SUMMER/FALL 2019

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

The Search for Einstein and Montefiore researchers Autism Therapies are testing promising treatments

Collaborating to Cure Cancers • ECHO Clinic Marks 20 Years • An Out-of-This-World Clerkship EINSTEIN A Message from the Dean Science at the Heart of Medicine Summer/Fall 2019 The magazine for alumni, faculty, y first year as Einstein’s students, friends, and supporters of dean has educated and Albert Einstein College of Medicine and Montefiore invigorated me. When I walked on stage for this Published by Myear’s Commencement, I felt tremen- The Philip and Rita Rosen Department of Communications and Public Affairs dous pride for our graduates, the first to Gordon Earle, Associate Dean receive diplomas carrying the Einstein Office of Development seal (page 4). This milestone fittingly Rachelle M. Sanders, Vice President and occurred on the 60th anniversary of our Chief Development Officer initial graduating class (page 69). Director, Science and Research Content Our newest graduates are the best Larry Katzenstein of the best, taught by a faculty doing Senior Director, Strategic Communications and External Relations outstanding work. A prime example is Deirdre Branley given in our cover story, “The Search Managing Editor for Autism Therapies,” which begins Susan Byrne

on page 16. It describes the research of Director, Creative Services Eric Hollander, M.D., a national leader Einstein Community Health Marie L. Kurtz

in seeking new treatments for autism Outreach free clinic marks 20 years Senior Director of External Relations, spectrum disorders, which affect 6,000 of service to Bronx residents who lack Development Rachel Eddey children in the Bronx and another 12 health insurance (page 28). And one million nationwide. There are shock- of our May graduates, Jennifer Ma, Associate Director of External Relations, Development ingly few treatments for autism symp- M.D., was part of a select group that Sean McMahon

toms, which include an impaired experienced the life of a flight sur- Art Director ability to communicate and form social geon during her month in NASA’s Lorene Tapellini

relationships. Dr. Hollander directs Aerospace Medicine Clerkship pro- Associate Art Director the Autism and Obsessive Compulsive gram (page 38). Jeneffer Gonçalves Lee Spectrum Program at Einstein and These are exciting times to be in Illustrations Montefiore, and he and his team are science and medicine, and I’m look- Tatyana Starikova Harris evaluating promising therapies. ing forward to another dynamic and Digital Imaging Donna Bruno Another example of our outstand- productive year. ing research is a decade-long partner- Photography jtorresphoto.com ship to develop better treatments for Multimedia Communications bone-marrow and blood diseases that Sunita Reed, Director currently have low survival rates. The article “Collaborating to Cure Cancers” Address correspondence to: Editor, Einstein Magazine (page 32) describes the efforts of Amit Jack and Pearl Resnick Campus Verma, M.B.B.S., and Ulrich Steidl, 1300 Morris Park Avenue, Belfer 905 M.D., Ph.D., to cure myelodysplastic Bronx, NY 10461 GORDON F. TOMASELLI, M.D. syndrome and acute myeloid leukemia Email: [email protected] The Marilyn and Stanley M. Katz Dean Website: www.einstein.yu.edu by finding their root causes. Albert Einstein College of Medicine Copyright © 2019 Our students are doing some great Executive Vice President, Chief Academic Officer Albert Einstein College of Medicine things as well. This year the student-run Montefiore Medicine All rights reserved SUMMER/FALL 2019 IN THIS ISSUE COVER STORY 16 THE SEARCH FOR AUTISM THERAPIES Einstein and Montefiore researchers are testing scientifically promising treatments, from cannabis to whipworms FEATURES 28 NO INSURANCE? NO PROBLEM! The student-run Einstein Community Health Outreach 16 clinic marks 20 years of service to Bronx residents

32 COLLABORATING TO CURE CANCERS Einstein scientists raise hopes for treating two closely intertwined bone-marrow and blood diseases

38 AN OUT-OF-THIS-WORLD CLERKSHIP NASA’s aerospace program gives an Einstein student a glimpse of space medicine

52 SPOTLIGHT: MONTEFIORE SCHOOL HEALTH PROGRAM Clinics reach one in four Bronx public-school students 32 60 MEETING OVER THE MIND Two men from different worlds find common ground in neurological surgery DEPARTMENTS 2 Campus News 8 Mavens of Medicine: Dr. Sharmila Makhija 10 Research Notes 12 Lab Chat: Dr. Helena M. Blumen 42 Passionate Pursuits: Cyclist Wouter Hoogenboom 44 Einstein Editions 52 46 Crossword: Albert’s Puzzler 47 Motivations: The Front Line of Philanthropy 49 Continued Connection: Dr. Harvey Karp 64 Class Notes 69 A Look Back Visit magazine.einstein.yu.edu ON THE COVER: Carlos Rodriguez, 14, is one of 6,000 children in or scan code the Bronx who fall somewhere on the autism spectrum. Einstein and Montefiore researchers are testing promising treatments for autism (page 16). Cover and page 16 photos: © Rick Guidotti, Positive Exposure CAMPUS NEWS Dr. Cuervo Elected to National Academy of Sciences

na Maria Cuervo, M.D., finding that autophagy slows with Ph.D., has been elected to the age. Her current research focuses on A National Academy of Sciences, developing therapies to restore autophagy, becoming the 14th current or former thereby preventing the accumulation of faculty member to join the academy. toxic protein by-products that can lead to Dr. Cuervo is a leader in the field of age-related conditions such as Alzheimer’s autophagy, the cellular-waste manage- disease, Parkinson’s disease, and diabetes. ment process that is critical to human “I’m very happy for the people in health. my lab. The team really deserved it— Among her early major discoveries, they are the ones who are driving the Dr. Cuervo found that autophagy research,” Dr. Cuervo says of her election, is highly selective, not random as which was announced on April 30. Dr. was previously thought. In addition, Cuervo is a professor of developmental she and her collaborators discovered and molecular biology, of anatomy and that specialized proteins guide old structural biology and of medicine, and and damaged proteins to lysosomes is the co-director of the Institute for for digestion, a process they dubbed Aging Research. She holds the Robert “chaperone-mediated autophagy.” and Renée Belfer Chair for the Study of Dr. Cuervo also made the major Neurodegenerative Diseases at Einstein.

New Chair of Pediatrics at Einstein and Montefiore

ichael deCastro Cabana, and improving the Pennsylvania School of Medicine and M.D., M.P.H., has been diagnosis, preven- the Wharton School. He completed his M named a professor and the tion, and manage- residency at Johns Hopkins, where he Michael I. Cohen, M.D., University ment of common received his master’s degree in public Chair of Pediatrics at Einstein and childhood con- health. Dr. Cabana completed his physician-in-chief at Children’s Hospital ditions such as fellowship as a Robert Wood Johnson at Montefiore. pediatric asthma. Clinical Scholar in 1999 before mov- Dr. Cabana was most recently a He has conducted ing to the University of Michigan and, professor of pediatrics and of epidemiol- clinical trials on the effect of probiotics later, UCSF. ogy and biostatistics at the University of and prebiotics on asthma, infant colic, He is a member of the editorial California, San Francisco (UCSF), where and growth. board of The Journal of Pediatrics and he also served as the chief of the division Dr. Cabana received his bachelor of edited the popular pediatric textbook of general pediatrics. He assumed his arts degree magna cum laude in gov- The Five-Minute Pediatric Consult. He new role at Montefiore and Einstein in ernment at Cornell University and is currently serving a four-year term on September. his M.D. and M.A. at the combined- the United States Preventive Services His research focuses on understanding degree program at the University of Task Force.

2 EINSTEIN : SUMMER/FALL 2019 Tenure for 16 Einstein Drs. Joan Berman Professors Leonard H. Augenlicht, Ph.D. and Chinazo Cunningham Professor of Medicine and of Cell Biology Karen A. Bonuck, Ph.D. Give Presidential Lecture Professor of Family and Social Medicine, of Obstetrics & Gynecology and Women’s he third annual Presidential treating opioid-use disorder and car- Health, and of Pediatrics Lecture, which highlights out- ries a low risk of overdose and misuse, Anne R. Bresnick, Ph.D. T standing research conducted at making it appropriate for office- and Professor of Biochemistry Einstein and Montefiore, featured the community-based treatment. Philip E. Castle, Ph.D. work of Joan W. Berman, Ph.D., and Dr. Berman is a professor of pathol- Professor of Epidemiology & Chinazo Cunningham, M.D., M.S. ogy and of microbiology & immunol- Population Health Their speeches, given on June 3, ogy and holds the Irving D. Karpas Kelvin Davies, Ph.D. focused on buprenorphine, a drug used Chair in Medicine at Einstein. Dr. Professor of Urology and of Physiology & Biophysics in medication-assisted treatment to Cunningham is the associate divi- help people reduce or quit their use of sion chief of general internal medi- Andras Fiser, Ph.D. Professor of Systems & Computational heroin or other opiates. Dr. Berman, cine at Einstein and Montefiore and Biology and of Biochemistry who studies the interaction of HIV with a professor of medicine, of family and Evripidis Gavathiotis, Ph.D. the central nervous system, including social medicine, and of psychiatry and Professor of Biochemistry and of Medicine neuroAIDS, spoke about buprenorphine behavioral sciences at Einstein. Andreas Jenny, Ph.D. as a novel therapy for HIV-associated Professor of Developmental and neurocognitive disorders. Molecular Biology and of Genetics WATCH THE VIDEO Dr. Berman was followed by Dr. View the Presidential Lecture: Gregoire Lauvau, Ph.D. Cunningham, whose research has shown magazine.einstein.yu.edu/ Professor of Microbiology & Immunology that buprenorphine is highly effective in lecture19 David M. Loeb, M.D., Ph.D. Professor of Pediatrics and of Developmental and Molecular Biology, and Chief of Pediatric Hematology/Oncology Carlos Rodriguez, M.D., M.P.H. Professor of Medicine and of Epidemiology & Population Health Jonathan Shuter, M.D. Professor of Medicine and of Epidemiology & Population Health David Q. H. Wang, M.D., Ph.D. Professor of Medicine and of Genetics Tao Wang, M.D., Ph.D. Professor of Epidemiology & Population Health Melissa P. Wasserstein, M.D. Professor of Pediatrics and of Genetics and Chief of Pediatric Genetic Medicine Liang Zhu, M.D., Ph.D. From left, Dean Gordon F. Tomaselli, M.D.; Pamela Stanley, Ph.D., presidential lecture Professor of Developmental and chair and professor of cell biology; Dr. Chinazo Cunningham; Dr. Joan Berman; and Molecular Biology, of Ophthalmology and Montefiore Medicine CEO Steven M. Safyer, M.D. Visual Sciences, and of Medicine

MAGAZINE.EINSTEIN.YU.EDU 3 CAMPUS NEWS

CNN’s Dr. Sanjay Gupta at Einstein’s Commencement

anjay Gupta, M.D., CNN’s chief Children’s Hospital at Montefiore in medical correspondent and a 2016. His in-depth account of the boys’ S practicing neurosurgeon, delivered life before, during, and after their opera- the commencement address at Einstein’s tion won the News & Documentary graduation ceremony on May 23, held Emmy Award for Outstanding Science, at David Geffen Hall in Lincoln Center. Medical, and Environmental Reporting Einstein conferred 156 M.D. and 31 in 2018. Einstein conferred an honorary Ph.D. degrees as it celebrated its 61st Doctorate of Humane Letters on him. commencement. In addition, 16 graduates Dr. Gupta told the graduates that of Einstein’s Medical Scientist Training “there can be tremendous value in Program received both an M.D. and a embracing fear” and to challenge those Ph.D. degree. who doubt their abilities: “I’m talking This year’s ceremony was the first about savoring it when someone tells in which graduates received diplomas you no, that it can’t be done. Because with the Einstein seal, after the College you know deep down, you now have an of Medicine was awarded independent opportunity to do the impossible.” degree-granting authority earlier this year. WATCH THE VIDEO Dr. Gupta reported on the successful See Dr. Gupta’s 27-hour surgical separation of conjoined commencement address: twins Jadon and Anias McDonald at magazine.einstein.yu.edu/Gupta19

First Diversity and Inclusion Chief Named

erys Benfield, M.D., M.P.H., launched in She received a bachelor’s degree has been named Einstein’s 2017 under from Harvard College, an M.D. from N first senior associate dean for the dean- the University of California, San diversity and inclusion. Currently an ship of Allen Francisco, and a master’s degree in associate professor of obstetrics & gyne- Spiegel, M.D., public health from the University of cology and women’s health at Einstein with leadership California, Berkeley. and director of family planning and from Edward Dr. Benfield arrived at Einstein and the fellowship in family planning at Burns, M.D., Montefiore in 2011 following her Montefiore, Dr. Benfield will report executive dean, fellowship. “I was drawn to the diver- directly to Gordon Tomaselli, M.D., Irene Blanco, sity of the staff, faculty, and patients,” the Stanley and Marilyn Katz Dean at M.D., associate dean for the office of she says. She started a diversity and Einstein, in her new role. diversity enhancement, and Yvonne inclusion group in her department The creation of this position was Ramirez, vice president of human and has focused on recruiting at the the top recommendation of Einstein’s resources and diversity. Dr. Benfield will resident, fellow, and faculty level. Strategic Plan for Diversity and work closely with them, as well as with Nationally, she co-chairs the diversity, Inclusion, which reflected the input of Dorcas Lind, assistant vice president of equity, and inclusion group for the more than 90 participants. The plan was diversity and inclusion at Montefiore. Society of Family Planning.

4 EINSTEIN : SUMMER/FALL 2019 Forbes Ranks Einstein Einstein M.D./Ph.D. Student Wins Among the Nation’s Best Midsize Employers Lasker Essay Contest Einstein has been recognized by Forbes magazine as one of the country’s best midsize employers in 2019. Forbes ranked Einstein in the top 200 overall nationally among midsize employers, and • 3rd within the education category in New York State, • 9th within the education category nationally, and • 16th among all midsize employers with New York State headquarters. Forbes selected America’s Best Peter John, M.D./Ph.D. student Employers based on an anony- mous, independent online survey hen it comes to educa- “Video games have been effective for of a diverse group of more than tion, Einstein M.D./Ph.D. teaching other subjects, such as his- 50,000 full- and part-time employ- W student Peter John knows tory,” Mr. John says. “Thanks to new ees of midsize and large com- what motivates students to learn. “The technologies, they have great potential panies employing at least 1,000 most-effective lessons are intellectually for teaching science as well.” He gives people in their U.S. operations. engaging and entertaining. Electronic an example of teaching immunology Overall scores were based on games are a good strategy for achieving by using a strategy-game format where a combination of two elements: both goals,” he says. players coordinate different types of employees’ willingness, on a rating He wrote an essay about just that— immune cells to fight off pathogens. scale of 0 to 10, to recommend “Making It All Fun and Games in the One of three co-winners of the essay their employers to friends or fam- Biomedical Sciences”—and submitted it contest, Mr. John also met the winners ily members, and their willingness earlier this year for consideration in the of the 2019 Lasker Award at a luncheon to recommend other employers 2019 Lasker Foundation Essay Contest. in New York City in September. The in their respective industries to He found out in July that his nearly Lasker Awards have been given annu- acquaintances. 800-word essay had earned the top prize ally since 1945 to recognize people who of $10,000, to be used for educational have made major contributions to bio- expenses. logical discoveries that improve human The rising sixth-year student, who health; they are sometimes referred to as studies cancer immunology in the lab “America’s Nobels” and have often iden- of Xingxing Zang, Ph.D., proposed tified future winners of the Nobel Prize. the creation of video games that would READ MORE immerse young players in biomedical Find Mr. John’s prize-winning research, providing an instructive yet essay here: rewarding experience. magazine.einstein.yu.edu/Lasker19

MAGAZINE.EINSTEIN.YU.EDU 5 CAMPUS NEWS

Dr. Dominick P. Purpura, Longest-Serving Dean, Dies at 92

ominick P. Purpura, M.D., DEANSHIP AT EINSTEIN who served as the Marilyn After Dr. Purpura served as dean at D and Stanley M. Katz Dean at Stanford’s School of Medicine for two Einstein from 1984 to 2004, died on years, Einstein recruited him to come May 16, 2019, at the age of 92. back to the Bronx as dean in 1984. His Dr. Purpura joined Einstein in 1967 vision and leadership positioned the as a professor and the chair of anatomy. College of Medicine as the educational In 1969, he was appointed the scientific hub of a network of major hospitals. director of Einstein’s Rose F. Kennedy During his tenure, Einstein became Center, which focuses on research into the first private medical school in New the causes of intellectual and develop- York City to establish a department of mental disabilities; he was named the family medicine. He also established center’s director in 1972. Two years an academic department of emergency later, he founded the department of medicine to complement Montefiore’s. neuroscience, which was named in his “Dr. Purpura revolutionized the honor in 2006. way medical education was taught,” “Dr. Purpura says Edward R. Burns, M.D., executive PIONEERING NEUROSCIENTIST revolutionized the way dean at Einstein. “He recognized that In presenting Dr. Purpura with the 1996 students could more successfully retrieve medical education was Presidential Award from the Society for long-term memories of the science they taught.” Neuroscience, Dr. Pasko Rakic noted that learned when it was taught by great Dr. Purpura “was a neuroscientist before teachers who informed them broadly, — DR. EDWARD R. BURNS the word ‘neuroscience’ was invented to rather than by research experts who denote our multidisciplinary field.” focused more narrowly on their own

Dr. Purpura’s exceptional contribu- particular lab work, as was the tradition tions span the field and had a significant at medical schools at the time.” This impact on a range of conditions, includ- new approach was adopted by medical ing epilepsy and developmental disabili- schools across the nation. ties. Dr. Purpura served for 30 years as In the commencement address he gave editor-in-chief of Brain Research, and upon his retirement, Dr. Purpura said, held leadership roles in numerous pro- “It is no secret that Einstein graduates fessional organizations, including presi- are among the most effective and skilled dent of the American Epilepsy Society interns and residents in any program. … and of the Society for Neuroscience. I predict you will be a joy to your attend- He also was elected to the National ings and a savior to your patients.” Academy of Sciences and was one of just

two scientists in the nation to receive an READ MORE inaugural National Medical Research Learn more about Dr. Purpura or Award, bestowed at a White House leave a remembrance: ceremony in September 1988. magazine.einstein.yu.edu/Purpura19

6 EINSTEIN : SUMMER/FALL 2019 MAGAZINE.EINSTEIN.YU.EDU 7 MONTEFIORE AND EINSTEIN MAVENS OF MEDICINE

A Champion harmila Makhija, M.D., M.B.A., is a for Women’s professor and the Chella and Moise Safra SChair in Obstetrics & Gynecology and Health Women’s Health at Einstein. She is a gynecologic oncologist and translational researcher who Q&A With has published and lectured widely on cancer Dr. Sharmila Makhija therapeutics. Dr. Makhija joined Montefiore- Einstein in 2015, after holding leadership positions at the University of Alabama at Birmingham (UAB), Emory University, and the University of Louisville.

8 EINSTEIN : SUMMER/FALL 2019 You have a Southern accent. Where What was your role in the HPV an impact. If not, we should be asking, is it from? vaccine trials? “How can we do better?” We initiated My parents are from India and completed Our research team collaborated with monthly meetings with the leadership graduate school in the United States. Merck & Co. to enroll patients into quality and safety team to address prob- My dad accepted a teaching position in trials at UAB. We noted flaws in the trial lems—not to assign blame, but rather to Alabama, where I was born and raised. design and helped Merck revise the observe patterns and find solutions. trials to better enroll patients and Did your parents influence your address the vaccine’s clinical impact. As What has been the reaction? career? the top recruiter, I was the lead author. Changing culture is disruptive. We My dad was a college chemistry pro- We also helped educate physicians and reminded ourselves of our mission fessor, my mom a high school biology patients about the vaccine. to improve the care we deliver and teacher. At dinnertime, we would talk recruited faculty who align with this about the day’s events and how we could Why did you get an executive mission. Our relationship with Every make things better for others. I try to M.B.A. degree? Mother Counts, a nonprofit focused on bring the same approach to department In 2008, when I was recruited as divi- respectful maternal care, has broadened meetings. You can get a bit removed sion chief of gynecologic oncology at our knowledge of patients’ needs. We from day-to-day clinical practice as you Emory University, all budgets were cut will always strive to improve—and this move along the administrative path, so I by a third because of the financial crisis. year, for the first time, our department feel it’s important to communicate and While trying to convince the finance was nationally ranked in U.S. News and connect often with others. team that we needed more resources for World Report, a testament to our dedi- clinical research programs, I realized we cated and caring faculty and associates. Tell us about your work in India. weren’t speaking the same language. I I worked with Tata Hospital and its visited Emory’s Goizueta Business School Are you taking advantage of the oncologists to improve cervical cancer and enrolled in the executive M.B.A. recent affiliation between Einstein care. Though it is a preventable disease program to learn accounting and finance. and Montefiore? and the early stages are treatable, barriers But most important was what I learned We encourage our faculty to become to accessing care in rural India often lead about organizational behavior and the more involved in research at Einstein. to diagnoses at incurable, late stages. complexities of human behavior. We have an established collaboration Most women can’t afford to spend days with colleagues in molecular pharmacol- traveling to a clinic, and a cancer diag- What attracted you to Einstein and ogy and, most recently, in genetics. nosis carries a social stigma for women Montefiore? I see a direct benefit in learning from that can lead to abandonment. For I knew about Einstein’s reputation for one another to improve the health of social survival, women often ignore both research, which has always been an our patients. cancer symptoms and attending to basic important part of my career. As I learned healthcare needs. It was a valuable lesson more about Montefiore, I was drawn How did you become a movie on the importance of taking culture into to its dedication to the social aspects of producer? account in healthcare delivery. care. I haven’t seen this level of commit- A neighbor asked me about a Bollywood ment at any other place I’ve worked. actress for a movie she was producing. It’s Does that experience inform your based on the true and fascinating story work here in the Bronx? What has been your biggest of undercover female spies for the British Yes. Patients often can’t keep appoint- challenge in your department? during World War II. I created a produc- ments for social and financial reasons. Changing the culture in delivering care. tion company, and the movie, Liberté: A Having a diverse faculty helps bring It is easy to say, “We have always done it Call to Spy, is my first project. It pre- awareness of cultural issues to the fore- this way, and we are pretty good at it.” miered at the Edinburgh International front of how we deliver care. What matters is whether we’re making Film Festival in June 2019.

MAGAZINE.EINSTEIN.YU.EDU 9 RESEARCH NOTES First Complete Wiring Diagram of a Nervous System

n a study published (302 in the hermaphrodite/ online this past July in female sex, 385 in the male) I Nature, Einstein research- makes it one of the best animal ers described the first models for understanding the complete wiring diagram billions-times-more-complex THE INTERNATIONAL WEEKLY JOURNAL OF SCIENCE of the nervous system of THE INTERNATIONAL WEEKLY JOURNAL OF SCIENCE human brain. It was also the first an animal, the roundworm multi-cellular organism to have Caenorhabditis elegans, used its entire genome sequenced. by scientists worldwide as a THE WORM-WIDE WEB Dr. Emmons’ study builds on model organism. The study THE WORM-WIDE WEB the groundbreaking work of the included adults of both sexes late South African-born biolo- and revealed substantial gist Sydney Brenner, who in differences between them. 2002 shared the Nobel Prize in The findings mark a Physiology or Medicine for his major milestone in the field C. elegans research. Dr. Brenner’s of “connectomics”—the laboratory published the first effort to map the myriad Complete map of the C. elegans nervous neural connections in a nervous systemsComplete system in 1986, after painstak- nervousmapped systems for brain, brain region, or bothmapped sexes of for ingly analyzing neural structures bothC. elegans sexes of nervous system to find the C.PAGES elegans 40 & 63 visible on thousands of serial specific nerve connections PAGES 40 & 63 electron micrographs. That tour ENGINEERING DEVELOPMENT MACHINE LEARNING NATURE.COM 4 July 2019NATURE.COM £10 ENGINEERING DEVELOPMENT MACHINE LEARNING Vol. 571, No. 7763 responsible for particular ARTIFICIAL UNSCRAMBLED ON THE 4 July 2019 £10 de force effort, 20 years in the CIRCULATIONARTIFICIAL UNSCRAMBLEDEGGS PAPERON TRAIL THE Vol. 571, No. 7763 behaviors. SyntheticCIRCULATION vascular system Unpicking theEGGS evolutionary Text PAPERmining spots TRAIL hidden making, launched the field of Syntheticpowers robot vascular fish system Unpickinghistory of insectthe evolutionary ova propertiesText mining of materials spots hidden powersPAGE 5 robot fish historyPAGES 24 of & insect 58 ova propertiesPAGES 42 & of 95 materials “Structure is always PAGE 5 PAGES 24 & 58 PAGES 42 & 95 connectomics and established central in biology,” says Copyright © 2019, Springer Nature the roundworm as an essential study leader Scott Emmons, animal model for studying biol- Ph.D., professor of genetics and in the are “connectopathies”—that is, prob- ogy and human disease. Dominick P. Purpura Department of lems caused by “faulty wiring.” “This “Since the roundworm nervous sys- Neuroscience and the Siegfried Ullmann hypothesis is strengthened by the find- tem contains many of the same mol- Chair in Molecular Genetics at Einstein. ing that several mental disorders are ecules as the human nervous system, “The structure of DNA revealed how associated with mutations in genes that what we learn about the former can genes work, and the structure of proteins are thought to determine connectivity,” help us understand the latter,” says Dr. revealed how enzymes function. Now Dr. Emmons says. “Connectomics has Emmons, who is currently studying the structure of the nervous system is the potential to help us understand the how the roundworm connectome is revealing how animals behave and how basis of some mental illnesses, possibly encoded by its genome. neural connections go wrong to cause suggesting avenues for therapy.” disease,” Dr. Emmons says. Because C. elegans is so tiny—adults WATCH THE VIDEO are just one millimeter long and have Researchers have hypothesized that See Dr. Emmons explain some neurological and psychiatric disor- only about 1,000 cells—its simple ner- his research: ders, such as schizophrenia and autism, vous system of a few hundred neurons magazine.einstein.yu.edu/worm19

10 EINSTEIN : SUMMER/FALL 2019 New Acute-Migraine Therapy Shows Promise

drug belonging to a new which were introduced in the 1990s. generation of acute-migraine People not helped by triptans, or who A treatments eliminated pain can’t take them, may benefit from and reduced bothersome symptoms for the new class of drugs called gepants, people with migraine in a large-scale which includes rimegepant. trial reported in the July 11 issue of The Gepants work by targeting the New England Journal of Medicine. The receptors for a small protein, called drug, rimegepant, may offer advan- CGRP, long implicated in migraine. tages over currently available migraine During migraine attacks, CGRP is medications. released, resulting in pain. Gepants The study’s first author was Richard relieve the pain and other symptoms tablet during a migraine attack. Two B. Lipton, M.D., the Edwin S. Lowe of migraine by blocking the CGRP hours after taking their tablets, 19.6% Chair and vice chair of the Saul R. pathway. of patients in the rimegepant group were Korey Department of Neurology at Rimegepant was assessed in a ran- free from pain, compared with 12% in Einstein and director of the Montefiore domized, double-blind trial involving the placebo group—a statistically sig- Headache Center. more than 1,000 men and women with nificant difference. Freedom from their Currently, many people with migraine at 49 centers in the United most bothersome symptoms occurred migraine take triptan drugs (such as States. Each participant took a tablet in 37.6% of patients in the rimegepant sumatriptan, eletriptan, and rizatriptan), of rimegepant or a matching placebo group and 25.2% in the placebo group. How Lupus Occurs in the Brain atients with the autoimmune dis- ease systemic lupus erythematosus P (SLE) have poor outcomes despite aggressive treatment with immunosup- pressive drugs. In a study published this past June in JCI Insight, Chaim Putterman, M.D., and colleagues identi- fied how SLE develops in the central nervous system (CNS) independent of node—deep within the brain. The lupus, which is extremely difficult to its occurrence elsewhere in the body. newly discovered structure may be the treat. Dr. Putterman is a professor of The scientists found that the immune route through which the immune sys- medicine and of microbiology & immu- system forms a tertiary lymphoid struc- tem promotes CNS lupus. The find- nology at Einstein and chief of rheuma- ture—which functions like a lymph ings may lead to new therapies for CNS tology at Einstein and Montefiore.

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

elena M. Blumen, Ph.D., is a cognitive neuroscientist who studies the brain networks we use to walk, reason, make H decisions, and form memories. An assistant professor in the department of medicine and in the Saul R. Korey Department of Neu- rology, Dr. Blumen was born in Sweden, came to the United States to attend college, and landed at Einstein in 2013, after completing a postdoctoral fellowship at Columbia University Medical Center.

What is your research focus? What’s your opinion of brain- I’m interested in optimizing gait and training programs, such as cognition in older people. My colleagues Lumosity or CogniFit? and I view cognition and mobility— I think some of them have particularly in the elderly—as being potential, but we don’t know yet closely related. For older people, walk- if they work. I’m now involved ing is not so automatic as it was when in two trials that are assessing they were young, and they have to think whether behavioral interventions about the steps they’re taking. So walk- can help. One is an imagery ing becomes a cognitive task that relies study in which we teach older on the same or similar brain networks people to imagine themselves as cognitive processes such as memory walking. The idea is that imagin- and attention. Our studies will inves- ing walking will stimulate the tigate whether training older people to brain regions involved in actual improve their gait can also improve their walking and improve walk- cognitive processes, and vice versa. ing ability—and, by extension, cognitive processes as well. This If you had to focus on improving might especially help people Dr. Helena M. Blumen, left, works with a participant just one—gait or cognition—which who are frail and not able to in a study of gait and cognition. would you choose? get outside. The other trial is I’d say improving gait. It would improve comparing social dancing with What else do you do in your spare cognition as well. Plus, when brain treadmill exercising with respect to gait time? function declines in the elderly, gait and cognitive outcomes. Well, I have two kids, a 15-year-old problems usually precede cognitive girl and a 5-year-old boy, so there’s not decline and dementia. So improving Where in Sweden are you from? much of that! someone’s gait could conceivably help I was born in the town of Luleå, a delay cognitive difficulties. couple of hours by car from the Arctic Do you make any Swedish dishes? Circle. I make my own gravlax, which is cured What do you especially like about salmon. You rub a mixture of salt, sugar, working with older people? Did you ski there? lemon, and pepper into two salmon The people who participate in our stud- Yes, I was an athlete growing up and filets, then use a heavy object to press ies are very happy to be here and excited did cross-country skiing, and also the meat sides of the filets against each about being involved in research. And played soccer. I don’t ski much any- other for a couple of days in the refrig- from our perspective, we really value the more but I stay active by doing cross- erator. It’s not that hard to make, and it research data they provide. training exercises at a health club. tastes great.

12 EINSTEIN : SUMMER/FALL 2019 RESEARCHRESEARCH NOTES NOTES

MAJOR NIH RESEARCH AWARDS

Focusing on Post-HIV Problems Targeting Deadly Viruses Obesity and Hypertension The National Institutes of Health The National Institute of Allergy and Dongsheng Cai, M.D., Ph.D., received (NIH) has awarded Kathryn Anastos, Infectious Diseases (NIAID) has awarded two NIH grants totaling $4.5 million M.D., and Anjali Sharma, M.D., a an international consortium led by to study the role of the hypothalamus seven-year, $23 million grant to study Kartik Chandran, Ph.D., a five-year, $22 in obesity and hypertension. Dr. Cai HIV and the chronic illnesses that often million grant to develop antibody-based has found that sustained activation of accompany HIV infection, including therapies against four lethal viruses for astrocytes (cells that surround and sup- cardiovascular and lung disease, diabe- which approved vaccines or treatments port neurons) may contribute to the tes, and cancer. The multicenter trial are lacking. The viruses are the tick-borne metabolic dysregulation and subsequent merges two existing studies that for Crimean-Congo hemorrhagic fever virus weight gain caused by pro-inflammatory decades have followed women and men and three hantaviruses, which are spread signaling in the hypothalamus. He was who are HIV positive or at risk for HIV by rodents: Andes virus, Sin Nombre awarded a four-year, $2 million grant to infection. The team will enroll 2,500 virus, and Puumala virus. The NIAID study how hypothalamic astrocytes are new participants as well. Researchers has designated all except the Puumala altered in inflammation and how those will also study disease-related outcomes virus as category A agents—emerging altered astrocytes influence hypothalamic such as heart attacks and strokes, con- infectious diseases or pathogens that neurons to dysregulate metabolism. Evi- duct neuropsychiatric testing to assess pose the highest risk to national security dence also indicates that inflammation- cognition, and administer detailed and public health. Other participating induced activation of hypothalamic psychiatric evaluations. Dr. Anastos is a institutions are the U.S. Army Medical astrocytes plays a role in obesity-related professor of medicine, of epidemiology Research Institute of Infectious Diseases, hypertension (OHT), which accounts & population health, and of obstet- Mapp Biopharmaceutical, the University for 75% of hypertension cases and is dif- rics & gynecology and women’s health of Texas at Austin, and Adimab, a biotech ficult to control. The second grant, for at Einstein and a general internist at company. Dr. Chandran is a professor $2.5 million over four years, sponsors Montefiore. Dr. Sharma is an associate of microbiology & immunology and the Dr. Cai’s research into how the astrocyte- professor of medicine at Einstein and an Harold and Muriel Block Faculty Scholar neuron relationship in obesity contrib- internist and infectious-disease physi- in Virology at Einstein. utes to OHT. Dr. Cai is a professor of cian at Montefiore. molecular pharmacology at Einstein.

MAGAZINE.EINSTEIN.YU.EDU 13 RESEARCH NOTES

MAJOR NIH RESEARCH AWARDS

Opioids, HIV, and Brain Damage A Potential Path to an HIV Cure Targeting Signals in Alzheimer’s HIV can invade the brain and cause Curing HIV-infected individuals has not Diminished somatotropic signaling (i.e., chronic neural inflammation and, ulti- been possible because neither the human signaling that stimulates body growth) mately, cognitive impairment in most immune system nor antiretroviral therapy leads to delayed aging and longer life HIV-infected people. Antiretroviral can eliminate cells that are latently spans in both model organisms and peo- therapies don’t completely relieve the infected with HIV. These cells become ple. Centenarians, in fact, have several inflammation or reduce brain dam- reactivated and reintroduce systemic mutations that weaken somatotropic age—and opioid abuse makes things infection when treatment is halted. The signaling. Sofiya Milman, M.D., has worse. The National Institute on Drug NIAID awarded Harris Goldstein, M.D., received a five-year, $4 million grant Abuse has awarded Joan W. Berman, and Steven Almo, Ph.D., a five-year, $4.2 from the National Institute on Aging to Ph.D., and Harris Goldstein, M.D., a million grant to develop novel immu- identify genes and gene functions that five-year, $4.2 million grant to investi- nomodulatory biologics to precisely and inhibit growth-related signaling. She and gate molecular mechanisms that worsen markedly expand HIV-specific CD8+ her colleagues will study participants in HIV-related inflammation in people who (“killer”) T cells to target and elimi- Einstein’s LonGenity study—a cohort abuse opioids. By analyzing HIV and nate latent HIV-infected CD4+ T cells of 1,400 older adults, half of them the opioid-induced gene-expression changes, intentionally reactivated to make them offspring of centenarians. The researchers they hope to identify new drugs to quell “visible” to the CD8+ cells. The novel will investigate the role that somatotropic HIV-caused brain inflammation. Dr. treatment strategy could lead to long- signaling plays in the brains of aging Berman is a professor of pathology and of lasting HIV remission or even a func- humans. They hope to identify mecha- microbiology & immunology at Einstein, tional cure for HIV infection. Dr. nisms that confer cognitive resilience the Irving D. Karpas Chair in Medicine, Goldstein is the director of the Einstein- by delaying aging—findings that could and the senior academic adviser to the Rockefeller-CUNY Center for AIDS lead to therapies to help protect against Sue Golding Graduate Division of Research. Dr. Almo is a professor and the Alzheimer’s and other aging-associated Biomedical Sciences. Dr. Goldstein is a chair of biochemistry, a professor of phys- diseases. Dr. Milman is an associate professor of pediatrics and of microbi- iology & biophysics, and the Wollowick professor of medicine and of genetics at ology & immunology and the Charles Family Foundation Chair in Multiple Einstein and an attending physician in Michael Chair in Autoimmune Diseases. Sclerosis and Immunology at Einstein. medicine at Montefiore.

14 EINSTEIN : SUMMER/FALL 2019

Unraveling the B-Cell Response MS Patients, Mobility, and Falls Sleep and Cognitive Decline Against TB Impaired mobility is the most obvious Disturbed sleep is common among older The bacterial species Mycobacterium symptom of multiple sclerosis (MS), adults and may lead to cognitive decline tuberculosis (Mtb) caused 1.6 mil- and falls are common. The life expec- and Alzheimer’s disease. Carol A. Derby, lion tuberculosis-related deaths in tancy of MS patients has increased, but Ph.D., has received a four-year, $4 mil- 2017, according to the World Health studies on mobility and falls among lion grant from the National Institute Organization. Infection triggers a well- older MS patients are scarce. Research on Aging to partner with the ongoing studied T-cell response against Mtb, but by Roee Holtzer, Ph.D., suggests that Einstein Aging Study (EAS) to examine the B-cell immune response that leads the integrity and proper functioning the association between sleep patterns to antibody production is not clearly of the brain, especially the prefrontal and cognition in 500 older Bronx adults. understood. John Chan, M.D., received cortex, are critical for cognitive control The research will be a collaboration with a five-year, $3.5 million grant from the of mobility. He has received a five-year, Pennsylvania State University profes- NIAID to investigate IgM antibod- $3.5 million grant from the National sor Orfeu Buxton, Ph.D. In Dr. Derby’s ies—the first antibodies that respond Institute of Neurological Disorders project, EAS participants will wear to infection—and their role in the host and Stroke to identify brain systems special watches to collect daily informa- immune response to Mtb. Dr. Chan and governing mobility in older adults tion on sleep and will wear devices to colleagues will use mouse and ex vivo (120 MS patients and 120 controls) measure their oxygen levels overnight. macaque tuberculosis (TB) models to to determine whether brain function The data may reveal sleep’s impact on better understand the role and impor- during active walking can predict falls. cognition and suggest strategies for pre- tance of IgM in immune regulation Neuroimaging techniques will measure venting cognitive decline. Dr. Derby is during the early and chronic stages of prefrontal cortex activity and assess the a research professor in the Saul R. Korey TB. Findings from this study may lead brain’s structural integrity. The findings Department of Neurology and in the to novel therapies against TB infection. may identify biomarkers that can be department of epidemiology & popula- Dr. Chan is a professor of medicine modified to prevent falls. Dr. Holtzer tion health and is the Louis and Gertrude and of microbiology & immunology at is a professor in the Saul R. Korey Feil Faculty Scholar in Neurology at Einstein and an attending physician in Department of Neurology at Einstein. Einstein. infectious diseases at Montefiore.

MAGAZINE.EINSTEIN.YU.EDU 15 16 EINSTEIN : SUMMER/FALL 2019 The Search for Autism Therapies From cannabis to whipworms, scientifically promising treatments are being tested at Einstein and Montefiore

BY GARY GOLDENBERG

arlos Rodriguez of the Bronx seemed like talking, if sparingly, and enabled him to attend a a healthy, happy baby. But as his first mainstream school with special services. birthday approached, he began to scream Carlos has a loving home, a supportive school, and cry at the slightest provocation. His and top-notch specialty care—yet these are not C“twos” were particularly terrible. While his peers enough. Now 14, he avoids eye contact, can’t were learning to talk, Carlos communicated only by tolerate busy or noisy environments, doesn’t take grunting and pointing. Even worse, he would throw part in sports, and abhors the slightest deviation tantrums, banging his head against anything and from his daily routine. At home he prefers being everything. alone in his room, watching YouTube videos and The family’s pediatrician suspected a serious playing with Transformers, his favorite toys. developmental problem and referred Carlos to Six thousand children who live in the Bronx Children’s Hospital at Montefiore. There he was and another 12 million nationwide fall some- diagnosed with autism spectrum disorder (ASD) where on the autism spectrum. Only a small per- and received the latest behavioral, educational, centage will successfully outgrow their diagnoses and medical therapies. The interventions got him (see related article on page 26).

At left, Carlos and his mom, Maribel, enjoy a day at a playground in the Bronx.

MAGAZINE.EINSTEIN.YU.EDU 17 THE SEARCH FOR AUTISM THERAPIES Filling the Treatment Void

“One of our goals is to subject potential therapies to the rigor of solid scientific research so we can inform parents and clinicians about the therapies’ usefulness.”

­— DR. ERIC HOLLANDER

he U.S. Food and Drug Admin- Compulsive Spectrum Program at repetitive behaviors in particular and istration (FDA) has approved Einstein and Montefiore. “One of our ASD-symptom severity in general. In a T only two drugs for ASD: the goals is to subject potential therapies to 2012 study, they found similar results drugs risperidone and aripripazole, both the rigor of solid scientific research so we in adults. Prozac is now one of the most for treating ASD-related irritability. But can inform parents and clinicians about commonly used treatments for ASD. no treatments exist for the core symp- the therapies’ usefulness.” “Prozac seemed worth investigat- toms of ASD: deficits in social interac- For the past two decades, Dr. ing,” Dr. Hollander says. “The drug tion and communication, repetitive Hollander has been a national leader influences brain levels of serotonin, and behaviors, restricted interests, and diffi- in the search for new ASD treatments. serotonin dysregulation appears to be culty with new situations. That absence In research published in 2005, he and common in people with ASD. Plus, of therapies has created desperation. his colleagues were the first to assess Prozac and other SSRIs [selective sero- “We know that parents are trying all fluoxetine (Prozac) for relief of ASD tonin reuptake inhibitors] are front- kinds of alternative therapies on their symptoms. Their placebo-controlled, line treatments for disorders that—like children who have ASD,” says Eric double-blind trial, involving 45 chil- ASD—can involve repetitive behaviors. Hollander, M.D., professor of psychiatry dren and adolescents with ASD, found But not all patients with ASD respond and behavioral sciences at Einstein and that low-dose liquid Prozac was more to Prozac, and not everyone tolerates it, director of the Autism and Obsessive effective than a placebo in reducing so we decided to test other treatments.”

18 EINSTEIN : SUMMER/FALL 2019 AUTISM EXPLAINED

eople with autism spectrum disorder (ASD) have trouble communicating Pand forming social relationships, and they may also have restricted interests and repetitive behaviors. These symptoms impair Irritability and their ability to function well in school, work, impulsivity and other areas of life. The U.S. Centers for Disease Control and Prevention estimates that ASD affects 1 in 59 children in the United States, primarily boys, with the initial signs and symptoms usually appearing in the first two years of life. ASD is called a “spectrum” disorder ASD because of the wide variation in the type and Impaired social severity of its symptoms. Roughly 40% of in- is a neurological interaction condition that affects dividuals with ASD have intellectual disability & communication (defined as an IQ of less than 70), but many how people experience have normal to above-average intelligence, the world and interact and some have exceptional abilities. with others There’s no single cause of ASD. Research suggests that the disorder often develops from a combination of genetic and environ- mental influences that affect critical aspects of early brain development—particularly how neurons or entire brain regions communicate with one another. Becoming a parent at an Repetitive older age increases the risk of having a child behavior with ASD. Complications related to preg- nancy, such as extreme prematurity, low birth weight, and closely spaced pregnancies, can also increase the risk. Vaccines do not affect the risk of developing ASD. ASD is usually treated with early- intervention services, which include a mix of speech and occupational therapies and Restricted range applied behavior analysis (the main of interests evidence-based treatment for ASD).

Difficulty deviating from 1in59 normal routine children in the U.S. Boys are 4x more likely is affected by ASD than girls to have ASD

MAGAZINE.EINSTEIN.YU.EDU 19 THE SEARCH FOR AUTISM THERAPIES Righting an Imbalance

EASING IRRITABILITY Risperidone and aripripazole have been approved by the FDA for treating irritability related to ASD. Both were originally approved as antipsychotic medications and can have serious side effects, including significant weight gain. Dr. Hollander realized that valproate, a drug approved for treating seizures in epilepsy, might be a better alternative. For one thing, valproate may normal- ize the E/I balance, since it appears to work by raising levels of gamma amin- obutyric acid, a neurotransmitter that inhibits neuron signaling in the brain. And in studies involving other condi- tions, the drug relieved symptoms also found in ASD—reducing aggression in people with borderline personality disorder, for example. Similar drugs have proved to be useful in treating disorders with repetitive and impulsive features, such as compulsive gambling and binge eating. Dr. Hollander and his colleagues have conducted two randomized, ther treatments evaluated by regulates behavior,” Dr. Hollander says. placebo-controlled clinical trials assess- Dr. Hollander’s group include “The imbalance triggers seizures, and ing valproate’s effectiveness in treat- O the hormone oxytocin; the we believe it’s also responsible for the ing ASD patients, primarily children antiepilepsy drug valproate; a marijuana core ASD symptoms that we can’t treat and adolescents. Both trials found that extract; and the eggs of a parasite that effectively yet. So we look for interven- valproate was significantly more effec- infects pigs—diverse therapies that each tions that show promise for correcting tive than a placebo in relieving repetitive address a widely accepted cause of ASD: the E/I imbalance and, hopefully, easing behaviors and irritability and agitation an excitatory/inhibitory (E/I) imbalance the symptoms of people with ASD.” in people with ASD. Valproate, however, in brain neural circuits. As his colleague Bonnie P. Taylor, is no panacea for those symptoms. It can Considerable evidence, from animal Ph.D., assistant professor of psychiatry have significant side effects of its own, and human studies, suggests that ASD and behavioral sciences at Einstein, puts including weight gain, liver inflamma- is accompanied by overexcitation of the it: “We’re open to testing therapies that tion, and tremor. brain’s neural circuits, due to either an look promising. New therapies for kids increase in excitatory neuron signaling who have ASD are urgently needed. So or a decrease in inhibitory signaling. if there’s a rationale for a treatment and At right, a child who has autism works on “This E/I imbalance alters the way we’re confident that it’s safe, we’ll figure an IQ test at the Einstein campus under the brain processes information and out a way to develop a trial.” the supervision of Dr. Bonnie P. Taylor.

20 EINSTEIN : SUMMER/FALL 2019 MAGAZINE.EINSTEIN.YU.EDU 21 THE SEARCH FOR AUTISM THERAPIES A Drug Tailor-Made for ASD

xytocin is a peptide hor- possibility, in a double-blind, placebo- ”Oxytocin had mone secreted by the pitui- controlled trial whose results were potential for O tary gland. It floods the published in 2003. His oxytocin-related bloodstreams of mothers giving birth, research led directly to a phase 2 clini- improving the social facilitating uterine contractions and cal trial now evaluating the first drug deficits that are a core stimulating milk letdown for breast- designed specifically to treat ASD. feeding. Oxytocin also plays a crucial “Studying oxytocin made sense to symptom of ASD.” role in so-called affiliative behaviors: us,” Dr. Hollander says. “It had poten- It helps initiate the emotional bond tial for improving the social deficits that ­— DR. ERIC HOLLANDER between mother and infant, for exam- are a core symptom of ASD. And it ple, and enhances the social attachments might help correct the E/I imbalance in connecting friends and lovers. ASD, since one of its modes of action In the 1990s, several researchers pro- involves strengthening signals sent by posed that abnormalities in the oxytocin inhibitory neurons.” system might play a role in ASD, which Dr. Hollander’s clinical trials have typically involves poor social skills. Dr. found that oxytocin significantly Hollander was the first to study that reduced repetitive behaviors in people

22 EINSTEIN : SUMMER/FALL 2019 FEVERS, WHIPWORMS, AND with ASD and made them better aware THE ROOT CAUSES OF AUTISM of social cues in conversation. But administering oxytocin is difficult: The ver the past several Dr. Hollander and his col- protein must usually be given intrave- decades, parents and leagues carried out a double- nously or intranasally, since it’s broken Ophysicians have observed blind, 12-week crossover trial down in the gut when swallowed. To get that some children with ASD involving 10 young adults with around that problem, the Swiss phar- improve when they have a fever, ASD. Half the participants first maceutical company Roche designed only to regress afterward. Those swallowed 2,500 whipworm eggs an oral ASD drug that boosts oxytocin’s anecdotes suggest that an inter- every two weeks for 12 weeks and effectiveness by blocking a chemical vention that duplicates a fever then took a matching placebo for competitor called vasopressin. might also calm ASD symptoms— the next 12 weeks. The other five Oxytocin and vasopressin have a lot and perhaps provide insight into participants were treated in re- in common. The structurally similar ASD’s underlying causes as well. verse order—first the placebo and peptide hormones are both released by Hence an experimental therapeu- then the whipworm eggs. (When the pituitary gland, and both strengthen tic trial using the pig whipworm people swallow whipworm eggs, social bonds by binding to the same Trichuris suis made sense. the worms that develop can’t receptors in the brain—but oxytocin is “Fevers are typically a re- penetrate the human intestine and considered more helpful. sponse to inflammation and don’t cause illness.) During the Balovaptan, the drug developed by immune-system arousal,” says study, clinicians and parents as- Roche chemists, prevents vasopressin Eric Hollander, M.D., who leads sessed the participants for inflex- from binding to a type of vasopres- the Einstein-Montefiore effort to ibility, social withdrawal, and other sin receptor called V1a. By blocking find new ASD therapies. “Previous behaviors associated with ASD. vasopressin, balovaptan allows oxytocin trials had suggested that T. suis Results were reported in 2018 molecules to bind to those receptors infections in people can tamp in The World Journal of Biological unchallenged—and, it is hoped, will down those processes, both of Psychiatry. Overall, differences help people with ASD become more which are overactive in ASD. between the two groups were not socially engaged. T. suis seems to reduce inflamma- statistically significant, but par- Balovaptan has already been shown tion by normalizing the excitatory/ ticipants treated with whipworm to improve social behavior and reduce inhibitory balance in nerve signal- eggs did show large reductions of cognitive impairment in an animal ing, which we consider essential repetitive behavior and irritability. model of ASD and in adult ASD for effective ASD therapies.” patients. In 2018, the FDA granted bal- ovaptan “breakthrough therapy” status, a process in which the agency speeds its review of drugs that “demonstrate substantial improvement over available therapy” for treating serious conditions. Dr. Hollander is now leading Einstein’s participation in a nationwide clinical trial of balovaptan. This phase 2 (safety and efficacy) trial, called the aV1ation Study, will include 300 high- functioning children and teens with ASD at 30 sites around the country. Participants will take either of two doses of the drug or a placebo for 24 weeks.

MAGAZINE.EINSTEIN.YU.EDU 23 THE SEARCH FOR AUTISM THERAPIES A Marijuana Extract for Autism

24 EINSTEIN : SUMMER/FALL 2019 ore than 100 chemicals endocannabinoid receptors, but they “This research shows known as cannabinoids are nevertheless produce important effects. M found in cannabis plants, In two of the few trials that have that CBDV has including marijuana and hemp. In evaluated CBD in people, New York anti-inflammatory, 1964, researchers identified terrahydro- University (NYU) scientists found that cannabinol (THC) as the cannabinoid the compound significantly reduced immune-modulating, responsible for marijuana’s “high.” seizure frequency in patients with antianxiety, and This finding revealed an important Lennox-Gastaut syndrome and Dravet signaling system in the brain—one that syndrome, two rare forms of epilepsy anticonvulsant regulates such physiological and cogni- with similarities to ASD. In 2018 the properties.” tive processes as appetite, stress, mood, FDA approved Epiodolex, the liquid memory, social behavior, and pain CBD formulation used in the epilepsy ­— DR. ERIC HOLLANDER sensation. THC activates this signaling trials, for treating those conditions. system by binding directly to receptors CBD’s antiseizure properties suggest in the brain. The human body was later that CBD and CBDV may both help to found to produce its own cannabinoids, correct the E/I imbalance observed in dubbed “endocannabinoids,” which are people with ASD. involved in what is called the “endocan- Preliminary studies have found that nabinoid signaling system.” CBDV is effective in treating pediatric Recent studies involving animal epilepsy, and animal studies suggest it models suggest that disrupted endocan- could be valuable for treating ASD. nabinoid signaling may play a role in “The research shows that CBDV ASD. For example, in a study published has anti-inflammatory, immune- earlier this year, Stanford researchers modulating, antianxiety, and anticon- found that the blood plasma of chil- vulsant properties,” Dr. Hollander dren with ASD contained significantly says. “And in one recent study, CBDV lower levels of the endocannabinoid improved social behavior in an animal anandamide compared with levels model of Rett syndrome, an autism- in neurotypical children. In keep- related condition. So CBDV appears to ing with its outside-the-box approach, be a promising ASD treatment that we Dr. Hollander’s team is investigating need to explore further.” whether cannabinoids might relieve chil- Last year, the Department of Defense dren’s ASD symptoms by normalizing (DoD) awarded researchers at Einstein, endocannabinoid signaling. Montefiore, and the NYU School of The Einstein team has focused Medicine a $1.3 million grant to study on a nonpsychoactive cannabinoid the safety and efficacy of CBDV in chil- called cannabidivarin (CBDV), whose dren with ASD. molecular structure closely resem- Dr. Hollander is leading the study bles that of cannabidiol (CBD)—the along with NYU’s Orrin Devinsky, popular nonpsychoactive cannabinoid M.D., who conducted the CBD epi- now being sold online and over the lepsy trials. The hope is that CBDV can counter in tinctures, oils, and lotions help with “protest behavior”—the sud- for conditions ranging from anger to den temper tantrums that often plague Alzheimer’s. Unlike THC, CBD and people with ASD, particularly those CBDV don’t seem to bind directly to with severe symptoms.

MAGAZINE.EINSTEIN.YU.EDU 25 “These tantrums make it hard for families to go to a restaurant, travel on public transportation, or do much of anything outside the home,” Dr. Hollander says. “It’s a huge burden, one that causes many couples to separate or divorce.” Military families who have children with ASD face the same issues, which is why the DoD is supporting the study. “Those families need access to a lot of services, which limits where they can live, which in turn affects military CAN KIDS AGE OUT OF ASD? readiness,” Dr. Hollander adds. ccording to a new study from researchers at Einstein and The Einstein-Montefiore-NYU Montefiore—the largest of its kind, with the most rigorous trial—the first to study CBDV—will A diagnostic follow-up—the answer is a qualified “yes.” A small enroll 100 children with above-average minority of children with an initial diagnosis of ASD no longer qualify for levels of irritability. Patients will take it later on, yet most of them still have difficulties that require therapeutic an oral CBDV solution or a placebo and educational support. “It’s certainly encouraging to confirm that a twice a day for 12 weeks, and results are subset of children with early ASD diagnosis can in essence recover from expected in three years. The researchers the disorder and go on to have typical social and cognitive functioning,” will use the new Montefiore-Einstein says lead author Lisa Shulman, M.D., pictured above, who is a profes- Rigidity Scale—Revised (MERS-R) sor of pediatrics at Einstein and interim director of the Rose F. Kennedy to assess the participants’ social and Children’s Evaluation and Rehabilitation Center at Montefiore. “But by cognitive functioning before and after and large, these children continue to struggle with daily life. Almost all treatment. of them still contend with language and learning disabilities and a vari- “We previously had to rely on parents’ ety of emotional and behavioral problems.” observations about the children’s behav- In the study, Dr. Shulman and her colleagues reviewed the clinical ior on scales that were either too specific records of 569 young children who were diagnosed with ASD. Most had or not specific enough,” Dr. Taylor says. received early-intervention services. When followed up an average of “When we realized we weren’t captur- four years after their initial diagnoses, 38 children—7% of the group—no ing all of their behaviors, we decided we longer met the diagnostic criteria for ASD. Of those 38, two-thirds still ex- needed a better scale.” hibited language or learning disabilities; half had externalizing behavior MERS-R looks at three domains of problems, such as attention-deficit/hyperactivity disorder, and a quarter behavior: behavioral rigidity (difficulty had internalizing behavior problems, such as anxiety disorder. Only three adjusting to or managing behavior in of the 38 children who recovered from ASD had no other problems, the new, unfamiliar, or unexpected situa- authors reported earlier this year in the Journal of Child Neurology. tions); cognitive rigidity (lack of flexible What is going on with these children who no longer have an ASD thinking); and protest (behavioral reac- diagnosis? “Our sense is that some children with ASD respond to inter- tion in response to an interruption to vention and others have unique developmental trajectories that lead to the subject’s rigidity). “It takes just 20 improvement. Those children who evolve in a positive direction gener- minutes to administer the MERS-R, ally have the mildest symptoms to begin with,” Dr. Shulman says. “The which assesses the level, the length, and message from our study,” she adds, “is that some of our kids do amaz- the severity of each domain and puts a ingly well, but most of them have persistent difficulties requiring ongo- number on it,” Dr. Taylor says. ing monitoring and therapeutic support.” The findings from the CBDV study

26 EINSTEIN : SUMMER/FALL 2019 Military families who could have applications beyond ASD. Einstein-Montefiore trial, but that didn’t have children with “The repetitive features of ASD are also deter his parents from enrolling him in common in a variety of other compulsive the balovaptan trial. They realize the ASD face the same disorders,” Dr. Hollander says. “The goal urgency of finding therapies that will issues, which is why of our work is to discover ways to target help Carlos and other kids with ASD. the causes of these conditions, ease the “I’ll be his advocate to the end of the the Department of associated symptoms, and improve the day,” says his mom, Maribel. “I don’t Defense is supporting quality of life for many, many people.” want him to feel that he cannot have a Recruiting children for the balovap- life like everyone else. But I do worry the study. tan and CBDV trials shouldn’t be dif- about his future. When I try to talk to ficult. “Many parents are willing to try him about what he’s going to do when anything that might help their chil- he gets older, he says, ‘I’m not leaving. dren,” says Casara Jean Ferretti, M.S., a I’m staying with you.’” doctoral student at the Ferkauf Graduate School of Psychology, who helped write the CBDV grant application. READ MORE It’s an attitude that certainly char- Learn about other autism acterizes Carlos Rodriguez’s parents. research at Einstein: Carlos didn’t benefit from a previous magazine.einstein.yu.edu/autism19

MAGAZINE.EINSTEIN.YU.EDU 27 NO INSURANCE? NO PROBLEM!

The student-run Einstein Community Health Outreach clinic marks 20 years of service to Bronx residents

BY GREG DAUGHERTY

28 EINSTEIN : SUMMER/FALL 2019 tep inside the building at the corner of Walton Avenue and S East 177th Street in the Bronx on a Saturday morning and you might think you were at any other busy medi- cal clinic in New York City. About two dozen men and women patiently wait in a reception area with bright-green walls to see one of two doctors as a few more people check in at the front desk. “How can I help you today?” one of the receptionists asks a young woman, who says she is there for a medical clear- ance before starting a new job. She’s handed a clipboard as a nurse announces the next patient to be seen. Some people have come for blood tests or vaccinations. Others need help with a respiratory condition or a skin Einstein Ph.D. student Noelie Cayla, left, and second-year medical student Stephen problem. Still others are following up Liang, right, collect and record blood and urine samples at the ECHO clinic under the after surgery. Each of these services direction of Sadia Ahmed, center, a fourth-year medical student. might cost $400 or more out of pocket. But at this clinic, the receptionists are Walton Family Health Center on Sept. Counselors will also help eligible Einstein students and the doctors vol- 25, 1999, it was the first student-run, patients apply for Medicaid and other unteer their time. And the patients are physician-supervised free clinic in New insurance programs and provide them charged nothing for their visits. York City. It soon became a model for with a pharmacy card to ensure that similar clinics across the nation. they can get the medications that are A NATIONAL MODEL Today ECHO serves some 25 to prescribed to them. “The idea is to tran- The free health clinic exists because two 35 adults each Saturday. “We’re meet- sition them into the healthcare system,” decades ago a group of Einstein students ing the needs of community members Dr. Cortijo says. “We see ourselves as had an idea. They wanted to serve Bronx who may be afraid or unable to access the gateway.” residents who had no health insurance— healthcare because of the cost,” says including both members of the working Amarilys Cortijo, M.D., ECHO’s TAKING CARE OF PATIENTS poor and those who were not eligible medical director. To be seen, patients Just as ECHO has established itself as because of their immigration status. cannot have health insurance and must a vital community resource, it has also Partnering with the nonprofit be over age 18. Each ECHO patient become a key component of an Einstein Institute for Family Health, the students qualifies for two free well-care visits, medical education. More than two- launched the Einstein Community or four visits if he or she has a chronic thirds of the first-year students, 110 Health Outreach clinic, or ECHO for condition such as diabetes. After that, to 120 in all, volunteer at the clinic short. When ECHO opened at the the patients are encouraged to use one an average of one Saturday a month. of the full-time health centers operated Sharan Shah, a fourth-year medical stu- Fourth-year medical student Ryan Corbo, by the Institute for Family Health or dent at Einstein who recently served as far left, and interpreter Christopher another clinic of their choice. executive clinical chair at ECHO, esti- Fuentes, a pre-health student, walk with patient Reynalda Cohetero at the Einstein At the institute, they pay for care mates that 2,700 Einstein students have

Photos by Bernardo Restrepo Photos by Bernardo Community Health Outreach clinic. on a sliding-fee scale based on income. contributed their time and skills to the

MAGAZINE.EINSTEIN.YU.EDU 29 NO INSURANCE? NO PROBLEM!

clinic since it began. Dr. Cortijo arrived listen and how to speak to patients. at ECHO in early 2001 and has worked Medical students rarely get this opportu- with most of those students, who call nity anywhere else.” her the “heart and soul” of the clinic. That opportunity has, in fact, become Staffing a medical facility largely with a selling point for many students choos- student volunteers presents some chal- ing a medical school. One of them was lenges. One is the need to train a fresh Sarah Nosal, M.D., Class of 2004, who batch of recruits every year. “They’re knew from an early age that she wanted very bright and have a lot of energy, but to be a physician and work with an they’re often totally inexperienced,” Dr. underserved population. The year she Cortijo says. was applying to medical schools was On any given Saturday, there are the very year ECHO was established. likely to be about 40 Einstein students “When I found out I got into Einstein, on hand, along with two attending I dropped my other applications,” she “They improve their physicians to supervise them. In the recalls. “I said, ‘I have to go there.’” interpersonal skills; summer, undergraduate students from Dr. Nosal went to Einstein and other area colleges who are interested in joined ECHO; she has maintained the they learn how to listen medical careers can volunteer as inter- connection ever since. She now plays and how to speak preters or receptionists through ECHO’s an integral role in the running of the Pre-Health Summer Program. clinic, as well as serving as vice president to patients. Medical “Our students learn how to take care for innovation and optimization at the students rarely get of patients, under close supervision,” Institute for Family Health. Dr. Cortijo says. “They improve their Dr. Nosal seconds her colleague’s this opportunity interpersonal skills; they learn how to sentiment that students gain something anywhere else.”

— DR. AMARILYS CORTIJO

Second-year medical student Lawrence Li and fourth-year medical student Delia Shen, both ECHO coordinators, review imaging results with Dr. Sarah Nosal, center.

30 EINSTEIN : SUMMER/FALL 2019 from ECHO they’re unlikely to get else- where. “Doing some of the administra- tive tasks around the clinic, like working the front desk, helps them appreciate those roles and how important they are,” she says. “There’s just no place to teach that in the typical medical school curriculum.”

OUTSIDE THE CLINIC Lisa Kremen, Class of 2021, recently finished a stint as ECHO’s community education coordinator. “ECHO has been eye-opening for me, and it reinforced my desire to work in an underserved community,” says Ms. Kremen, who hopes to pursue a career Dr. Dan Kelly, during his final year in medical school, with three patients who in psychiatry. “You learn about people’s had amputations and were living at the Wardu resettlement community in Kono District, Sierra Leone, Africa. frustrations. For example, you see how hard it is for them to talk about mental health issues like depression, especially A CLINIC IN AFRICA WITH ROOTS IN THE BRONX among people from different cultures.” Dan Kelly, M.D., Class of 2008, says a major reason he chose Einstein Mr. Shah, the fourth-year student, after graduating from Princeton University was the opportunity to work hopes to become an ear, nose, and in the ECHO clinic. “I was so excited that I even started at ECHO sev- throat specialist. Like many first-years, eral weeks before medical school began,” he says. he started at ECHO’s front desk and Two years before he graduated, Dr. Kelly cofounded a medical clinic rose through the ranks to his position on for the poor in Sierra Leone, Africa, with a local doctor there. The clinic, the clinical board, which recruits, trains, which has since been integrated into Partners in Health–Sierra Leone, and schedules volunteers. “I’ve spent currently sees 250 to 300 patients a day, Dr. Kelly says. hundreds of hours at ECHO,” he says. “Without ECHO I don’t think I’d have been able to start a clinic from “I’ve learned a tremendous amount, and scratch,” he says. “In medical school you’re taught how to take care of it’s one of the things I’m proudest of. We patients, but you don’t learn about the operational and administrative get to see the very direct impact we have details that are needed to create the physician experience—how to set on the lives of our patients.” up the environment, how to organize patient records, all of those differ- Dr. Cortijo agrees. “Sometimes I get ent pieces.” up on a Saturday after working all week, Today Dr. Kelly is an infectious-disease specialist and epidemiologist and I don’t feel like going in,” she says. at the University of California, San Francisco. His work focuses on ways “But then I get there and am so happy, to improve Ebola prevention and care, primarily in Sierra Leone and so energized. It’s a rejuvenating experi- Liberia but also the Democratic Republic of the Congo. ence, a joyful experience. I think many “ECHO was a great experience for me—and not just for the practical of my colleagues feel the same way.” skills I picked up,” he says. “I think it’s important for medical students to get a broader view of their potential role in the world, what social WATCH THE VIDEO justice is, why healthcare should be a human right.” See Einstein students at work: magazine.einstein.yu.edu/ECHO19

MAGAZINE.EINSTEIN.YU.EDU 31 COLLABORATING TO CURE CANCERS Einstein scientists raise hopes for treating bone-marrow and blood diseases

BY GARY GOLDENBERG

32 EINSTEIN : SUMMER/FALL 2019 he names “Verma and Steidl” don’t roll off the tongue the way “Brady and Belichick” and “Bert and Ernie” do. But it would be Thard to imagine a more productive research duo. That’s because over the past decade, Center in Heidelberg before pursuing “blasts” become dysplastic (that is, they longtime Einstein colleagues Amit postdoctoral studies at Harvard Medical develop abnormally) and multiply rap- Verma, M.B.B.S., and Ulrich Steidl, School, with a focus on AML. idly. Abnormal blasts churn out defec- M.D., Ph.D., have coauthored several Dr. Verma arrived at Einstein in tive blood cells and leave people with dozen peer-reviewed papers, adding 2007, followed by Dr. Steidl the next too few normal ones. Different types immensely to the understanding of two year. “We met right after I joined the of MDS can decrease different blood closely intertwined diseases: myelodys- faculty and discovered very quickly that cells—most commonly red cells, result- plastic syndromes (MDS) and acute we had complementary skills,” says Dr. ing in anemia. myeloid leukemia (AML). (For more Steidl, who is now a professor of cell The incidence of MDS in the about these conditions, see page 37.) biology and of medicine, the Diane United States is unclear, with estimates Drs. Verma and Steidl were among the and Arthur B. Belfer Faculty Scholar in ranging from 10,000 to 40,000 new first researchers to demonstrate that Cancer Research at Einstein, and the cases annually. The only cure is a bone- MDS, a common precursor of AML, associate chair for translational research marrow transplant—a therapy not easily arises from wayward bone-marrow stem in oncology at Montefiore. “My work is tolerated and therefore reserved for the cells; the pair’s findings have raised hopes more lab-based; his is more translational, youngest, most resilient patients. Most for treating or preventing both diseases. with a clinical component. I was looking people diagnosed with MDS, however, for a partner who could help bring my are elderly. Deaths result from bleed- COMPLEMENTARY SKILL SETS laboratory findings to the clinic.” ing, infection due to low blood-cell The researchers began their journeys to In Dr. Steidl, Dr. Verma found counts—and from MDS progressing to Einstein from vastly different parts of the someone with expertise in cell sorting, AML, which occurs in about one-third world. Dr. Verma studied medicine at the cell identification, and animal models of MDS patients. (This is why MDS All-India Institute of Medical Sciences of myeloid diseases (i.e., those pertain- was once described as a “premalignant” in New Delhi and then relocated to the ing to bone marrow). “He provided a condition but is now generally regarded United States for postgraduate training perfect counterpart to my lab’s expertise as a form of cancer.) at the University of Illinois at Chicago in deciphering cell-signaling and epi- AML is an aggressive and usually Medical School, ultimately focusing his genetic pathways and studies of clini- fatal blood cancer that begins in the research and clinical practice on MDS. cal samples,” says Dr. Verma, professor bone marrow. It afflicts about 21,000 Around the same time, Dr. Steidl studied of medicine and of developmental and Americans each year and is diagnosed medicine at the University of Heidelberg molecular biology at Einstein and direc- when massive numbers of defective blast in Germany and then cell and tumor tor of hemato-oncology at Montefiore. cells are detected in the bone marrow biology at the German Cancer Research The pair soon began to collaborate on and blood. As is true for MDS, AML MDS and AML research. usually can be cured only with a bone- marrow transplant and mainly affects At left, an abnormal blast cell (shown in CANCERS THAT CAN OVERLAP older people. Just 28% of AML patients purple) produces defective blood cells (shown in blue), leading to myelodysplastic MDS, a cancer of the bone marrow, survive for five or more years after syndromes. occurs when blood-forming cells called diagnosis.

MAGAZINE.EINSTEIN.YU.EDU 33 COLLABORATING TO CURE CANCERS

Research collaborators Dr. Amit Verma, left, and Dr. Ulrich Steidl at work in the lab.

SEEKING THE CAUSE OF MDS success if it significantly reduced the Targeting the blasts By 2008, when Drs. Verma and Steidl blast count,” Dr. Verma says. “This began collaborating, studies had shown approach was effective at improving “is like mowing that AML arises from defective hemat- symptoms in many patients, even put- dandelions in your opoietic (blood-forming) stem cells, the ting some into remission. But invariably, bone-marrow cells that develop into the disease would come back.” Targeting lawn. They’ll always blasts and, ultimately, all the blood’s the blasts, says Dr. Steidl, “is like mow- regrow unless you cell types. By contrast, cases of MDS ing dandelions in your lawn. That will were thought to begin later in blood-cell get rid of them, but they’ll always regrow get to the root of development, when blood-progenitor unless you get to the root of the weed.” the weed.” cells became dysplastic and could no So what is the actual cause of MDS? longer produce fully mature red cells, Relying on animal evidence, Drs. Verma — DR. ULRICH STEIDL white cells, and platelets, instead pro- and Steidl, along with a few other scien- ducing an excess of malignant blast cells. tists, suspected that MDS—like AML— These defective blasts were the target of originated from defective hematopoietic MDS treatments. stem cells. “An MDS therapy was viewed as a “It was hard to get our MDS research

34 EINSTEIN : SUMMER/FALL 2019 funded,” Dr. Steidl adds. “Grant review- using hydrocarbon “staples”). Aileron ”Our findings made it ers would comment: ‘The problem in Therapeutics developed ALRN-6924 MDS is clearly the blasts and dysplastic to reactivate the p53 tumor-suppressor clear that we needed cells. Why waste your time studying gene, which prevents impaired or can- to wipe out the these tiny, barely detectable populations cerous cells from multiplying. of hematopoietic stem cells?’” The p53 gene is inactivated in virtu- abnormal stem cells to But the Einstein researchers persisted. ally all cancers and in the mutated stem improve cure rates.” In a seminal study published in 2012 in cells that develop into AML, so reacti- the journal Blood, they analyzed bone- vating p53 might be expected to stop — DR. AMIT VERMA marrow stem cells and their slightly tumor cells in their tracks. But so far, more differentiated progeny (progeni- no stapled-peptide drug has advanced to tor cells) from 17 patients with various clinical trials—until now. types of MDS and 16 healthy controls. In a novel approach, Aileron scien- Genome-wide analysis revealed wide- tists designed ALRN-6924 to reacti- spread genetic and epigenetic alterations vate p53 indirectly by simultaneously in stem cells from MDS patients, but inhibiting two proteins, MDMX and not in stem cells taken from healthy MDM2, that are overexpressed in cancer controls. Those same gene alterations and act together to suppress key p53 were also found in patients’ blasts, functions. The company then turned which evolve from stem cells. to Drs. Verma and Steidl to test the “Equally important,” Dr. Verma says, drug’s effectiveness in preclinical models “we found that abnormal stem cells of AML and to learn more about its persist in the bone marrow even after mechanism of action. standard chemotherapy for MDS. So The Einstein researchers found that although the patient may be in remis- ALRN-6924 had a profound impact on sion, those stem cells resist chemo- AML, tripling the median survival time therapy and the disease will inevitably in an animal model of human AML return. Our findings made it clear that (mice transplanted with human leuke- we needed to wipe out the abnormal mia cells) from 50 to about 150 days. stem cells to improve cure rates.” “This is a very striking response,” Dr. Steidl says. “Most experimental A NEW GENERATION OF drugs for leukemia achieve an increase THERAPIES in survival of only a few days in these Since publishing their initial paper, Drs. preclinical models. More important, Verma and Steidl have sought ways to ALRN-6924 effectively cured about disable abnormal stem cells in patients 40% of the treated mice, meaning they with MDS and AML. Thus far they’ve were disease-free more than one year found a half-dozen vulnerabilities in after treatment—essentially a lifetime such stem cells, and experimental drugs for a mouse.” targeting them are now in clinical trials. The researchers confirmed that A key recent contribution involves ALRN-6924 targets both MDMX and ALRN-6924, the first of a novel MDM2, blocking their interaction with class of drugs called stapled peptides p53 in AML cells. That effect was seen (small chains of amino acids with in both immature and mature AML helical structures that are stabilized cells. Furthermore, those same molecular

MAGAZINE.EINSTEIN.YU.EDU 35 COLLABORATING TO CURE CANCERS

LINEAR MODEL Mutated Unmutated HSCs HSCs MDS AML

PROPOSED MODEL MDS .

Premalignant/

malignant Medicine Nature MDS SCs Unmutated HSCs

Premalignant/ malignant AML SCs AML

Premalignant Premalignant HSCs AML SCs Illustration by Tatyana Starikova Harris. Adapted from Starikova Harris. Adapted from Illustration by Tatyana Why do one-third of MDS patients eventually develop AML? i.e., cell groups that descend from a single mutated cell very early The standard linear model (at top) proposes that hematopoietic in disease development. MDS (which, for unknown reasons, often stem cells (HSCs) accumulate additional mutations that ultimately precedes AML) evolves from premalignant/malignant MDS stem cause MDS to evolve into AML. But after conducting single-cell cell subclones; AML independently evolves from aberrant stem- genomic sequencing of stem cells (SCs) from seven patients with cell subclones that differ from those that led to MDS and that may MDS who later developed AML, Drs. Verma and Steidl created a have been present for many years before MDS or AML develops. model (above) positing that MDS and AML are actually separate Dotted lines indicate uncertainty regarding exactly when one diseases that evolve from different aberrant stem-cell subclones, stem-cell type progressed to another in some patients. changes were observed in blood cells of have led to a phase 1/phase 2 clinical What causes one-third of MDS cases an AML patient who was given the drug trial for patients with advanced AML or to progress to the usually fatal AML? on a compassionate-use basis. MDS, now underway at Montefiore and In research published in Nature “This test was not designed to assess three other centers. Dr. Verma is lead- Medicine in 2019, they and their col- the efficacy of the drug in humans— ing Montefiore’s portion of the trial. He leagues carried out single-cell genomic that has to be done in a proper clinical directs Montefiore’s MDS Center, which sequencing of stem cells and blast cells trial,” Dr. Steidl says. “Our goal was to offers a variety of treatments and clinical from seven patients with MDS that determine whether it can hit the desired trials for patients with the disease and is progressed to AML. target in human cells in a clinical set- recognized as a national “center of excel- “The old linear model—MDS blast ting, which it did in this individual.” lence” by the MDS Foundation. cells accumulate increasing numbers The ALRN-6924 findings, reported Earlier this year, Drs. Verma and of mutations, which ultimately lead to in Science Translational Medicine in 2018, Steidl tackled another vexing question: AML—didn’t hold up,” Dr. Steidl says.

36 EINSTEIN : SUMMER/FALL 2019 “Instead, we found that the progres- THE ABCS OF MDS AND AML sion from MDS to AML begins earlier, with a diverse spectrum of mutations he myelodysplastic syndromes (MDS) are a diverse group of in hematopoietic stem cells. A defec- disorders in which mutated hematopoietic stem cells result in tive stem cell will evolve into MDS, but the formation of vast quantities of defective red blood cells, it is not those MDS cells that develop T white blood cells, and platelets. In most cases, the cause of these into AML. Rather, other aberrant stem mutations is not known. People at elevated risk for developing MDS cells—ones that arise from different are smokers or have been exposed to cancer therapies (such as defective stem-cell ‘subclones’—acquire chemotherapy and radiation), toxic chemicals, or heavy metals—all of additional mutations that ultimately which can damage DNA. lead to AML. So to prevent MDS from Patients with MDS are typically treated with specialized chemo- evolving into AML, we need to focus therapies to reduce the number of blood-forming cells called our efforts on detecting and targeting “blasts,” plus symptom management and supportive care, such as those early aberrant stem cells.” (See blood transfusions. Treatment puts some patients into remission, illustration on page 36.) sometimes for years, but the disease almost always returns. Survival varies widely depending on the disease type; it ranges from nine ONCE AND FUTURE months for those with very high-risk MDS to 8.8 years for those with COLLEAGUES very low-risk disease. For the first time in their careers, Drs. Although one-third of MDS patients eventually develop acute my- Verma and Steidl are optimistic that bet- eloid leukemia (AML), the majority of AML cases arise without being ter therapies for MDS and AML—ones preceded by MDS. AML shares many symptoms with MDS, including that target stem cells—are close at hand. fatigue, shortness of breath, pale skin, susceptibility to infections, and “The survival rates for MDS and AML frequent nosebleeds. have not improved for the last half- Treatment for AML depends on the stage and subtype of the century, and nobody understood why,” disease, but usually includes chemotherapy, symptom management, Dr. Steidl says. “Now we know it’s and palliative care. Survival is heavily age dependent: For people because we weren’t focusing on the right diagnosed before age 20, the five-year survival rate is 67%; for those cells. It makes me very hopeful.” 20 and older, it’s only 24%. They expect to continue their part- nership. “We’re very good friends,” says Dr. Verma about his colleague. “Uli’s AML AT A GLANCE a great guy, very sharp, with the abil- ity to solve complex problems logically. 1.2% Beyond that, we have built the research 21,450 10,920 1.8% estimated new of all new estimated of all cancer infrastructure for our work. Science is cases in 2019 cancer cases deaths in 2019 deaths so much more complex these days. It’s tough for one lab to have mastery of every possible technique.” Adds Dr. Steidl: “I don’t think Percent Surviving 5 Years Median Age at Diagnosis we’ve ever had an argument about our research. We try to take our egos out of 28.3% 68 years the equations as much as we can. I feel very fortunate to have such a great col- laborator. It was luck that we connected SOURCE: NATIONAL CANCER INSTITUTE and clicked.”

MAGAZINE.EINSTEIN.YU.EDU 37

AN OUT-OF-THIS- WORLD CLERKSHIP

NASA program gives an Einstein student a glimpse of space medicine

BY MANDY WALKER

38 EINSTEIN : SUMMER/FALL 2019 eciding on a patient’s treatment two years while at Einstein. She became “I realized the program can be challenging. Imagine interested in the clerkship when she D how much more complicated learned that one of NASA’s research might give me a that would be if your patient were in a priorities is the study of radiation risk new perspective on spacecraft more than 200 miles above for astronauts. “I realized the program the Earth. might give me a new perspective on radiation.” That’s just part of the job description radiation,” she says. — DR. JENNIFER MA of a NASA flight surgeon. These special- Dr. Ma was one of only 18 people ists care for NASA astronauts before, accepted into the four-week program. during, and after their time in space. Like the other participants, she was Johnson Space Center for 11 days. The They oversee the astronauts’ fitness train- assigned a group research project. But first-aid kit must address any conditions ing and manage their various physiologi- she was one of just a few clerks given that the crew members might face dur- cal responses to their flights. two mentors: Johnny Conkin, Ph.D., an ing their space mission, which is set for Jennifer Ma, M.D., who graduated environmental physiologist, and Joseph the first quarter of 2020. from Einstein in May, was part of a select Dervay, M.D., a flight surgeon and the “We wanted to include medications group that experienced the life of a flight leader of the medical operations group. for many common ailments, such as surgeon during her month in NASA’s infections or allergic reactions, in order Aerospace Medicine Clerkship program FIRST AID FOR SPACE TRAVEL to ensure that the experiment wouldn’t at the Johnson Space Center in Houston, Her group’s challenge: To create an end prematurely because of a minor Texas, last fall. augmented first-aid kit for an upcoming medical issue that worsened during the Dr. Ma had worked in the radiation flight-simulation experiment in which study,” Dr. Ma says. Other necessities biology lab of Simon Powell, M.D., eight people—two medical staff mem- included medications for insomnia and Ph.D., at Memorial Sloan Kettering bers and six volunteers—will live inside an upset stomach as well as supplies Cancer Center in New York City for a three-story, 20-foot-tall chamber at the such as gauze, tourniquets, and band- ages to treat minor trauma. “They won’t be doing anything considered dangerous, but there is a nar- row metal staircase that someone could trip on, and low ceilings where they might hit their head,” Dr. Ma says. The two medical staff members on board will be able to administer any needed treatments. The chamber will undergo pressure changes at six-hour intervals throughout the experiment to simulate an astro- naut’s potential schedule of extravehicu- NASA program gives an Einstein student lar activities while in space, so Dr. Ma Opposite page: Dr. Jennifer Ma stands a glimpse of space medicine outside a flight simulation chamber at the Johnson Space Center in Houston, Texas. At left, she sits at the mission control center with NASA flight surgeon William Tarver, M.D., where she was able to listen to live communications with astronauts on

Photos courtesy of NASA JSC Aerospace Medicine Clerkship, October 2018 Photos courtesy of NASA JSC Aerospace the International Space Station.

MAGAZINE.EINSTEIN.YU.EDU 39 AN OUT-OF-THIS-WORLD CLERKSHIP

Above left, Dr. Jennifer Ma sits at the “They obtain blood also had to factor that in when consider- controls of the NASA Orion spacecraft ing which medications to bring on board. training mockup with a fellow clerkship samples from team member. Above right, she runs on a “We were concerned that anything in NASA treadmill wearing a special weight- astronauts before, blister packs might burst after frequent ed vest that serves as a countermeasure pressure changes, so we put those medica- for muscle and bone loss while in orbit. during, and after tions in bottles,” she says. “And we had to space flights, and they check with a pharmacist about whether SANS,” Dr. Ma explains. While fluids the liquid medications would still be sta- in the body are pulled downward by analyze those samples, ble after repeated pressure changes.” gravity here on Earth, they can shift in looking for changes.” a person’s skull during space travel and SPACE EDUCATION affect an astronaut’s vision. SANS is — DR. JENNIFER MA Not all of her time at the Johnson Space thought to be caused by this increased Center was spent working on her project. pressure in the head and especially in “Most days we heard lectures or toured the eye area during and after long flights different parts of the facility, which was in space. a ton of fun,” she says. Lecture top- Radiation exposure is also a major ics included space physiology, envi- concern. “Astronauts are exposed to ronmental health, exercise physiology, a chronic low level of radiation while space nutrition, an in-depth look at the in space, which NASA can attempt to International Space Station, and Mars offset with shielding,” Dr. Ma says. But mission scenarios. there are also unpredictable solar storms, “We also learned about spaceflight- which can expose astronauts to high associated neuro-ocular syndrome, or radiation levels. “Traveling to Mars takes

40 EINSTEIN : SUMMER/FALL 2019 a long time, so you have a higher risk of radiation exposure overall,” she says. Because of her keen interest in the topic, Dr. Ma asked for a closer look at the radiation biology lab at the Johnson Space Center. She not only was granted a tour, but also got to talk to the head of the lab, Honglu Wu, Ph.D., about the lab team’s current research and the clini- cal data it collects. “They obtain blood samples from astronauts before, during, and after space flights, and they analyze those samples, looking for changes.”

NEXT STEPS At the end of the four weeks, each clerk- ship group created a scientific poster HANGING OUT WITH ASTRONAUTS that summarized its results. “I presented A NASA clerkship has its perks: The 18 students in the fall session were them to everyone at the space center invited onboard a life-size version of the International Space Station who was interested, and we got to meet on site at the Johnson Space Center called the Space Vehicle Mockup everyone’s mentors plus many of the Facility (SVMF). They were also invited to visit the Sonny Carter Training other NASA staff in a wide spectrum of Facility, which houses the Neutral Buoyancy Laboratory, where they departments,” Dr. Ma says. watched astronauts (above) conduct underwater maneuvers. She had the chance to reunite with During their visit to the SVMF, “we got lucky and bumped into an many of her NASA clerkship colleagues Italian astronaut and engineer, Luca Parmitano. He lived on the space last May when her abstract had been station and was giving a tour to two of his friends,” says Jennifer Ma, accepted for poster presentation at the M.D., ‘19. “He invited us to join his tour, too, so instead of having a 2019 annual meeting of the Aerospace guide who said, ‘This is this module and what it does,’ he shared more- Medical Association in Las Vegas. There personal details, like ‘This is where I would hang out,’ and ‘I don’t like she was awarded the Stanley R. Mohler, this area because sometimes it gets smelly.’” M.D., Aerospace Medicine Endowed Dr. Ma’s tour group was again in luck during its visit to the Neutral Scholarship, worth $750 and intended Buoyancy Laboratory, which prepares astronauts for space walks. “It’s to fund research activities. basically a giant indoor pool that’s large enough to house a version of Dr. Ma matched at her top residency the International Space Station surrounded by 6.2 million gallons of choice, Memorial Sloan Kettering, for water,” Dr. Ma says. They arrived just as an astronaut training session radiation oncology. She is completing was starting, so they witnessed two astronauts don their space suits, get her transitional year now at Presence hooked up to oxygen, and be lowered into the pool. Then they watched Saint Francis in the Chicago area. Dr. the astronauts on video screens carrying out simulations of extravehicular Ma calls the NASA clerkship one of the activities, which are excursions performed outside a spacecraft. highlights of her time in medical school.

“I never thought I’d have the opportu- WATCH THE VIDEO nity to do half of the things I did,” she See an astronaut train for a space walk says. “I’ve made great friends and hope in NASA’s Neutral Buoyancy Laboratory: to continue collaborating on research magazine.einstein.yu.edu/NASA19 projects.”

MAGAZINE.EINSTEIN.YU.EDU 41 PASSIONATE PURSUITS Snapshots From the Bike Lane

BY WAYNE COFFEY

he Dutch city of Leiden is known for its tulips, for its canals, and T for being Rembrandt’s birth- place. It’s where Wouter (VOW-ter) Hoogenboom grew up, riding his bicycle everywhere, as is the local custom. He and his friends would create their own flower-laden Tour de France courses, pretending viaducts were French Alps and traffic signs were finish lines, each of them dreaming of cycling glory. “In the Netherlands, everybody has a bike,” he says. “You go to school with a bike. You go grocery shopping with a bike. It’s a way of life.” Here in the United States, Mr. Hoogenboom, age 38, is a competitive cyclist who powers through four-hour training rides. He is also an award- winning photographer, a medical researcher specializing in sports-related concussions, a husband and the father of two boys, and—since 2013—a Ph.D. candidate at Einstein, working in the lab of Michael Lipton, M.D., Ph.D., professor of radiology and of psychia- try and behavioral sciences at Einstein A cyclist with a prosthetic leg checks out a race in Harlem’s Marcus Garvey Park. Einstein and medical director of MRI Services at Ph.D. student Wouter Hoogenboom snapped this photo last year, which won third place Montefiore. in an international photography competition focused on road cycling. “Wouter has a thoughtful, quiet, powerful way about him, and is very assiduous in figuring out what needs

42 EINSTEIN : SUMMER/FALL 2019 “There is a great feeling of camaraderie when you are on a long ride with others. ... It’s a true addiction—a healthy one.”

— WOUTER HOOGENBOOM

have also been accompanied by injuries. A nasty fall triggered persistent back pain, forcing him to take a break from competitive cycling. Eager to stay con- nected to his team during his recupera- tion, Mr. Hoogenboom began to take photos. He wound up winning several awards in a competition that honors the best cycling photography around the world. These pages include some of his more-recent photos.

TEAM PLAYER Celine Hoogenboom’s favorite image of Clockwise from top: Cyclists whirl around a bend in the 14-mile Bear Mountain Classic at her husband, though, has nothing to do Harriman State Park in New York; Wouter Hoogenboom speeds ahead during a race; and with a camera lens. Several years ago, a cyclist hoists his bike over a barrier at a cyclocross competition. Mr. Hoogenboom and a teammate were riding through Manhattan at 5 a.m., to be done and how to get it done,” Washington Bridge into New Jersey bound for the next segment of a tight Dr. Lipton says. and heads north along the west bank race at Brooklyn’s Prospect Park. But of the Hudson River, covering up to 70 on the ride to Brooklyn, the teammate’s COMMITTED TO CYCLING miles round trip. The rides are grueling bike broke. Without hesitation, Mr. After getting his undergraduate physical tests, and Mr. Hoogenboom Hoogenboom said, “Take my bike. You degree in psychology in Holland, Mr. savors them. are the leader. Finish strong.” Hoogenboom pursued his master’s in “The best parts about cycling are His grateful teammate rode off. Mr. neuropsychology, finishing up with an being outdoors, exploring new roads, Hoogenboom, who had been in second internship at Harvard Medical School. and escaping busy city life,” Mr. place in the uphill sprints category, He brought his bike with him to the Hoogenboom says. “There is a great took the subway to Prospect Park with United States and began to race com- feeling of camaraderie when you are the broken bike. His teammate rode petitively, up to 200 miles a week. The on a long ride with others. It’s also a superbly and won. racing continued when he relocated to great feeling when you’ve completed the “Part of cycling is sacrificing your- Einstein to study under Dr. Lipton. ride. Frankly, it’s a true addiction—a self for the good of the team,” Mrs. On his long training rides, he healthy one.” Hoogenboom says. “That’s just how typically bikes across the George Mr. Hoogenboom’s bike rides, alas, Wouter works.”

MAGAZINE.EINSTEIN.YU.EDU 43 EINSTEIN EDITIONS

A Better Way to Approach Dementia

Tia Powell, M.D. Director of the Montefiore Einstein Center for Bioethics, the Dr. Shoshanah Trachtenberg Frackman Faculty Scholar in Biomedical Ethics, and professor of epidemiology & population health and of psychiatry and behavioral sciences at Einstein.

ementia has, over the ages, been hard to pin Ddown. From the Latin demens, “out of one’s mind,” the word dementia was histori-

cally used loosely, lumped in Courtesy of Penguin Random House with a broad range of mental illnesses. Losing the ability to of the Medicare budget. Nonetheless, the main message of the feed and dress oneself was often book is that dementia can and should be less frightening to chalked up to madness, possibly people than it is today. With better understanding, planning, caused by demonic possession care, and policies, we can ease the aspects of dementia that are and often treated with punishment. scary for everyone involved, she explains. Author Tia Powell, M.D., writes in Dementia Reimagined Dr. Powell was motivated in part to write Dementia that when she was a medical student in the 1980s, demen- Reimagined because of the experiences of her grandmother and tia was finally recognized as a neurocognitive disorder, but mother, and she explores the disease in depth. Chapters are still wasn’t a priority in the healthcare community. Dementia devoted to the politics and economics of dementia and to sci- mainly happened to very old people, and no treatments entific research on the disorder. For families who are touched existed. Why devote resources to a relatively rare condition by this fatal disease, the book offers guidance on caregiving, that affected those who had just a few years left to live? whether the patient remains at home or goes to an assisted- While a cure still eludes us, that dismissive attitude toward living facility. Dr. Powell emphasizes the necessity of planning dementia has changed in recent decades, Dr. Powell notes. and of making the patient’s wishes known, to limit the finan- Americans are now living longer—and when they reach age cial and emotional burdens in the final few years of the disease. 85, their chance of having dementia approaches 40%, accord- Dementia Reimagined concludes by helping readers plan for ing to a 2019 report from the Alzheimer’s Association. The a good death, with the author outlining just what she’d like for condition now affects more than 5 million Americans, and hers. She notes that shifting the balance from curative care to that number will rise as baby boomers grow older. palliative care can make all the difference. “Keep me comfort- Dr. Powell notes in her book that dementia is hard for able,” she asks. “And don’t stand between me and the exit.” both the person with the illness and his or her caregivers, as patients lose their ability to walk, talk, and even swallow. PUBLISHED BY: Avery, an imprint of Penguin Random Dementia is expensive, too, and consumes an impressive share House, 2019

44 EINSTEIN : SUMMER/FALL 2019 The African American Experience

Arnold Birenbaum, Ph.D. Professor emeritus in the department of pediatrics at Einstein, co-author of Norms and Human Behavior, and co-editor of Social Problems: Private Troubles and Public Issues and People in Places: The Sociology of the Familiar.

ace relations in America have never been an easy Rtopic to discuss. By carefully examining histori- cal evidence going back to the 18th century, author Arnold Birenbaum, Ph.D., sheds light on the lives of African

Americans in the 21st century Courtesy of Routledge Books and their continuing struggle for social justice. to treat African Americans in a way that established distance Dr. Birenbaum uses that historical evidence to help answer and reaffirmed Europeans’ feelings of privilege. key questions now confronting the country: Why are African Moving into the 20th century, the book delves into the Americans disproportionately impoverished in the United rise of white nationalism as the United States evolved from a States? Are government policies to blame? And what about largely agrarian society to an industrial one—and addresses healthcare, housing, and the justice system? Why are resources the accompanying civil rights movement, which threatened distributed so unequally in those areas? And can all of this be the white power structure. reversed? Dr. Birenbaum offers solutions to what’s standing in the Different aspects of the African American experience have way of social justice for African Americans, including closing converged to create today’s racial divides, Dr. Birenbaum the gap in health services, increasing income and reducing notes. A chief culprit is geographically segregated communi- wealth inequality, challenging educational disparities, mak- ties, which he likens to the relationship that exists between a ing housing more affordable and stable, enhancing the urban colony and its mother country, where the institutions of soci- environment, reforming criminal justice, protecting voter ety are rigged against the colonists—except the “colonists” live rights by ending voter suppression, and reconsidering the case right in the American homeland. for reparations for the descendants of slaves. A Nation Apart also discusses the systematic undoing of Filled with annotated research and well-crafted arguments, civil rights and federal support for African Americans after the Dr. Birenbaum’s study of America’s racial injustices promises Civil War, tracing these injustices from Reconstruction to Jim to inform and inspire. But, as he notes, there’s a great deal of Crow laws to separate-but-equal policies. work that remains to be done. Northern states after the war also encouraged racial divi- sion. Immigrants just off the boat were told to avoid intimate contact with people of color, implying that interracial rela- PUBLISHED BY: Routledge, an imprint of the Taylor & tionships were dangerous. European immigrants were taught Francis Group, 2019

MAGAZINE.EINSTEIN.YU.EDU 45 ALBERT’S PUZZLER 1 2 3 4 5 6 7 8 9

BY DEIRDRE BRANLEY 10

11

12 13 14

15 16 Adventures

in the Bronx 17 18 19

20 Across 6 The Bronx Bombers (7) 21 22 23 24 8 Cemetery for Celia Cruz, Miles Davis, 25 26 27 and Irving Berlin (8) 10 What you do from the mound (5) 28 11 First name of native Bronxite singer Joel (5) 29 30 31 12 “Once we accept our _____, we go 32 33 34 35 36 37 38

beyond them.” —Albert Einstein (6) 39 40 14 American Indians who were 41 here first (6) 15 Little Italy in the Bronx (9) 42 16 Bronx author of “The Tell-Tale 43 44

Heart” (3) 45 17 Best seafood (10) 46 18 Crotona Park’s Indian ____ and Boathouse (4) 47 48 49

20 The river that marks the borough’s 50 western boundary (6) 51 21 Hyperuricemia describes high ____ acid (5) 22 Not quiet (4) 24 Common infection, sinu___ (5) Down 25 Free to ___ ... You and Me (2) 1 Nonreactive (5) the largest food-distribution facilities in 27 Bronx-born inventor of the maneuver the world (10) that helps when you are choking (8) 2 What podiatrists focus on (4) 29 The county north of the Bronx (11) 28 Hip-hop term for the Bronx (10) 3 Bronx beach (7) 30 After receiving test results, a doctor can 32 A common chemistry suffix (3) 4 The genes of every individual in a population, gene ____ (4) provide a ______diagnosis (10) 35 Spike Lee joint filmed here (11) 5 The periodic _____ (5) 31 In fact, or in effect (2,5) 40 Student housing on campus (3) 7 Neighborhood that sounds like an 33 Neighborhood where Wave Hill is 41 Our 1,100-acre park (12) angry demon (13) located (9) 42 Opened in 1909 as NYC’s response 8 The shorter bridge to NE Queens (10) 34 Our borough’s namesake (11) to the Champs-Élysées, the Grand 36 Epigenetic markers, _____ group (6) ______(9) 9 Robert, who built Co-op City (5) 37 Bronx-born, self-described overweight 43 Not daughter but ___ (3) 13 Southernmost neighborhood in the Bronx (9) rapper (3) 44 Bronx resident, director of the Hayden 38 Our neighborhood, ______Park (6) Planetarium, Neil deGrasse ______(5) 14 Graduate of Bronx Science who won the Nobel for Chemistry in 2012 (9) 39 Name of a Bronx road and university (7) 45 Sight, hearing, taste, smell, 46 Actor Palminteri (5) and ______(5) 15 A gene variant (6) 48 When you have one, you want to 47 Neighborhood home of Boricua 19 The New York ______Garden (9) scratch it (4) College (7) 23 Give off (4) 49 Fluorescein isothiocyanate, for short (4) 49 Old-school Bronx DJ, Grandmaster 24 What kids don’t want at the doctor’s (4) ______(5) 25 Home to more than 4,000 animals of 50 A requirement for a Ph.D. thesis 650 species (8) ______(7) 26 Avoid this by placing babies on their See how well you did at: 51 The largest housing cooperative in the backs to sleep (4) magazine.einstein.yu.edu/ world, for short (8) 27 Bronx neighborhood home to one of puzzler2019

46 EINSTEIN : SUMMER/FALL 2019 MOTIVATIONS The Front Line of Philanthropy at Einstein and Montefiore

IN THIS ISSUE 48 From the Chair of the Development Committee 49 Continued Connection: Dr. Harvey Karp 52 Spotlight: Montefiore School Health Program (pictured) 60 Your Impact: David B. Keidan Chair in Neurological Surgery 64 Class Notes 68 In Memoriam To learn more, please visit: montefiore.org/supportmontefiore and einstein.yu.edu/deans-fund

MAGAZINE.EINSTEIN.YU.EDU 47 MOTIVATIONS

A Message From the Chair of the Development Committee Montefiore Medicine Board of Trustees MELISSA CERIALE

Two years ago, the Montefiore School Health Program (MSHP) team identified a problem. Their founding vision of integrating comprehensive health services into every public school setting in the Bronx was well underway—but they were outgrowing their infrastructure. MSHP found a partner in the Jeffrey H. and Shari L. Aronson Family Foundation. The Aronson Family Foundation provided funding for initiatives such as hiring qualified staff, expanding our school- based health clinic network, propelling enrollment rates, and guiding long-term sustainability. Today, Rosy Chhabra, Psy.D., is leading MSHP to become a model for school health nationwide (page 52). Identifying and solving problems is a trend across Montefiore and Einstein. Harvey Karp, M.D. ’75, came up with an ingenious solution to reduce the rate of sudden infant death syndrome, fueled by the compassionate learning he experienced while at Einstein (page 49). My fellow trustee David B. Keidan partnered with Emad Eskandar, M.D., to support innovations in neurological surgery across Montefiore and Einstein (page 60). When you walk across our campuses, read our publications, and speak with our students, faculty, and clinicians, you will see such problems—and solutions!—at every corner. As chair of the development committee within the Montefiore Medicine Board of Trustees, I hope to inspire problem-solving through philanthropy. From giving Einstein students opportunity through scholarships to fueling life-changing research to combating social issues in our community and around the world, every contribution—of dollars, of mentorship, of research, of clinical commitment—supports a solution. Montefiore and Einstein model what it means to be thoughtful stewards of such investment. While we’ve accomplished a lot, there’s still so much we can do. I support Montefiore and Einstein through my time and philanthropy. What’s your solution?

With gratitude,

Melissa Ceriale

48 EINSTEIN : SUMMER/FALL 2019 MOTIVATIONS | CONTINUED CONNECTION

A Message From the Chair of the Development Committee Montefiore Medicine Board of Trustees DR. HARVEY KARP MELISSA CERIALE CLASS OF ’75 BY TERESA CARR

Trusted pediatrician nventors often point to a moment and author of inspiration when the solution to a Iproblem suddenly appears. Einstein helps parents alumnus Harvey Karp, M.D., experi- enced that flash of insight after giving a Inc. Courtesy of Happiest Baby, calm fussy babies talk on sudden infant death syndrome, or SIDS, in 2011. SIDS is the leading cause of death for infants 1 month to 1 year old, and a parent’s worst fear: Seemingly healthy babies unexpectedly stop breathing in their sleep. It’s also known as “crib Harvey Karp, M.D. ’75 death” because many victims are found lifeless in their cribs. says. “Unlike a colt or a calf, we don’t After the lecture, Dr. Karp remem- hit the ground running. In the early bers, he expressed his frustration to a months, babies need us to mimic the friend. “Why hasn’t someone come up womb’s sensations through cuddling, with a way to help prevent this?” he rocking, and shushing for hours a day.” asked. His friend replied: “Well, why Their underdevelopment also means don’t YOU?” that infants may fail to awaken or to It was a fair question. Dr. Karp is one move their heads when not receiving of America’s most trusted pediatricians enough oxygen. Studies have shown and child-development experts—a repu- that putting infants to sleep on their tation he earned by researching infant backs on a firm, flat surface away from behavior and developing science-based loose bedding—hence the “back to techniques to soothe fussy infants and sleep” public health campaign—has help them sleep. Millions of bleary-eyed significantly reduced the rate of SIDS in parents around the world have sought the United States and other countries. advice from his best-selling books and In addition, Dr. Karp knew from his videos: The Happiest Baby on the Block, own research that imitating the womb The Happiest Toddler on the Block, and often calms babies—even mid-cry. The Happiest Baby Guide to Great Sleep. Infants are most vulnerable to SIDS BABY ROCKER RECALL in the first few months of life, which For the past decade, manufacturers have Dr. Karp terms “the fourth trimester.” claimed that the rocker-like infant-sleep “Humans are really born three months products they’ve marketed to parents too early; they are incredibly immature will soothe their fussy babies. But those compared to other animal species,” he rockers (also called “nappers”) keep

MAGAZINE.EINSTEIN.YU.EDU 49 MOTIVATIONS | CONTINUED CONNECTION the baby semiupright—increasing the says. Medicine seemed like a natural likelihood of airway compression and fit—and Einstein, with its high level suffocation and prompting the American of academics and what Dr. Karp calls Academy of Pediatrics (AAP) to warn “attention to the social environment,” that the rockers put babies’ lives at risk. was the perfect place for him to study. In April 2019, under pressure from While at Einstein he learned not the AAP, Fisher-Price recalled 4.7 million only about the science of medicine,

Rock ’n Play infant sleepers following Courtesy of HarperCollins Publishers but also about what it takes to assume reports that 32 infants had died in Rock the mantle of physician and healer. “I ’n Plays since 2011. Some of the infants was taught that providing healthcare rolled over while unrestrained, and some was a privilege,” he says. “People who were unable to breathe because of their are ill are in a vulnerable position, and position. Other companies have since it’s our responsibility to treat them recalled their inclined sleepers—now with respect. As students we were given linked to more than 50 deaths, accord- opportunities to get into the commu- ing to the Consumer Product Safety nity and meet with patients, to see the Commission (CPSC)—but some manu- human face of medicine,” he adds. facturers are still selling the products. Because they saw so many Spanish- “Many babies have died because their speaking patients, Dr. Karp joined sleep-deprived parents trusted those “To this day, pediatric with other students to hire a tutor products,” Dr. Karp says. “Parents trying books say that colic is a and learn the language. “We had class to comply with the back-to-sleep advice every week and ate lunch together to have yielded to the dangers of rockers mysterious condition. But improve our Spanish-speaking skills,” because their babies don’t sleep well on I believe the chief cause he says. “That way we could talk their backs.” The AAP has called on the directly to our patients without having CPSC to take action against the remain- is clear: too little rhythmic an interpreter in the middle.” ing products on store shelves to prevent stimulation.” Perhaps the most formative aspect further tragedies. of his medical training, he says, was Dr. Karp says he thought that an — DR. HARVEY KARP “realizing the joy of discovery.” He still automatically rocking crib with a flat vividly recalls learning neuroanatomy surface could create a safe environment as a first-year student from Dominick for sleep. He and his wife, Nina Monteé than 40 million hours, Dr. Karp says. Purpura, M.D., who would later go on Karp, cofounder of their company, “There are people in this world who to serve as dean of Einstein for 22 years Happiest Baby, decided to invent one. are always looking for better ways to (page 6). Throughout the semester, Dr. That led to a collaboration with indus- do things,” says Gordon F. Tomaselli, Karp says, “Dr. Purpura periodically trial designer Yves Béhar and Deb Roy, M.D., the Marilyn and Stanley M. Katz displayed a picture of a smiling boy and Ph.D., director of the Laboratory for Dean at Einstein. “That’s Harvey Karp. asked: ‘What’s wrong with Grant?’” At Social Machines at the Massachusetts He has taken his expertise in pediatrics the end of the semester, Dr. Purpura Institute of Technology. In 2016, after and applied innovation to it.” shared Grant’s diagnosis: He had severe “many, many prototypes,” Dr. Karp says, hydrocephalus. Fluid filled the space the SNOO smart bassinet was born. THE HUMAN FACE OF MEDICINE where his brain should be; his brain The robotic crib has since found its Dr. Karp set his sights on becom- tissue was limited to a narrow band way to homes across the United States, ing a doctor at a young age. “I was around the inside of his skull. Canada, and Australia. To date, babies always socially conscious and wanting “And yet, Grant appeared smiling have safely slept in the SNOO for more to understand how things work,” he before us, looking entirely normal,”

50 EINSTEIN : SUMMER/FALL 2019 Dr. Karp says. “It is a medical mystery. How could this boy lack so much of the brain yet act almost normally? Dr. Purpura’s message was clear: We know so much yet have so much to learn.”

THE COLIC CONUNDRUM Inc. Courtesy of Happiest Baby, By his second year of medical school, Dr. Karp had decided to go into pediat- rics. He would later do groundbreaking research on what his youngest patients were trying to communicate with their cries. “I’ve always been attracted to unsolved problems,” he says. “To this day, pediatric books say that colic is a mysterious condition. But I believe the chief cause is clear: too little rhythmic stimulation.” Daphne Hsu, M.D., chief of the division of pediatric cardiology at Montefiore and professor of pediatrics at Einstein, agrees with Dr. Karp that colic can be treated. “Sometimes babies cry excessively because they are unable to soothe themselves as they adjust to Dr. Harvey Karp places an infant in the SNOO, a flat-surfaced robotic bassinet he life outside the womb,” she says. “In invented that gently rocks a baby to sleep. utero they are used to falling asleep with movement and noise around them. you can do that, parents become more mental and physical health.” They respond to maneuvers that mimic comfortable, too.” Impressed by Dr. Karp’s lifetime of that environment to help them go to work, Einstein’s Board of Governors sleep peacefully.” LIFE’S WORK HONORED honored him as a finalist for Einstein’s Dr. Karp’s study of colic revealed that Ultimately, Dr. Karp says he thinks Distinguished Alumnus award this year. infants are born with a “calming reflex,” that the SNOO robotic bassinet will “It’s a prestigious award, given our his- an irresistible response to stimuli that do more than just give harried par- tory of graduates who have gone on to mimics the womb: swaddling that cre- ents a break. He says that studies now have a profound impact in the medical ates a snug feeling, shushing that sounds underway and others set to start soon sciences,” Dr. Tomaselli says. “Dr. Karp like blood flow, and gentle jiggling like will explore potential SNOO benefits, continues in that tradition by applying what the baby experienced when Mom including preventing SIDS and postpar- advancements in science to improving moved through her day. Dr. Karp’s tum depression and improving care for people’s lives.” books and videos offer techniques that premature infants. parents can use to recreate that comfort- But even without that evidence, ing environment. improving sleep has clear benefits— “Harvey’s innovation is that it’s baby- and not just for babies. “When babies TO DONATE focused,” Dr. Hsu says. “The idea is to sleep better, parents sleep better,” Dr. einstein.yu.edu/donors/ make the baby more comfortable and, if Tomaselli says. “That’s so important for SupportScholarships

MAGAZINE.EINSTEIN.YU.EDU 51 MOTIVATIONS | SPOTLIGHT

HEALTHIER KIDS, HEALTHIER COMMUNITIES

From vaccines to dental visits, the Montefiore School Health Program helps 1 in 4 public-school students in the Bronx

BY TERESA CARR

52 EINSTEIN : SUMMER/FALL 2019 Rosy Chhabra, Psy.D., center, stands with students at one of the 94 schools that receives comprehensive care through the Montefiore School Health Program. The centers provide healthcare access to more than 42,000 students in pre-K through 12th grade, reaching 25% of all public-school students in the Bronx.

MAGAZINE.EINSTEIN.YU.EDU 53 MOTIVATIONS | SPOTLIGHT

athima Lye remembers her high Those school-based centers reach more “Having access to school health center as “very than 42,000 children in pre-kindergarten the health clinic at Fwelcoming. You could stop by through 12th grade—25% of all public- without an appointment even if you just school students in the Bronx. school made me take wanted to have a chat with one of the “Healthcare providers at each site charge of my own nurses. It provided a safe space.” deliver services such as primary-care Ms. Lye says she and her classmates visits, mental health counseling, dental needs. And the care could count on access to healthcare— care, chronic disease management, is the same as what whether they were feeling ill or anxious, emergency care, and health education, had questions about sexual health, or a model that has been tremendously you would receive at even had a toothache. successful,” says program director Rosy a local health provider, “Having access to the health clinic Chhabra, Psy.D. Kids with access to at school made me take charge of my school-based healthcare are 40% less except that it’s more own needs,” she says. “And the care that likely to go home sick, for example, convenient.” you get is the same as what you would which means stronger school perfor- receive at a local health provider, except mance for the kids and less missed work ­— FATHIMA LYE that it’s more convenient.” for their parents. Ms. Lye’s alma mater is one of 94 And learning health literacy along schools that receives comprehensive with academics can have a lifelong care through the 31 Montefiore School impact. “I saw a model that showed Health Program (MSHP) health centers. the shocking amount of sugar in juice

Learning about healthier food options is part of the Montefiore School Health Program curriculum. At left, Bronx grade- school students create a nutritious yogurt snack with their teacher.

54 EINSTEIN : SUMMER/FALL 2019 “Healthcare providers at each site deliver services such as primary-care visits, mental health counseling, dental care, chronic disease management, emergency care, and health education, a model that has been tremendously successful.”

­— DR. ROSY CHHABRA

At left, Karesa McPhoy, N.P., creates a comfortable space to teach her patient about health. Below, a Bronx high school student receives a dental exam at her school.

SCIENCE AT THE HEART OF MEDICINE 55 MOTIVATIONS | SPOTLIGHT and soda,” Ms. Lye says. “Those visuals her husband and three adult children, made me much more aware of what I supports the program through the was drinking.” Jeffrey H. and Shari L. Aronson Family Adds Dr. Chhabra, “This is the per- Foundation. Mrs. Aronson says that her fect time to reach children, while they family also found it appealing that their are dealing with the physical, mental, contribution would help jump-start new and emotional issues surrounding grow- clinics, which would quickly become ing up. If you involve them in learning self-sustaining. to care for their health when they’re Philanthropy helps put the organi- young, those lessons stay with them for zational framework in place to develop courtesy of the UJA-Federation of New York, the rest of their lives.” programs, make capital improvements, Family Foundation H. and Shari L. Aronson Jeffrey Former director David K. Appel, and hire staff. Once clinics are up and M.D., who founded the program 35 running, costs are covered by Medicaid Jeffrey and Shari Aronson, pictured years ago and continues to consult, or other insurance; city, state, and federal above, are helping jump-start new says the MSHP has developed “in ways funds; and grants. school health clinics in the Bronx through their family’s foundation. beyond what we ever imagined. We There’s no cost to students; the clinics At right, an MSHP nurse teaches started with the expectation that all do not collect co-pays, and they provide two students techniques for self- children should have access to health ser- all services free of charge to those with- management of asthma. vices they need and took it from there.” out health insurance. “I feel like we are “MSHP really resonated with us,” laying the foundation for the program to says Shari Aronson, who, along with expand,” Mrs. Aronson says.

Impact of School-Based Health Centers

A child’s health can significantly predict School-based health centers have resulted in: how well he or she performs in school academically. As the largest and most comprehensive school-based health network in the country, the Montefiore School Health See how well you did at: Less emergency room use Increases in grade-point Program (MSHP) serves as a model for magazine.einstein.yu.edu/ among students averages for students who puzzler19 public school systems nationwide. MSHP’s use mental health services comprehensive services have made a considerable impact in the Bronx since its founding 35 years ago.

Greater use of Fewer hospitalizations mental health services and school days missed among teens for children with asthma

Source: Journal of Adolescent Health and JAMA Pediatrics’ Archives of Pediatrics and Adolescent Medicine “If you involve them in learning to care for their health when they’re young, those lessons stay with them for the rest of their lives.”

­— DR. ROSY CHHABRA

MAGAZINE.EINSTEIN.YU.EDU 57 MOTIVATIONS | SPOTLIGHT

MORE-EFFECTIVE HEALTHCARE diabetes were cut by nearly one-third. “I’ve found that the Dr. Chhabra has researched disease Dr. Chhabra is especially proud of prevention and school health nationally the MSHP’s mental health outreach Bronx is a community and internationally, but she says that, to for issues such as anxiety and depres- of amazing strength her, the Bronx is special. “It’s a high- sion. “Students are better prepared to needs community, one of the poorest in ask for help when they need it—and and resources. In the country,” she says, with dispropor- to actually receive care before problems my experience, the tionately high rates of asthma, diabe- become more severe,” she says. Nearly tes, obesity, mental illness, and other all students referred for mental-health reason that programs health conditions. “At the same time,” help follow up with counselors in their are successful is that she adds, “I’ve found that the Bronx is schools. Before that was available, only a community of amazing strength and about one in 10 of those referred actu- the community takes resources. In my experience, the reason ally sought help in the community. ownership.” that programs are successful is that the Two years ago, under Dr. Appel’s community takes ownership.” leadership, the MSHP began to lay ­— DR. ROSY CHHABRA This approach has resulted in more- the groundwork for an optometry effective—and more-efficient—health- program in MSHP schools. He and care for children. Emergency room visits Dr. Chhabra expect all of the clinics and hospitalizations for children with to conduct eye exams in three to five asthma dropped by half after students years. Children who need eyeglasses started receiving treatment through the will get a free pair, courtesy of eyeglass MSHP. Hospital costs for children with maker Warby Parker. Below, Dr. Rosy Chhabra counsels a high school student in the Bronx.

58 EINSTEIN : SUMMER/FALL 2019 A MODEL FOR THE NATION While the MSHP’s record in the Bronx is impressive, Dr. Chhabra plans to standardize programs so that they can easily be adopted by other cities. “We have the opportunity to be a model for the nation,” she says. Achieving those ambitious goals requires investment from both public and private partners. “School health can be transformative,” Dr. Chhabra says. “It becomes the heart of health for the community. If we can secure the funding to make that happen, the payoff is huge.” Mrs. Aronson, who has spent time at MSHP centers in the Bronx, says that she could easily see the model replicated in other cities. “I have worked in other Advocacy Work at City, State, high-need cities, and I can say with and Federal Levels certainty that a model like this could change the trajectory of children’s health Key to the success of Montefiore’s School Health Program outcomes and contribute to family sta- (MSHP) has been the advocacy and public policy work at the bility at remarkable scale,” she says. city, state, and federal levels. MSHP is a lead member of the “We have something that can really New York School-Based Health Alliance (SBHA), which has move the needle—and, with the right been instrumental in advancing these efforts. The New York partners and supporters in place, trans- form entire communities,” she adds. SBHA is part of the national SBHA, founded in 1995, which But for her, the real measure of success serves as a voice for school-based healthcare programs across is students such as Ms. Lye, who, Mrs. the country. Aronson says, “go on to college and By providing resources, training, and advocacy for health career and pay it forward.” and education partnerships, with a particular focus on the Ms. Lye, who is now in college, says school-based health clinic model, the New York SBHA is a that her experience with the program strong voice in supporting common standards, encourag- cemented her plans to pursue a career in nursing. “It opened my eyes. When you ing experiential learning, and inspiring young people to take give students the resources to take care responsibility for their own health. MSHP partnered with the of their health, they’re better equipped Primary Care Development Corporation to develop the first to create healthy communities.” national standards for school-based health centers, adopted nationwide in November 2017.

TO DONATE montefiore.org/ SupportSchoolHealth

MAGAZINE.EINSTEIN.YU.EDU 59 MOTIVATIONS | YOUR IMPACT

MEETING OVER THE MIND Two men from different worlds find common ground in neurological surgery at Einstein and Montefiore

BY GARY GOLDENBERG

60 EINSTEIN : SUMMER/FALL 2019 ven an expert statistician would have trouble calculating the odds Ethat David B. Keidan and Emad Eskandar, M.D., would ever cross paths. The former is a septuagenarian Jew from India who runs an investment manage- ment firm in Manhattan. The latter is a 50-something Coptic Christian from Egypt who practices neurosurgery in the Bronx. And yet these two men, from different countries, cultures, generations, and professions, share an interest in rais- ing neurological surgery at Einstein and Montefiore to new heights.

INVESTOR AND PHILANTHROPIST Mr. Keidan was born into the small community of Baghdadi Jews of Bombay (now Mumbai) who migrated Georgia and David B. Keidan, above left, attend an event benefiting the Montefiore from Iraq to India in the late 1700s. Einstein Center for Cancer Care at Blue Hill at Stone Barns in Pocantico Hills, New York. Mr. Keidan left home for the United States in 1962 to study at Harvard other hospitals would not hire, to serve “The Bronx is a melting College and then at Harvard Business patients other institutions could not, or pot par excellence— School. Degrees in hand, he landed a would not, help,” Mr. Keidan says. “Its job at Wertheim & Co., a Manhattan mission was, and is, a perfect example of much like Montefiore investment bank. A little over a dec- ‘tikkun olam,’ or ‘repair of the world.’” and Einstein. Different ade later, he launched his own com- His first visit to Montefiore was to pany, now called Buckingham Capital the Center for Abused Women and perspectives, cultures, Management, which he runs to this day. Children. “That went right to my and ideas allow for As Mr. Keidan prospered, he made heart,” says Mr. Keidan, who joined a point of supporting Jewish organi- the Board of Trustees in 2004. Later, he synergies that can and zations, mostly those affiliated with decided to support the pediatric critical- do repair the world.” Harvard—taking up the mantle of his care unit, now named after him and his ancestors, the affluent and philanthropic wife, Georgia. ­— DAVID B. KEIDAN Sassoon family of India, often called In recent days, Mr. Keidan has the “Rothschilds of the East.” In the turned his philanthropic attention to early 2000s, Mr. Keidan began search- neurological diseases such as Parkinson’s, ing for a worthy cause closer to home. Alzheimer’s, stroke, and depression. John Gutfreund, a longtime member “These are growing problems for our of the Montefiore Board of Trustees, aging population, with a devastating suggested he look at Montefiore. “The impact on families as well as patients,” more I looked into it, the more I liked he says. “We have a first-rate, interdis- it—a hospital started by Jewish phi- ciplinary team at Montefiore to address lanthropists, for Jewish doctors that these issues, and I want to do what I can

MAGAZINE.EINSTEIN.YU.EDU 61 MOTIVATIONS | YOUR IMPACT to help this institution develop cutting- Egypt for Nebraska, seeking religious edge treatments.” freedom and economic opportunity. Mr. Keidan’s latest gift to Montefiore A lover of all things scientific, Dr. is an endowment to establish the Eskandar found that a career in neuro- David B. Keidan Chair in Neurological surgery was ideally suited to his talents. Surgery, which Dr. Eskandar now After completing his training, he joined holds. At Einstein, Dr. Eskandar is the faculty at Harvard Medical School also the Jeffrey P. Bergstein Chair in and over the next 18 years developed Neurological Surgery in the Leo M. a reputation as one of the world’s top Davidoff Department of Neurological neurosurgeons, specializing in the treat- Surgery. ment of epilepsy, trigeminal neuralgia, “I’m proud of what this institution Parkinson’s disease, and brain tumors, has done,” Mr. Keidan says. “Not only employing and refining such advanced has our great leadership team created techniques as deep-brain stimulation, keyhole surgery, and stereotactic electro- a unique model for community care, “I enjoyed my time at which has attracted the attention of encephalography. He also ran a basic- Albany and Washington, D.C., but science laboratory, studying the basal Harvard, but I felt there ganglia, a cluster of brain neurons that it also had the foresight to invest very was a tremendous early in electronic health records, which plays a role in learning, motivation, has put us at the forefront of leverag- depression, and drug addiction. opportunity here in In 2018, Dr. Eskandar joined ing health data for better care and better the Bronx to develop management. Einstein and Montefiore. “I enjoyed “I admire the goals and the effective- my time at Harvard, but I felt there was new clinical programs, a tremendous opportunity here in the ness of our community programs, which promote new research, have done things like reduce unwanted Bronx to develop new clinical programs, pregnancies in schools, improve access promote new research, and reach out and reach out to a to a much broader group of patients,” to fresh, healthy foods, and reach into much broader group of homes to take care of patients who are he says. “Neurological surgery is quite too sick to come to us,” he says. “This strong at Einstein and Montefiore,” patients.” is unconventional medicine, outside Dr. Eskandar adds. “However, there’s a the usual hospital mandate. But then, huge mismatch between the scope of the ­— DR. EMAD ESKANDAR we are not a ‘usual’ hospital. The Bronx department and the size of the popula- is a melting pot par excellence—much tion we serve, especially with the expan- like Montefiore and Einstein. Different sion of Montefiore’s health system.” perspectives, cultures, and ideas allow Under Dr. Eskandar’s leadership, for synergies that can and do repair the Montefiore has opened a comprehen- world.” sive stroke center (the only one between the Bronx and Albany, New York) and A CLASSIC IMMIGRANT TALE a comprehensive spine center (a joint The first physician to hold the David B. effort with the departments of orthope- Keidan Chair in Neurological Surgery is, dics and rehabilitation medicine). There like Mr. Keidan himself, an immigrant are also plans for a center for surgical who has risen to the highest ranks of optimization within the spine center, a his chosen profession. Emad Eskandar neurovascular center, and a skull-based- was just 9 years old when his family left tumor center.

62 EINSTEIN : SUMMER/FALL 2019 In addition, Dr. Eskandar intends Unconventional thinking is “With the Keidan family’s to invest heavily in research. “I’m a sci- nothing new for Dr. Eskandar. In entist at heart, injecting research into 2014, he earned a master’s degree generous support, everything I do,” he says. in business administration from the we’ll be able to study “This is where the resources of Massachusetts Institute of Technology, the Keidan chair are invaluable,” he seeking to apply the principles of busi- new paradigms, such adds. “Many people don’t realize that ness management to healthcare. as neuromodulation, the National Institutes of Health, the “There’s a whole body of knowl- largest funder of biomedical research, edge about optimizing systems in dif- for the treatment of tends to support fairly well estab- ferent industries. We can learn lessons addiction, Alzheimer’s, lished ideas—but not the edge-of-the- from this work and use it to better envelope studies that can transform manage everything from emergency and other devastating healthcare. With the Keidan family’s rooms to operating rooms to imaging diseases.” generous support, we’ll be able to suites,” he says. “Healthcare is notori- study new paradigms, such as neuro- ously complicated and inefficient. We ­— DR. EMAD ESKANDAR modulation [the application of electri- need new fixes.” cal currents to modify parts of the brain], for the treatment of addiction, TO DONATE Alzheimer’s, and other devastating einstein.yu.edu/donors/ Drs. Emad Eskandar, left, and Patrick diseases.” SupportNeurosurgery LaSala, vice chair of neurosurgery, prepare the first implant of a responsive neurostim- ulator to treat epilepsy at Montefiore. MOTIVATIONS CLASS NOTES

1950s Mark David Reiss, M.D. ’59, maintains San Francisco Ballet orchestras. Their Louis M. Aledort, M.D. ’59, and coordinates the directory for the daughter, Justine, is an actor and voice- has received the 2019 Alumnus Class of 1959—Einstein’s first graduat- over teacher. Dr. and Mrs. Reiss have Humanitarian Award from the School ing class. There are currently 31 living four grandchildren, ages 15 to 19. of Medicine and Dentistry, University class members from the original graduat- of Rochester. The award recognizes ing class of 50 (see “A Look Back,” page his lifetime commitment to finding a 69). Dr. Reiss retired from his radiol- 1960s cure for clotting disorders, especially ogy practice at age 56 to pursue musi- Noah Lightman, M.D., F.A.C.R. hemophilia. Dr. Aledort continues to cal goals; he is a classical pianist. His ’69, is a proud member of the Alpha work full time and to teach, travel, wife, Joan Reinhardt Reiss, is a former Omega Alpha Honor Medical Society. and lecture internationally. His grand- world-class distance runner. She and Throughout his career, Dr. Lightman daughter is a current medical student Dr. Reiss celebrated their 60th wedding held various roles around the coun- at George Washington University. Dr. anniversary this past June. They mar- try, including positions in Einstein’s Aledort and his partner, Natasha, have ried three days before graduation from department of medicine, the U.S. been together for six years. Einstein. Their son, Craig, is a violinist Public Health Service Hospital, and the with both the San Francisco Opera and Johns Hopkins Hospital department of

HELPING CHILDHOOD CANCER SURVIVORS After graduating from become the director of Cure and Beyond, a pro- Einstein, Michael B. gram for childhood cancer survivors at the Joseph Harris, M.D. ’69, trav- M. Sanzari Children’s Hospital, Hackensack Meridian eled to the Children’s Health, and to serve as a professor of pediatrics at Hospital of Philadelphia both the Hackensack Meridian School of Medicine to complete his pedi- at Seton Hall University and Rutgers New Jersey atric residency and Medical School. hematology-oncology Throughout his career, Dr. Harris says, he has had Michael B. Harris, M.D. ’69 fellowship. Since finishing the privilege of treating many courageous children; his training in 1974, he they have, he adds, “taught me the importance of has served as the chief of the division of pediatric living each day to the fullest.” He says his proud- hematology-oncology at both the Children’s Hospital est accomplishment is his family. Dr. Harris and his of Pittsburgh and Mount Sinai Hospital, as well as in wife, Freida, married the year he graduated from other positions. Einstein and now, 50 years later, they have “four In 1987, Dr. Harris became the founding director of wonderful children and 11 grandchildren”—all of the division of pediatric hematology-oncology at the whom remind him daily that he is “just an ordinary Children’s Cancer Institute (formerly the Hackensack guy who graduated from Einstein, got married, had University Medical Center). After nearly three dec- great children and grandchildren and, luckily, found ades of service to the institute, he stepped down to a job [he] love[s].”

64 EINSTEIN : SUMMER/FALL 2019 CLASS NOTES

“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. MOTIVATIONS | CLASS NOTES STAY IN TOUCH radiology. He has been married “for hobby of garden railroading, and Ina has Keep your classmates up to 51 wonderful years” to Ellen Frank become a familiar face in Tucson’s com- date by submitting@ your news Lightman. He reports that their chil- munity theater scene. Their two elder to Einstein magazine. We dren and grandchildren bring them daughters, Judy and Nadia, followed look forward to including you great joy. their father’s lead and moved to Tucson, in our next issue. Email us at while the youngest, Michele, lives in Peter D. Lowitt, M.D. ’69, cur- Portland, Oregon, where she is a physi- [email protected]. rently works part time, concentrat- cal therapist. ing on opioid-dependence treatment using buprenorphine and naloxone Ira Sussman, M.D. ’69, and his wife, (Suboxone). Nancy Sussman, M.D. ’69, became He says that he loved attending the a hematologist and radiologist, respec- 25th and 40th reunions at Einstein and Laurence J. Marton, M.D. ’69, serves tively. Today, Dr. Nancy Sussman is enjoys seeing old friends and colleagues. on four nonprofit and eight for-profit fulfilling her lifelong desire to create boards, mostly focused on cancer. wheel-thrown pottery. Dr. Ira Sussman Randall S. Smith, M.D. ’75, currently Additionally, he is chair of a scientific has spent most of his circuitous aca- serves as the medical director of the advisory board, is an adviser to both demic career at Einstein and Montefiore, laboratory at St. Dominic Memorial Ciitizen and the Precision Medicine first doing research on von Willebrand Hospital in Jackson, Mississippi. His World Conference, and serves on disease and eventually becoming the wife, Brenda, works with the clini- the editorial board of The Journal vice chair of pathology. They have three cal skills program at the School of of Precision Medicine. Previously, he children, none of whom is in medicine, Medicine, University of Mississippi held the deanship of the University of and five grandchildren. The Sussmans Medical Center, and consults at local Wisconsin Medical School and chaired are enjoying retirement—babysitting, hospitals in the area. Their children the department of laboratory medicine theater, opera, ballet, concerts, dining, and grandchildren live near Jackson, at the University of California, San and book clubs. Dr. Ira Sussman has Mississippi, and in Ohio and Texas. Francisco, where he was a professor in maintained his lifelong love of football the departments of laboratory medi- and the New York Giants. Michael A. Grodin, M.D. ’76, recently cine and neurological surgery. published an article in the journal Surgery to unpack the ethics of using Ian M. Shivack, M.D. ’69, moved 1970s medical reference books that include to Tucson, Arizona, in 1996 with his Richard I. Hansen, M.D. ’74, retired illustrations of Nazi victims, namely wife, Ina, after a career in psychiatry as an ophthalmologist/retina surgeon in Pernkopf’s Atlas: Topographical Anatomy and neurology. Today, he says, he is December 2014 after 34 years in private of Man. Dr. Grodin collaborated enjoying the delights of retirement. Dr. practice in Newton, New Jersey. He has with Rabbi Joseph A. Polak, a Boston Shivack became involved in resident taught full time at the Medical School University Hillel House rabbi emeritus, training at the University of Arizona of the University of Florida and held on the project. Dr. Grodin says that Health Sciences Center, teaching a a volunteer teaching position at Jacobi his experience working with Holocaust course in psychopharmacology and Medical Center in the Bronx. He and survivors at Einstein sparked his interest providing resident supervision at the his wife, Lee, he reports, have two won- in resiliency and survivorship. He has University Medical Center and its derful grandchildren. been on the faculty at Boston University Veterans’ Affairs Hospital affiliate. He School of Medicine for 40 years and and his wife report that they love liv- Richard Hoetzel, M.D. ’74, lives currently serves as professor of health ing in Tucson and feel as if their life is on Manhattan’s Upper West Side and law, ethics, and human rights at the an extended vacation. Dr. Shivack is maintains a private psychiatry practice Boston University School of Public able to devote more time to his lifelong for the treatment of adults and children. Health and professor in the Elie Wiesel

66 EINSTEIN : SUMMER/FALL 2019 Center for Jewish Studies at Boston University, where he directs a project on medicine and the Holocaust. EXAMINING THE HEALTH EFFECTS OF SPACE TRAVEL The two identical-twin NASA astronauts 1980s made for the perfect case-control study: Maureen M. Goodenow, Ph.D. Mark Kelly stayed on Earth while Scott ’83, received the 2019 Esperanza spent a year on the International Space Francine Garrett-Bakelman, M.D./ Award from the Latino Commission Courtesy of University Virginia Station. on AIDS in June. Dr. Goodenow has Ph.D. ’05, was a first coauthor on aScience been researching HIV/AIDS for 30 paper published in April that compared years and currently serves as associate Francine Garrett-Bakelman, how they fared. director for AIDS research and director M.D./Ph.D. ’05 Before, during, and after Scott’s flight, of the Office of AIDS Research at the Dr. Garrett-Bakelman, assistant professor of medicine and of bio- National Institutes of Health. She also chemistry and molecular genetics at the University of Virginia School has been awarded the Jefferson Science of Medicine, and her team evaluated both brothers, assessing the Fellowship from the National Academies molecular and physiological traits that space travel may affect. of Science, Engineering, and Medicine, One focus was on possible changes in the length of telomeres, the and is the Stephany W. Holloway protective caps at the ends of chromosomes that get smaller with each Endowed University Chair for HIV cell division and with age. During Scott’s space flight, his telomeres Research at the University of Florida became significantly longer than Mark’s but shortened rapidly to near College of Medicine. preflight length upon his return to earth. Adverse effects from space travel included DNA damage and reduced cognitive function. Mark Klapholz, M.D. ’86, has served “Still, most things we looked at did not change during space as both chair of medicine at the Rutgers travel,” Dr. Garrett-Bakelman says. “Or if they did change, they later New Jersey Medical School and, since returned to their preflight state, suggesting that human health can 2012, chief of medical services at mostly be sustained over a longer spaceflight, which is reassuring.” University Hospital, Newark. Dr. Garrett-Bakelman, a physician-scientist who runs a cancer research lab concentrating on acute myeloid leukemia, says she hopes Don J. DeCrosta, M.D. ’88, began his the NASA study forms the basis “for many more to come.” new position as the head of anesthesiol- ogy at Southside Hospital in Bay Shore, New York, part of Northwell Health, in January. Prior to this role, Dr. DeCrosta served as the chair of quality assur- Courtesy of NASA ance and director of thoracic anesthesia at NYU Winthrop Hospital in Long Island, New York, for many years. He lives in Bay Shore with his wife, four daughters, three grandchildren, and three dogs.

Mark Kelly, left, a NASA astronaut, served as the control for Dr. Garrett- Bakelman’s study while his twin brother, Scott, spent a year in space.

MAGAZINE.EINSTEIN.YU.EDU 67 MOTIVATIONS | CLASS NOTES

1990s 2010s at Einstein, the two were engaged, Marcy Goldstein, M.D. ’90, has for Elizabeth Tubridy-Peters, M.D. ’18, and they married two years later the past seven years been chosen as the married Jonathan “Jono” White Peters in Riverside, Connecticut. Dr. “Best Dermatologist” in Bergen County, Jr. this past summer. Dr. Tubridy-Peters Tubridy-Peters is a second-year New Jersey, in a reader poll for the Jewish and her husband met while she was obstetrics and gynecology resident Standard. She and her husband of 36 studying at Georgetown University. at NYU Langone Health in New years have four children, three grandchil- After she completed her third year York City. dren, and one grandchild on the way.

Craig Zalvan, M.D., F.A.C.S. ’95, was lead author in a study published in IN MEMORIAM October 2017 in JAMA Otolaryngology— comparing a Head & Neck Surgery Chester Martin Berschling, M.D. Herbert Lukashok, M.S., age 97, plant-based Mediterranean-style diet ’59, age 85, psychiatrist, member of clinical associate professor emeri- with alkaline water against proton- Einstein’s first graduating class, Dec. tus, department of epidemiology & pump inhibitor medication to treat 29, 2018, Chevy Chase, Maryland. population health, May 22, 2019, laryngopharyngeal reflux. Study partici- New York City. pants had as good, if not better, results Joan Iris Casey, M.D., age 91, pro- with the diet. Dr. Zalvan was again lead fessor emerita, department of medi- Karen Roman, age 67, long- author in a study published in January cine (infectious diseases), May 6, time administrator, department of 2019 in Laryngoscope showing that the 2019, Halifax, Nova Scotia, Canada. genetics, April 16, 2019, Yorktown use of nasal irrigation, topical nasal anti- Heights, New York. histamines/steroids, and a plant-based Mediterranean-style diet with alkaline Brian L. Cowen, M.B.B.S., age 73, water was effective in stopping chronic professor, department of obstetrics Alfred Spiro, M.D., age 88, pro- neurogenic coughing without the use of & gynecology and women’s health fessor emeritus, the Saul R. Korey systemic medication. Dr. Zalvan, from (reproductive endocrinology and Department of Neurology (pedi- ENT and Allergy Associates, serves as infertility), Sept. 12, 2018, White atric), and director of Einstein’s the medical director for the Institute Plains, New York. Muscular Dystrophy Association for Voice and Swallowing Disorders at Muscle Disease Clinic for more than Phelps Hospital in Sleepy Hollow, New Quentin B. “Chip” Deming, 30 years, April 17, 2019, Scarsdale, York, and professor of otolaryngology at M.D., age 99, professor emeritus, New York. New York Medical College, Valhalla. department of medicine (general internal medicine), Jan. 21, 2019, Felix Wimpfheimer, M.D., age 98, Hanover, New Hampshire. visiting associate professor, depart- 2000s ment of medicine (endocrinology), Philip Green, M.D. ’06, recently opened Doris Jane Wolf Escher, M.D., June 14, 2019, Riverdale, New York. an interventional cardiology practice age 101, founder and first direc- in Elmwood Park, New Jersey, expand- tor of Montefiore’s Cardiac Jutta Zankl, age 70, longtime ing Columbia University Irving Medical Catheterization Laboratory and administrator, department of epide- Center’s presence. His focus is on com- professor, department of medi- miology & population health, Oct. plex coronary and peripheral arterial cine (cardiology), April 3, 2019, 19, 2018, Pine Bush, New York. disease. Dr. Green lives in Teaneck, New Larchmont, New York. Jersey, with his wife and children.

68 EINSTEIN : SUMMER/FALL 2019 A LOOK BACK

Graduation, Then and Now Sixty years ago, on June 10, 1959, the 50 medical students in Einstein’s first graduating class received their diplomas under a tent in a parking lot of what is now the Harold and Muriel Block Building (formerly the Abraham Mazer Building). This year’s considerably larger graduation ceremony, pictured above, was held on May 23 at Lincoln Center’s David Geffen Hall in New York City. Einstein conferred 156 M.D. and 31 Ph.D. degrees; 16 graduates of the Medical Scientist Training Program received both degrees.

MAGAZINE.EINSTEIN.YU.EDU 69 Jack and Pearl Resnick Campus 1300 Morris Park Avenue Bronx, NY 10461 www.einstein.yu.edu

Summer/Fall 2019

Visit magazine.einstein.yu.edu or scan code

Science at the Heart of Medicine

EINSTEIN IMAGE

Lynch syndrome is an inherited condition that greatly increases risk for intestinal cancer. In this image, the drug rapamycin has eliminated differentiated tumor cells from the small intestine of a Lynch syndrome mouse model, but two types of cancer stem cells have resisted rapamycin: Lgr5+ (green) and Bmil+ (purple) stem cells. (Also visible are Lgr5+ stem cell–associated Paneth cells, in red.) Tumors return when rapamycin therapy is stopped—and Lgr5+ cells, in particular, are suspected of regenerating tumors. Winfried Edelmann, Ph.D., and colleagues are studying a drug that makes Lgr5+ cells sensitive to rapamycin by inhibiting the membrane pro- tein MDR1 (multi-drug resistance 1), which pumps out rapamycin and other anticancer drugs. Dr. Edelmann is a professor of cell biology and of genetics and the Joseph and Gertrud Buchler Chair in Transgenic Medicine at Einstein.

Image courtesy of Kyeryoung Lee, Ph.D., a research associate in Dr. Edelmann’s lab