Resnick Gerontology Center in of Chicago with a B.A. in philoso- memory of the Resnick family phy in 1956 and then joined Jack patriarch and matriarch, Jack and Resnick & Sons, Inc., the New Pearl, whose devotion to Einstein York real estate development, con- is recognized through the naming struction, ownership, and man- of Einstein’s Jack and Pearl Resnick agement business that his father Campus. founded in 1928. The company’s The Resnick and Katz fami- holdings include a long list of resi- lies also teamed with Burt’s and dential and commercial buildings, Marilyn’s brother Ira to honor the many of which helped shape New memory of their late sister, estab- York City’s real estate industry and lishing the Susan Resnick Fisher its skyline. At the time of his death, Chair in Brain Cancer Research. Burt was chair and chief execu- This chair supports the research tive officer; his son Jonathan has of Dr. I. David Goldman, director served as president since 2007 and of the National Cancer Institute– is the third generation to lead the designated Albert Einstein Cancer 92-year-old enterprise. the Judith and Burton P. Resnick Chair Center. The Katz family’s generous sup- Working closely with Sam in Translational Research. port of the College of Medicine includes Weinberg and other members of The Resnicks also funded the Judith the creation of a cancer prevention Einstein’s board, Burt championed and Burton P. Resnick Chair in Cell program and is recognized in the title of construction of the Michael F. Price Biology, currently held by Arthur Einstein’s dean: the Marilyn and Stanley Center for Genetic and Translational Skoultchi, Ph.D., and encouraged M. Katz Dean. Medicine/Harold and Muriel Block medical student research through the Burt is predeceased by his parents Research Pavilion. Burton P. Resnick Medical Student and by his sister Susan. He is survived Burt and his wife of 57 years, Research Award in Aging, presented by Judith; their three sons, Jonathan, Judith, were major supporters of annually. Scott, and Peter, and their wives; his research at Einstein. They partnered sister and brother-in-law Marilyn and with John Condeelis, Ph.D., professor A FAMILY LEGACY Stanley M. Katz; his brother and sister- and co-chair of anatomy and structural With his sister Marilyn and her hus- in-law Ira M. and Paula Resnick; and biology, who is the inaugural holder of band, Stanley M. Katz, the Resnicks nine grandchildren.

MAGAZINE.EINSTEIN.YU.EDU 53 MOTIVATIONS | CONTINUED CONNECTION DR. RACHEL KATZ CLASS OF ’95 BY RACHEL EDDEY & SEAN MCMAHON

A family’s gift eases any years before Rachel Katz, M.D. ’95, arrived at Einstein, the burden of medical Mshe had a strong connection to debt for several the school. Dr. Katz’s mother, Monique, is a Vassar graduate and Einstein 1963 Einstein students alumna, and her father, Mordecai, served on the Yeshiva University Board of Trustees. Both were—and remain— generous philanthropic supporters. Dr. Katz’s connection to Einstein became that much stronger in 2001, six years after her graduation, when her parents created a scholarship in honor of her and her husband. For nearly two Rachel Katz, M.D. ’95 decades, the Rachel Katz and Robert Sidlow Scholarship Fund has afforded her Orthodox religious observance. medical students the financial oppor- Dr. Rachel Katz followed her moth- tunity to study, discover, and grow at er’s path to Einstein after earning bach- Einstein. elor’s and master’s degrees in English “When I learned that my parents and comparative literature at Columbia planned this scholarship, I was over- University. She completed her residency whelmed with pride—but not at all training in pediatrics at Einstein. She is surprised,” Dr. Katz says. “They are very currently the vice chair for undergrad- modest and never wanted credit for it. uate medical education at the Lewis They’d just say, ‘This is what we’re going M. Fraad Department of Pediatrics at to do.’ My parents have always served as Jacobi Medical Center, the site leader role models for how to help others, and for Jacobi’s pediatrics clerkship, and a this scholarship joins a long list of exam- professor of pediatrics at Einstein. She ples they have set throughout my life.” also serves as assistant dean of Einstein Her parents’ motivation to support at Jacobi Medical Center. Einstein was the college’s commitment to Jewish values, including its belief A SHARED PASSION FOR in diversity and the need to provide a MEDICINE welcoming environment for all. On a This year’s Rachel Katz and Robert personal level, Dr. Monique Katz had Sidlow Scholarship recipient, Ashley chosen to attend Einstein for the oppor- Force, Class of 2022, was similarly tunity to obtain an outstanding educa- inspired by her own mother’s path. tion in an environment that facilitated Born and raised in St. Petersburg,

54 EINSTEIN : WINTER/SPRING 2020 “My parents have always served as role models for how to help others, and this scholarship joins a long list of examples they have set throughout my life.”

— DR. RACHEL KATZ

Monique Katz, M.D., second row, center, is surrounded by her fellow residents from Jacobi Medical Center shortly before giving birth to her daughter, Rachel.

Florida, Ms. Force developed a love of Einstein made the choice easy. Not only medicine at a young age. Her mother, was everyone warm and engaging, but Estella Martinez, emigrated to the Ms. Force also loved how passionate the United States from Colombia and professors were about teaching. worked as a healthcare aide to put her- self through nursing school. A HEAVY DEBT LOAD Ms. Force would often accompany With the cost of medical education con- her mother to nursing homes and stantly increasing, philanthropy becomes assisted-living residences and would help ever more important. According to her mother prepare for exams at the the Association of American Medical dining room table, holding a stack of Colleges (AAMC), the medical school flash cards and quizzing her. The study class of 2019 had a four-year cost of sessions launched a mother’s career attendance of more than $330,000 for in nursing and sparked a daughter’s students enrolled in private institutions direction in life. and more than $250,000 for those in “I was so enthusiastic about all the public medical schools. The median Monique Katz, M.D. ‘63 things my mother was learning,” Ms. debt load for U.S. medical students is Force says. “I found the body to be $194,000, as calculated by the AAMC fascinating and was genuinely moved by in October 2018. the science.” The Katz family recognizes the mon- After graduating summa cum laude etary sacrifices required for an Einstein from the University of Florida, Ms. education, and Dr. Katz says she is Force applied to medical schools up proud that her parents’ scholarship has and down the East Coast. Her visit to already assisted several students. As with

MAGAZINE.EINSTEIN.YU.EDU 55 MOTIVATIONS | CONTINUED CONNECTION Photo by Jason Torres Scholarship recipient Ashley Force, second from left, meets with other members of Einstein’s chapter of Building the Next Generation of Academic Physicians, all members of the Class of 2022: Alexander Ferrera, left, Juan Pablo Forero, and Kripali Gautam. all scholarships, an internal leadership “I’m here because someone who “Einstein is a place where committee selects recipients each year. came before me cared—and I mean that When Ms. Force learned that she about my mother, who set such a strong people encourage and had received the Rachel Katz and example, as well as the Katz family,” Ms. nurture medical students Robert Sidlow Scholarship, she says, she Force says. “The power of the narrative “couldn’t have been happier. Einstein is not lost on me, especially in the field of all backgrounds. is a place where people encourage and of compassionate medicine.” Because of the Katz nurture medical students of all back- Ms. Force is passing on that gener- grounds, a place where people do what- osity of spirit. She is the treasurer of the family, I can focus more ever is possible to help those students Einstein chapter of Building the Next on why I came here and accomplish their goals. Because of the Generation of Academic Physicians, Katz family, I can focus more on why I an organization that provides medical less on how I’ll stay.” came here and less on how I’ll stay.” students and residents from diverse — ASHLEY FORCE backgrounds with the resources to start LOOKING FORWARD, careers in academic medicine. GIVING BACK Adds Dr. Katz: “I believe it is our job Ms. Force has a particular interest in in life to help each other—across fami- spinal surgery, though she doesn’t know lies and across generations. I am proud for sure what her professional future will of my parents, how they have lived their hold. What she does know is that she lives, and how they are providing for TO DONATE will forever appreciate the Katz family future generations.” einstein.yu.edu/donors/ for helping her. SupportScholarships

56 EINSTEIN : WINTER/SPRING 2020 “We’re using our economic power to fund and inspire support for research that improves human health.”

— Trudy F. Schlachter, Co-President, Albert Einstein College of Medicine, Women’s Division

“Women are making a tremendous difference by funding biomedical research through private philanthropy.”

— Terri L. Goldberg, Co-President, Albert Einstein College of Medicine, Women’s Division

Leading the way at Albert Einstein College of Medicine (clockwise from left): Trudy Schlachter; Ana Maria Cuervo, M.D., Ph.D., Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases; Terri Goldberg; and Chinazo O. WOMEN Cunningham, M.D., M.S., Professor, Department of Medicine FUNDING SCIENCE The Women’s Division of Albert Einstein College To learn more, visit of Medicine in New York City has raised millions of einstein.yu.edu/womensdivision or call the office of development at 718.430.2411. dollars to support world-class science at Einstein. To learn more, visit More than 1,000 women strong, we are dedicated to einstein.yu.edu/womensdivision or call the elevating research at every level—from the bench to Office of Development at 718-920-6656. the bedside—through philanthropy. Our extraordinary volunteers are funding science and truly saving lives.

MAGAZINE.EINSTEIN.YU.EDU 57 MOTIVATIONS | SPOTLIGHT CARING FOR THE LITTLEST HEARTS

BY AMY O’CONNOR New fetal cardiac program addresses critical concerns for expectant mothers he news was a shock: A young expectant mother learned that Ther soon-to-be-born daughter had a major heart defect. The woman had only recently immigrated to the Bronx from Yemen and wasn’t fluent in English. She needed someone to explain what was wrong and tell her whether her baby would survive. But more than anything, she needed someone who could help save her baby’s life—and communicate with her in a sensitive way about what that meant. Fortunately, a contact referred her From left: Fetal heart nurse coordinator Guytree Keso watches as Dr. Choueiter goes to the John H. Gutfreund Fetal Heart over a model of an infant heart with maternity patient Tawhida Rahman and her husband, Program at the Children’s Hospital at Mohammad Zahid Hessain. Montefiore (CHAM), where she met Nadine Choueiter, M.D., associate professor of pediatrics at Einstein and the “I’m happy to say that the baby “We provide medical and program’s director. received lifesaving surgery successfully,” genetic counseling to all “I speak Arabic, so I could under- Dr. Choueiter says. “She is now nearly a stand her as well as her core values,” year old and doing well.” of our families and make says Dr. Choueiter, a native of Lebanon. sure they receive the “We cared for her and built a personal A COMMON BIRTH DEFECT relationship with her. We provide med- Such success stories are common in support they need.” ical and genetic counseling to all of our the program, which provides care to families and make sure they receive the an underserved community. The range — DR. NADINE CHOUEITER support they need.” of services includes expert diagnoses, Dr. Choueiter (pronounced SHWAY- interventional cardiology, postpartum ter) explained to the young woman support, quality-of-life counseling, and, that her fetus had a serious condition when needed, neonatal cardiac sur- called transposition of the great arter- gery in a state-of-the-art facility. The ies (TGA). In TGA, the two main program team also cares for expectant arteries leaving the heart are reversed, mothers with diabetes or other condi- so blood pumped from the heart to tions that can affect fetal heart devel- the rest of the body contains too little opment. In keeping with Montefiore’s oxygen. Fortunately, surgery in the first mission, practitioners treat all patients few weeks of life—a so-called arterial regardless of ability to pay. switch—can correct the condition. Congenital heart problems are relatively rare, affecting 1% of babies, Left: Nadine Choueiter, M.D., uses but are the most common of all birth a fetal heart monitor as she talks to defects. In most cases, there’s no known maternity patient Tawhida Rahman cause for congenital heart disease, and at the John H. Gutfreund Fetal Heart Program’s Montefiore Hutchinson there’s nothing the parents could have

Photos on this and facing page by Jason Torres Photos on this and facing page by Jason Torres Campus in the Bronx. done differently to prevent the heart

MAGAZINE.EINSTEIN.YU.EDU 59 MOTIVATIONS | SPOTLIGHT

“We serve a community in defect from happening. In some cases, we weren’t here for these babies with the Bronx with so many it’s thought that genetic factors and cer- heart problems, or if they had been tain maternal environmental exposures born in a different place, they would different cultures and may result in abnormal growth or for- not be alive today.” languages and provide mation of the heart early in pregnancy. The Stavros Niarchos Foundation Each year, the John H. Gutfreund (SNF) provided the initial funding excellent care to people Fetal Heart Program’s team of profes- for the program in memory of John who would otherwise not sionals—cardiologists, obstetricians, H. Gutfreund, a philanthropist and surgeons, maternal/fetal-medicine longtime member of Montefiore Health receive it.” specialists, nurses, social workers, and System’s Board of Trustees, who died allied health practitioners—provides in 2016. “Supporting the program — DR. NADINE CHOUEITER comprehensive care to more than 1,000 just made sense,” SNF’s co-president expectant mothers and their families Andreas C. Dracopoulos says. “The from the Bronx and across the tristate medical expertise, the vision, the lead- area. Dr. Choueiter and Daphne Hsu, ership support and, most important, M.D., professor of pediatrics at Einstein the need to care for these vulnerable and co-director of the Pediatric Heart children were all there. Dr. Hsu and Dr. Center at CHAM, launched the pro- Choueiter love what they do, and that gram in 2017. feeling is contagious.” “It is the most gratifying feeling to save a life,” Dr. Choueiter says. “We A COMMITMENT TO THE BRONX serve a community in the Bronx with so J.P. Gutfreund, the son of Mr. Gutfreund, many different cultures and languages is a current Montefiore trustee and and provide excellent care to people supports the program with his time, who would otherwise not receive it. If passion, and philanthropy.

Daphne Hsu, M.D., listens to a child’s heart at the Pediatric Heart Center at the

Children’s Hospital at Montefiore. Photo by Jason Torres

60 EINSTEIN : WINTER/SPRING 2020 Susan Gutfreund, center, cuts the ribbon on the fetal heart center named in honor of her late husband, John Gutfreund, who served Montefiore as a board member for decades. Her son, J.P. Gutfreund, a current Montefiore trustee, is at left; former Montefiore chief executive officer Steven Safyer, M.D. ‘82, is at right.

“My father was a true New Yorker to so many families and are saving so “That these doctors offer with a strong sense of civic duty,” the many children’s lives is truly John’s leg- top-tier care to so many younger Mr. Gutfreund says. “He acy,” Mr. Moskowitz says. “It takes the believed that less-affluent communi- latest technology and the greatest people families and are saving ties deserved quality healthcare. So for to make this work. Through Heal-a- so many children’s lives is more than 50 years, he had an unwav- Heart and my personal philanthropy, ering commitment to Montefiore and I’m proud to do my part in ensuring truly John’s legacy. It takes the Bronx.” As plans for the program that this legacy endures.” the latest technology and progressed, the younger Mr. Gutfreund Adds Dr. Choueiter: “We treat very and his wife learned they were expect- sick children and, after they have gone the greatest people to ing their first child. “Infant and family through a lifesaving surgery, we do make this work.” health were definitely on my mind,” everything we can to make sure they will he says. always be well. Every member of the — JON MOSKOWITZ In keeping with his family’s tradi- team is deeply committed to serving the tion of giving back, Mr. Gutfreund and community. It is so gratifying for us to his longtime friend Jon Moskowitz, a make a difference for so many children member of the Montefiore and Einstein and their families.” Council (an affinity group designed to The baby born to that young Yemeni help shape the future of the institution), mother continues to seek care at CHAM. persuaded fellow donors to participate Thanks to the staff at Montefiore—and in the 2019 inaugural Heal-a-Heart Golf the commitment of generous donors Tournament at the Bayonne Golf Club such as SNF and the Gutfreund and in Bayonne, New Jersey—all to benefit Moskowitz families—the crucial support TO DONATE the program. that began before her birth will continue einstein.yu.edu/donors/ “That these doctors offer top-tier care long into her future. SupportFetalHeart

SCIENCE ATMAGAZINE.EINSTEIN.YU.EDU THE HEART OF MEDICINE 61 61 MOTIVATIONS | YOUR IMPACT

TARGETING A SURPRISINGLY COMMON CAUSE OF CANCER Thanks to one family’s philanthropy, researchers are moving closer to new treatments for Lynch syndrome

BY GARY GOLDENBERG

62 EINSTEIN : WINTER/SPRING 2020 Photo by Jason Torres I MMR defects also causesome20%of lifetimes—20 timestheusual risk. ing colorectal cancerduringtheir have uptoan 80%riskofdevelop As aresult, Lynch syndrome sufferers ing DNAerrors togouncorrected. copy islikelytosufferdamage—allow ple reach their30sor40s,thatgood errors forawhile.But by thetimepeo MMR genecanstillhandlemismatch their remaining “good” copyofthe out ourgeneticcode. any typosintheDNAbasesthatspell During cellreplication, MMRcorrects called DNAmismatchrepair (MMR). of genescontrolling avitalprocess a mutationinonememberofpair Einstein. research, mainlyatMontefiore and mit topromoting Lynch syndrome motivated herandfamilytocom and wouldtellyou thattheyhave vered through aseriesofhealthcrises colon cancersurgery. She hasperse undergone adoublemastectomyand in more waysthanone. positive, profoundly changingherlife middle adulthood. The testcameback orectal cancer, typicallybeginningin risk forahostofcancers,especiallycol a heritabledisorder thatraisesone’s her togettestedforLynch syndrome, 29, anastutegeneticcounseloradvised diagnosed withcolorectal canceratage medical history, includingabrother from most. disease. However, hercasewasdifferent of otherwomenwiththisdreaded with breast cancer, joiningmillions Hills, New Jersey, wasdiagnosed n 2009,LoriFeinberg KanyofShort For peoplewithLynch syndrome, People withLynch syndrome inherit Since thatfatefulday, Lorihas After learningofherfamily’s ------of Lynch syndrome inhumans. molecular, genetic, andclinicalaspects model thatcloselymimicsthe key best known forcreating thefirstmouse is aleadingauthorityonMMR. He is Medicine atEinstein. Dr. Edelmann BuchlerGertrud Chairin Transgenic ogy andofgeneticstheJoseph and Edelmann, Ph.D., professor ofcellbiol theresearch of underwritten Winfried Simons(Jami andRandiFeinberg)—has brother (Peter Feinberg), andtwosisters ing hermother(Betty Feinberg), her For adecadenow, Lori’s family—includ SYNDROME RESEARCH SUPPORTING LYNCH logical, andurological cancers. cers aswell asasubsetofbreast, gyneco sporadic (noninherited)colorectal can underlying coloncancerdevelopmentcausedbydefectiveDNAmismatchrepair. Winfried Edelmann,Ph.D.,andEinsteincolleagueElenaTosti, Ph.D.,studythemechanisms - - - - for a host of cancers, for ahostofcancers, that raisesone’s risk Lynch syndrome is adulthood. a heritabledisorder cancer, andtypically especially colorectal begins in middle begins inmiddle MAGAZINE.EINSTEIN.YU.EDU

63 MOTIVATIONS | YOUR IMPACT

Thanks to this advance, the National cancer cells in Lynch syndrome are “When we treated our Lynch syndrome Institutes of Health recently awarded highly sensitive to rapamycin, a drug mouse model with rapamycin plus a Dr. Edelmann and his colleagues a commonly used to prevent organ- drug that inhibits MDR1, rapamycin five-year, $3.1 million grant to study transplant rejection and to treat certain was able to almost completely wipe out how genetic and dietary interactions cancers. In one mouse study, treatment one type of cancer stem cell. We don’t in their mouse model affect signaling with rapamycin nearly eliminated Lynch know yet if these results will be long- and regulatory pathways in intestinal syndrome tumors within two to three lasting, though this is a promising step stem cells, problems which give rise weeks—a response that stunned the toward a new treatment.” to colorectal cancer. Findings from researchers. They are now working with Partial credit for this fruitful collab- this research could lead to advances Sanjay Goel, M.B.B.S., professor of oration belongs to Peter Feinberg, who in detecting, preventing, and treating medicine at Einstein and gastrointestinal knew of Dr. Vilar-Sanchez’s work at Lynch syndrome in particular and oncologist at the Montefiore Einstein MD Anderson and thought it would be colorectal cancer in general. Center for Cancer Care, to set up a beneficial to put the two researchers in “The Feinberg family helped us clinical trial to assess rapamycin’s use in touch. “I wanted to do something that greatly in our efforts to develop our Lynch syndrome patients. could leverage their respective knowledge mouse model,” Dr. Edelmann says. Drs. Edelmann and Vilar-Sanchez are and bring two renowned institutions “More importantly,” he adds, “they also trying to make rapamycin therapy together,” he explains. “I pinch myself. initiated my collaboration with Dr. last longer, since the tumor returns It’s a dream turning into a reality.” Eduardo Vilar-Sanchez,” a physician- once treatments are stopped. “We have “I’m president of the Winfried scientist and Lynch syndrome specialist since learned that cancer stem cells Edelmann Fan Club,” jokes Lori, a at MD Anderson Cancer Center in have a membrane protein called MDR1 retired lawyer and active philanthropist. Houston. (multi-drug resistance 1), which pumps “But seriously, I wish I had so much Together, Drs. Edelmann and Vilar- out any toxins (including rapamycin) more to give. His brain is limitless, Sanchez discovered that colorectal that get into them,” Dr. Edelmann says. but his funds are not. Our goal is that

“When we treated our Lynch syndrome mouse model with rapamycin plus a drug that inhibits MDR1, rapamycin was able to almost completely wipe out one type of cancer stem cell.”

— DR. WINFRIED EDELMANN

Dr. Edelmann holds a slide containing sections of the liver and spleen of a mouse

model of Lynch syndrome. Photo by Jason Torres

64 EINSTEIN : WINTER/SPRING 2020 “Philanthropy was what we knew growing up. Our parents instilled in us a tremendous sense of obligation to help make the world a better place. We’d like to think we’re doing that.”

— RANDI FEINBERG

Betty Feinberg, a longtime Einstein trustee, helps fund Einstein’s research on Lynch syndrome and hopes to raise awareness of the condition.

somebody sees this article and they tell a cancerous or when they’re still treatable. friend about his work, and then they tell “I live by the creed that what I have a friend.” won’t necessarily kill me, but ignoring it might,” Lori says. THE WAY OF THE FEINBERGS The siblings’ philanthropic work In addition to supporting Lynch syn- was inspired by their parents: Betty, a drome research, the Feinbergs hope to longtime Einstein trustee, and her late raise awareness of the condition, which husband, Sheldon, a prominent business affects about 1 in 370 people in the leader in the second half of the 20th United States. “I’m amazed at how few century. people know about the syndrome,” says “Decades ago, my parents recognized Jami Simons, a retired teacher and active the need to fund brilliant researchers in community volunteer. “When people the embryonic stages of their careers, hear about breast cancer, they think when money is so tight,” says Peter, a ‘BRCA,’ the so-called breast cancer former banker whose work now focuses gene. But anyone with a family history on “impact investments” that help put of breast or ovarian or colon cancer medical and social innovations into ought to find out if they have one of the everyday practice. Lynch syndrome genes. All it takes is a “Philanthropy was what we knew simple blood test.” growing up,” Randi Feinberg adds. While there’s no cure for Lynch “Our parents instilled in us a tremen- syndrome, people who test positive dous sense of obligation to help make TO DONATE can undergo regular cancer screen- the world a better place. We’d like to einstein.yu.edu/donors/

Photo by Jason Torres ings to catch growths before they turn think we’re doing that.” SupportLynchResearch

MAGAZINE.EINSTEIN.YU.EDU 65 MOTIVATIONS CLASS NOTES

1960s 22 years at the U.S. Food and Drug Joel Cohen, M.D. ’83, moved with Joyce Lowinson, M.D. ’62, was hon- Administration and 14 years in indus- his four adult children and his wife, ored at the “On the Front Lines of the try. She still loves to work and does Pearl, to Jerusalem, where he has been Opioid Epidemic” conference held at not foresee retiring anytime soon. This working in the stroke unit at Shaare Montefiore and Einstein in September past spring she was honored to receive Zedek Medical Center. During the past 2019 (see page 4). She is the found- the Alumni Association’s Distinguished year each of his children has married: ing director of the division of sub- Ph.D. Alumna Award from Einstein. Tova to Gil Herrmann, Natan to Sarah stance abuse and a professor emerita of Bayer, Meir to Ahuva Ross, and Sara to psychiatry and behavioral sciences at Nancy Scattergood Donavan, M.D. Chanina Landesman. In October Dr. Einstein. ’78, was named the 2019 Southwestern Cohen welcomed his first grandson, Vermont Health Care Foundation’s Ariel Yona Landesman. Anna Chao Pai, Ph.D. ’64, recently Health Care Leadership Honoree. She published her memoir, From earned a bachelor’s degree in biology Joshua Lipsman, M.D. ’83, married Manchurian Princess to the American from Franklin & Marshall College in his partner of five years, Jonathan Sorge, Dream. The book highlights the hard- Pennsylvania and studied at the College on July 6, 2019. For the past year they ships of immigration, the discrimina- of Medicine and Dentistry at Rutgers have been living in the Hudson Valley tion that she and her family endured University in New Jersey before attend- in the riverside village of Athens, New when they moved to the United States ing Einstein. Dr. Donavan completed York, where Dr. Lipsman is a trustee from China when she was 4 years her internship and residency at the on the village board. Earlier this year old, and her enduring faith in the University of Wisconsin–Madison. She he became the medical director for American dream. has been a member of Southwestern Humana’s Medicare Advantage product Vermont Medical Center since 1983 line. He also partnered with associates in and staff president since 1996. June to open his second boutique med- 1970s ical start-up in New York City, Ever/ Harold Pincus, M.D. ’75, was named Body, a cosmetic dermatology practice. 2019 Mentor of the Year at Columbia 1980s University’s Irving Medical Center. He Hasan Bazari, M.D. ’83, had first Linda Broyde Haramati, M.D. ’85, is a professor and the vice chair of psy- thought an inability to speak fluently is still happy to be at Einstein after all chiatry at Columbia’s Vagelos College after he suffered a stroke four years ago these years. She leads the cardiotho- of Physicians and Surgeons, and is could have ended his career. But with racic imaging division in radiology the co-director of Columbia’s Irving renewed determination, he has con- at Montefiore. She and her husband, Institute for Clinical and Translational tinued to be active. Today he teaches, Nogah, enjoy spending time with their Research. He is also the national pro- oversees reflection sessions in the cardiac three grandchildren; the oldest is 2. gram director for the Health and Aging care unit, attends conferences, and is Policy Fellows Program and serves proud to be able to venture outside his Michael Zelefsky, M.D. ’86, is the as a senior scientist at the RAND comfort zone. At Massachusetts General vice chair of and a professor in the Corporation. Hospital, he was the program direc- department of radiation oncology, tor of internal medicine from 1994 to clinical research, and is the chief of the Kathryn (Katy) Stein, Ph.D. ’76, is 2014. He now serves on the Alumni brachytherapy service, at Memorial currently a biotechnology consultant Association Board of Governors at Sloan Kettering Cancer Center. He was (see katystein.com) after having spent Einstein. also appointed to the newly established

66 EINSTEIN : WINTER/SPRING 2020 Greenberg Chair in Prostate Cancer reconstruction and sports medicine. STAY IN TOUCH Research. He pioneered the develop- Although he has not attended many Keep your classmates up to ment of MSK Precise, which comprises Einstein reunions, he gives a shout-out hypofractionated radiotherapy, real-time to the Class of 1991. date by submitting@ your news image guidance, magnetic resonance to Einstein magazine. We imaging planning, and the use of a Ian Walters, M.D. ’93, was recently look forward to including you. hydrogel spacer between the rectum and named chief executive officer of Email us at einsteinalumni@ the prostate. Portage Biotech Inc. As board director, einsteinmed.org. he was instrumental in leading the Neal Shipley, M.D. ’87, lives on company’s recent acquisition of the Manhattan’s Upper West Side and is drug-development company SalvaRx married; he has three children and Limited, which he founded in 2015 two dogs. He has spent most of the and led in its production of cancer 2000s past 20-plus years as an emergency immunotherapy drugs. In a career Kyle Lapidus, M.D., Ph.D. ’09, is the department physician and emergency spanning more than 20 years, he has founder of Affective Care, an organiza- department director. In 2010 he contributed to four significant oncology tion that provides and oversees psychiat- co-founded an urgent-care business in drug approvals. Before founding ric care and treatment throughout New Manhattan. Dr. Shipley is currently the SalvaRx he worked at Bristol-Myers York State. He completed his residency medical director for Northwell Health Squibb (BMS), where he managed in psychiatry at Mount Sinai Medical GoHealth Urgent Care, which has 51 physicians overseeing the international Center’s Icahn School of Medicine, locations in the metropolitan New York development of oncology compounds as and is board-certified by the American area and treated more than 500,000 well as biomarker and related diagnostic Board of Psychiatry and Neurology. In patients in 2019. work. Dr. Walters was a core member addition to his experience with mood of BMS’s strategic transactions group, and anxiety disorders, Dr. Lapidus has which evaluated and executed licensing particular clinical expertise in the man- 1990s agreements, mergers and acquisitions, agement of treatment-resistant depres- Yvette Calderon, M.D. ’90, was clinical collaborations, and the sion and obsessive-compulsive disorder. elected to the board of directors of company’s immune-oncology strategy. His pioneering studies have appeared the American Board of Emergency in many scientific publications related Medicine. She was also honored with David Markenson, M.D. ’94, was to the treatment and development of Crain’s 2019 Notable Women in Health recently inaugurated as the president ketamine and dTMS, along with other Award. She is the chair of the depart- of the Colorado Medical Society. He novel approaches to improving patient ment of emergency medicine at Mount also became the chief medical officer outcomes. He is dedicated to developing Sinai Beth Israel Hospital. of the American Red Cross, a position cutting-edge treatments, and he co- he says he could not, when he was in created Validose, an intranasal medical Alan Dayan, M.D. ’91, is proud to medical school, have imagined ever device that facilitates the delivery of report that his oldest son began his first holding. As a volunteer for the past medication. year at Einstein in August, and was 15 years, he has served as the chair of thrilled to join him for the White Coat the National Science Council of the Ceremony. Dr. Dayan currently lives in American Red Cross. He also co-chaired 2010s Brooklyn with his wife, Perline. They the evidence group for the International Caitlin McMullen, M.D. ’10, gave have five children; the older ones are on Federation of Red Cross and Red birth to a baby girl in February and their way to making their own nests. Crescent Societies, which is the parent is loving family life in Florida. She He practices orthopedic surgery at New group of the 192 Red Cross national reports that her mother retired in 2018 York University, specializing in adult societies. after a rewarding 38-year career as a

MAGAZINE.EINSTEIN.YU.EDU 67 MOTIVATIONS | CLASS NOTES neonatologist and is transitioning to Hospital/Columbia University Medical medicine residency at Harbor-UCLA “civilian life” by spending lots of time Center. She is excited to work with Medical Center in June 2019. with her two granddaughters and pets. Einstein medical students and plans to focus on expanding the health curric- Alana Warhit, M.D. ’18, was married Lauren Tannenbaum Roth, M.D. ’16, ulum for lesbian, gay, bisexual, trans- on May 27, 2019. She is a resident in has returned to Einstein as an attend- gender, and queer patients, particularly psychiatry at NewYork–Presbyterian ing physician in the Comprehensive within pediatrics. Hospital/Weill Cornell Medical Family Care Center and as an instruc- Center. Her husband, Kevin Sean tor of pediatrics at Children’s Hospital Evan Tamura, M.D. ’16, started the Beckoff, is an associate in the real estate at Montefiore. She recently completed Refugee Health Alliance listserv in group of Kirkland and Ellis LLP in her residency at NewYork–Presbyterian November 2018 and completed a family Manhattan.

IN MEMORIAM

Perry Eck, M.D. ’65, age 79, Ernest Kalman, age 85, former member Paula Neyman, M.D., age 93, MASH (mobile army surgical of the Einstein Board of Overseers for clinical associate professor emerita hospital) unit physician in the many years, co-founded the Hallenbeck/ of pediatrics at Einstein; Oct. 23, Vietnam War, in private practice for Kalman Cancer Research Laboratory at 2019, Monroe, New York. nearly 40 years; March 24, 2019, Einstein; Jan. 16, 2020, Bedford Hills, Rochester, New York. New York. John Robbins, M.D., age 86, former associate professor of Jacob Gerstenfeld, M.D. ’60, Thomas Kaye, M.D. ’78, age 67, pediatrics at Einstein, National age 84, retired ophthalmologist neurosurgeon in the Springfield, Institutes of Health researcher, and member of Einstein’s second Massachusetts, area for 30 years; Jan. 27, vaccine pioneer, and winner of the graduating class; June 5, 2019, 2020, Longmeadow, Massachusetts. 1996 Albert Lasker Clinical Medical Palm Beach Gardens, Florida. Research Award; Nov. 27, 2019, John Larkin, M.D. ’92, age 57, Manhattan. Asao Hirano, M.D., age 92, primary care physician in Tipton professor emeritus of pathology County, Tennessee, since 2005, formerly Detlef Schlondorff, M.D., age 77, and of neuroscience at Einstein, in practice in Manhattan; Dec. 16, renal investigator for more than the former Harry M. Zimmerman 2019, Covington, Tennessee. five decades and Einstein’s former Professor of Neuropathology director of nephrology; Oct. 16, at Montefiore, former associate Charles Robert Michael, age 82, 2019, Manhattan. program director of diagnostic investor and philanthropist who neuropathology (electron microscopy endowed the Charles Michael Chair Jonathan Warner, Ph.D., age 82, studies), and author of more than in Autoimmune Diseases at Einstein; professor emeritus and former chair 800 articles in medical journals and Dec. 5, 2019, Saddle Brook, New Jersey. of the department of cell biology; textbooks translated into several Sept. 5, 2019, Pelham, New York. languages; July 25, 2019, Sleepy Tim Nelson, age 63, Einstein’s Hollow, New York. telecommunications technician for more than 15 years; Sept. 24, 2019, the Bronx, New York.

68 EINSTEIN : WINTER/SPRING 2020 A LOOK BACK Photo by Jason Torres Lymph Notes, Then and Now Decades ago, a histology lesson inspired Einstein medical students to call their a cappella group the Lymph Notes—a name that has stuck. Those Lymph Notes, at top, “sang at the slightest provocation,” according to the 1960 yearbook, “and it was hard to keep them shut up for very long.” Their repertoire ranged from folk songs to numbers by Richard Rodgers and Oscar Hammerstein II, and included tunes such as “If I Loved You” from the musical Carousel. The songs have changed over the past 60 years, but the Lymph Notes are still harmonizing. Between 12 and 20 medical students practice every week, and the group performs at an annual concert each spring in the Mary and Karl Robbins Auditorium. Organizer and second-year student Sarah Kellner, at bottom far right, says, “It’s a way to keep music in our lives, and art and medicine go hand in hand.” Listen to the Lymph Notes at magazine.einstein.yu.edu/notes20.

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Winter/Spring 2020

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Science at the Heart of Medicine

EINSTEIN IMAGE

Cell movement is essential for crucial biological processes. It can help heal wounds but also lead to the spread of cancer cells (metastasis). It’s triggered when actin protein molecules combine, or polymerize, into actin filaments. Growing actin filaments push the cell membrane outward, forming projections called lamellipodia that propel the cell. Visualizing this highly dynamic activity has proved challenging. To find the stains and preservation techniques that best capture actin poly- merization within lamellipodia, researchers in Einstein’s Analytic Imaging Facility and the lab of John Condeelis, Ph.D., took motile cells from a rat breast cancer cell line, preserved (fixed) them in five different ways, and labeled the actin with nine different stains. The double- stained image shown here, using structural illumination microscopy, was judged the most accurate and detailed. Phalloidin Alexa-488 (green) revealed most of the cell’s actin filament network. Anti-actin antibody AC15 Alexa-555 (red) showed actin staining that was limited to areas closer to the membrane. Image credit: Vera DesMarais, Ph.D., and Robert Eddy, Ph.D.