Medicine Columbia University Vagelos College of Physicians & Surgeons INTO the FUTURE

Columbia 2019 ANNUAL REPORT Medicine Columbia University Vagelos College of Physicians & Surgeons INTO THE FUTURE

TOMORROW’S EDUCATION, SCIENCE, AND PATIENT CARE Features:

4 11 16 The Future is Now: The Future—and The Future of A Diverse and the End?—of AIDS Gene Editing

Inclusive Faculty On two floors of Hammer Several innovations in Whether at the department Health Sciences Center, recent years have helped level, such as efforts David Ho and the Aaron scientists, but CRISPR to attract more women Diamond AIDS Research has been transformative. and people of color to Center will join Columbia’s CRISPR is not merely emergency medicine, or at leading HIV/AIDS a way to create gene the school level, such as an researchers to focus on therapies; it has become an enhanced parental leave a goal announced by the important tool for discovery policy, VP&S has shown federal government in at VP&S, with basic that efforts to improve early 2019: End AIDS and scientists developing new diversity and inclusion decrease the number of CRISPR-based tools that among its faculty ranks are new HIV infections translational researchers more about commitment by 90% by 2030 in the use to reveal new insights than compliance. United States. into human disease and how to treat it. http://ps.columbia.edu/ ColumbiaMedicine | 2019 Annual Report Issue

Departments:

2 Dean’s Message

22 Philanthropy News

28 2019 Year in Highlights

47 About VP&S · Trustees Committee on the Health Sciences · CUIMC Administration · CUIMC Board of Advisors · CUIMC Advisory Group Chairs · Vagelos College of Physicians & Surgeons Administration · Executive Committee of the Faculty Council · Department Chairs · Institutes, Centers, and VP&S Schoolwide Initiatives and Their Directors · Affiliated Hospitals 45 · Facts and Statistics

On the Cover Whether introducing and validating a new standard of care in heart surgery, improving on the latest scientific tool, strengthening the commitment to diversity and inclusion among the faculty, or complementing Columbia’s AIDS programs, VP&S scientists, researchers, clinicians, and teachers have made progress this year that will improve the future for everyone touched by academic medicine.

Illustration by Davide Bonazzi

2019 Annual Report Office of the Chief Executive and Dean of the Faculties Editor: Bonita Eaton Enochs of Health Sciences and Medicine Columbia University Irving Medical Center Principal Writer: Sharon Tregaskis 630 W. 168th St. Contributing Writers: Avichai Assouline, New York, NY 10032 Kristin Bundy, Susan Conova, Laura Gilbert Communications Office Art Director: Eson Chan Vagelos College of Physicians & Surgeons Illustrator: Davide Bonazzi 701 W. 168th St., Box 153 New York, NY 10032 Produced by the Communications Phone: 212-305-3900 Office at Columbia University Fax: 212-305-4521 Vagelos College of Physicians & Surgeons Christopher DiFrancesco, Office of Development Chief Communications Officer Columbia University Irving Medical Center 630 W. 168th St., P&S 2-421 Printed in September 2019 New York, NY 10032 Phone: 212-342-0088 • DEAN’S MESSAGE

TO INFINITY … AND BEYOND

his 2019 annual report of the Vagelos College Psychiatric Institute) were included in the calculation. of Physicians and Surgeons surely addresses Our researchers were cited in the 2019 Nature Index T our traditional obligation to review our recent Annual Tables, which named Columbia University collective accomplishments, but its primary goal is to Irving Medical Center the top health care institution look to the future. This primary goal is critical because for scientific research. The index identifies institutions the strength of these ongoing accomplishments has put with the highest output of top-quality research in the us in an enviable position to create an even stronger natural sciences over the past year, based on articles 2020 … and beyond. published in 82 scientific journals. Columbia placed We take seriously our legacy and reputation as one first in the rankings of health care institutions, with of the nation’s best medical schools—and second old- 375 publications in leading journals in 2018. est. The values that infuse everything we do reflect our Precision medicine continues to inform our research JÖRG MEYER commitment to pursue the best in teaching, scientific and patient care programs. The local All of Us research investigation, patient care, and community service. program, a consortium led by David Goldstein at CUIMC and joined by Weill Cornell Medicine, NYC The features in this year’s annual report illustrate that Health + Hospitals/Harlem, and NewYork-Presbyte- range of commitment: rian, has enrolled more than 17,500 New York City • The move of the Aaron Diamond AIDS Research participants, over 85% of whom are from communi- Center from Rockefeller University to VP&S will ties that have been underrepresented in biomedical augment Columbia’s AIDS research efforts with the research. Our New York City consortium is part of the distinguished career David Ho has built in his many national NIH All of Us program to enroll 1 million or years as an HIV researcher. more participants to harness the promise of precision medicine by exploring differences in people’s lifestyles, • Increasing the diversity of our faculty has been among our most important accomplishments in recent Artist’s rendering of a new research building years, and we have reinforced our dedication to diversity and inclusivity by implementing recommendations from two dean’s advisory committees. We are committed to ensuring that we meet the career development needs of all of our faculty.

• Despite the important ethical issues it raises, CRISPR is one of the most promising scientific innovations of this generation, and Columbia researchers are at the forefront in using the gene editing tool to advance—and hasten—research discoveries.

In the highlights section of this report, you can read about dozens of patient care advances, research discoveries, and educational programs that show how our faculty and students influence health through prevention, diagnosis, and treatment. Our NIH grant growth has outpaced the NIH budget for 10 years in a row and we now would rank #2 among U.S. medical schools if all awards to our faculty in psychiatry (whose awards are credited instead to the New York State

2 ColumbiaMedicine environments, and genetic makeup. To complement this effort and address the national shortage of genetic counselors, VP&S recently created a two-year genetic counseling master’s degree program, in which the first 12 students began their coursework this fall. Also new to campus this fall is the VP&S Class of 2023, 140 extraordinary students who are in the second class to be offered scholarships instead of loans to meet their financial needs throughout medical school. The 70 women and 70 men were chosen from among nearly 8,000 applications reviewed by our new admissions dean, Anne Armstrong-Coben, MD, and her admissions committee. Our scholarship program—in which all need-based financial aid is provided by scholarships without loans—was created through the generosity of Roy Vagelos’54 and his wife, Diana, along with many other alumni and friends. This program has further ele- of your foresight.” We add our words of appreciation vated our school and continues to allow us to attract the in paying tribute to this physician, mentor, benefactor, The late Ken Forde with Lee Goldman and best and brightest medical school applicants, indepen- and true gentleman who was enormously admired and Roy Vagelos in 2017 dent of their financial need. In turn, our students will is now missed by so many. be able to pursue their passions in medicine and science without the constraints of medical school debt. The lthough the tradition of an annual report is to makeup of the new class underscores our commitment A look back at the previous year’s accomplishments to diversity and inclusion: 21% of the class members and milestones, it is also important to look forward. are underrepresented minority students. And that is particularly important for me. In May, I This year also saw the completion of the first phase announced my intention to step down as dean and chief of Haven Plaza, a gathering place we anticipate will executive of the medical center at the end of the 2019-20 be shared enthusiastically by our medical center com- academic year, which will give me the privilege of hav- munity and our neighbors. A stretch of Haven Ave- ing stewarded VP&S and CUIMC for 14 years. In my nue, from 168th Street to 169th Street, was closed to final year, our goals remain lofty yet achievable. Among become a pedestrian plaza for all to enjoy either indi- them are to plan new facilities to increase our faculty’s vidually or in group events. Please see the latest photos capacity for research and patient care, including a new of Haven Plaza on the back cover of this report. research building and a new cancer building shared with Our celebration of this past year’s successes was tem- NewYork-Presbyterian. We also hope to add 50 primary pered by the June 2019 loss of Ken Forde, our alum- care physicians by 2022 and grow our multispecialty nus, faculty colleague, renowned surgeon, university practice sites in Manhattan and Westchester. trustee, and hospital trustee. His generosity was both Thank you for your continued support of the initia- traditional—he contributed to VP&S scholarships and tives that have made this school such an extraordinary created a teaching scholars fund that you can read place and that will make us even greater in the year about in this issue—and pioneering—he foresaw the to come. future of surgery in endoscopy and led the way in its implementation in his surgical specialty. Surgeon Spen- With best wishes, cer Amory, MD, in speaking at Dr. Forde’s memorial service in July, thanked his mentor for sharing his skills in endoscopy and for modeling exceptional communication, diagnostic skills, humility, and compassion. Of Dr. Forde’s support in promoting minimal access surgery at Columbia and beyond, Dr. Amory said, Lee Goldman, MD, Dean “Patients and surgeons continue to enjoy the rewards [email protected]

2019 Annual Report ColumbiaMedicine 3 his spring during her maternity leave, Stephanie Lovinsky-Desir, MD, updated progress reports to the NIH on her research into asthma among kids living in urban areas, reviewed grant applications and abstracts for the American Tho- Tracic Society, flew to Chicago to present an abstract at an American Society for Clinical Investigation meet- students nationwide. Racial and ethnic diversity like- ing, and drove to Baltimore to give an oral presenta- wise continues to increase among medical students, tion of her research at a Pediatric Academic Society with nearly 50% of medical students in the United meeting. “When an opportunity presents itself, it’s States identifying as non-white. And while great strides really hard to say no,” says the pediatric pulmonolo- have been made in diversifying the ranks of academic gist and mother of three. “Junior faculty members are medical faculty—both at Columbia and across the expected to have exponential growth in this early part country—women and people of color remain under- of our careers—but it overlaps with when we’re rais- represented at the highest levels of academic ranks, ing young families.” administration, and leadership. To address the issue, And yet, says Dr. Lovinsky-Desir, compared with the VP&S administrators have dedicated recruitment, hir- shorter leaves she had after her older two children were ing, and programmatic efforts to expanding the pipe- born, the 13-week parental leave policy instituted across line of women and underrepresented minority faculty Columbia University Irving Medical Center (CUIMC) to serve the educational, clinical, and research missions in January 2018 was a significant benefit. “While it was of VP&S and to take on leadership roles. still hard to come back to work, especially leaving a “Diversity at all levels of medicine, including stu- new baby with a cold, it was really nice to have that dents, trainees, faculty educators, researchers, and extra month of bonding time with her,” she says. practitioners, is critically important to educate stu- In 2017, for the first time, more women than men dents to understand medical problems that quickly enrolled in VP&S. This past year, women were the and easily cross global borders; to deliver culturally majority of both medical school applicants and enrolled sensitive health care to a population that is multicultural, multinational, and multilingual; and to bring new and different research perspectives to the research agenda,” says Anne Taylor, MD, vice dean for academic affairs. “American medical education, practice, and research can only remain the best by using the full THE FUTURE intellectual capital derived from recruiting the most committed, accomplished, and talented workforce from every segment of our population.” The effort at VP&S got a substantial boost in April IS NOW: A 2018 when Lee Goldman, MD, dean of the faculties of health sciences and medicine and chief executive of CUIMC, convened two faculty committees—one DIVERSE AND dedicated to the particular career challenges faced by INCLUSIVE women and the other to those of underrepresented

FACULTY BY SHARON TREGASKIS

THE FUTURE IS NOW: A DIVERSE AND INCLUSIVE minorities—to develop recommendations that would of 39%. Even at the highest ranks, 29% of VP&S full FACULTY strengthen ongoing efforts to promote opportunities professors are women compared with 25% nationally, for career success at VP&S for all faculty. Dr. Gold- and 35% of the medical school’s tenure-track faculty man reviewed the recommendations submitted jointly are women, leading Columbia’s peer group of medical by the two committees and accepted them in full this schools. Racially and ethnically diverse people make year. (See Page 9 for a full list of recommendations.) up 20% of the faculty at VP&S, with 11% (compared “While the recommendations were developed by advi- with 8% nationally) from groups traditionally under- sory committees, their implementation will position represented in the professoriate. VP&S to be the best place for academic medical fac- In recent years, the academic tracks were restruc- ulty to flourish,” says Dr. Taylor, whose office pro- tured to create a transparent, objective basis for aca- vided administrative support for the committees. demic advancement and to minimize arbitrary and Convening the committees was part of the medical potentially exclusionary promotion practices. Param- school’s ongoing efforts over the past decade to be sure eters of equity, such as numbers of women and diverse that career development needs of all faculty are met. faculty in leadership positions and on key committees These efforts also recognize that women and under- that review candidates for promotion and honors, are represented minority faculty face additional unique closely monitored to assure a balanced representation challenges to career development that require more of the faculty, and salary equity between men and professional development efforts. Earlier efforts have women is regularly measured. To ensure continued resulted in measurable progress. Among VP&S faculty efforts, VP&S committed $50 million to programs to 47% are women, compared with the national average recruit and support women and diverse faculty. Chief among the recommendations Dr. Goldman endorsed to promote the success and retention of new recruits and current faculty is creation of an Office for Women and Diverse Faculty. “All of our programs are driven by faculty interest and faculty demand,” says Dr. Taylor. Hired in late 2007, about 18 months after Dr. Goldman became dean, Dr. Taylor now holds the John Lindenbaum Professorship of Medicine and also serves as senior vice president for faculty affairs and career development for CUIMC. From that vantage point, she sees implementation of the committees’ recommendations as the latest advance in the work with which she was charged when she joined Columbia. “When I came to the medical school, there were no professional development programs for faculty,” says Dr. Taylor. “VP&S hires some of the most gifted faculty members in the country, so it is our responsibility to support their career success and satisfaction.” Her office now oversees ori- entation programs; leadership and management training, including sessions for all women and diverse faculty cohorts; workshops focused on career development and academic advancement for educators, researchers, and clinicians; and workshops focused on teaching skills, negotiation skills, and management of research teams. Working with women faculty, Dr. Taylor helped to develop the Virginia Kneeland Frantz Society for Women Faculty. “Implementation of the advisory committees’ recommendations will allow for expanded professional development programs but importantly will offer the opportunity to create further changes in the overall culture and climate around diversity and equity.” When Hilda Hutcherson, MD, arrived at Columbia Anne Taylor

PHOTOS BY JÖRG MEYER in 1981, she was the first African American woman

6 ColumbiaMedicine Hilda Hutcherson Christine Rohde

resident in obstetrics & gynecology. “On this campus, what was once a small office dedicated to recruitment there were few African American residents at the time in of underrepresented minority medical students into an any department, or even faculty members,” she recalls. office with a broader set of programs that support all “When I started as an assistant professor in ’85, there medical center students, she founded and leads the Ken- were no programs to encourage minorities or women to neth A. Forde Diversity Alliance, which is dedicated to pursue academic medicine.” Now a professor of obstet- recruiting, retaining, and recognizing a diverse commu- rics & gynecology and senior associate dean for diver- nity among students, residents, faculty, and alumni. sity and multicultural affairs, Dr. Hutcherson served on the Committee for Faculty Diversity and Inclusion—and she is pleased that the committee’s work has been so All departments will offer training in detecting enthusiastically endorsed by the dean. “When the list of and fighting implicit bias—the unconscious recommendations was put together, I don’t think anyone attitudes and stereotypes that can affect behavior. was thinking we’d get 100%,” she says. “I’m so happy that Dr. Goldman took all of the recommendations.” In the absence of formal programs to support her own Informal associations like that with Dr. Hutcherson career development, says Dr. Hutcherson, informal rela- and Dr. Thomson—whereby higher-ranking profession- tionships were key to her success. During her early years als in the field champion the career trajectories of junior on the faculty, Gerald E. Thomson, MD, now the Samuel faculty—play a critical role in sustaining diversification Lambert and Robert Sonneborn Professor Emeritus of of leadership of academic medicine, says plastic surgeon Medicine, took note of her passion for encouraging stu- Christine Rohde, MD. These relationships, which differ dents from diverse backgrounds and urged her to con- significantly from the peer-to-peer mentorship and net- sider formal opportunities to mentor others. “It wasn’t working many professionals already enjoy, are impor- something I was pursuing at first,” says Dr. Hutcherson. tant but should be supplemented by formal mentoring “Dr. Thomson thought I would be really good and a and sponsorship opportunities available to all, says Dr. natural fit and encouraged me to apply—that’s how I Rohde. The Office of Faculty Professional Development, ended up in this position.” She not only transformed Diversity & Inclusion led by Clara Lapiner, MPH, pro-

2019 Annual Report ColumbiaMedicine 7 Richard Francis Angela Mills

motes mentorship and sponsorship for faculty within and 20 underrepresented faculty have received funding departments but also has made sponsorship of faculty support to attend AAMC career development semi- for outside career development part of its mission. nars. Faculty who have received such support share A sponsorship opportunity from the Office of Fac- what they have learned with others. “At the end of that ulty Professional Development, Diversity & Inclusion course I wrote a list of the things I wanted to try to do provided funding support from the Virginia Kneeland in my work life and some were very, very specific—talk- Frantz Society for Dr. Rohde to attend an AAMC ing to a particular individual about things I wanted to mid-career development training program for women achieve in the future—and others were more general faculty. Since the program began in 2016, 29 women about how I could grow, contribute, increase visibility,” says Dr. Rohde. “Sponsors have really put me forward for things I wouldn’t have thought of myself.” As vice chair of faculty development and diversity for Who’s Who the Department of Surgery and chief of microvascular services at CUIMC, Dr. Rohde now has opportunities to · Richard Francis, MD, PhD, · Angela Mills, MD, the J.E. mentor and sponsor colleagues earlier in their careers, assistant professor of pathology Beaumont Professor of Emergency with a particular eye on cultivating diversity among & cell biology Medicine and department chair those being recommended for leadership. “There are · Hilda Hutcherson, MD, professor · Christine Rohde, MD, associate scholarships geared toward women, underrepresented of obstetrics & gynecology at professor of surgery at CUMC minorities, and I’ll find people in my department who CUMC and senior associate dean · Anne Taylor, MD, the John are eligible, encourage them to go for it, talk to people for diversity and multicultural Lindenbaum Professor of Medicine affairs at VP&S who will nominate them,” she says. And as a Chinese at CUMC, vice dean for academic American mother of three, she chooses to take on high- · Stephanie Lovinsky-Desir, MD, affairs at VP&S, and senior vice assistant professor of pediatrics president for faculty affairs and visibility roles—as co-chair of the Women Physicians of career development at CUIMC NewYork-Presbyterian, as a leader in her professional societies, as a member of the dean’s advisory committee for women faculty, and now as she applies for a full pro-

8 ColumbiaMedicine fessorship, a pursuit relatively rare among female surgical faculty. “I’m very conscious of what I do and what that means for other people who may want to follow Faculty Initiatives Accepted my career path in academic plastic surgery,” she says. and Funded “The kids are watching—if we say diversity is important, but the field is not, I think they pick up on that.” The list of recommendations submitted to VP&S Dean Lee Pathologist Richard Francis says he has seen sig- Goldman, MD, about ways to strengthen women faculty and nificant shifts in the institutional culture at VP&S faculty diversity and inclusion was a comprehensive one, since he was a student in the MD-PhD program and but it took little time for Dr. Goldman to accept them in full— since he was hired as faculty in 2011. “I feel like it and pledge funding for their implementation. is sincere, the idea of making this a better place for Below are the recommendations made by the Dean’s Advisory people to work, for patients to be seen, for people to Committee for Women Faculty and the Dean’s Advisory Committee receive their education,” says Dr. Francis, who directs for Faculty Diversity and Inclusion. the Special Hematology and Coagulation Laboratory and served with Dr. Hutcherson on the dean’s advi- • Create an Office for Women and Diverse Faculty. sory committee for faculty diversity and inclusion. “I don’t get the impression that it’s just lip service, but • Expand the work of successful faculty development programs, real follow-through where you can see differences.” such as the Virginia Kneeland Frantz Society for Women Faculty He sees particular promise in the dean’s endorsement and the Kenneth A. Forde Diversity Alliance. of the faculty recommendation that all departments offer training in detecting and fighting implicit bias— • Require each department to submit an annual diversity update. the unconscious attitudes and stereotypes that can affect behavior. “It feeds back into interviewing students, • Emphasize broad engagement with faculty and the VP&S residents, faculty,” he says. “People need to understand community around issues of gender and diversity. how they view people, how that affects who they recom- PHOTOS BY JÖRG MEYER mend, and how they approach trainees and job offers.” • Seek funding to create an endowment to expand leadership In his own career, he has found connection through training and other ongoing development programs for women programs like a Harold Amos Medical Faculty Devel- and diverse faculty. opment Program award from the Robert Wood John- son Foundation, which expanded his access to mentors. • Increase transparency around service on key school “As you get further along, having people to mentor committees, leadership positions, and opportunities. you who are more like you, look like you, have gone through things that you’ve experienced matters more.” • Expand implicit bias training for all departments, key To provide that kind of access among the residents committees, and searches at all levels. he meets in clinical rotations, Dr. Francis keeps lines of communication open, often helping trainees process • Strengthen the medical school’s existing successful initiatives, their own encounters with implicit bias. Much of that such as regular salary equity reviews, parental leave, and work boils down to acknowledging and validating pain- work/life services, including child care options. ful experiences. Sometimes he shares insights from his own journey or offers advice. “It’s not that someone’s trying to disrespect you,” says Dr. Francis. “They’re updating their schema—sometimes it works and some- As chair of the Department of Emergency Medicine times it doesn’t and there’s friction in that process.” since January 2018, Angela Mills, MD, has hired 34 Diverse perspectives advance the kind of problem- new faculty. Among them are 21 women and nine solving central to academic medicine, Dr. Francis people of color. “Diverse teams are smarter, and teams notes. Acknowledging the friction that can some- that are both gender and culturally diverse are more times emerge and working through difficult processes likely to introduce innovations,” says Dr. Mills. Both are critical steps for achieving the potential a diverse as problem solvers and as educators, she says, leaders workforce promises. “You have to do something to in academic medicine must innovate. Yet implicit bias foster that environment, make sure everyone has an often interferes with the recruitment and retention of equal voice, that they know that what they have is a diverse team. To reduce that risk, Dr. Mills has stan- something of value,” he says. “Everyone needs to dardized as much of the process as possible by requir- know that their perspective will be heard.” ing that nominating committees define hiring criteria

2019 Annual Report ColumbiaMedicine 9 medicine, however, only 37% of residents are women. “And the number keeps falling off,” she says. “The question is how do we promote emergency medicine as a specialty that supports women, promotes women, and allows women to successfully transition into academic medicine if they choose?” She has found that the new 13-week parental leave policy helps recruitment. “I use that as a selling tool, and I’ve had just as many men as women take parental leave,” she says. “It’s a great benefit to all parents.” She also is optimistic about the potential of #SHEmergency, a professional development group that fosters community and develops methods for awareness of gender bias among female-identified residents and emergency medicine faculty. The group’s article, “#Shemergency Presents: Recruitment & Retention of Female Resi- dents,” appeared this summer in AAMC’s journal, Aca- demic Medicine. “We developed specific events where residents and faculty partner on strategies and plans to combat disparities—everything from mentorship to speaking invitations, awards and recognition, salaries.” Like Dr. Francis and Dr. Rohde, Dr. Lovinsky-Desir credits an early career development award for providing the professional connections and coaching she Stephanie Lovinsky-Desir needed to take a tactical approach to her own career JÖRG MEYER advancement. “In my regular circles on the academic campus, often I’m the only woman of color,” she says. “It’s important to see people in leadership who “It’s important to see people in leadership who look look like you, who have gone through similar like you, who have gone through similar experiences. If they’ve made it, I too can make it.” experiences. If they’ve made it, I too can make it.” Among members of the dean’s advisory committee for faculty diversity and inclusion, the power of solidarity in advance and search committees develop a panel of and connection made the idea of an Office for Women questions each candidate must answer. “What we ask and Diverse Faculty particularly attractive, says Dr. candidates and how we evaluate them is really impor- Lovinsky-Desir. “As the odd person out, sometimes your tant when we’re talking about diversity,” she says. voice gets lost. It’s a little harder to speak up,” she notes. “Without clearly defined criteria, people tend to rede- “If there’s a space where we can unite, uplift one another, fine characteristics of what they’re seeking to promote I think it will empower us as we go back into our teams.” male candidates, less diverse candidates.” Already, says Dr. Lovinsky-Desir, she sees other As a member of the dean’s advisory committee for changes emerging from the recommendations advanced women faculty, Dr. Mills brought to the table her per- by the dean’s advisory committees—a powerful, self- sonal experience as a first-generation college student, reinforcing effect both on campus culture and the woman, and mother of two rising through the ranks advancement of women and minorities across VP&S. of emergency medicine, as well as her scholarship on She was recently invited to serve on a search committee. the gender gap in her field. In February, the Society Not only was she able to lend her perspective on the for Academic Emergency Medicine published her search itself, Dr. Lovinsky-Desir was fascinated by the analysis—co-authored with colleagues at Harvard— insights she gleaned about what search committees pri- on gender differences in faculty rank among academic oritize when assessing candidates for senior leadership emergency physicians in the United States. Later that positions. “We often don’t get that as junior faculty, month, she gave a VP&S grand rounds lecture on the women, minorities,” she says. “I learned so much about gender gap in academic medicine. Nationally, Dr. Mills what features are valued in a person in senior adminis- notes, more than 50% of medical students are women. trative leadership, and that perspective will enhance my Among all residents, 46% are women; in emergency growth here as a junior faculty member.” v

10 ColumbiaMedicine THE FUTURE — AND THE END? — OF AIDS

BY KRISTIN BUNDY hroughout much of the world, a diagnosis of HIV/ Much of ADARC’s research focuses on AIDS that once meant a certain death sentence now antibodies to prevent HIV transmission. means living with a chronic, controllable disease. “If One antibody in particular, engineered you think about the fact that this epidemic was only by ADARC six years ago, obstructs viral recognized in 1981, the progress has been enormous,” entry into the host cell. “It turns out to be Tsays David Ho, MD, the AIDS pioneer who was recruited to extremely powerful in blocking HIV infec- VP&S this year as the Clyde’56 and Helen Wu Professor of Medi- tion in the lab and in laboratory animals,” cine. “We do not have a vaccine. We do not have a cure. But we says Dr. Ho. He and his team have initiated have turned a deadly disease into a manageable condition.” a year-long, phase 1 trial of the antibody Dr. Ho has witnessed that transformation firsthand. He saw in infected patients and healthy volunteers. some of the earliest AIDS cases in the United States as a resident The trial is also being conducted at Colum- at Cedars-Sinai Medical Center in Los Angeles in 1980. “I will bia, led by Magdalena Sobieszczyk, MD, always remember the young man who came to the hospital with chief of the infectious diseases division. a multitude of infections,” he recalls of his first case. “He was If all goes well in this and subsequent treated but, nevertheless, died within a few weeks after leaving human trials, Dr. Ho foresees the antibody the hospital.” being delivered every few months by sub- Soon, another young man with pneumonia and other infections cutaneous injection to protect against HIV came to the hospital, was treated, and, again, died very quickly. “It infection, much like a long-acting contra- was this second, then third case, that began to raise alarm,” says ceptive prevents pregnancy. Dr. Ho. Within a year, those patients were included in the first case Dr. Ho’s antibody research is one vital report submitted to the Centers for Disease Control and Preven- endeavor amid a broader and urgent effort tion on what would become known as the AIDS epidemic. to prevent new HIV infections worldwide, What he saw in the clinic moved Dr. Ho to pursue HIV research and ADARC is joining existing Columbia throughout the 1980s. His renown grew, and by 1990 Dr. Ho had research programs with the same goal. The been named scientific director and chief executive officer of the Aaron goal announced by the U.S. president in Diamond AIDS Research Center, or ADARC, the largest independent early 2019—to end AIDS including decreas- nonprofit organization dedicated to basic research in HIV/AIDS. ing the number of new HIV infections by JÖRG MEYER His work has played a key role in what is now known about HIV. 90% by 2030 in the United States—is a He helped elucidate the nature of HIV replication, developed a num- bold one, notes University Professor and ber of antiretroviral drugs, and at global director for ICAP at Columbia University Wafaa El-Sadr, “And I believe the 1996 International AIDS Con- MD. “While there has been a huge scale-up in terms of treatment over the next ference presented his team’s break- domestically and globally, we are not on track to reach the goal of through study results that proved HIV prevention in terms of the number of new infections. More five or 10 years, combination therapy could reduce than a million are still reported globally every year.” we are going to HIV viral loads to undetectable lev- In May, the New England Journal of Medicine published a see tremendous els for at least one year. “That was perspective on the 2030 target by Dr. El-Sadr and coauthored by progress in a turning point in the treatment Miriam Rabkin, MD, associate professor of medicine and of epi- preventing HIV efforts,” says Dr. Ho. demiology (in Columbia’s ICAP) with colleagues at the Fenway This year, Dr. Ho is bringing Institute and the University of West Virginia. “HIV affects the infection, not just ADARC to Columbia. “The Aaron most vulnerable among us,” they noted, highlighting the dispro- with drugs like Diamond AIDS Research Center portionate number of new cases among people of color, transgen- PrEP, but with is a world-leading center for the der people, people in rural areas who use injectable drugs such as antibodies and study of HIV and AIDS,” says Lee opioids, and those most affected by poverty and unstable housing. perhaps even Goldman, MD, dean of the facul- The medical community already has the tools to overcome these ties of health sciences and medicine challenges, says Dr. El-Sadr, who is co-principal investigator of with vaccines.” and chief executive of Columbia the NIH-funded HIV Prevention Trials Network, or HPTN. In University Irving Medical Center. 2016, an HPTN study confirmed that HIV treatment is, itself, a “Our faculty are excited about the new collaborations that will highly effective form of prevention. “When you treat people living advance our understanding of HIV and how to treat and prevent with HIV,” she says, “not only does the person being treated ben- this viral infection.” efit, but you also decrease the risk of transmission of HIV to oth- ADARC will move into a new, specially designed facility on two ers.” Thus, the scale-up of HIV treatment has been a fundamental floors of the Hammer Health Sciences Center. Says Dr. Ho: “There global priority championed as well by ICAP in the countries where is nothing like having a home at an academic medical center.” it works.

12 ColumbiaMedicine David Ho

For individuals who are HIV-negative, several preventive options stigma and discrimination. Adding HIV makes it doubly difficult are now available. An important one is pre-exposure prophylaxis, in so many ways.” or PrEP, an approach where persons can protect themselves by tak- To fight back, Dr. El-Sadr marshals creativity and engagement. ing a daily pill. Post-exposure prophylaxis, on the other hand, offers Many of the ICAP-led projects she has created train and empower protection by taking medications after a suspected sexual or occu- peer educators to share their own experiences, talk about how they pational exposure to prevent infection. overcame similar challenges, and encourage others to participate in As co-PI of HPTN, Dr. El-Sadr designs and implements HIV research studies as well as programs. That approach has been the prevention research across the United States and in Latin America, backbone of her work since the late 1980s, when she established Africa, and Asia. “Our goal is to design the best possible research the first HIV research unit at Harlem Hospital. “Peer educators are to identify new prevention tools and determine how to use them. from the same communities as those we seek to serve. They know Then, importantly, we need to get what we know works to the what is going to resonate. They also know how to model behaviors. people who need it so we can demonstrate the benefits at a popu- They have been a huge part of our work, whether it be in Tanzania, lation level.” The same values infuse ICAP, the Columbia-based Swaziland, Kazakhstan, or right here in New York.” global health center that Dr. El-Sadr founded in 2003 to develop Outreach has been central to the peer educators’ roles, says and deliver comprehensive, family-focused HIV services and evi- Dr. El Sadr. For example, in Tanzania, the ICAP-supported teams dence-based initiatives to bolster national health systems. work to reach those most disenfranchised, going wherever they Despite more positive attitudes toward people living with HIV, are needed and doing whatever is needed. They organize festive Dr. El-Sadr notes that stigma still impedes testing, status disclo- campaigns in village centers, visit artisanal miners, brothels, drug sures, and access to prevention and treatment among many people dens, fishing villages where the population is transient. Carrying in high-risk populations. “Keep in mind that some of these same backpacks loaded with supplies, peer educators talk to people, populations, even without HIV, are stigmatized,” she says. “If you gain their trust, set up mobile units and tents, or do whatever is are a young man having sex with men in a Southern rural commu- needed to get them the prevention and treatment they need. “If nity in the United States, if you are a transgender woman, even in you get out of the comfort zone of health facilities, clinics, hospi- New York City, your whole outlook on life is shaped by prevailing tals, or research labs, get creative and collaborative, and sit with

2019 Annual Report ColumbiaMedicine 13 viruses, and identified cellular proteins that COLLABORATING TO HASTEN interact with and sabotage retroviral replication, laying the groundwork for today’s THE END OF AIDS HIV combination therapies. His current work focuses on the chromatin and histone he move of the Aaron Diamond dalena Sobieszczyk, MD. Faculty have modifications involved in silencing HIV-1 AIDS Research Center to Columbia helped set standards of care for the treat- in the latent reservoir of infected cells. T and appointment of its leader, David ing community, led major clinical trials of Ho, MD, as the Clyde’56 and Helen Wu antiretroviral agents resulting in changes SCOTT HAMMER, MD Professor of Medicine will amplify the in approach to effective treatment, demon- The Harold C. Neu Professor of Medicine ongoing basic and clinical research in HIV/ strated that measurement of plasma HIV-1 and former chief of the Division of Infec- AIDS at VP&S. RNA (viral load) can be a surrogate for tious Diseases focuses on the treatment The Division of Infectious Diseases in the clinical disease progression thus eliminat- and prevention of HIV. He is a co-PI Department of Medicine sees the move of ing the need to do clinical endpoint (AIDS of the NIH-funded HIV Vaccine Trials ADARC to Columbia as a transformative or death) trials for registrational studies of Network and an investigator in the NIH- event for both ADARC and infectious dis- antiretroviral agents in the United States, sponsored AIDS Clinical Trials Group. He eases faculty who have been at the forefront elucidated approaches to treatment of has partnered with ADARC on clinical tri- of the response to the HIV/AIDS pandemic HIV-1 drug resistance, and studied new als since 2000. He is the current protocol since its onset in the 1980s. Under the lead- classes of antiretroviral agents. chair of HVTN 505, an advanced phase 2 ership of the former chief, Scott Hammer, In the past decade, Drs. Sobieszczyk and study of the preventive HIV vaccine regi- MD, the division’s clinicians delivered state- Hammer have intensified their focus on men developed by the Vaccine Research of-the-art care to patients and pursued cut- HIV-1 prevention, leading HIV-1 preven- Center at the National Institute of Allergy ting-edge research to improve patient care. tive vaccine trials (early phase through and Infectious Diseases. “Numerous individuals and groups across efficacy studies), and studying the safety CUIMC have contributed to the impressive and efficacy of broadly neutralizing mono- PETER KWONG, PHD progress seen in managing and preventing clonal antibodies in prevention of HIV-1 The longtime adjunct professor in the HIV disease both domestically and inter- acquisition. Division members have also Department of Biochemistry & Molecular nationally,” says Dr. Hammer. “There isn’t developed and implemented one of the Biophysics and a 1995 Columbia PhD sufficient space in this article to give credit largest programs in New York City to graduate is chief of the structural biology to those who have given of themselves so provide pre-exposure prophylaxis (PrEP) section of the Vaccine Research Center at mightily over the past 35 years.” and access to HIV prevention and sexual the NIH. Early in his career, Dr. Kwong “Faculty members in the infectious dis- health services to individuals of all ages, solved the structures of the HIVgp120 eases division have matching and comple- genders, and sexualities. Much of this envelope glycoprotein and of CD4 (the mentary interests to those of ADARC,” work has focused on building collabora- human receptor to which HIV binds) along says the division’s current chief, Mag- tions with local community-based organi- with a set of broadly neutralizing antibod- zations and city, state, and federal public ies isolated from people infected with HIV. health programs to provide this care to For the past several years, his group at the communities at high risk of HIV acquisi- Vaccine Research Center has focused on tion, including the Washington Heights applying the atomic-level tools of structural and northern Manhattan neighborhoods. biology to the development of antibody- Among the VP&S faculty who will col- guided vaccines against HIV-1 and other laborate with or join ADARC: viral pathogens; promising candidate vaccines are currently being developed against STEPHEN P. GOFF, PHD respiratory syncytial virus, human para- The Higgins Professor of Biochemistry influenza viruses types 1-4, and HIV-1. At in the Departments of Biochemistry & Columbia, Dr. Kwong is working to extend Molecular Biophysics and Microbiol- his structure-based antibody-to-vaccine ogy & Immunology conducts detailed paradigm through Antibodyomics, the genetic analysis of the replication cycle of informatics of antibody recognition, devel- the human immunodeficiency virus type opment, and improvement. 1 (HIV-1). In hundreds of peer-reviewed studies, Dr. Goff has defined the functions LAWRENCE SHAPIRO, PHD Magdalena Sobieszczyk of many viral gene products, character- The professor of biochemistry & molecu- and Scott Hammer

JÖRG MEYER ized host proteins that are exploited by the lar biophysics and ophthalmic science

14 ColumbiaMedicine (in ophthalmology and in the Naomi Ber- rie Diabetes Center) is a principal investigator at Columbia’s Zuckerman Institute. His work relating development of effective antibodies to their structural biology has revealed molecular mechanisms by which antibodies can achieve broad neutraliza- tion of HIV. These studies have character- ized sites of vulnerability on the virus, identifying promising targets ripe for exploitation in the search for a vaccine.

MAGDALENA SOBIESZCZYK, MD The clinician and associate professor of medicine is PI of the NIH-funded Colum- bia HVTN and ACTG Clinical Research site and chief of Columbia’s Division of Wafaa El-Sadr Infectious Diseases. Her research focuses on developing, testing, and implementing biomedical strategies to prevent HIV infec- the people, listen to their concerns, speak in their language and tion, specifically preventive HIV vaccines offer them prevention, offer them treatment, right where they need and pre-exposure prophylaxis (PrEP). it, guess what? They are quite willing to engage.” Her particular interests include assessing With nearly four decades of experience in the field, Dr. El-Sadr combination biomedical prevention strate- counsels diligence to achieve the ambitious U.S. HIV goals. First, gies such as vaccines and PrEP. This work she says, adequate funding is critically important. Second, the also includes testing novel technologies to affected communities must be fully engaged. Third, resources and improve uptake of and adherence to bio- actions must be focused on the populations and locations where medical prevention modalities. She is co- they are needed, informed by evidence and data. And finally, hard chair of a phase 2b HIV vaccine protocol science must drive policy. “We need to do what is supported by to determine the safety and efficacy of the evidence,” she says. “There should be no room for DNA prime-Ad5 boost vaccine regimen in “We need to political expediency.” individuals at risk of HIV infection (HVTN do what is Dr. Ho takes a cautiously optimistic stance on 505) and site PI for several studies evaluat- the 2030 target. “It is possible, but a daunting ing broadly neutralizing antibodies for the supported task,” he says. “It requires political leadership, prevention and treatment of HIV infection. by evidence. political will, and making sure that resources are There should properly given to the effort.” MICHAEL YIN, MD be no room Over the past decade, ADARC has received The associate professor of medicine and for political nearly $50 million collectively from the Gates co-director of the Biobehavioral Core of Foundation and the NIH to advance its research, the HIV Center for Clinical and Behavioral expediency.” with more to come. “I think we could move the Studies at the New York State Psychiat- work we are doing with antibodies into the clinic ric Institute focuses on optimization of and into at-risk communities to block HIV transmission even more HIV treatment and care. In particular, his effectively,” says Dr. Ho. “And I believe over the next five or 10 research focuses on evaluating and prevent- years, we are going to see tremendous progress in preventing HIV ing metabolic complications associated infection, not just with drugs like PrEP, but with antibodies and with chronic inflammation and antiretro- perhaps even with vaccines.” viral therapy throughout the lifespan, from Decades of innovations, action, and partnerships have ushered children with perinatal HIV acquisition in a new era in the global HIV response—one that could mean to older adults living with HIV. He is an the end of AIDS. “We are at a moment in history where we know active investigator in Women’s Interagency enough to stem this epidemic, and we need to take what we know HIV Study, ACTG, and HVTN and a co- into action,” says Dr. El-Sadr. “At the same time, we must con- investigator on the Columbia Partnership tinue to seek new discoveries through research in the laboratory, for Prevention and Control of HIV/AIDS in the clinic, and in the community. Both discovery and action are Clinical Trials Unit. needed as we move forward.” v

2019 Annual Report ColumbiaMedicine 15

n the 19th century, the Swiss military contracted for a multifunctional pocket I knife for officers to carry in the field. In addition to having a short blade, the com- pact gadget featured a fold-out can opener and two implements vital for maintaining the standard-issue Swiss rifle: a screwdriver, essential for disassembling and reassembling the firearm for cleaning, and a reamer, used to smooth burrs in the gun’s metal barrel. Today, the Swiss Army knife comes in dozens of models, each featuring tools curated for a particular audience—gardeners, hunt- ers, locksmiths, even oenophiles. The iconic tool also is an analogy for CRISPR. For 3 billion years, unicellular bacteria have deployed CRISPR—Clustered THE FUTURE Regularly Interspaced Short Palindromic OF GENE EDITING

Repeats—to defend themselves against viral attacks. In 2012, scientists demonstrated that CRISPR could be reprogrammed to modify the DNA of eukaryotes. Think precision scalpel, gene silencer, gene amplifier, and— like the modern-day Swiss Army knife—an expanding inventory of additional tools. At VP&S, CRISPR has become a mainstay of discovery, with basic scientists developing new CRISPR-based tools while translational COLUMBIA SCIENTISTS USE researchers put those tools to use, revealing new insights into human disease and AND REFINE CRISPR TO PROVIDE its management. INSIGHTS TO HEALTH “There are so many variations on the core theme,” says Sam Sternberg, PhD, assistant professor of biochemistry & molecu- BY SHARON TREGASKIS lar biophysics, who—with his PhD adviser, THE FUTURE OF GENE EDITING

CRISPR pioneer Jennifer Doudna—advanced the Swiss Army knife creates an RNA copy, the genetic equivalent of a wanted poster. analogy in “A Crack in Creation: Gene Editing and the Unthinkable As the bacterium’s adaptive immune system continues surveilling Power to Control Evolution,” a 250-page book on the discovery of the prokaryotic cytoplasm, it peruses those sheaves of wanted CRISPR and its implications for the life sciences. posters. In the event of a positive ID, it uses a CRISPR-associated As a graduate student, Dr. Sternberg worked with Dr. Doudna protein (Cas, for short) like a precision scalpel to mount a brisk to develop one of the earliest CRISPR-based tools. Since joining and robust defense, snipping the offending DNA to pieces and Columbia in 2018, Dr. Sternberg has broadened his search, look- stopping the invader in its tracks. ing for additional gene-editing systems found in nature’s earliest Eukaryotes—from fungi to humans—boast a nucleus to contain life forms and detailing how they can be deployed to advance and protect DNA, making targeted gene modification a time-con- genomic discovery in the lab. “Bacteria have been fighting off suming and technically challenging enterprise. Using a combina- viruses for a long time and the diversification of their immune tion of chemicals, electrical current, viruses, and micropipettes, systems is a treasure trove for building new technologies,” he says. technicians break through the cellular membrane and into the “We’re not done discovering new biology, and the more we find, cell nucleus to induce breaks in the DNA—all without killing the the more we can leverage for tool development.” cell. Then they rely on homologous repair, an innate quality con- The work emerges from the predominantly unicellular life forms trol system that cells use to fix broken strands of DNA. (It’s a lot known as prokaryotes, the organisms that lack a nucleus or other like patching a pair of jeans: If the patch and the hole correspond dedicated organelles. With DNA floating freely throughout their around the edges, the splice will hold.) cytoplasm, prokaryotes can’t afford to get sloppy about detect- Technological innovations in recent decades—gene sequencing, ing and neutralizing foreign genes that could prove their undoing. cell cloning, RNA interference, zinc finger nuclease technology, Enter the innate DNA surveillance tool that serves as a protean and transcription activator-like effector nucleases, for example— adaptive immune system. Each time a bacterium vanquishes have given scientists greater control of their tinkering, allow- pathogenic DNA, it captures a few characteristic snippets—those ing them to turn on or off target genes to create “knock-in” or clustered regularly interspaced short palindromic repeats—and “knockout” animals. CRISPR, however, has been transformative,

Steven Siegelbaum and Bina Santoro

PHOTOS BY JÖRG MEYER

18 ColumbiaMedicine allowing scientists to cut and paste strands of DNA at specific locations, all within the nucleus of living cells. First, they create a CRISPR RNA seeded with snippets of a target genetic sequence. Then they inject it, along with a Cas enzyme, into the nucleus of a eukaryote. Cas zeroes in on the location specified by the RNA and induces double-strand breaks. “CRISPR-Cas immune systems have completely transformed the ways biologists study biology,” says Dr. Sternberg. “It has given basic scientists a new and more powerful way of asking questions like, ‘What genes are involved in cancer becoming metastatic?’ and opened new avenues for drug development. Across campus, people are using CRISPR as a better way to design their experiments.” Neuroscientist Steven Siegelbaum, PhD, has spent decades digging into the mechanisms of HCN1, a gene that serves as an electrical pacemaker within the human cortex, the part of the brain responsible for higher thought processes. In recent years, genomewide association studies have implicated HCN1 mutations in forms of infantile and pediatric epilepsy that cannot be explained by a head injury, infection, metabolic disorder, or other clinical evidence. In some cases, seizures are so severe they lead to progressive brain dysfunction and developmental delays. To develop the mouse models that could reveal how those mutations wreak such havoc, Dr. Siegelbaum and associate research scientist Bina Santoro, PhD, a longtime lead investigator in the Lorraine Clark Siegelbaum lab’s HCN1 research, turned to CRISPR. “It’s very fast, it’s comparatively cheaper than the traditional way of introducing point mutations, and there are a lot of these mutations tal mice,” he explains. “And if they also develop seizures, that’s in human patients that affect different parts of the HCN1 gene,” strong evidence that the mutation is a cause of the disease, not just associated. That’s our goal: We want to demonstrate that it’s the HCN1 mutations in the patients that are causing the disease.” One of the tools we spend a lot of time By simultaneously exploring multiple HCN1 variants and their on is improving how we can use CRISPR to role in seizures, Dr. Siegelbaum and Dr. Santoro also hope to turn genes on and off. gain insights into a basic conundrum about epilepsy, that seizure disorders take myriad forms and the drugs that can ameliorate symptoms in some patients aggravate the condition in others. “If says Dr. Santoro. “We wanted to generate not just one mouse line, in the mouse we can tie different mutations to different kinds of but a collection of mutations in the HCN1 gene, which are also epilepsy,” says Dr. Santoro, “then we can see which mutations present in human patients, to see the extent to which the mice respond better to which drugs, or which drugs exacerbate which reproduce the human condition.” forms of the disease.” Using support from a Columbia Precision Medicine Initiative Like Dr. Siegelbaum and Dr. Santoro, Lorraine Clark, PhD, assis- program and expertise in the Columbia transgenic mouse shared tant medical director of the Laboratory of Personalized Genomic resource, Dr. Siegelbaum and Dr. Santoro have already developed Medicine, mixes genomewide association studies, basic biochem- four lines of mice with HCN1 mutations and seizure disorders and istry and functional studies, and mouse models to reveal how gene begun analyzing the morphology of their brains for preliminary variants affect brain function. Her research focuses on such neuro- clues about how the mutations affects brain anatomy and bio- degenerative diseases as Parkinson’s and essential tremor. chemistry. “In the best case, you save a year with CRISPR, maybe Scientists already know that p.E326K, a specific variant of the 12 to 18 months, depending on how lucky you are with the tech- glucocerebrosidase (GBA) gene, has been implicated in the sever- nique,” says Dr. Siegelbaum. “The general proof of principle, that ity of Gaucher disease and is one of the most common risk factors these mutations are causing the seizures, will happen pretty soon.” for Parkinson’s disease and dementia with Lewy bodies. Research Deeper understanding—about the mechanisms by which pro- suggests that the problem common to all three conditions has to teins altered by the mutation affect electrical activity in the brain— do with how GBA encodes for the enzymes vital to the function will take considerably longer. “By using CRISPR we know that of lysosomes, the organelles responsible for cellular digestion and this one mutation to HCN1 is the only one in our experimen- waste removal. But scientists do not understand the specific mech-

2019 Annual Report ColumbiaMedicine 19 THE FUTURE OF GENE EDITING

anisms by which p.E326K disrupts enzyme production. Without to protect themselves against bad proteins, including apoptosis, or that crucial insight, targeted therapies to ameliorate symptoms programmed cell death. Dr. Chavez wants to find both the genes remain out of reach. that buffer the effect of misfolded proteins and those that amplify To learn more about how p.E326K alters lysosomal function, their effect. “We’re looking for which levers to pull,” he says. Dr. Clark is combining an award from the Columbia Precision “Nothing works in isolation. You need to know the connections Medicine Initiative with an R03 award from the NIH to generate a to pick apart the system.” mouse model that has the gene variant so she can characterize the The same holds true of the basic biology from which CRISPR resulting brain pathology. “CRISPR is cost-effective, convenient, derives. To boost the understanding of how best to leverage that and easy to use,” says Dr. Clark. “Determining the disease mecha- biology to refine existing tools and build better ones, a cadre of nism associated with p.E326K may open up new therapeutic tar- junior faculty convenes regularly to review the projects under- gets and could have a major impact on treatment of Parkinson’s way in their laboratories and troubleshoot technical challenges. disease and dementia with Lewy bodies.” They call themselves SLCC (pronounced slick) for Sternberg, Lu, Alex Chavez, MD, PhD, assistant professor of pathology & cell Chavez, and Ciccia. “Everyone comes from different angles,” says biology, spends roughly half of his time digging into how CRISPR Dr. Sternberg. Chao Lu, assistant professor of genetics & develop- works, trying to make it more effective and more efficient. He has ment, focuses on the epigenome—proteins that turn genes on and been awarded a dozen patents; 10 of those feature CRISPR technol- off. Alberto Ciccia, also assistant professor of genetics & devel- ogy. This spring, Columbia filed the first patent application for his opment, investigates the mechanisms that repair DNA lesions work to rapidly generate hundreds of cell lines, each with targeted and maintain genome integrity. Says Dr. Sternberg: “We’re each mutations. “One of the tools we spend a lot of time on,” he says, thinking about the science from a unique angle—that’s when you “is improving how we can use CRISPR to turn genes on and off.” achieve intellectual synergy.” When not developing new CRISPR-based tools, Dr. Chavez uses In June, Nature published the first paper from Dr. Sternberg’s lab the tools to investigate cancer and neuropathology. By activating at Columbia—a report on how a CRISPR-like system found in the and silencing genes implicated in such conditions as Alzheimer’s, bacterium Vibrio cholera can be modified to insert genetic mate- he hopes to reveal the role of each gene in the disease process. In rial at a precise location, without first blasting a hole in the target particular, he has homed in on the genes that help a neuronal cell DNA. Dubbed “INTEGRATE,” the new system relies on parasitic tolerate proteins perturbed in Alzheimer’s and some other neuro- “jumping genes” known as transposons that can insert themselves degenerative afflictions. Healthy neuronal cells have myriad ways into a strand of DNA, using an enzyme that works like molecular glue. “Rather than introduce DNA breaks and rely on the cell to repair the break,” says Dr. Sternberg, “INTEGRATE directly inserts a user-defined DNA sequence at a precise location in the genome, a Who’s Who capability that molecular biologists have sought for decades.” Even as scientists develop more technically advanced CRISPR- · Paul S. Appelbaum, MD, the Dollard Professor of Psychiatry, based tools and use them to increase understanding of human dis- Medicine, & Law and director of the Division of Law, Ethics, ease and how to treat it, questions mount. “Scientists have been and Psychiatry actively discussing the more technical issues,” says Dr. Sternberg, · Alex Chavez, MD, PhD, assistant professor of pathology “but on the societal and ethical side, we need a lot more people & cell biology present, including members of the public who will be affected— · Alberto Ciccia, PhD, assistant professor of genetics & disability rights activists, disease advocacy groups, people of all development and member of the Herbert Irving Comprehensive stripes who just want to understand this better.” Cancer Center To promote such conversations, Dr. Sternberg has made out- · Lorraine N. Clark, PhD, associate professor of pathology & reach to off-campus audiences a high priority. “Part of my role cell biology (in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at CUMC and assistant medical here is not just to train postdocs, grad students, and undergradu- director of the Laboratory of Personalized Genomic Medicine ates in the laboratory,” he says, “but to be involved in educating · Chao Lu, PhD, assistant professor of genetics & development others too.” To that end, he hosts visiting high school students from the metro New York area in his laboratory and participates · Bina Santoro, PhD, associate research scientist in Steven Siegelbaum’s lab in a program that uses web conferencing to connect scientists with classrooms across the country. This spring, he also participated · Steven Siegelbaum, PhD, the Gerald D. Fischbach, MD, in Taste of Science, a program that invites scientists to talk about Professor of Neuroscience, professor of pharmacology, and chair of the Department of Neuroscience their research in local watering holes. Together with a scientist from the New York Genome Center, Dr. Sternberg discussed · Sam Sternberg, PhD, assistant professor of biochemistry & molecular biophysics CRISPR at a bar in the East Village. “There were people there who have definitely never set foot in a research lab, but they’re curious,” says Dr. Sternberg. “They want to know how CRISPR

20 ColumbiaMedicine Sam Sternberg and Alex Chavez

JÖRG MEYER can be used and want to think about how companies are going to clinician’s geography, raising the possibility that scientists with apply this technology, what’s ethical, what’s safe, and so on.” ambitions curtailed in their home countries might move to more Ethicist Paul S. Appelbaum, MD, was exploring the ethics of favorably regulated environs. And, no consensus has emerged gene modification long before CRISPR came on the scene. When on the mechanisms that might be used to impose international he launched Columbia’s Center for Research on Ethical, Legal & standards for how CRISPR is used. “There are a variety of pos- sibilities,” says Dr. Appelbaum. “You could have legislation that controls or proscribes use of CRISPR or other gene-editing tech- Are we treating individual patients or are nologies, you could have voluntary self-regulation by the research we seeking interventions that will affect the community, or rules imposed by funders, or a completely unregu- next generation and future generations? lated environment, in which researchers and clinicians are free to do what they want with technology that’s available to them.” As the technology advances, Dr. Appelbaum anticipates that Social Implications of Psychiatric, Neurologic & Behavioral Genet- society will be forced to confront profound questions about what ics, CRISPR was still an obscure phenomenon observed among uni- it means to be human. “The assumption that we can identify con- cellular organisms. But in November 2018—just six years after the ditions that should be extirpated from the human gene pool— first paper detailing how CRISPR could be used to modify a eukary- assuming that were possible, which given the heterogeneous bases otic cell—a Chinese scientist announced that the genomes of twin for many conditions is extremely unlikely—makes the question girls born earlier that month had been modified using the technology. of whether it would be desirable a real one.” Consider, he sug- While the Chinese case brought to the fore myriad technical gests, the enormous creativity in mathematics demonstrated by and ethical questions about human gene editing, Dr. Appelbaum some individuals on the autism spectrum or the cultural contribu- sees the central issue raised by CRISPR as this: whether particular tions of artists afflicted by mood disorders. “There are questions modifications die with the individual or can be passed to the next of neurodiversity,” he says, “but also the reality that the same generation. “Are we treating individual patients on one hand,” gene, the same variant may have multiple consequences, particu- he asks, “or are we seeking interventions that will affect the next larly when we’re talking about complex traits.” And, he notes, it generation and subsequently future generations after that? They may be impossible to fully comprehend the choices we confront. have very different ethical implications.” “As we begin to be able to edit the gene pool it may be the case The current regulatory environment varies among nations, with that we can’t anticipate some of the consequences of the changes the legality of human gene modification depending heavily on a we’re making.” v

2019 Annual Report ColumbiaMedicine 21  PHILANTHROPY NEWS HELP FROM OUR FRIENDS

THIS REPORT gives us an opportunity to recognize they are passionate about without letting a burden the many friends and partners who have helped of medical student debt impact their choices. us continue our extraordinary progress as a leader These efforts have been recognized well beyond the in medicine. Through this support, we continue to borders of our campus: We have seen an increase in make tremendous advances in research, education, applicants, allowing us to bring in the most talented clinical care, and community service. students and nurture them early in their careers, As part of this effort, we not only are recruiting regardless of their current financial capacity. and training the brightest young minds in medicine, Roy and Diana Vagelos also have been a driving we also are providing them with opportunities to force in another of our top priorities: precision make the greatest possible difference over the medicine. Their commitment to Columbia’s Precision course of their careers and in the lives of patients. Medicine Initiative and related programs at the These opportunities begin from the very start of medical school has made us a magnet for talent and the destination of choice for faculty recruits in this area. These experts are helping us to build on the accomplishments of leading faculty members, including our newest Nobel laureate, Joachim Frank. Nowhere is the promise of precision medicine more evident than in our work in the field of cancer. We are expanding and advancing our cancer research and treatment programs thanks to the generosity of the late Herbert and Florence Irving. Their transformative estate gift allowed us to recruit Anil Rustgi, MD, the outstanding new director of the Herbert Irving Com- prehensive Cancer Center, and will help to build upon the center’s programs in immunotherapy, neurooncology, and genomics and expand our clinical trials, which translate the discoveries from our laboratories directly into improving the lives of patients. Roy and Diana Vagelos At VP&S and across the medical center, our philanthropic partners have been vital to the success medical school. Contributions from Roy and Diana of our programs, which have one shared goal: to Vagelos and many other alumni, faculty, friends, improve the lives of our patients, communities, and and supporters have helped to eliminate loans for populations. We are grateful for this tremendous all VP&S students who have financial need and support and commitment, which have made us a replace them entirely with scholarships. This new leader in health care over the past 250 years, this scholarship program, launched in Fall 2018, allows past year, and into the next generation of teachers, our graduates the opportunity to pursue careers scientists, and healers.

22 ColumbiaMedicine Cardiology Division Renamed in Recognition of Flanzer Philanthropic Trust Gift

The Louis and Gloria Flanzer Philan- to the success of both institutions and thropic Trust of Sarasota, Florida, made the medical center as a whole, says Lee a gift of $32.5 million this year to benefit Goldman, MD. With this portion of her the Division of Cardiology in the Depart- legacy, Mrs. Flanzer honors her family ment of Medicine. The gift is in honor of and her association with Dr. Schwartz. Allan Schwartz, MD, chief of the division. In addition to naming the division, the In recognition of the gift, the Columbia gift establishes the Seymour, Paul and University Trustees renamed the division Gloria Milstein Professorship of Cardiol- the Seymour, Paul and Gloria Milstein ogy. Upon Dr. Schwartz’s retirement from Division of Cardiology. This is the first the faculty of VP&S, the professorship named division in the history of VP&S. will be renamed the Allan Schwartz, MD The naming reflects Gloria Flanzer’s Professorship of Cardiology. wish to recognize the contributions that The gift creates an endowed fund of her brothers, Seymour and Paul, and $30 million to support clinical, research, Louis and Gloria Flanzer the entire Milstein family have made and educational activities in the Division to Columbia University Irving Medical of Cardiology. The remaining $2.5 million to the teaching and research of the Center and NewYork-Presbyterian. The of the gift establishes an endowment faculty member occupying the Milstein Milstein family’s support has been integral to pay the salary and expenses related Professorship of Cardiology.

Kenneth A. Forde’59 Teaching Scholar Fund Berrie Foundation Gift Launches Diabetes Simulation Program Before the recent death of Kenneth A. Forde’59, the Kenneth A. & Kareitha O. Forde Private Family Foundation committed $1 million to The Russell Berrie Foundation has pledged establish the Kenneth A. Forde, MD Teaching Scholar Fund in the Division $1.1 million to support a new medical educa- of Cardiology in the Department of Medicine. This gift honors David I. tion initiative that will use simulation training Sahar, MD, professor of to prepare physicians to improve clinical care medicine at CUMC. The for patients with diabetes. The program is a endowment payout from the collaboration between Columbia’s Michael and fund will be used to support Mary Jaharis Simulation Center and the Naomi an annual award to clinical Berrie Diabetes Center and will be led by the educators in the Division of Simulation Center’s medical director, Arnold Cardiology at the discretion Advincula, MD, and the Berrie Center co-direc- of the chief of the division. tor, Robin Goland, MD. Currently, most simula- Upon Dr. Sahar’s retirement tion training focuses on fundamental, mandated from the faculty of VP&S, skills rather than specialized care. This pilot pro- the fund shall be renamed gram is a unique opportunity to develop simula- the David I. Sahar, MD tion curricula tailored to a specific disease area. VP&S’80 Teaching Scholar In the long term, Drs. Advincula and Goland Fund, and award recipients believe the program could help develop a new will be known as David I. paradigm for training medical professionals who Sahar, MD VP&S’80 treat patients with diabetes, both primary care Ken and Kareitha Forde Clinical Educators. providers and specialists.

2019 Annual Report ColumbiaMedicine 23  PHILANTHROPY NEWS

Thompson Family Foundation Honored at Crown Awards

VP&S at its annual Crown Awards Gala honored the Thompson Family Foundation for its most recent gift of $12 million to support research at Columbia on neurodegenerative disorders, such as Alzheimer’s disease, multiple sclerosis, and Parkinson’s. Historically, these diseases have had a devastating impact, and progress in treating them has been modest. With a universitywide commitment, the recruitment and retention of the brightest and most promising scientists and clinicians, and the support of the Thompson Family Foundation, all of that is changing. Meaningful improvements in the diagnosis and treatment of these diseases is already happening with the prospect of even more significant breakthroughs in sight. The Thompson Family Foundation’s first gift to Columbia was to support research into painful neuropathies, a frequently debili- Alan Siegel, Amanda J.T. Riegel, Richard Mayeux, and Lee Goldman tating side effect of chemotherapy that can make cancer treatment at the December 2018 Crown Awards not just difficult but intolerable, a tradeoff no patient should have to make. This support has brought together faculty from across departments, disciplines, and campuses to foster the collaboration ensures the Thompson Family Foundation’s continued leadership that is necessary for change and better treatments for patients. with wide-ranging philanthropy that impacts New York City and Since its inception in 1986, the Thompson Family Founda- the entire nation. tion has donated millions to medical, scientific, educational, Alan Siegel, Mr. Thompson’s longtime friend and attorney and cultural organizations in the New York metropolitan area. and a visionary and dedicated director of the Thompson Family The Thompson Family Foundation was established by Wade Foundation, died in March 2019. Columbia remains dedicated F.B. Thompson, co-founder of Thor Industries, the world’s larg- to collaborating with the Thompson Family Foundation to carry est manufacturer of recreational vehicles. The president of the out the important projects Mr. Siegel helped establish, including Thompson Family Foundation is Amanda J.T. Riegel, the late the development of effective and much-needed new treatments Mr. Thompson’s daughter, who stewards her father’s legacy and for neurodegenerative diseases.

Stewart J. Rahr Foundation Supports Eating Disorders Research

The Stewart J. Rahr Foundation, a longtime supporter of the Columbia Center for Eating Disorders in the Department of Psychiatry, amplified its generosity this year with a $2 million gift to enhance the work supported by the Rahr Eating Disorders Research Project Fund, which the foundation established in 2007. The newest gift brings the foundation’s support of the center to over $7 million and will advance important research on eating disorders. “The Stewart J. Rahr Foundation has been transformational for the Eating Disorders Program at Columbia,” said Evelyn Attia, MD, director of the center, at this year’s Gray Matters at Columbia benefit luncheon, which honored the Rahr Foundation. “The foundation’s generosity for more than 10 years, Felicia Bersh, center, accepts the Gray Matters at Columbia Award on behalf of as well as its commitment to continued support over the Stewart J. Rahr Foundation. She is photographed with Jeffrey Lieberman, chair of psychiatry, and Evelyn Attia. the next five years, is driving progress in the diagnosis, treatment, and prevention of eating disorders.”

24 ColumbiaMedicine Walentas Gift Will Advance Nearness of You Glaucoma Genetics Volunteer leader Susan Brecker David Walentas has donated $1 million to again helped to lead the biennial the Department of Ophthalmology’s glau- Nearness of You concert at coma division to help prevent unnecessary Lincoln Center in January 2019 blindness from glaucoma. The division, to support cancer research at under the direction of Jeffrey Liebmann, Columbia University Irving MD, will use the gift to lead new research Medical Center and specifically emphasizing gene discovery and the the work of Azra Raza, MD, development of new glaucoma treatments. and Siddhartha Mukherjee, MD, Points of emphasis include the genetic DPhil. The event, which is held in causes of pigmentary glaucoma, a subtype memory of Ms. Brecker’s husband, of glaucoma affecting patients in their 20s 15-time Grammy Award-winning and 30s, and the pursuit of a new treat- saxophonist Michael Brecker, ment to reverse exfoliative glaucoma, a featured performances by Patti common form of glaucoma affecting older Austin, Hugh Jackman, James patients. Both conditions are causes of Taylor, Harolyn Blackwell, and glaucoma-related blindness. Mr. Walentas Bernie Williams among others and Azra Raza and Siddhartha Mukherjee is a New York City real estate developer. raised more than $1.3 million.

Marsal Family Fund to Support Junior Faculty’s Cardiology Programs The Marsal Family Foundation has committed $1 million to establish the Marsal Family Fund in the Division of Cardiology in the Department of Medicine. This current-use fund will provide support for junior faculty in research and activities related to heart disease, particularly focused on cardiac precision medicine. Awards from the fund will be determined by the chief of the Division of Cardiology, Allan Schwartz, MD.

Faith Tenenbaum, Janet Carrus, Joseph Tenenbaum, and Cathey Romano.

Gerald and Janet Carrus Foundation Endows House Staff Fund The Gerald and Janet Carrus Foundation has committed $1,250,000 to establish an endowed fund for medical house staff training in the Department of Medicine. The endowment payout from the fund will be used to support the educational and training activities of the training program at the discretion of the program’s director. The gift honors Joseph Tenen- baum, MD, the Edgar M. Leifer Professor of Medicine at CUMC, for his many years of dedication and commitment to Bryan and Kathleen Marsal with Dorette and Peter Sacripanti educating residents and physicians in humanistic patient care.

2019 Annual Report ColumbiaMedicine 25  PHILANTHROPY NEWS

Project ALS

Project ALS has made a gift of $1.5 million pledge of $6.3 million. An effort unlike research community, filling a previously to the Project ALS Therapeutics Core in any other, this core program takes a unmet need to evaluate new drugs and the Motor Neuron Center at Columbia rational, evidence-based approach to the biological therapies for their potential to University as part of a larger multiyear development of new therapies for ALS by stop, slow, or prevent the onset and pro- utilizing the most predictive laboratory gression of ALS. models of the disease and rapidly and Project ALS, which recently marked thoroughly testing the most promising its 20th anniversary, has a long history drug candidates for safety and potential of visionary philanthropy at Columbia efficacy before they reach clinical trials. University, giving nearly $20 million for Directed by Serge Przedborski, MD, programs such as the Jenifer Estess Labo- PhD, Hynek Wichterle, PhD, and Neil ratory for Stem Cell Research and the Shneider, MD, PhD, the Project ALS Ther- ongoing ALS Families Project. “Columbia apeutics Core leverages Columbia’s many is proud to partner with Project ALS, institutional resources and works with which has advanced the field through its academic and industry partners to fast- unique and trailblazing support of open, track the best drug candidates to clinical collaborative research and team-based sci- trials in patients. Advancing the mission ence, as we continue to search together for BRIGITTE LACOMBE of Project ALS, this open and collabora- effective treatments for this devastating Jenifer Estess tive effort is a major resource for the ALS disease,” says Dr. Przedborski.

Lisa Baker’s Rheumatology Pledge Velocity Ride Will Advance Autoimmune Studies More than 800 participants came out in 2018 for Velocity, A $1 million gift from Lisa Baker will advance autoimmune Columbia’s Ride to End Cancer, which raised more than research led by the Division of Rheumatology. The gift established $1.2 million. The goal of the ride is to raise money to sup- the Lisa Baker Autoimmunity Innovation Fund to be led by Joan port cancer research and care at Columbia’s Herbert Irving Bathon, MD, chief of rheumatology. The fund will provide start-up Comprehensive Cancer Center. All funds raised support support for new and innovative research. The fund has already cancer research, patient services, and essential infrastructure contributed to Dr. Bathon’s recruitment of Adam Mor, MD, PhD, to improve treatment outcomes for cancer patients. The ride a rheumatology investigator whose research focuses on T lym- each year begins in Pomona, New York, and continues south phocytes adhesion, a key cause of autoimmune inflammation. Ms. through the scenic Hudson Valley before all riders cross the Baker is director and chief curator of the HBC Global Art Collec- George Washington Bridge and arrive at Columbia Univer- tion and a member of the medical center’s Board of Advisors. She sity Irving Medical Center for a Finish Line Festival. is a member of the New York State Council on the Arts, appointed by Gov. Andrew Cuomo, and serves on the boards of numerous art institutions, including the Herbert F. Johnson Museum of Art at Cornell University, the Solomon R. Guggenheim Photogra- phy Committee, and the Solomon R. Guggenheim International Director’s Council Committee. Her philanthropic partnership with Columbia is inspired by a desire to expand the potential of science to improve human health. Autoimmunity is poorly understood and not well funded by the National Institutes of Health, yet it is the driving force behind diseases ranging from rheumatoid arthritis to lupus to type 1 diabetes that are a leading cause of death among young and middle-age U.S. women. The Lisa Baker Autoimmunity Innovation Fund will launch new studies to advance understanding of these and other disease areas.

26 ColumbiaMedicine Second Annual Joint Symposium of the Wu Family China Center for Health Initiatives

The legacy of the late Helen and Clyde’56 Wu is growing at Columbia. The Wu Family China Center for Health Initia- tives held its second annual joint symposium in October 2018 to support collaboration in medical research and education between Columbia and Zhejiang University School of Medicine in China. The event featured 24 speakers, including 10 from Zhejiang University. The 2018 Dr. Clyde Y.C. Wu and Mrs. Helen Wu Award in International Understanding was presented to Stanley Chang, MD, the K.K. Tse and K.T. Ying Pro- fessor of Ophthalmology at Columbia, and In the front row at the 2018 joint symposium of the Wu Family China Center for Health Initiatives at Columbia VP&S are, from left, David Wu, MD; Yi Sun, MD, PhD; David Ho, MD; Roy Vagelos, Yi Sun, MD, PhD, dean of the Institute of MD; Anke Nolting, PhD; Roger Wu, MD; and Nancy Wexler, PhD. Translational Medicine and vice dean of the School of Medicine at Zhejiang University. Roger Wu, MD, and David Wu, MD, onto its faculty committee. A pilot visiting- with Columbia researchers Michael Yin, have continued to underline their parents’ scholar program was inaugurated with the MD, and Utpal Pajvani, MD, PhD. Future commitment to medicine, VP&S, and visit of Junwei Su, MD, a physician from exchanges are being planned. Columbia’s historic ties with China with the Department of Infectious Diseases of The third annual Wu Family China Cen- ongoing support of the Wu Family China the First Affiliated Hospital of Zhejiang ter joint symposium is scheduled for Octo- Center, which is welcoming David Ho, MD, University. He spent 2017-18 working ber 2019 in Zhejiang, Hangzhou, China.

Foley Commits $2.25 Million to Eye Research, Moynihan Clinical Research Fellowship Training Fellowship Program Established by the Leon Levy Foundation David Foley has pledged $2.25 million to the Department of Ophthalmology The Leon Levy Fellowship Program in the Depart- to support eye research and medical ment of Psychiatry continues to recruit, nurture, training for ophthalmologists. The and train the most promising young physician- gift will advance stem cell studies led scientists, providing them with the resources and by Tongalp Tezel, MD, director of the mentorship to expand understanding of the work- department’s vitreoretinal division. ings of the brain and how they go awry in psychi- This research seeks to restore sight to atric illness. This year, the Leon Levy Foundation patients with macular degeneration, a created an ambitious new program to focus on retinal disease that is a leading cause translational clinical research: Moynihan Clinical of vision loss in older patients. The Research Fellowships. Named by the Leon Levy gift also includes an endowment to Foundation for U.S. Sen. Daniel Patrick Moynihan, establish the Foley Clinical Retina Moynihan Fellows are MDs or MD-PhDs con- Fellowship, which will provide tinuing their training with a particular interest in training to young ophthalmologists patient-oriented research who will work under the David Foley specializing in retinal care and mentorship of leading investigators at Columbia. clinical research. Mr. Foley is a senior Their work will focus on translating pioneering sci- managing director of the Blackstone Group, a private equity firm, and ence into clinical applications for patients, building CEO of Blackstone Energy Partners. bridges between laboratories and patient care.

2019 Annual Report ColumbiaMedicine 27 2019 Research Highlights

Revealing the Role of Stem Cells in Gut Regeneration

n the laboratory of Kelley Yan, MD, and its vigorous regeneration is enabled tuitous, helping to solidify Dr. Yan’s own PhD, the Dorothy L. and Daniel H. by highly active intestinal stem cells,” scientific direction. I Silberberg Assistant Professor of Med- says Dr. Yan, whose interest in gastro- Today, the Yan Laboratory at Columbia icine in the Division of Digestive and Liver enterology and training in basic science focuses on understanding tissue renewal Diseases, studies of intestinal stem cells are research began as a medical student in the in health and disease using the intestine shedding light on the mechanisms of gut MD-PhD program at the Icahn School of as a model system to study adult stem regeneration in normal circumstances and Medicine at Mount Sinai. cell biology. under conditions of injury. As a physician- It was only a short time before Dr. To better understand the behavior scientist, Dr. Yan has set her sights on Yan began her GI fellowship and a post- of stem cells, Dr. Yan and her team use applying the discoveries made in her lab to doctoral research fellowship conducting mouse models and human organoids improve tissue healing and treatment for studies in intestinal stem cell biology at derived from patient tissues that are the many diseases that can affect the gut. Stanford University that scientists, for the grown as “mini-guts” in dishes to study “The intestinal epithelium is the most first time, had identified and isolated a intestinal stem cells as they divide to pro- rapidly self-renewing tissue in the body stem cell in the gut. The timing was for- duce more cells to endlessly replenish or repair the intestinal epithelium. “The intestine is remarkably dynamic,” says Dr. Yan. “Cells that line the intestine get replaced every few days throughout life by new cells generated by intestinal stem cells. These stem cells are the mother of all other cells. They face the most decisions. Stem cells generate more stem cells but they also generate all the mature cell types that work in nutrient absorption, hormone secretion, and interfacing with the external world. So the main question that we had was, Given all its choices, how does a stem cell actually decide what it wants to do? Is a stem cell hardwired to act in a predictable fashion or can we alter its behavior?” For Dr. Yan this is the most fundamental question in stem cell biology, with an answer that she and her team deciphered in the intestine itself. “It turns out that the intestinal stem cell takes instructional cues from its environment. In fact, it requires multiple types of signals from its surround- ings,” explains Dr. Yan. “It requires Wnts and R-spondins, which are signals released Kelley Yan by other cells in the vicinity. Wnts convey

JOHN ABBOTT a signal to the stem cells that they are in

28 ColumbiaMedicine the right location and prepares them to act. R-spondins New Markers Could a cell’s nucleus—to study the then instruct them to divide and to generate more stem Improve Chemotherapy function of a gene or try to cells. Stem cells are so powerful that two separate sig- for Breast Cancer develop a gene therapy—the nals are needed to activate their power. If either signal is In mouse models of breast antivirus system silences the lost, then ‘stemness’ is lost and a stem cell becomes just cancer, tumor-associated mac- DNA. Now, scientists may be another typical cell destined to die after a few days. rophages (TAMs) promote able to disable the antivirus “These signals not only control tissue regeneration, the growth and spread of system, based on new findings but they also are involved in the development of can- the tumor and suppress the from research led by Stephen cer,” says Dr. Yan. “Colorectal cancer, for example, immune system’s attempts to P. Goff, PhD. The researchers starts from mutations within the Wnt pathway, which fight back. A new study of identified a molecule that inac- is activated by the Wnts and R-spondins that control human breast cancer shows tivates the antiviral system in stem cell behavior. There is growing evidence that can- that TAMs also promote the cell nucleus, a finding that cer originates from a runaway stem cell that no longer human malignancy and has could have widespread impact, is reliant on environmental signals for its activity.” identified uniquely expressed from more effective gene thera- The results Dr. Yan and her colleagues published in genes in human TAMs that pies to simpler laboratory tech- Nature provided a major advance in identifying dis- may provide new therapeutic niques for scientists. The study crete and separate functions of the Wnt and R-spondin targets and diagnostic/prog- was published in Nature. proteins. “We developed tools for manipulating levels nostic markers. The study of Wnts and R-spondins that enabled us to iden- was published in Cancer Cell. Growing Hair tify their function within an animal,” says Dr. Yan. “Cancer is not just a group Two recent studies led by “Essentially, we revealed the external cues that a stem of cells, it is an evolving and Angela Christiano, PhD, cell receives from its environment to enable it to act ever changing landscape where describe novel ways to com- as a stem cell. We were very excited to discover that many actors take the stage and bat pattern hair loss in men stem cell behavior is malleable. We were able to easily play an important part,” says and women. In the first study, manipulate stem cells to make the choices we desired co-author Lisa S. Wiechmann, researchers discovered previ- once we decoded and understood their signals. This MD. “The lead, of course, is has broad implications for precision control of tissue the cancer cell, but the sup- regeneration and for treatment of cancer.” porting actors can make or The Yan Lab at Columbia is focused on bringing break the performance. By these findings into clinical practice. “My love for clinical bolstering the players that gastroenterology drew me to the science, and my goal is interfere with cancer’s success, to help patients through our discoveries,” says Dr. Yan. and suppressing those who “If we can understand the mechanisms for how the gut help, we may be able to create normally regenerates and how it regenerates under con- improved therapies.” ditions of injury, then we will actually be able to promote and enhance the process of healing after injury. Possible Way to Improve “The gut is really interesting because it has so many Gene Therapy different functions,” says Dr. Yan. “It absorbs nutri- An antivirus system that ents and it is our major interface with the outside evolved eons ago in vertebrate ously unknown cells that keep world and with the immune system. The gut is also a cells helps to defend us against mouse hair follicles in a resting powerful endocrine organ that regulates appetite and viruses. But it also vexes sci- state and show that inhibiting metabolism. I want to use stem cell biology to enhance entists. Whenever researchers the activity of these cells can all those functions.” try to insert foreign DNA into reawaken dormant follicles. In One of her long-term goals is to use stem cell biol- another study, the team created ogy to enhance the gut’s endocrine function. “We have a way to grow human hair in shown that we can manipulate stem cell behavior to a dish, which could open up influence the types of cells produced in the gut. I want hair restoration surgery to more to figure out how to make more of the types of cells people, including women, and that would optimize our metabolism to treat diseases improve the way pharmaceuti- like obesity and diabetes, which we normally think cal companies search for new of as endocrine rather than GI diseases. My vision is hair-growth drugs. The papers to ultimately tailor your gut cells to your individual were published in Cell Stem Cell needs. A designer gut, if you will.” and Nature Communications.

2019 Annual Report ColumbiaMedicine 29 2019 Research Highlights

Open Hysterectomy for social aggression. And because diseases have the opposite achievements have grown Early Cervical Cancer CA2 dysfunction has been problem—the affected tissues from excellent and rigorous A new study shows that implicated in psychiatric dis- attract the immune system— scientific research like we are women with early-stage cervi- eases, such as schizophrenia suggesting that cancer immuno- doing here at Columbia, but cal cancer who underwent and bipolar disorder, these therapies could be improved by there are still many things to minimally invasive hysterec- results provide further support taking a page from the autoim- tomy had a 65% higher risk that altered CA2 function may mune playbook. The new study of death compared with those contribute to abnormal social showed that a gene that recruits who had open surgery. The behaviors associated with such T cells to hair follicles in auto- study, which contradicts illnesses. The research, pub- immune hair loss is turned off the general assumption that lished in Nature, was led by in various types of cancer, pro- minimally invasive surgery is Steven Siegelbaum, PhD, and tecting them from the immune safer than conventional open Eric Kandel, MD. system. If the gene could be surgery, was published in turned back on, it could make the New England Journal of More Bad News for those cancers vulnerable to the Medicine. “We suspected that Couch Potatoes immune response. there might be a difference Sitting for long periods of time Emmanuelle Passegué in survival between the two has been linked to increased New Home for approaches, but the extent of risk of cardiovascular disease Stem Cell Research be done, and we need more the difference was surprising,” and early death, but not all Scientists in the Columbia basic, translational, and clini- says co-principal investigator types of sitting are equally Stem Cell Initiative moved cal research to develop more of Jason D. Wright, MD. unhealthy. A study led by into new and enhanced facili- these therapies of tomorrow.” Keith Diaz, PhD, shows that ties this year. The initiative The Brain and leisure-time sitting—while provides support and expertise Autism Linked to Social Aggression watching TV—was associ- to more than 50 laboratories Shape of Cerebellum Columbia scientists have iden- ated with a greater risk of across the university that are Structural differences in the cer- tified a brain region that regu- heart disease and death among engaged in stem cell research. ebellum may be linked to some lates social aggression. This the study’s more than 3,500 The goal is to promote the use aspects of autism spectrum dis- brain area, called CA2, is part participants. The good news: of stem cells to model human order, according to a Columbia of the hippocampus, the brain Moderate-to-vigorous exercise diseases, develop new diagnos- neuroimaging study published structure known to be criti- may reduce or eliminate the tics and therapies, and create in PLOS ONE. The researchers cal for our memory of people, harmful effects of sedentary new cells and tissues to replace found that the boys with autism places, things, and events. CA2 television watching. The study damaged, aged, or diseased had significantly lower fractal was already known to spe- published in the Journal of the body parts. Says initiative dimension—indicating a flatter cialize in social memory, the American Heart Association director Emmanuelle Passegué, surface structure—in the right ability to remember encoun- did not show the same danger PhD: “Stem cells are every- cerebellar cortex compared ters with others. These new for people who sit for long where and they are certainly at with the controls. Because the findings reveal that a single periods of time at work. the heart of modern medicine. right side of the cerebellum brain region can control both Incredible progress has already supports language processing higher order cognition, such Hair Loss Gene and been made. We can take bone in typically developing indi- as social memory, and innate, Cancer Immunotherapy marrow stem cells and treat viduals, this finding suggests instinctual behavior, such as A gene associated with an auto- many hematological and other that having a flatter cerebellar immune form of hair loss could disorders with transplantation. surface may be related to com- be exploited to improve cancer We can harness the regenera- munication difficulties in those immunotherapy, suggests a tive potential of skin’s stem with autism. “Our findings sug- Columbia mouse study pub- cells to replace the entire skin gest we may need to rethink the lished in Cell Systems. “Most of children suffering from a role of cerebellar function and cancer patients do not benefit genetic skin disorder, allowing structure in young individuals from immunotherapies because them to live. We can also use at risk for atypical brain devel- their tumors are able to evade the power of embryonic stem opment,” says senior author the immune system,” says study cells to regrow the retina and Kristina Denisova, PhD. “Early leader Angela M. Christiano, restore some level of vision life differences in perception, PhD. People with autoimmune in blind patients. All of these including timing, e.g., atypical

30 ColumbiaMedicine detection of pauses in conver- mechanism behind one of biol- Humanized Mice for Diabetes Precision Medicine sation, could shape cerebellar ogy’s long-standing myster- Mice with human immune Pilot Awards development and account for ies: why individuals carrying systems—dubbed personalized Three proposals were chosen the current structural findings identical gene mutations for a immune (PI) mice—are impor- from among 34 applications to in boys with autism.” disease have varying severity or tant tools in the study of type 1 receive awards during the sec- symptoms of the disease, a phe- diabetes. At Columbia, most of ond year of the Roy and Diana Intestine’s Role in nomenon called variable pen- the bone marrow donors for PI Vagelos Precision Medicine Organ Transplantation etrance. Reporting in Nature mice are type 1 diabetes patients Pilot Awards. The awards pro- The human intestine may pro- Genetics, the researchers at the Naomi Berrie Diabetes vide seed money for research vide up to 10% of blood cells provide evidence for modified Center. Each bone marrow into new ideas in precision in circulation from its own penetrance, in which genetic aspiration creates up to 30 PI medicine. The three proposals reservoir of blood-forming variants that regulate gene mice, giving researchers an cover epilepsy, neurooncology, stem cells, a Columbia study activity modify the disease opportunity to study everything and tissue engineering. found. Scientists previously risk caused by protein-coding from the genesis to the genetics thought that blood cells are gene variants. The study links of human type 1 diabetes and • “Development of novel created exclusively in the modified penetrance to specific other autoimmune diseases, therapies for STXBP1 bone marrow from a special diseases at the genomewide says Megan Sykes, MD. Her encephalopathy,” Michael population of hematopoietic level, which has implications team, which described the PI Boland, PhD, Neurology stem cells, but the intestine’s for future prediction of the mice in Science Translational and Institute for Genomic reservoir of blood-forming severity of serious diseases such Medicine, is working with the Medicine; Wayne Frankel, stem cells was discovered when as cancer and autism spectrum Berrie Center to recruit bone PhD, Genetics & Develop- researchers led by Megan disorder. Tuuli Lappalainen, marrow donors both with and ment; Sophie Colombo, PhD, Sykes, MD, noticed that PhD, led the study. without type 1 diabetes to study associate research scientist patients who had received the causes of autoimmunity in the Institute for Genomic intestinal transplants also had Microglia and Alzheimer’s using PI mice. Medicine; and Sabrina Petri, the donor’s blood cells. The in Elderly Brains staff associate in the Institute researchers tracked the donor’s Microglia, the resident Alzheimer’s Drug Not for Genomic Medicine immune cells of the brain, Effective in Depressed have important roles in brain Results from a clinical trial • “Molecular characterization health, but little is known conducted at Columbia of gliomas under immuno- about the regulation and and Duke suggest that the therapy,” Raul Rabadan consequences of microglial Alzheimer’s drug donepezil PhD, Biomedical Informatics activation in the aging human does not improve cognitive and Systems Biology; Fabio brain. Researchers, including performance in people at risk Iwamoto, MD, Neurology; Philip De Jager, MD, PhD, and for Alzheimer’s disease who and Junfei Zhao, PhD, asso- other Columbia investigators, also have depression. The ciate research scientist in blood cells back to their reported in Nature Commu- study’s findings, published Systems Biology source: hematopoietic stem nications that the proportion in the American Journal of cells in the donated intestine. of morphologically activated Geriatric Psychiatry, run coun- • “Exploiting the basic mecha- The blood cells created from microglia (PAM) in postmor- ter to the common practice nism of Notch activation to cells in the donor’s intestine tem cortical tissue is strongly of treating people who have develop new diagnostic, thera- also may be beneficial to the associated with β-amyloid, tau- both depression and cognitive peutic, and tissue engineering transplant recipient. The more related neuropathology, and impairment with cholinesterase tools for precision medicine,” donor blood cells a patient had the rate of cognitive decline. inhibitors like donepezil. “It is Gary Struhl, PhD, and Paul in circulation, the less likely Effect sizes for PAM measures critical to find effective thera- Langridge, PhD, Genetics & that person was to reject the are substantial, comparable to pies for this population,” says Development (in Neurosci- transplant. The research was that of APOE ε4, the strongest study author D.P. Devanand, ence) and Zuckerman Mind published in Cell Stem Cell. genetic risk factor for Alzheim- MD. “Both late-life depres- Brain Behavior Institute er’s disease, and mediation sion and mild memory loss Genetic Mutations and Disease models support an upstream are established risk factors Neurons with Clean Habits Researchers at Columbia and role for microglial activation for dementia, and when they Resist Alzheimer’s the New York Genome Center in Alzheimer’s disease via accu- co-occur, the risk for future Some neurons in the brain pro- have uncovered a molecular mulation of tau. dementia is even higher.” tect themselves from Alzheim-

2019 Annual Report ColumbiaMedicine 31 2019 Research Highlights er’s with a cellular cleaning SCAPE’s ability to reveal the to certain pieces of information system that sweeps away toxic inner workings of the nervous and invest in acquiring them. tau proteins associated with the system in unprecedented detail. Neuroscience tells us that there disease, according to a study By creating 3D, live-action are limits to our attention, published in Nature Neurosci- images of nerve cells in larvae says Dr. Gottlieb. Our brains ence. The study was led by as the animals crawled, SCAPE bias us toward certain sources Columbia’s Karen Duff, PhD, allowed the researchers to see of information by releasing and coauthors from Ohio State how those cells along the body chemicals that reward us for University and the University wall reported movements back focusing on certain things. By of Cambridge. Dr. Duff and to the brain. “We know that the Memory Storage combining the mathematical her colleagues also identified brain receives sensory signals A new study by Columbia neu- models of economics and the a protein, called BAG3, that though electrical pulses passed roscientists provides evidence brain-monitoring techniques along neurons, but we didn’t that learning and memory are of neuroscience, the professors understand why some kinds of not relegated to a few select hope to gain greater insights neurons are located in specific regions but instead may per- into both of their fields. They positions or how particular meate the brain. The research, published the initial results signaling patterns represented published in Cell Reports, of this work—revealing the different movements,” says Dr. reported that a primitive brain diversity of motives that guide Grueber, the paper’s co-senior region known for processing human curiosity—in Nature author. “To understand this basic sensory information also Human Behavior. process, we needed to know can guide complex feats of what signals the neurons are mental activity. In mice, the Studying Memory with the sending while the larva crawled researchers found, the somato- Help of Chickadees around unconstrained.” sensory cortex plays a key role Chickadees have phenomenal controls the cleaning system: in reward learning, a sophis- memories: A single bird can, “If we can develop therapies to Colliding Genomes Cause ticated type of learning that in one day, store as many as support these natural defense Transplant Failure allows the brain to associate 7,000 bits of food—each in a mechanisms and stop tau from A genomic collision could an action with a pleasurable different spot—and remem- accumulating, we might be able explain why many kidney outcome, such as connecting ber many of those locations to prevent, or at least slow, the transplants fail, even when our work to a paycheck or an for weeks. That natural abil- development of Alzheimer’s donors and recipients are A+ to studying for a test. “Our ity caught the attention of and other tau-related neuro thought to be well matched, brains are masterful at making Dmitriy Aronov, PhD, who degenerative diseases.” according to a Columbia connections, or associations, thinks the birds will bring a study published in the New between seemingly disparate fresh approach to studying Fruit Fly Nerve Cells: Live! England Journal of Medi- pieces of information, but how brains create memories. Columbia neuroscientists cine. The genomic collision where those associations are In many laboratory studies and engineers have created is a genetic incompatibility stored has remained an unre- of memory, rats or mice are 3D videos of individual nerve between kidney donor and solved question,” says Randy trained to perform certain cells moving, stretching, and recipient, causing the recipi- Bruno, PhD, the paper’s senior tasks. “The kind of memory switching on inside fruit fly ent to mount an immune author. The new research involved in learning these larvae. Data gleaned from the attack against a protein on shows that these associations tasks is different from the videos reveal how nerve cells the donated kidney. The find- can be made in the primary kind of memories we form called proprioceptive neurons ings could lead to more precise sensory cortex, which has not about our daily experiences, work together to help the body matching between donors and previously been believed to like remembering a time you sense where it is in space. The patients. The same genomic have that capacity. researchers harnessed SCAPE, a collision may potentially occur cutting-edge microscope devel- in heart, liver, and lung trans- Diverse Motives for oped at Columbia that images plants. “This project illustrates Human Curiosity neurons at lightning fast speeds. how genetic analysis is empow- Neuroscientist Jacqueline Gott- Findings published in Cur- ering clinical care by enabling lieb, PhD, and a Columbia eco- rent Biology from the labs of better matching,” say senior nomics professor are working Elizabeth Hillman, PhD, and authors Ali G. Gharavi, MD, together to understand what Wesley Grueber, PhD, illustrate and Krzysztof Kiryluk, MD. motivates us to pay attention

32 ColumbiaMedicine saw a shooting star or where ate—higher levels of the signal. patients, on respiratory func- ries but also for discriminating you put your keys,” says Dr. Relatively weaker “loser” tion. Results of the study of between safe and dangerous Aronov. As a result, in rodent neighbors cannot tolerate the 744 ALS patients internation- contexts,” says study senior models it is difficult to link the levels released by healthier ally were published in the leader Rene Hen, PhD. The process of storing and recalling cells and die. If a cell plays fair, journal Amyotrophic Lateral findings, published in Science, memories to specific, neural it will produce only an amount Sclerosis and Frontotemporal may help researchers develop activity within the hippocam- of killing signal that it can tol- Degeneration. Although the new treatments for memory loss pus itself. “By caching and erate. But some cells can cheat study did not show a meaning- then retrieving food items, the the system, the study found, ful effect of tirasemtiv on slow birds are effectively telling the by producing high levels of the vital capacity, subanalyses observer what they remember death signal, while simultane- suggest that tirasemtiv had a and when,” which may allow ously shutting down its ability biological effect and the drug researchers to better under- to respond to the death signal. class remains worthy of further stand how the hippocampus These same mechanisms may study. Dr. Andrews led early creates spontaneous memories. help explain why emergent phase studies that previously cancer cells get a foothold found that a similar-acting Those Cheatin’ Cells to establish territory within drug, reldesemtiv, has the and mood disorders and may During development, cells healthy tissues. potential to produce a larger explain why electroconvulsive compete with each other for pharmacodynamic effect than therapy works for many patients high stakes. Within a grow- Gene Identification and tirasemtiv. Results from a with severe depression. ing tissue, the stronger “win- Disease Discovery recent trial of reldesemtiv sug- ner” cells expand to take up Wendy Chung, MD, PhD, and gest that patients who received Dynamic Spatial Structure of a team in Indiana published the drug declined less on all Human Seizures a landmark study identifying outcomes measured than The increasing use of micro- the first human mutations in patients receiving placebo with electrodes in epilepsy sur- the deoxyhypusine synthase improved tolerability. gery has made it possible to (DHPS) gene. The study iden- apply principles derived from tified five children from four Young Neurons: Few decades of laboratory research unrelated families who all but Mighty to the problem of mapping developed similar if not iden- Though few in number, neu- the spatiotemporal structure tical symptoms of unknown rons that are created in the of human focal seizures and cause, until the identification brain during adulthood during characterizing the correspond- of common DHPS mutations. neurogenesis have an outsized ing EEG signatures. Catherine The research was published impact on mood and memory Schevon, MD, PhD, and col- in the American Journal because of their unparalleled leagues have provided a com- more space in the tissue and of Human Genetics. “The networking and communica- prehensive review of the key the weaker “loser” cells are families affected by this disease tion abilities, according to a spatial and temporal properties eliminated. These interactions, have been so supportive of our study by scientists at Columbia, of seizure activity in humans, known as cell competition, are work, which was essential to Hunter College, and NYU. The at both the microscale and thought to rid tissues of cells the success of the study,” says study, conducted in adult mice, macroscale. The new frame- that are potentially dangerous Dr. Chung. “In the short time showed that unlike other neu- work, published in Neurobiol- to the tissue. Cells have to rec- we’ve been working together, rons in the brain, young neurons ogy of Disease, is important ognize differences among each the DHPS Foundation has also can directly connect with their for investigating open ques- other for competitive interac- been formed, which continues mature counterparts and send tions in ictogenesis and how tions to work. A study led by to help get the word out and out tailored messages depend- this model can inform targeted Laura Johnston, PhD, and support other families living ing on the source of incoming epilepsy therapies. published in Developmental with this disease.” information. “Without these Cell found that cells produce cells, we would be incapable Sensing Brain Signals and emit “death signals” rela- ALS Drug Study of distinguishing similar situa- Jennifer Gelinas, MD, PhD, tive to their own ability to tol- A phase 3 study led by Jinsy tions from each other, a process and a Columbia engineering erate the signal. In a group of Andrews, MD, studied the sometimes termed pattern faculty member, Dion Kho- cells, some cells “win” because efficacy of tirasemtiv, a new separation, which is critical not dagholy, PhD, developed the they release—and can toler- class of drug tested in ALS only for forming novel memo- first biocompatible ion driven

2019 Annual Report ColumbiaMedicine 33 2019 Research Highlights transistor that is fast enough nant mice. In another study chemistry: low serotonin. The partum period has been identi- to enable real-time signal sens- published in EMBO Reports, study, conducted in mice and fied as a particularly vulnerable ing and stimulation of brain Dr. Han found that the same published in Gastroenterol- time. Some studies in other signals. The internal-ion-gated bacterium can accelerate the ogy, shows that a shortage of countries suggest maternal organic electrochemical tran- growth of colon cancer and serotonin in the neurons of suicide is much more common sistor—IGT—provides a min- exacerbate cancer progression. the gut can cause constipa- than previously thought and iaturized, soft, conformable tion, just as a serotonin short- even a leading cause of death.” interface with human skin, Statistics and What age in the brain can lead to using local amplification to Your Brain Knows depression. Led by Kara Gross Ciliates Help Us Understand record high quality neural sig- Brains have a remarkable abil- Margolis, MD, at Columbia Our Genome nals suitable for advanced data ity to spot new objects and with researchers at Duke, A new study of a single-celled processing. This could lead to figure out how to manipulate the researchers also found eukaryote with 16,000 tiny safer, smaller, and smarter bio- them. Scientists have long an experimental drug treat- chromosomes may shed light electronic devices that could be believed that the brain accom- ment developed by two of on a recently discovered fea- implanted in humans over long plishes this by methodically the study’s co-authors raised ture of the human genome. periods of time, the researchers interpreting visual and tex- serotonin levels in the gut’s Methyladenine, or 6mA—a reported in Science Advances. tural cues, such as an object’s neurons and alleviated consti- modification of DNA common edges or boundaries. But a pation in the mice. The slow- in Oxytricha trifallax—has Mice, Omega-3 Fatty Acids, Columbia study suggests that release drug delivery of 5-HTP, only recently been found in and Miscarriages the human brain requires only a precursor of serotonin, multicellular organisms, with A new study in mice reveals a tiny bit of information, as works in part by increasing the some studies suggesting a role that omega-3s, a type of fat well as previous experience, number of GI neurons in adult in human disease and develop- found in fish oil, reduce fetal to calculate a complete mental mice. The study is one of the ment. Finding the enzymes that and neonatal deaths. Accord- representation of a new object. first to show that neurogenesis lay down the methyl marks will These results help to explain in the gut is possible. be critical to understanding the mental mathematics that what 6mA is doing in Oxytri- enable us to easily know what Maternal Mortality Assessment cha and other organisms, but a novel object looks like sim- Maternal mortality has more the enzymes have been difficult ply by touching it or imagine than doubled in the United to identify. The research pub- the way an object feels from States since 1990, and the lished in Cell reveals how 6mA sight alone. The study, led United States has the highest marks are made to the Oxytri- by researchers at Columbia, rate among wealthier nations. cha genome and suggests why the University of Cambridge, But the rate may be even the enzymes have been hard and Central European Uni- higher if deaths from suicide to find: Evolution recruited versity and reported in the and accidental overdoses are journal eLife, illustrates the counted, according to a new brain’s natural power to learn report from Columbia research- quickly and generalize. “Our ers who say that rising rates brains’ ability to single out one of opioid use, depression, and ing to research led by Yiping object from many by touch is maternal mortality are closely Han, PhD, and published in a broadly used skill and key connected. “Most estimates of JCI Insight, compounds found to our ability to interact with maternal mortality only report in fish oil prevent pregnancy the world,” says neuroscien- deaths caused by complications complications, including pre- tist Daniel Wolpert, PhD, the of childbirth, such as stroke, term birth, neonatal death, study’s co-senior author. preeclampsia, or hemorrhage,” and stillbirth, in mice when says Kimberly Mangla, MD, the complications are caused Moody Gut and Depression who with Catherine Monk, by a common oral bacteria, For people with depression, PhD, coauthored the review two DNA-binding proteins F. nucleatum. The experiments gastrointestinal distress is published in the American Jour- to transform an enzyme that showed that supplements con- common, and a Columbia nal of Obstetrics and Gynecol- normally methylates RNA taining omega-3 fatty acids study suggests that for some, ogy. “Yet pregnancy does not into a complex that methylates also inhibited inflammation the two conditions arise from protect against depression and DNA. Except for the lack of and bacterial growth in preg- the same glitch in neuron substance abuse, and the post- centromeres, Oxytricha’s chro-

34 ColumbiaMedicine mosomes have everything we looked. In their latest study, elination have genetic predis- by great distances could be reg- have—including telomeres, his- the researchers analyzed data positions to abnormal white ulated in coordination. A study tones, and base modifications— from 15,030 people, includ- matter development. led by Stavros Lomvardas, PhD, so they provide elegant models ing many Caribbean Hispanic found the answer. When a neu- for the study of chromatin participants in the Washington Albuminuria and ron makes the receptor choice, biology and how DNA is pack- Heights, Hamilton Heights, Respiratory Diseases its genome rearranges itself aged,” says the study’s senior Inwood Community Aging A large-scale, prospective study into a multichromosomal hub author Laura Landweber, PhD, Project. Their work, published led by Elizabeth Oelsner, MD, that brings the receptor genes who has been studying Oxytri- in JAMA Neurology, identi- provides strong support for cha for two decades and previ- fied PINX1, a gene involved the endothelial hypothesis of ously uncovered Oxytricha’s in telomere integrity, and chronic obstructive pulmonary 16,000 chromosomes. TREM2, a gene that codes for disease (COPD). Preliminary an immune receptor found in studies suggested that albumin- Clinical Trial for microglia, associated with the uria, an indicator of endothelial Progressive MS late-onset form of the disease damage, is associated with Columbia is a clinical site for in both Caribbean Hispanics COPD development, but the NeuroNEXT, the Network for and non-Hispanic whites. The studies were small and incon- Excellence in Neuroscience finding could help researchers clusive. The new study followed Clinical Trials, which was cre- develop genetic tests that bet- 14,213 people over time and ated to conduct studies of treat- ter predict Alzheimer’s risk and found that greater albuminuria ments for neurological diseases identify potential new treat- was associated with accelerated through partnerships with aca- ments. The research team was decline in lung function and together. The findings were pub- demia, private foundations, and led by Richard Mayeux, MD. increased rates of respiratory lished in Nature, and in a com- industry. Columbia’s Claire S. disease events. Current medi- mentary that accompanied the Riley, MD, was coauthor of a Milestones in Children with MS cal therapies for COPD and article, an expert said, “These New England Journal of Medi- Research published in the other chronic lower respira- exciting findings show that cine paper about a phase 2 trial Journal of Child Neurology tory disease target the airways. interchromosomal interactions of ibudilast for progressive MS, has shown that children who The new study suggests that can have a determinant role in which has limited treatment develop pediatric multiple scle- endothelial and microvascular regulating gene expression.” options. Ibudilast was associ- rosis are not delayed, relative mechanisms may be promising Dr. Lomvardas speculates that ated with slower progression to healthy controls, in acquisi- targets for COPD prevention such interactions may cause the of brain atrophy than placebo, tion of the early motor and ver- and treatment. The study was genomic translocations that are though with higher rates of bal developmental milestones published in the American known to cause cancer. gastrointestinal side effects, of walking independently and Journal of Respiratory and headache, and depression. using two-word phrases, and Critical Care Medicine. Southern Diet Helps Fuel About a dozen drugs have been children with MS were less Hypertension Disparity approved for the treatment of likely to be delayed in walking How the Nose Knows The high prevalence of relapsing-remitting MS, but few independently. Results suggest The human olfactory system hypertension among African therapies are available for the that in patients with multiple can distinguish 1 trillion differ- American adults is a major progressive stage of the disease. sclerosis diagnosed in child- ent scents, a feat it accomplishes contributor to disparities in life hood, the disease might not with just several hundred dif- expectancy, but the causes for Late-Onset Alzheimer’s have extended into the infancy ferent odor receptors. To make higher incidence of hyperten- and Ethnicity and toddler period. It is possi- such fine distinctions with so sion are unknown. A new anal- Alzheimer’s researchers at ble, say the researchers, includ- few receptors, each of the 10 ysis, published in JAMA, found Columbia are using next- ing Wendy Vargas, MD, that million olfactory neurons in the that adherence to a Southern generation sequencing methods time to walking independently nose chooses—at random—just diet was the biggest factor in to uncover rare genetic vari- and using two-word phrases one receptor to express. How explaining the difference in ants that are hard to find but are not sensitive enough mea- each neuron makes the choice hypertension between black have a big impact on disease sures to detect subtle changes has perplexed scientists, because and white participants for both risk. Rare variants tend to be in toddlers. These data are in the receptor genes are spread men and women, accounting ethnicity specific, so lack of contrast with reports that some throughout the genome on dif- for 52% of the excess risk diversity in genetic studies can patients who go on to develop ferent chromosomes: It seemed among black men and 29% of cause some genes to be over- multiple sclerosis-like demy- impossible that genes separated the excess risk among black

2019 Annual Report ColumbiaMedicine 35 2019 Research Highlights women. Other factors included Beyond the Science of Genetics this year to lead the Division of emerging genomic technologies, the dietary ratio of sodium to Medical anthropologist San- Ethics in the new Department and she has published widely potassium and education level dra Soo-Jin Lee, PhD, is co-PI of Medical Humanities & Eth- in genomics, medical, bioethics, and, among women, waist cir- on a $7.1 million grant from ics. The new Center for ELSI and social science literature on cumference and BMI. Under- the National Human Genome Resources and Analysis will be patient consent, governance of standing the reasons behind the Research Institute to develop a the first of its kind and build on data and biological samples, disparity could guide efforts national center on ethical, legal, Columbia’s foundation of ELSI and commercialization of to prevent hypertension and and social implications (ELSI) research, including work by biotechnology and academic reduce the difference in mortal- of genetics. Dr. Lee will co-lead Paul Appelbaum, MD, Wendy entrepreneurship. Recent pub- ity between black and white the center with a colleague at Chung, MD, PhD, and George lications have focused on ethics populations. The research team Stanford University, where Dr. Hripcsak, MD. Dr. Lee’s work in precision medicine research included Columbia’s Jennifer J. Lee spent nearly two decades focuses on the sociocultural and the importance of increas- Manly, PhD. before being recruited to VP&S and ethical dimensions of ing diversity in research.

2019 Education Highlights

Community Service Formalized with New Office

VP&S Office of Community 1980, Dr. Lantigua has been a dean’s spe- Service Programs has been cre- cial adviser for community health affairs A ated to expand the commitment since 2011. His clinical and research inter- of VP&S to community service, with a est has focused on promoting the health of focus on the Washington Heights/Inwood the diverse community in upper Manhat- community, Upper Manhattan, and parts tan and improving access to care for the of the Bronx. community’s growing aging population. The new office will build upon the The recently established Service-Learn- school’s many ongoing efforts to improve ing Program, which was created as part the health and education of adults and of the VP&S strategic plan, will function children through a range of community within the Office of Community Service Rafael Lantigua engagement and health promotion activi- Programs to develop and coordinate com- ties, in part by developing new opportu- munity service-learning opportunities for The new VP&S Office of Community nities made possible by the creation of faculty, students, and staff. Service Programs will be housed in the Haven Plaza, which opened during the Dr. Lantigua also will facilitate the cre- medical school within the Office of Gov- summer of 2019. ation of a new VP&S Academy of Com- ernment and Community Affairs, but it The founding director of the Office of munity and Public Service to recognize will be closely aligned with community Community Service Programs is Rafael medical school faculty who make substan- programs at the Mailman School of Pub- Lantigua, MD, professor of medicine at tial contributions to community and public lic Health, School of Nursing, College of CUMC, who will have the additional title health. The academy will be modeled after Dental Medicine, and the New York State of associate dean for community service in two other VP&S academies, the Virginia Psychiatric Institute. Programming for the VP&S. A native of the Dominican Repub- Apgar Academy of Medical Educators and office will include health fairs and student lic and faculty member at Columbia since the Academy of Clinical Excellence. learning opportunities.

36 ColumbiaMedicine Mentoring Pregnant Teens

n a cozy space near 174th Street, eration; a mentee is always paired with a a small group of female medical mentor who speaks her language. I students and teenage mothers-to-be “Mentor” may be a misnomer, says Ms. gather to share information, hopes and Wadden. “We have never been in their situ- dreams, and looming fears regarding a ation. One of the first questions the girls ask soon to be life-changing event. us is if we have ever been pregnant.” The gathering is part of APOYO, an On Wednesday evenings in the fall, the adolescent pregnancy program in Wash- group gathers to discuss specific topics ington Heights run by VP&S medical with an expert. The discussion is infor- students. The program began in 2012 as mal and gives the adolescents space to a project by a VP&S student in the Daniel ask questions and voice concerns. Top- Noyes Brown Primary Care Scholars Pro- ics include everything from what bodily gram and became a student-run outreach changes one can expect during pregnancy, program within the P&S Club in 2015. nutritional advice, and delivery options APOYO, a Spanish word for “support,” is to inter-relationship and/or domestic vio- exactly its mission: to empower, educate, lence, birth control choices, breastfeeding, and offer emotional support specifically and baby care. “We even have a psychia- Elena Wadden’22 and Natasha Natarajan’22 tailored to teenage motherhood. trist who comes in to discuss postpartum Natasha Natarajan’22 and Elena Wad- depression,” says Ms. Wadden. Natarajan. “In medical school, patient den’22 co-chair the organization. “We Many of the teenagers face a lack of contact is very brief. You’ll see the patient pair each teenager with a student mentor financial resources, and APOYO connects maybe once. Through this program, I to keep it intimate,” says Ms. Wadden. the mothers-to-be with programs available am able to witness a young woman go The number of mentors accepted each to them. For instance, the girls qualify through many transitions: pregnancy, year depends on how many adolescents for a doula companion after delivery, and delivery, and followup after delivery. It are interested. Last year the organiza- another organization provides free cribs. makes me aware that she has a home life tion mentored six pregnant adolescents. “Participating in APOYO has changed separate from when we see her—I see her Language barriers are taken into consid- the way I look at patient care,” says Ms. more holistically.”

STAR-U within the Taub Institute for foot lobby, now known as the The Summer of Transla- Research on Alzheimer’s Disease Schaefer Awards Gallery. tional Aging Research for and the Aging Brain. The pro- Undergraduates—STAR U— gram strives to increase diversity Integrated Spine Fellowship welcomed its first students in the field of neuroscience and A new integrated orthopedic during the summer of 2019. aging by providing mentorship and neurosurgery spine fellow- The program is funded by an and training for young scientists ship program offers orthopedic R25 grant from the National who have unique experiences and neurosurgery fellows for- Institute on Aging and housed and perspectives. mal rotations with both orthopedic surgeons and neurological Alumni Auditorium arms, charging stations, and surgery spine surgeons. The Renovation USB ports. The second phase one-year fellowship offers train- An Alumni Auditorium renova- enhanced the auditorium with ing in all aspects of the cervical, tion has reimagined the shared a soaring ceiling, LED lights, thoracic, and lumbar spine, learning and assembly space. high-end acoustic integrated from degenerative diseases and The first phase of the renova- walls, and a new audiovisual deformity to trauma injuries tion updated the 6,464-square- system. The second phase also and tumors. Fellows perform foot auditorium with 648 unveiled the three-story glass surgical cases that include new seats that feature table façade and the 3,000-square- complex scoliosis and kyphosis

2019 Annual Report ColumbiaMedicine 37 2019 Education Highlights corrections with three-column care professionals. The speaker their research with faculty, col- osteotomies and minimally at the 2019 ceremony, Emeritus leagues, and fellow students at invasive procedures for cervical Professor Gerald E. Thomson, the annual Student Research and lumbar disc disease. MD, urged the Class of 2023 Day. They described their find- to put patients first, calling the ings to judges, and awards were White Coat Anniversary values of medical ethics and given for top work in four cat- The Class of 2022 was wel- medical professionalism “supe- egories: research year, scholarly comed to VP&S in August rior guides for physicians.” projects, summer research, and 2018 at the 25th anniversary MD-PhD research. of the White Coat Ceremony. A New “New” Curriculum ence gives participating students Even though the current MD an opportunity to network, Learning to be curriculum, unveiled in 2009 learn about free clinics at other Education Researchers for the incoming Class of 2013, schools, and address unique or Faculty members from is now 10 years old, it is still shared challenges. Columbia throughout the medical center referred to as “the new curricu- has five student-run clinics: the participated in the first year lum” because of its sweeping Human Rights Initiative Asy- of the Medical Education changes for VP&S students. The lum Clinic, Columbia-Harlem Research Intensive Train- curriculum, which other schools Homeless Medical Partnership, ing (MERIT) program. A have emulated, is strong but Columbia Student Medical graduation event in June 2019 changes in educational resources Outreach, Columbia University allowed the 22 faculty gradu- and health care delivery over the Harm Reduction Clinic, and ates to display and present the Members of the class were past decade have prompted the Q Clinic: Primary Care for the cloaked in white coats and need for a review. The Vagelos LGBTQ Community. Keynote recited the Hippocratic Oath Education Center and its simu- speaker at this year’s confer- for the first time in the presence lation center did not exist when ence was 2011 VP&S graduate of families and friends, just as the current curriculum was Danny Neghassi, who urged more than 4,000 new students conceived, and new educational students to become advocates have done every year since the priorities, such as integrated for underserved communities. ceremony began in 1993. The curricula, interprofessional Dr. Neghassi volunteered with a late Arnold P. Gold, MD, cre- education, programmatic assess- clinic as a medical student and ated the ceremony to reinforce ment, and competency-based is now a family physician at a commitment to humanistic education, provide opportunities Hudson River HealthCare and research proposals developed practice. He also founded the that were inaccessible a decade instructor in clinical medicine in in the program. The MERIT Arnold P. Gold Foundation, ago. The comprehensive reas- the Center for Family and Com- program helps participants which has developed programs sessment of the curriculum as a munity Medicine at Columbia. hone their core skills in that support the education and whole will focus primarily on hypothesis generation, research training of humanistic health the first 18 months of medical Student Research design, methods, data analysis, school. Priorities for curriculum With topics ranging from program evaluation, and schol- renewal will be identified by epilepsy to electronic health arly writing to earn a Medical faculty working groups during records to Alzheimer’s disease, Education Research Certificate the 2019-20 academic year with 76 VP&S students shared from the Association of Ameri- a prototype for discussion with can Medical Colleges. the new incoming dean ready by late spring of next year. MD-PhD Student Research Research posters presented Conference for at the 14th annual MD-PhD Student-Run Clinics Student Research Symposium Columbia’s student-run clin- covered topics ranging from ics hosted this year’s New neurological diseases to stem York Student-Run Free Clinics cells. The symposium featured Regional Conference for more the work of 34 aspiring physi- than 120 students from 10 med- cian-scientists. A 2013 MD-PhD Gerald Thomson ical schools. The annual confer- graduate, Priya Rajasethupathy,

38 ColumbiaMedicine gave a lecture titled “The Evolv- departments who are full-time About the MD Class of 2019 ing Memory Trace.” Dr. Rajas- VP&S faculty. The program is ethupathy is the Jonathan M. led by Amanda Bergner, MS, Members of the VP&S Class of 2019— Nelson Family Assistant Profes- CGC, associate professor of the largest number of graduates since genetic counseling (in genetics 1992—received MD and PhD degrees & development). in a May ceremony attended by families and friends. The ceremony honored Interprofessionalism 172 students who received MD degrees and 60 students who Classes at VP&S and other received biomedical sciences PhD degrees from Columbia’s medical center schools were Graduate School of Arts and Sciences. A few months earlier, at cancelled April 2 and replaced the annual residency match, 166 students matched to residen- with workshops designed to cies in internal medicine, pediatrics, psychiatry, obstetrics & foster teamwork and respect gynecology, ophthalmology, dermatology, and other specialties. among all health care professionals. Nearly 1,400 students MORE ABOUT THE MD CLASS OF 2019: sor and head of the Laboratory participated in the second 50% women of Neural Dynamics and Cogni- annual Interprofessional Edu- 20 MD-PhD graduates tion at Rockefeller University. cation Day of Action, which Columbia’s MD-PhD program included more than 75 work- 3 graduates in the three-year PhD to MD program prepares students to become shops and lectures led by 1 graduate from the MD/MPH dual degree program biomedical leaders by combin- close to 200 faculty members, 5 received degrees in the master of science in biomedical ing clinical and scientific educa- students, and community orga- science program tion and offering faculty-student nizations. This year’s event— collaboration in research labora- organized around the theme of 4 received MD/MBA degrees tories across the University. social justice—was more closely 2 received MD/DDS degrees in the oral and maxillofacial integrated with the curricula of surgery program Master’s Degree in each school and program. Last 1 student received a master’s degree in biostatistics Genetic Counseling year’s IPE Day of Action led VP&S welcomed its first stu- to the creation of IPE Nights, 1 student received a master of education degree dents into a two-year program a monthly interprofessional 1 student received a master of fine arts degree in that will earn them master forum where students organize creative writing of science degrees in genetic workshops. “Based on that counseling. The 12 students experience, we included student- 23 students did an additional year of research in the class of 2021 come led workshops in this year’s 34% of the class took extra time for research or for a from across the United States, event, and I think they were dual degree Canada, and Israel. Only one More than a third of the class volunteered as a senior of the students is starting the student adviser for the class below them program directly from under- graduate school; the others Eight couples participated in the match, six of them are coming from diverse work in-house couples experiences. The VP&S pro- 24% of the graduates went abroad for their first-year gram was one of 49 programs summer experience, global health electives, scholarly project, that participated in a match or for master’s degrees, mostly to developing countries process during the spring. 23% matched at Columbia for part or all of their VP&S received an above postgraduate training average number of applications for a new program and some of the most successful,” 47% will remain in New York City interviewed approximately 60 says Rita Charon, MD, PhD, Six babies were born during medical school applicants. The program has a chair of medical humanities & 11 graduates were married during medical school, including broad faculty who will teach in ethics at VP&S, who started two in-house couples, and several more students are engaged the classroom and the clinics, Columbia Commons IPE, the with the majority being genetic Columbiawide unit that spon- Many students ran full or half marathons and participated counselors from a variety of sors the annual Day of Action. in triathlons

20192019 Annual Annual Report Report Columbia ColumbiaMedicineMedicine 39 39 2019 Clinical Highlights

A Better Prenatal Test

hole exome sequencing may To address this, some clinicians have By sequencing the genomes of the par- be the next improvement in begun offering whole exome sequencing, a ents and fetuses in the 234 pregnancies, W prenatal testing, a Lancet technique that reads the smallest details of the researchers were able to diagnose study by VP&S researchers suggests. all protein-coding genes in the genome, to an additional 10% of the fetuses with a The new kind of prenatal genetic testing obtain a genetic diagnosis of undiagnosed known genetic disorder. Another 20% of can improve obstetricians’ ability to diag- abnormalities. However, only a few stud- the fetuses had gene sequence signatures nose the underlying causes of fetal anoma- ies have looked at the utility of the tech- that were suggestive, though not defini- lies found during prenatal ultrasounds, but nique as a prenatal diagnostic tool, and tive, of a genetic disorder. the results require expert interpretation. much of the science connecting gene vari- The study was led by Ronald Wapner, The new test would be important for the ants to fetal anomalies remains unsettled. MD, director of reproductive genetics at approximately 3% of pregnancies that have The Columbia researchers enrolled Columbia’s Institute for Genomic Medi- an ultrasound that reveals a significant fetal 234 pregnant women who had abnormal cine (IGM) and vice chair of research in physical anomaly. Knowing the cause of the ultrasound findings but whose standard obstetrics & gynecology, and David Gold- anomaly can help doctors and parents be genetic tests were negative. “If an anomaly stein, PhD, director of the IGM. better prepared, both during the pregnancy is detected at ultrasound, the current “Based on our findings, whole exome and after delivery, but doctors sometimes standard of care is to obtain a sample of sequencing could serve as a valuable addi- cannot identify the underlying cause. Stan- amniotic fluid and perform karyotyping to tion to standard prenatal genetic tests, dard genetic tests are able to identify the determine if the fetus has the right number with the potential to improve perinatal cause in fewer than half of such anomalies. of chromosomes and if small regions are care for infants with genetic conditions When a cause cannot be identified, fam- missing,” says Vimla Aggarwal, MBBS, and ease parents’ fears by offering a clear ilies often embark on a diagnostic odyssey director of Columbia’s precision genomics diagnosis,” says Dr. Wapner, a maternal- that can last for years until the exact cause laboratory and an author of the study. But fetal medicine expert. can be determined, leaving them without this test can only pinpoint the underlying Since the science surrounding genomic information about whether future preg- cause for about 40% of anomalies found analysis is still developing, some of the nancies could be similarly affected. on ultrasound. gene sequence patterns had been associ-

Vimla Aggarwal Ronald Wapner David Goldstein PHOTOS BY JÖRG MEYER

40 ColumbiaMedicine ated—but not definitively linked—to specialists—is needed to ensure an accu- The researchers predict that the a specific developmental abnormality. rate interpretation of the test results. diagnostic yield of whole exome Clinicians need to balance their desire to “Future studies are needed to deter- sequencing, in combination with other give patients definitive answers against mine whether performing whole exome genetic tests, could increase to more the sometimes murky state of genomic sequencing on fetuses during pregnancy than 20% of cases as more information science. A team of multidisciplinary will lead to improved care and repro- about the genetics of fetal anomalies experts—clinical and molecular geneti- ductive counseling,” Dr. Wapner adds. comes to light. Sequencing data also may cists, genetic counselors, developmental Columbia researchers are conducting fur- be used to develop better tools to offer biologists, and maternal-fetal medicine ther studies. treatment before and after delivery.

Ketamine and Other Next Generation Brain Therapeutics

olumbia Psychiatry opened Ketamine program leaders a Next Generation Brain Joshua Berman, MD, PhD, C Therapeutics Program at and J. John Mann, MD ColumbiaDoctors Midtown in Fall 2018 to provide innovative and experimental treatments for mental and substance use disorders. The program provides the newest leading-edge treatments that are scientifically justified but may not yet be FDA-approved for people for whom standard treatments have been ineffective. Among the first treatments offered was ketamine for treatment-resistant depression and mood disturbances. The program offers medical and psychiatric evaluations, diagnostic procedures, and treatments. “The Next Generation Brain Therapeutics Program is urgently needed because patients who are suffering can’t always wait for the prolonged time it takes for the FDA to review and approve novel treatments,” says Jeffrey Lieberman, MD, the Lawrence C. Kolb Professor and

Chair of Psychiatry. “It is important that JÖRG MEYER Columbia Psychiatry offer the newest, most innovative treatments to ensure their says, “Our psychiatrists have many years ment to offer an exciting new option to safe and competent administration.” of experience both evaluating patients for those who have suffered so much from Columbia Psychiatry has pioneered ketamine treatment and safely and suc- this condition.” research into ketamine’s benefits for cessfully administering the treatments.” A few months after Columbia’s program people suffering from depression and sui- “Depression affects more than 16 mil- opened, the FDA approved a nasal spray cidal thoughts and carried out two large lion Americans every year,” says Louri- form of ketamine, resulting in a bump NIH-funded studies. The principal inves- val Baptista, MD, vice chair of clinical in interest. From January to June 2019 tigator of the studies, John Mann, MD, services in the Department of Psychiatry. alone, Columbia fielded more than 300 the Paul Janssen Professor of Translational “This program brings together the knowl- requests for this service and performed Neuroscience in Psychiatry and Radiology, edge and resources of our entire depart- more than 100 infusions of ketamine.

2019 Annual Report ColumbiaMedicine 41 2019 Clinical Highlights

Helping Kids with Congenital Research Network. Cancer result of updated annotations pirators and more complicated Heart Problems therapies can reactivate viral or the discovery of novel epi- to administer. Despite the extra Columbia surgeons have infections, and because patients lepsy genes. In five other cases, risk and effort, many believed expanded surgical treatments with viral infections are usu- the investigators provided new ECMO in 2009 saved the to help children born with a ally excluded from clinical tri- evidence to support or contra- lives of people struggling with vascular ring, which occurs als, it is not known how cancer dict the likelihood of variant when certain parts of the aorta treatments affect the clinical pathogenicity that had been develop abnormally, resulting outcomes of people with hepa- reported. One novel epilepsy in compression of the trachea titis or HIV. Cancer patients gene was discovered through and the esophagus. Minimally are rarely screened for viral dual interrogation of research invasive video-assisted thora- infections, a missed clinical and clinically generated whole coscopic surgery (VATS) vascu- opportunity, says Dr. Hersh- exome sequencing. lar ring repair has advantages man. “We have effective treat- over traditional open surgery, ments for HIV and hepatitis B, COPD Diagnosis including quicker recovery and hepatitis C can be cured.” Using data from the National time and less pain. Some vas- Experts disagree over the value Heart, Lung, and Blood Insti- cular rings are more severe of routine screening for hepa- tute Pooled Cohorts Study, a than others. When a vascular titis B and C and HIV in new resource developed at Colum- ring causes a child to have cancer patients, partly because bia to combine numerous ARDS, which is associated trouble breathing or swallow- screening is expensive. “This existing multiethnic cohort with a mortality rate that can ing, surgical repair is required. study is a first step toward studies to support large-scale exceed 50% in more severe The VATS minimally invasive determining the prevalence of studies of chronic obstructive cases, although at the time approach allows surgeons to viral infections among newly pulmonary disease (COPD), the benefits of ECMO were make repairs through three diagnosed cancer patients and researchers have identified the unproved and it remained a small incisions, avoiding a establishing new screening and optimal spirometry thresh- controversial therapy for years. larger open approach between treatment guidelines.” old to predict COPD-related Daniel Brodie, MD, director of the ribs. hospitalizations and deaths. the Adult ECMO Program at Epilepsy Database Used for A study team led by Eliza- Columbia and NYP, was a Hepatitis in Cancer Ongoing Sequencing beth Oelsner, MD, looked at senior author of a clinical trial Many newly diagnosed cancer The Epilepsy Genetics Initia- the records of 24,207 adults that was reported in the New patients also are infected with tive funded by Citizens United and confirmed the prognostic England Journal of Medicine hepatitis B or C virus and are for Research in Epilepsy significance of the diagnos- in 2018 and an author on a unaware of their viral status, was formed to create a cen- tic threshold for COPD that subsequent analysis of the trally managed database of is recommended by current study in JAMA. Together, these clinically generated exome guidelines. The research pub- studies demonstrated that sequence data. Investigators lished in JAMA now standard- ECMO saves lives in patients from Columbia’s Institute for izes the diagnosis of COPD, with the most severe forms of Genomic Medicine performed which has the potential to ARDS. “While we’ve come a a systematic research-based improve diagnosis, clinical long way in recent years, there reanalysis to identify new care, and clinical research. is still a lot to learn about how molecular diagnoses that were best to manage patients dur- not possible at the time of ini- ECMO for Patients with ARDS ing ECMO support,” says Dr. tial sequencing. This database During the flu pandemic of Brodie. “A lot more research also is used to aid in novel 2009–when large numbers of needs to be done.” gene discovery. Researchers patients were hospitalized with reported on the first three severe respiratory failure due Assessing Brain Injury years of the initiative’s work, to acute respiratory distress Using EEG during which 139 individuals syndrome or ARDS–many Close analysis of EEG data reported a study published with epilepsy underwent diag- doctors turned to ECMO, reveals that nearly one in in JAMA Oncology. Dawn L. nostic whole exome sequenc- or extracorporeal membrane seven brain-injured ICU Hershman, MD, was a senior ing but had not received a oxygenation. ECMO can act patients shows evidence of leader of the study, which was genetic diagnosis. Eight new as an artificial lung but is more hidden consciousness just run by the SWOG Cancer diagnoses were made as a invasive than mechanical res- days after injury, and these

42 ColumbiaMedicine patients are more likely to function.” The participants in co-chair Mathew S. Maurer, for two years in 80% of recover, Columbia neurologists the trial are getting new and MD, a heart failure specialist, patients who completed treat- found. The researchers used genetically engineered hemo- and colleagues. ment, a significant increase in a machine learning technique globin through a stem cell progression-free survival com- to analyze standard EEG data transplant using the patient’s Plastic Electronics May pared with placebo. Results collected from 104 unrespon- own stem cells. Stem cells Improve Epilepsy Surgery of the multicenter trial were sive patients hospitalized at are removed from a patient’s After nearly a century of published in the New Eng- NewYork-Presbyterian/Colum- blood and sent to a laboratory status quo, the hardware for land Journal of Medicine. “In bia to look for patient-specific where they are mixed together electrophysiology is evolving general, desmoids are locally brain activity indicating that with a new, corrected gene. and enabling a new wave of aggressive and often painful they could understand instruc- The genetically engineered research into epileptic disor- tumors for which there are tions to move their hands. If cells are then returned to the ders. Jennifer Gelinas, MD, the findings are confirmed in patient’s bloodstream, and PhD, and Dion Khodagholy, larger studies, the technique the hope is that the stem cells PhD, at Columbia are collabo- could help physicians better with the modified DNA will rating with multiple institutions predict which patients will start producing healthy red to develop and test biocompat- likely regain consciousness. blood cells. The new gene is ible polymer electrodes known The study, led by Jan Claassen, delivered to the patient’s stem as NeuroGrids, which offer the MD, was published in the New cells through a deactivated potential of improved signal England Journal of Medicine. virus that is especially good at recording and less morbidity inserting the new gene into the compared with conventional Promising Sickle Cell stem cell. Early participants metal electrodes. The polymer Treatment Being Tested have been followed for more in the new device conducts A team of Columbia experts than three years, and so far both ions and electrons, which is studying a potential new they have increased healthy is ideal for brain-machine inter- no effective therapies,” says way to treat sickle cell disease. hemoglobin levels and reduced action. The device could help Gary K. Schwartz, MD, chief “Patients who are born with pain episodes. surgeons more precisely locate of hematology/oncology and sickle cell disease, depending the origin of seizures to make a senior author of the paper. on the severity, have a reduced Reducing Deaths from surgery resection more efficient. “Sorafenib is an oral agent life expectancy, and so far Heart Failure that provides a new means to the only way of curing this A phase 3 clinical trial has Routine Genetic Testing directly target the ability of des- disease is through a bone mar- shown that a drug called for Kidney Disease moid tumors to grow and repre- row or stem cell transplant,” A new study has found that sents a new standard of care.” says Markus Mapara, MD, genes cause about one in 10 PhD, director of bone mar- cases of chronic kidney disease Improving Home Blood row transplantation and cell in adults, and identifying the Pressure Monitoring therapy. “Unfortunately, the responsible genes has a direct Obtaining out-of-clinic blood chances of having a matched impact on treatment for most pressure measurements to sibling donor, which provides patients. The study showed that confirm a diagnosis of hyper- the best outcomes, are only genetic testing can be used to tension is recommended before 25%.” A new approach is personalize the diagnosis and initiating treatment, but few being tested in a clinical trial management of kidney disease, studies have shown the num- at Columbia as part of a larger says Ali Gharavi, MD, chief ber of measurements needed multicenter trial to use gene tafamidis significantly reduces of nephrology and a co-senior to reliably estimate blood therapy. “Because sickle cell deaths and hospitalization in author of the study, which was pressure in home monitoring. disease is caused by only one patients with transthyretin published in the New England In a paper published in the errant gene, it ranks high on amyloid cardiomyopathy, Journal of Medicine. Journal of the American Heart the list of diseases that poten- a progressive form of heart Association, Natalie A. Bello, tially could be cured with gene failure that may be more Treating Rare Connective MD, and others described a therapy. If you could fix that common than doctors realize. Tissue Tumor community-based study of one defective gene, you could The findings were published In a phase 3 clinical trial, a adults who were not receiving potentially cure the disease in the New England Journal drug called sorafenib stopped any antihypertensive treat- and reverse the genetic mal- of Medicine by the trial’s progression of desmoid tumors ment. The study showed that

2019 Annual Report ColumbiaMedicine 43 2019 Clinical Highlights using the average of morning tion. Columbia’s ALS Families will inform the development with epilepsy can assist in and evening readings over at Project identifies asymptomatic of policy interventions such as the preoperative workup for least three days is needed to relatives and will follow them. the modification of beverage pediatric epilepsy surgery. reliably estimate out-of-office Since its launch in October, the attributes (e.g., taste and blood pressure and confirm a project has enrolled more than cost) or shifts in marketing How Exercise May Protect diagnosis of hypertension. 12 presymptomatic carriers and advertising of infant and Against Alzheimer’s and plans to expand. Partici- toddler products to reduce Evidence shows that exercise New IVF Center, Lab Open pants will come to Columbia consumption in the first 1,000 produces a hormone that may The Columbia University Fer- once or twice a year for exami- days of life. improve memory and protect tility Center features a new nation and testing. The ALS against Alzheimer’s disease, state-of-the-art IVF lab. “Our Families Project will share Getting Smarter About according to a study co-led division of reproductive endo- data with other academic and Brain Cancer Trials by Ottavio Arancio, MD, PhD. crinology and infertility cares industry researchers who are Columbia will be among The study, published in Nature for patients at a deeply sensi- looking for ALS biomarkers the first to enroll patients Medicine, looked for a link tive time in their lives, and it is and developing new therapies, with glioblastoma, the most between irisin, a hormone that critical for us to have a facility including gene therapies. common primary brain is released during physical that offers the highest degree cancer in adults, in a new activity, and Alzheimer’s. of comfort and convenience Microlearning Videos type of clinical trial that could Using tissue samples from as well as the most cutting on Insulin Management speed the identification and brain banks, the team found edge technology possible,” A company specializing in development of the most that irisin is present in the patient education has part- promising therapies for the human hippocampus and nered with a pharmaceutical disease, reports Andrew that hippocampal levels of company and Columbia’s Lassman, MD. Instead of the hormone are reduced in Naomi Berrie Diabetes Center evaluating each therapy in individuals with Alzheimer’s. and other diabetes programs its own separate clinical The findings suggest that irisin to offer “microlearning,” bite- trial, the program is designed could be exploited to find a sized (from 30 seconds to three to evaluate several drug novel therapy for preventing or minutes) digital information. candidates at once. treating dementia in humans. Available in Spanish and Eng- lish, the videos target patients Better Preparation for Why Some Brain Tumors who are new to using insulin, Childhood Epilepsy Surgery Respond to Immunotherapy including the fastest growing It has long been believed that Columbia researchers have populations with type 2 diabe- cognitive tasks cannot be learned why some glioblasto- tes—African Americans, South used to lateralize seizure onset mas—the most common type says Mary E. D’Alton, MD, Asians, and Hispanics. in children. A prospective, chair of obstetrics & gynecol- observational study published ogy. The fertility center is led Sugar-Sweetened Beverages in Neurology by Marla J. by Zev Williams, MD, PhD, in Early Life Hamberger, PhD, found that chief of reproductive endocri- Sugar-sweetened beverage language tasks she developed nology and infertility, and Eric consumption during the specifically for children Forman, MD, the medical and first year of life is linked to can reliably identify the laboratory director. sugar-sweetened beverage hemisphere of seizure onset consumption later in in pediatric epilepsy. Poorer Launch of ALS Families Project childhood. An article in the auditory naming predicted left By closely following the rela- American Journal of Public hemisphere epilepsy in both tives of some individuals with Health, authored by Jennifer group and individual analyses, familial amyotrophic lateral Woo Baidal, MD, and others, whereas no significant sclerosis (ALS), researchers discusses the need to curb laterality differences were at Columbia’s Eleanor and Lou sugar-sweetened beverages found on measures of visual Gehrig ALS Center hope to during pregnancy and avoid naming, general intelligence, find ways to detect the disease introduction during infancy. or other cognitive functions. of brain cancer—respond to before symptoms arise to allow Better understanding of the Lateralizing the hemisphere immunotherapy. The findings for early therapeutic interven- drivers of parental attitudes of seizure onset in children could help identify patients

44 ColumbiaMedicine TAVR: The Future that transcatheter aortic valve cations during open-heart a new aortic valve can be fitted of Treatment for replacement, or TAVR, per- surgery. In low-risk patients, inside the diseased valve without Heart Valve Disease formed better than open-heart open-heart surgery has been surgically opening the chest. surgery in low-risk patients the standard-of-care for aortic The first PARTNER (Place- Research led by Columbia with severe aortic stenosis (AS). valve replacement. However, ment of AoRtic TraNscathetER) and conducted in clinical tri- The study, published in the the procedure to insert a trans- trial, published in 2010, found als at multiple centers showed New England Journal of Medi- catheter heart valve is less that the procedure dramatically cine, found that one year after invasive and involves a smaller reduced the risk of death among the procedure, the rate of death, incision and shorter recovery inoperable patients compared stroke, or rehospitalization was time than open-heart surgery. with those managed medically; significantly lower with TAVR As many as 400,000 patients in subsequent PARTNER trials, than with surgery. The U.S. around the world with aortic published in 2011 and 2016, Food and Drug Administration stenosis have had TAVR. TAVR TAVR was also found to be has since approved the proce- was first introduced as an alter- effective for patients with dure for patients with severe AS native for patients who were high- and intermediate-risk of who are at low risk for death too sick to undergo open-heart death or serious complications or major complications associ- surgery, but clinical trials over from surgery. ated with open-heart surgery to the years have shown that it Patients in the study pub- replace a damaged valve. may be superior to surgery even lished this year will be followed Earlier research led to for patients with low operative for at least 10 years to assess approval of TAVR for patients risk. In TAVR, doctors thread a the long-term durability of the at intermediate or higher risk catheter through an artery in the replacement valve and to mea- for death or major compli- groin and into the heart so that sure their long-term outcomes.

who are most likely to benefit a benzodiazepine. Antidepres- endoscopic interventions, colleagues conducted a multi- from treatment with immuno- sants reduced the risk of hos- nutritional support, and center clinical trial of 226 early- therapy drugs and lead to the pitalization by 16% compared genetic testing. The program stage breast cancer patients, development of more broadly with antipsychotics and by 22% offers minimally invasive treat- all of whom had moderate to effective treatments. The study, compared with benzodiazepines. ment approaches for patients severe joint pain. The women led by Raul Rabadan, PhD, Antidepressants reduced the risk who previously would have were randomly assigned to get was published in the jour- of emergency room visits by undergone open surgery. Tra- acupuncture, sham acupunc- nal Nature Medicine. 8% compared with antipsychot- ditional surgery is available ture, or no acupuncture over six ics and by 18% compared when nonsurgical therapies weeks. The differences in aver- Finding the Best Drugs with benzodiazepines. have been exhausted. Dr. age pain, pain interference, and for Schizophrenia Schrope is among a small pain severity scores between the Patients with schizophrenia are Progressive Pancreatic Disease group of surgeons in the coun- acupuncture group and both often treated with more than The challenges of managing try who can perform total pan- control groups were statistically one type of psychiatric medica- acute and chronic pancreatitis createctomy with autologous significant, with nearly 60% tion, but a new study led by are being met with a new pan- islet cell transplantation. of women in the acupuncture T. Scott Stroup, MD, suggests creatitis program at Columbia group experiencing at least a that some combinations may be and NewYork-Presbyterian. Joint Pain and Breast two-point reduction in pain on more effective than others. The The program’s medical direc- Cancer Treatment a scale of 0 to 10. The research findings, published in JAMA tor, John M. Poneros, MD, Researchers found acupuncture was published in JAMA. Psychiatry, found that individu- and surgical director, Beth is associated with a statisti- als with schizophrenia who were A. Schrope, MD, PhD, say cally significant drop in joint New Salvage System for Lungs taking an antipsychotic and Columbia’s experience and pain among women taking A multidisciplinary team from added an antidepressant were large volume of patients led aromatase inhibitors, a type of Columbia and Vanderbilt less likely to use the emergency to the formalization of the hormonal therapy, for breast University has demonstrated room or hospital for a mental treatment of patients with pan- cancer. Columbia oncologist in a clinically relevant model health issue than those who creatic disease. The program Dawn Hershman, MD, coau- that severely damaged lungs started another antipsychotic or offers medical management, thor Katherine Crew, MD, and can be regenerated to meet

2019 Annual Report ColumbiaMedicine 45 2019 Clinical Highlights transplantation criteria. In sought to assess the clinical a study published in Nature utilization and performance of Ace Clinicians Communications, the research- the ME/PCR assay among 705 ers describe the cross-circula- inpatients who underwent test- The third class of clinicians was inducted into Columbia’s tion platform that maintained ing at Columbia over the course Academy of Clinical Excellence this year in recognition of the the viability and function of the of nearly a year. Their results, clinicians’ commitment to patient care and to training future donor lung and the stability of published in Frontiers in Neu- generations of clinicians. This year’s 46 new members—all the recipient for 36 to 56 hours. rology, found that the ME full professors with at least five years at Columbia who Current methodologies of lung panel had rapid turnaround devote more than half their time to patient care and training support are limited to only results, but routine availability the next generation—join 154 clinicians who were among the six to eight hours, too short a led to overutilization of diag- first two ACE classes. time for therapeutic interven- nostic tests; more than a third tions that could regenerate the of ME panel tests performed injured lung and improve its were ordered for patients with function. The research team little or no suspicion for CNS was co-led by Columbia’s Gor- infection. Overall, agreement dana Vunjak-Novakovic, PhD. between the ME panel results The collaborators hope their and clinicolaboratory assess- advance will lead to an increase ment was 98.2%. Of the 45 in the number of lungs avail- patients who tested positive, able for transplantation. 26.6% were determined likely to be clinically insignificant. Hands-Only CPR Researchers suggest that fur- A new patient safety initiative ther studies are needed to gain launched by ColumbiaDoctors insight into the bedside imple- teaches hands-only CPR and mentation of the ME panel in automated external defibril- the diagnostic evaluation and lator awareness. Hands-only management of CNS infections. CPR has been shown to be as in 2013. Co-chaired by Dr. from a clinical trial at the effective as conventional CPR Reducing Stroke Risk D’Alton, this initiative is a Herbert Irving Comprehensive in saving organs and lives, and During Pregnancy quality improvement pro- Cancer Center and other providing hands-only interven- The United States has expe- gram to reduce preventable centers. Data on the drug, tion immediately following a rienced a significant rise in pregnancy-related deaths from sacituzumab govitecan, were cardiac arrest can make the dif- maternal mortality since 2000, causes such as hypertension. published in the New England ference between life and death. as compared with a decrease in During the early implementa- Journal of Medicine. The drug many countries throughout the tion phase of the hypertension is part of an emerging class Clinical Application of a world. Hypertensive disorders program, reports showed more of “smart drugs” designed to New Test for CNS Infections during pregnancy constitute timely treatment of severe deliver a toxic payload directly To optimize patient care, pre- a disproportionate share of hypertension in the majority to tumor cells by fusing an sumed central nervous system preventable maternal mortality of participating New York antibody that recognizes a infections need to be rapidly and morbidity in the United state obstetric hospitals. The protein expressed by breast and accurately diagnosed. States, wrote Lynn Simpson, long-term success of the pro- cancer cells known as trop2 Major advances have been MD, Mary D’Alton, MD, and gram will depend on continued and the metabolite of an made recently, including the others in a report published participation and commitment established chemotherapy drug FDA-approved FilmArray in the American Journal of of the required resources in (irinotecan), SN-38. “I think Meningitis/Encephalitis multi- Perinatology Reports. To hospital settings. this drug has the potential plex polymerase chain reaction improve maternal outcomes to change practice, because panel for CNS infections, but and reduce risk of stroke and New “Smart Drug” for the data look so compelling, significant concerns related to other complications, District a Breast Cancer even with the relatively small costs and how to use and inter- II of the American College of A new “smart drug” has number of patients in the pret these tests effectively in Obstetricians and Gynecolo- shown promise for women trial,” says Columbia’s Kevin clinical practice remain. Kiran gists began the New York State with metastatic triple-negative Kalinsky, MD, the paper’s Thakur, MD, and colleagues Safe Motherhood Initiative breast cancer, based on data senior author.

46 ColumbiaMedicine aboutVPS& MEMBERSHIPS AND DATA CURRENT AS OF JULY 1, 2019, EXCEPT WHERE NOTED

Columbia University Trustees Ross Frommer, JD Joseph M. Murphy Urology Council Committee on the Vice President, Government and Lawrence Neubauer Gary Schaevitz, Chair Health Sciences Community Affairs John W. Rowe, MD Peter Sacripanti Weinberg Family Cerebral Palsy Noam Gottesman, Chair Christopher DiFrancesco, MA Thomas P. Sculco, MD Center Advisory Board Rolando Acosta Chief Communications Officer G. Lynn Shostack Debby Weinberg, Chair Andrew Barth Frank V. Sica Julissa Reynoso William Innes, MS Richard Silverman Women’s Health Care Council Chief Human Resources Officer Dinakar Singh Sarah Billinghurst Solomon, Chair Senior Administration, Andrew Solomon, PhD Columbia University Irving Erik Pupo, MBA Sarah Billinghurst Solomon Medical Center Senior Administration, Chief Information Officer Esta Stecher Vagelos College of Lee C. Bollinger, JD Peter Tombros Physicians & Surgeons President of the University General Counsel Leonard Tow, PhD Lee Goldman, MD Savio Tung Patricia Sachs Catapano, JD Dean Lee Goldman, MD Associate General Counsel Andy Unanue Executive Vice President and Joseph A. Walker Anne Taylor, MD Dean of the Faculties of Health Deborah Weinberg CUIMC Board of Advisors Vice Dean, Academic Affairs Sciences and Medicine and Richard E. Witten Membership as of June 19, 2019 Chief Executive of Columbia Roger Wu, MD Martha Hooven, MPA University Irving Medical Center P. Roy Vagelos, MD, Chair Paul A. Marks, MD, Vice Dean, Administration Philip L. Milstein, Vice Chair Emeritus Member Lorraine Frazier, PhD George D. Yancopoulos, Torsten Wiesel, MD, Steven Shea, MD Senior Vice President, CUIMC MD, PhD, Vice Chair Emeritus Member Senior Vice Dean, Affiliations Dean, School of Nursing Lisa M. Baker Keith T. Banks CUIMC Advisory Group Chairs George A. Cioffi, MD Linda P. Fried, MD, MPH Michael Barry Babies Heart Fund Vice Dean, Clinical Affairs, and Senior Vice President, CUIMC Stanley M. Bergman John Minio and Scott Roskind, President, ColumbiaDoctors Dean, Mailman School of Gary B. Bettman Co-Chairs Public Health E. Garrett Bewkes III Education Eugene Braunwald, MD Cancer Advisory Council Christian S. Stohler, DMD, Dana Buchman Ronald E. Drusin, MD Richard Witten and Dina Dublon, DrMedDent John A. Catsimatidis Vice Dean Co-Chairs Senior Vice President, CUIMC Anna Chapman, MD

Dean, College of Dental Medicine Neil L. Cohen Lisa Mellman, MD Center for Radiological Research Erica Dewan Senior Associate Dean for Advisory Council Development Harris Diamond Student Affairs Paul Locke, JD, DrPH, Chair Misook Doolittle Lynne Roth F. Jonathan Dracos Hilda Y. Hutcherson, MD Senior Vice President Children’s Board at Columbia John L. Eastman Senior Associate Dean for Karen A. Kennedy, MD, and Finance Loren Eng Diversity and Multicultural Affairs Lawrence Neubauer, Co-Chairs Helene Feldman William P. McKoy, MBA Marjorie Harrison Fleming Anne Armstrong-Coben, MD Senior Vice President/Chief Columbia’s Cardiac Council Carl Frischling Senior Associate Dean Financial Officer Peter J. Sacripanti, Chair Marc D. Grodman, MD for Admissions

Gerald L. Hassell Francine Caracappa, MBA, CPA Diabetes Advisory Board Ara K. Hovnanian Maurice Wright, MD Vice President, Finance, John, Jodie, Jay, and Ann F. Kaplan Senior Associate Dean, and Controller Katama Eastman, Co-Chairs Samuel L. Katz Harlem Hospital

Ilan Kaufthal Operations Precision Medicine Council Karen A. Kennedy, MD Jonathan Amiel, MD P. Roy Vagelos, MD, Chair Donna Lynne, DrPH Jonathan S. Leff Associate Dean for

Senior Vice President/Chief Ellen Levine Curricular Affairs Psychiatry Board of Advisors Operating Officer A. Michael Lipper Patricia and William Ramonas, Carol Ludwig, MD Joseph Giovannelli, MA Co-Chairs Amador Centeno, MS Paul J. Maddon, MD, PhD Associate Dean for

Vice President, Facilities Phyllis Mailman Education Administration Transplant Forum Management and Campus Services Robert F. Mancuso Monica Segal, MPH, MS, Chair Edward D. Miller Jr., MD

2019 Annual Report ColumbiaMedicine 47 aboutVPS& MEMBERSHIPS AND DATA CURRENT AS OF JULY 1, 2019, EXCEPT WHERE NOTED

Arthur G. Palmer III, PhD Stavroula Kousteni, PhD Medical Humanities & Ethics Surgery Associate Dean for Associate Professor of Physiology Rita Charon, MD, PhD Craig R. Smith, MD Graduate Affairs & Cellular Biophysics Medicine Systems Biology Elizabeth Shane, MD Usha Krishnan, MD Donald W. Landry, MD, PhD Andrea Califano, PhD Associate Dean of Student Research Professor of Pediatrics at CUMC Microbiology & Immunology Urology Henry Weil, MD Andrew R. Marks, MD Sankar Ghosh, PhD James M. McKiernan, MD Associate Dean, Professor of Physiology & Cellular Bassett Healthcare Biophysics; Clyde’56 and Helen Neurological Surgery Institutes, Centers, and Wu Professor of Molecular Robert A. Solomon, MD VP&S Schoolwide Initiatives Finance Cardiology (in Medicine); and and Their Directors Chair, Department of Physiology Neurology Robin Honig, CPA Naomi Berrie Diabetes Center & Cellular Biophysics Richard Mayeux, MD Chief Financial Officer and Robin S. Goland, MD Chief Business Development Rudolph L. Leibel, MD Officer for ColumbiaDoctors Edward Owusu-Ansah, PhD Neuroscience Assistant Professor of Physiology Steven A. Siegelbaum, PhD Center for Family and & Cellular Biophysics Research Community Medicine Obstetrics & Gynecology Richard Younge, MD Michael L. Shelanski, MD, PhD Amanda J. Powers, MD Mary E. D’Alton, MD Senior Vice Dean for Research Assistant Professor of Surgery Center for Motor Neuron (in Anesthesiology) at CUMC Ophthalmology Biology and Disease Jennifer Williamson Catania, George A. Cioffi, MD Darryl De Vivo, MD MS, MPH Carrie B. Ruzal-Shapiro, MD Serge Przedborski, MD, PhD Associate Vice Dean for Research Professor of Radiology at CUMC Orthopedic Surgery Hynek Wichterle, PhD Policy & Scientific Strategy William N. Levine, MD Karen Soren, MD Center for Radiological Research Muredach Reilly, MBBCh Professor of Pediatrics at CUMC Otolaryngology/ David Brenner, PhD, DSc Associate Dean for Clinical and Head & Neck Surgery Translational Research Jessica L. Spellman, MD Lawrence Lustig, MD Columbia Stem Cell Initiative Associate Professor of Emmanuelle Passegué, PhD Anil K. Rustgi, MD Anesthesiology at CUMC Pathology & Cell Biology Associate Dean for Oncology Kevin Roth, MD, PhD Department Chairs Columbia Translational Neuroscience Initiative Alumni Relations (as of Sept. 1, 2019) Pediatrics and Development Serge E. Przedborski, MD, PhD Anesthesiology Jordan Orange, MD, PhD Anke Nolting, PhD Ansgar Brambrink, MD, PhD Institute for Cancer Genetics Associate Dean and Pharmacology Riccardo Dalla-Favera, MD Executive Director Biochemistry & Molecular Cory Abate-Shen, PhD Biophysics Institute of Comparative Medicine Physiology & Cellular Biophysics Executive Committee of the Arthur G. Palmer III, PhD Brian Karolewski, VMD, PhD Faculty Council, 2018-2019 (interim) Andrew R. Marks, MD Cigdem I. Akman, MD Institute for Genomic Medicine Psychiatry Professor of Neurology at CUMC Biomedical Informatics David B. Goldstein, PhD George Hripcsak, MD Jeffrey A. Lieberman, MD Spencer Amory, MD (on sabbatical) Institute of Human Nutrition Radiation Oncology Jose M. Ferrer Professor Noémie Elhadad, PhD (co-interim) Richard J. Deckelbaum, MD Lisa Kachnic, MD of Surgery at CUMC Soumitra Sengupta, PhD (co-interim) Herbert Irving Comprehensive Radiology Joshua E. Hyman, MD Cancer Center Lawrence H. Schwartz, MD Professor of Orthopedic Dermatology Anil K. Rustgi, MD Surgery at CUMC David R. Bickers, MD Rehabilitation & Irving Institute for Clinical and Regenerative Medicine Gerard Karsenty, MD, PhD Emergency Medicine Translational Research Joel Stein, MD Paul A. Marks Professor of Angela M. Mills, MD Muredach P. Reilly, MBBCh Genetics & Development; – Programs in Professor of Medicine; and Genetics & Development Occupational Therapy Kavli Institute for Brain Science Chair, Department of Genetics Gerard Karsenty, MD, PhD Glen Gillen, EdD, Director Eric Kandel, MD & Development – Programs in Physical Therapy Debra Krasinski, PhD, Director 48 ColumbiaMedicine Gertrude H. Sergievsky Center Weinberg Family VP&S Hospital Affiliations Mary Imogene Bassett Hospital Richard Mayeux, MD Cerebral Palsy Center Cooperstown, NY NewYork-Presbyterian Hospital David P. Roye Jr., MD New York, NY Taub Institute for Research Stamford Hospital on Alzheimer’s Disease and Clyde and Helen Wu Center Stamford, CT New York State Psychiatric Institute the Aging Brain for Molecular Cardiology New York, NY Richard Mayeux, MD Andrew Marks, MD Helen Hayes Hospital Michael L. Shelanski, MD, PhD West Haverstraw, NY Harlem Hospital Wu Family China Center New York, NY Transplant Initiative for Health Initiatives Lawrence Hospital Jean C. Emond, MD David Ho, MD Bronxville, NY James J. Peters Veterans (effective January 2020) Administration Hospital Bronx, NY

FACTS & STATISTICS, FY19

MEDICAL SCHOOL ENROLLMENT, FALL 2018 DEGREES GRANTED, FY19 Total medical school enrollment ...... 620 MD...... 171 Enrollment of in-state residents ...... 176 PhD...... 80 Enrollment of international/nonresident students ...... 24 Doctor of physical therapy ...... 68 Enrollment of men ...... 315 MS in nutrition ...... 81 Enrollment of women ...... 305 MS in occupational therapy ...... 57 Certificate in psychoanalysis ...... 1 ENROLLMENT BY YEAR MALE .FEMALE APPLICATIONS (ENTERING CLASS 2018) First-year class 75 63 Number of applicants ...... 7,537 Second-year class 72 82 Number of applications considered ...... 6,796 Third-year class 95 85 Number of applicants interviewed ...... 1,007 Fourth-year class 73 75 Number of acceptance letters issued ...... 258 Total enrollment 315 305 Bassett Program applicants ...... 534

MEDICAL SCHOOL ETHNICITIES FACULTY, 2018-2019 ACADEMIC YEAR Hispanic/Latino...... 73 Full-time faculty ...... 2,189 Black or African American, non-Hispanic/Latino...... 63 White, non-Hispanic/Latino...... 277 FACULTY HONORS American Indian or Alaskan Native, non-Hispanic/Latino...... 2 Nobel Prize in Medicine ...... 3 Asian, non-Hispanic/Latino...... 129 National Academy of Sciences ...... 21 Native Hawaiian or other Pacific Islander, non-Hispanic/Latino.... 1 National Academy of Medicine ...... 49 Two or more races, non-Hispanic/Latino...... 15 American Academy of Arts and Sciences ...... 25 Race and/or ethnicity unknown...... 36 Howard Hughes Medical Institute ...... 6

OTHER STUDENTS FINANCIALS, FY19 (EXCEPT WHERE NOTED) MD-PhD students ...... 113 Budget ...... $2.1 billion PhD students ...... 424 Philanthropic support ...... $305 million Other students (PT, OT, Nutrition, Informatics) ...... 460 Endowment ...... $1.9 billion Endowed chairs/professorships ...... 295 NIH research support (FY 2018) ...... $501 million

2019 Annual Report ColumbiaMedicine 3 Vagelos College of Non-Profit Org. Physicians and Surgeons U.S. Postage Paid New York, NY 630 West 168th Street PERMIT NO. 3593 New York, NY 10032

PHOTOS BY PAVEL BENDOV Sharing a Bit of Haven with Our Neighbors

pedestrian plaza has transformed approximately 60,000 square feet of an area on Haven Avenue A and around nearby medical center buildings from West 169th Street to Fort Washington Avenue at 168th Street. Haven Plaza is now a public outdoor plaza shared by the medical center community and our Washington Heights neighbors. The project has transformed both public land (streets and sidewalks that make up about 40% of the area) and green space on medical center property (about 60% of the plaza). It is part of the New York City Department of Transporta- tion Plaza Program, which has created neighborhood plazas throughout the city in an effort to ensure that all New Yorkers live within a 10-minute walk of quality open space.