Research | Mount Sinai Today

“New Heights” of Achievement Marked at Convocation

Oct 22, 2018 | Community, Featured, Research

Dennis S. Charney, MD, delivered the State of the School Address.

A sense of accomplishment pervaded the 2018 Convocation Ceremony, which honored 13 renowned faculty members and celebrated the 50th anniversary of the Icahn School of Medicine at Mount Sinai. The event, held on Thursday, October 4, marked the beginning of the academic year and featured the annual State of the School Address by Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System.

“We are reaching new heights,” Dr. Charney said as he welcomed the honorees, their families and friends, faculty, staff , and Mount Sinai benefactors who filled Goldwurm Auditorium. “We have never had more endowed chairs than we are awarding tonight, which I think speaks for the health of our medical school and our Health System.” The honorees received named professorships in fields including computational biology, genetics and genomic sciences, personalized medicine, palliative care, geriatrics, therapeutics discovery, ophthalmology, and neuroscience.

Among its many accomplishments, Dr. Charney said, the Icahn School of Medicine at Mount Sinai received $348.5 million in National Institutes of Health (NIH) funding in fiscal year 2018—a 9.4 percent increase over the prior year—ranking the school No. 12 in the nation. “We also rank No. 4 in research dollars per investigator, which means our individual faculty are among the best in the country,” Dr. Charney said, citing figures from the Association of American Medical Colleges.

The School of Medicine has the largest Graduate Medical Education program in the nation, with more than 2,500 residents and fellows. Its master’s and PhD programs are growing in size and quality, and Mount Sinai is launching a biomedical data science program, “which is consistent with our overall commitment to be one of the best places in the country, if not the world, in genomic and data science,” Dr. Charney said. The matriculating class of medical students has a median grade point average of 3.84 (out of 4.0), and the Flex Med admissions program helped make it a well-rounded group. “We are always looking to recruit students who represent the spectrum of talents in America,” he said, “whether they major in humanities or hard science or have experience in the military.”

Among other high points:

Mount Sinai Innovation Partners, which translates research findings into health care products and services, generated 211 patents, 144 inventions, and 53 new licenses and options for the use of research. In addition, the new i3 Asset Accelerator funded four start-up projects based on Mount Sinai research, with seven proposals now under review.

The Mount Sinai Doctors Faculty Practice—the largest in the nation—had 7.8 percent higher revenues compared with 2017, and the number of calls to its Access Center rose to 3.48 million in 2018 from 2.67 million in 2017.

Mount Sinai, for the second consecutive year, was ranked No. 1 by DiversityInc magazine among hospitals and health care systems in the nation for excellence in diversity management and best practices. In addition, the Patricia S. Levinson Center for Multicultural and Community Affairs marked its 20th anniversary.

The Office of Well-Being and Resilience, led by Jonathan A. Ripp, MD, MPH, Senior Associate Dean, was created to support the well-being of students, staff, and faculty.

Mount Sinai launched an online series of articles in partnership with Scientific American Custom Media that marks the 50th anniversary of the Icahn School of Medicine and takes a sweeping look at research and innovation fueling the next generation of treatments.

Looking ahead, Dr. Charney said, “Our guiding principles are to take advantage of the size and excellence of our Health System, to have unrivaled excellence in our medical and graduate education, and to anticipate new areas of research. We developed a strategic plan in 2017, and we are now implementing that plan in 2018.” The latest initiatives include renovation at 3 East 101st Street that will create a 45,000-square-foot facility for data science and technology. In a comprehensive capital campaign, the Mount Sinai Health System is seeking to raise $1.5 billion or more to fund projects, including a Life Science Center at 102nd Street and Madison Avenue.

Among its research priorities, the School of Medicine is advancing immunology by exploring therapies that target cancer, heart disease, diabetes, and brain disorders. It also is making a major investment in precision medicine. “This is a big initiative of the NIH,” Dr. Charney said, “and Mount Sinai will lead the way” with the advantages of a large and diverse patient population and expertise in genomics, big data, supercomputing, and bioinformatics.

Marta Filizola, PhD, left, the Sharon and Frederick Klingenstein/ Nathan Kase, MD Professor, and Dean of the Graduate School of Biomedical Sciences, with Terry A. Krulwich, PhD, a pioneering predecessor in both roles.

Dr. Charney took a moment to recognize a “legendary leader,” Terry A. Krulwich, PhD, Professor Emeritus of Pharmacological Sciences, and Dean of the Graduate School of Biomedical Sciences from 1981 to 2002—one of the first women in the nation to fill this role. Dr. Krulwich, who recently retired, was a mentor and role model, and a groundbreaking bacteriologist who was continuously funded by the NIH for 40 years. Dr. Charney thanked her for decades of service to Mount Sinai, and she was acknowledged with lasting applause.

“I think we can be very proud of what the School of Medicine has become in just 50 years,” said Peter W. May, Chairman, Boards of Trustees, Mount Sinai Health System. “It is one of the nation’s top medical schools, in which we are training bright, creative, and innovative doctors. But we are also engaged in great medical research that generates new insights, diagnostics, and treatments.”

Kenneth L. Davis, MD, President and Chief Executive Officer, Mount Sinai Health System, noted these achievements and also urged the honorees to keep in sight the school’s core values, such as putting patients first, serving everyone who needs care regardless of their ability to pay, collaborating in the lab, and making discoveries that improve the lives of patients. “Fifty years ago, when I came to Mount Sinai as a medical student, I came to be a physician-scientist,” Dr. Davis said. “But the longer I have been here, the more I realized that my job was not just writing papers. It was not just getting millions of dollars in grants. It was about what would be left behind, what was lasting. My job was to be a steward of this institution—of its legacy and its heritage. That was my responsibility, and now it is yours.”

The Convocation Honorees

Front row, from left: Amy S. Kelley, MD, MSHS; Jian Jin, PhD; Ethylin Wang Jabs, MD; Marta Filizola, PhD; Kenneth S. Boockvar, MD, MS; Schahram Akbarian, MD, PhD; and Dennis S. Charney, MD. Back row, from left: Paul A. Slesinger, PhD; Eric Schadt, PhD; Rachel Saunders-Pullman, MD, MPH, MS; Richard B. Rosen, MD; Adam A. Margolin, PhD; Ruth Loos, PhD; Andrew B. Leibowitz, MD; and Peter W. May.

Schahram Akbarian, MD, PhD, Mount Sinai Professor in Psychiatric Epigenomics

Kenneth S. Boockvar, MD, MS, Anna A. Greenwall Professor of Geriatrics and Adult Development

Marta Filizola, PhD, Sharon and Frederick Klingenstein/Nathan Kase, MD Professorship

Ethylin Wang Jabs, MD, Mount Sinai Professor in Developmental Genetics

Jian Jin, PhD, Mount Sinai Professor in Therapeutics Discovery

Amy S. Kelley, MD, MSHS, Hermann Merkin Professor in Palliative Care

Andrew B. Leibowitz, MD, Mount Sinai Professor in Perioperative Care

Ruth Loos, PhD, Charles Bronfman Professor in Personalized Medicine

Adam A. Margolin, PhD, Jean C. and James W. Crystal Professor of Genetics and Genomic Sciences

Richard B. Rosen, MD, Belinda Bingham Pierce and Gerald G. Pierce, MD Distinguished Chair of Ophthalmology

Rachel Saunders-Pullman, MD, MPH, MS, Bachmann-Strauss Professor

Eric Schadt, PhD, Mount Sinai Professor in Predictive Health and Computational Biology

Paul A. Slesinger, PhD, Lillian and Henry M. Stratton Professor of Neuroscience

Advancing Research for Alzheimer’s Disease

Oct 22, 2018 | Community, Research

Ana C. Pereira, MD, with Christopher Smith, Executive Director, Alzheimer’s Association, New York City Chapter, left, and Keith Fargo, PhD, Director of Scientific Programs and Outreach, Alzheimer’s Association.

Two physician-scientists at the Icahn School of Medicine at Mount Sinai have each received a 2019 Alzheimer’s Association Research Grant of approximately $150,000 over the next three years for their respective research projects.

Ana C. Pereira, MD, Assistant Professor of Neurology, and Neuroscience, is studying the molecular profiling of glutamate and tau-mediated toxicity in Alzheimer’s disease. Andrew Varga, MD, PhD, is Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine). He is investigating the effect of chronic sleep disruption on brain tau phosphorylation spread.

The Alzheimer’s Association Research Grant program, which funds early-career researchers who have received their doctoral degrees or completed their residency within the past 10 years, aims to nurture a robust pipeline of fresh ideas while laying the groundwork for future grant applications.

Reprogramming Retina Cells to Restore Vision

Updated on Oct 8, 2018 | Featured, Research

From left: Postdoctoral Fellows Xinzheng Guo, PhD, and Ye Xie, PhD, with Bo Chen, PhD.

A team of researchers, led by Bo Chen, PhD, Associate Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai, has reversed congenital blindness in mice by changing the supportive Müller glia cells in the retina into functional rod photoreceptors—light-sensitive cells in the retina that signal the brain when activated.

The breakthrough research, published online in the August 15, 2018, issue of Nature, is expected to advance efforts toward retinal regeneration for diseases of the eye, such as age-related macular degeneration, degenerative glaucoma, and retinitis pigmentosa.

Funded in part by the National Eye Institute (NEI), an arm of the National Institutes of Health, the study drew praise from NEI Program Director Thomas N. Greenwell, PhD. “This is the first report of scientists reprogramming Müller glia to become functional rod photoreceptors in the mammalian retina,” says Dr. Greenwell. “Rods allow us to see in low light, but they may also help preserve cone photoreceptors, which are important for color vision and high visual acuity. Cones tend to die in later-stage eye diseases. If rods can be regenerated from inside the eye, this might be a strategy for treating diseases of the eye that affect photoreceptors.”

Macro view of retinal stem cells in the process of division.

Scientists have long studied the regenerative potential of Müller glia cells because in species such as zebrafish, they divide in response to injury and can turn into photoreceptors and other retinal neurons. In the lab, scientists have coaxed mammalian Müller glia to behave as they do in the fish, but not without injuring the tissue. Since injured tissue is counterproductive to restoring vision, Dr. Chen’s lab was able to achieve an effective method of achieving both goals, something others could not.

In pursuing this novel gene-transfer therapy, Dr. Chen, who is also Director of the Ocular Stem Cell Program at the Icahn School of Medicine at Mount Sinai, and his investigators followed a two-stage process. First, they demonstrated that Müller glia cells could be spurred to divide in mice by injecting their eyes with a gene to turn on a protein called beta-catenin. Then, weeks later, the mice were injected with transcription factors Otx2, Crx, and Nrl that encouraged the newly divided cells to develop into rod photoreceptors.

The investigators were encouraged to find that the newly formed cells looked structurally no different from real photoreceptors, and that synaptic structures that allow the rods to communicate with other types of neurons within the retina had also formed.

When the researchers took another step forward by testing the treatment in congenitally blind mice that were born without functional rod photoreceptors, the results were positive once again. The light responses recorded from retinal ganglion cells—neurons that carry signals from photoreceptors to the brain—and measurements of brain activity confirmed that the newly formed rods were integrating into the visual pathway circuitry, from the retina to the primary visual cortex in the brain.

“Our findings underscore that we are closer than ever to developing new therapies for people with severe degenerative eye disease,” says Dr. Chen. “Mice that were blind from birth were now able to see light for the first time following treatment.”

Dr. Chen says his next step will be determining whether the technique works on cultured human retinal tissue. In addition to receiving NIH funding, Dr. Chen’s research was supported by a $2 million grant from the McGraw Family Foundation.

Lab Discovery Leads to a Remedy

Oct 8, 2018 | Featured, Patient Stories, Research

Stuart Sealfon, MD

A drug that recently received approval from the U.S. Food and Drug Administration (FDA) for the treatment of pain associated with the gynecological disorder endometriosis had its genesis two decades ago in the laboratory of Stuart Sealfon, MD, at the Icahn School of Medicine at Mount Sinai.

The drug, Orilissa™, approved by the FDA in July, is the first oral regimen that specifically helps to ease the moderate to severe pain that accompanies endometriosis, a condition where the tissue that forms in the lining of the uterus continues to grow outside the uterus.

The disorder, which affects roughly one in ten women of reproductive age, negatively impacts quality of life, since the excess tissue growth is often accompanied by pain during menstruation, intercourse, or urination.

“Orilissa is a drug that resulted from the basic research we conducted at Mount Sinai, and it will help millions of women,” says Dr. Sealfon, Sarah B. and Seth M. Glickenhaus Professor and Chair Emeritus of the Department of Neurology. “At Mount Sinai, we discovered how to clone the drug target that was needed to develop this new drug.”

Indeed, as a young researcher more than two decades ago, Dr. Sealfon led the Mount Sinai team that cloned the gonadotropin-releasing hormone receptor (GnRHR) and genetically engineered host cells that express GnRHR. Gonadotropin-releasing hormone (GnRH), which is secreted by the hypothalamus, plays a key role in controlling reproduction, and acts via its receptor GnRHR.

The cloning procedure and primary structure of the receptor were described in two studies authored by Dr. Sealfon in 1992 and 1993, which were published in Molecular Endocrinology and Molecular and Cellular Endocrinology, respectively. The research provided a better understanding of the complex interplay of hypothalamic, pituitary, and gonadal hormones, which underlie pharmacotherapy and the reproductive system.

At the time, Dr. Sealfon says, a career-development grant provided him with the funding he needed to conduct his research. Two U.S. patents, in 1998 and 1999, assigned these inventions to Mount Sinai.

The oral application of Orilissa—also known by its generic name, elagolix—enables women to dial down the reproductive system. The dose-dependent drug suppresses the luteinizing hormone and the follicle-stimulating hormone, which leads to decreased blood concentrations of estradiol and progesterone. This reduces the growth of excess tissue, or lesions that form on the ovaries, fallopian tubes, or areas near the uterus, including the bowel and bladder that characterize endometriosis and cause pain.

The 20 years it took for elagolix to move from Dr. Sealfon’s laboratory to the marketplace demonstrates the length of time it can take for basic scientific discoveries to bear fruit, experts say. The drug was released by AbbVie, a global pharmaceutical company, in cooperation with Neurocrine Biosciences, Inc.

Endometriosis is considered one of the most common gynecologic disorders in the United States, but women can sometimes go years before having the laparoscopic procedure needed to render a proper diagnosis. In addition to the use of oral contraceptives, treatments have included nonsteroidal anti-inflammatory drugs, and opioids. In more extensive cases, women may undergo surgical procedures, including a hysterectomy.

In two Phase 3 clinical trials, Orilissa has been shown to be helpful in the treatment of uterine fibroids, as well. Fibroids are a common benign tumor that causes bleeding or pain in millions of women, and for which there are, currently, limited nonsurgical treatment options.

In the years since his initial discovery, Dr. Sealfon’s lab has continued to study GnRH receptor-mediated gonadotropin regulation and help guide future work in the field.

Mount Sinai Researcher Wins Young Investigator Award

Oct 8, 2018 | Featured, Research

Benjamin D. Greenbaum, PhD

Immunotherapy has been a game changer in treating some cancers, but it does not work for every patient. Building mathematical models that might predict a patient’s response is central to the work of Benjamin D. Greenbaum, PhD, Assistant Professor of Medicine (Hematology and Medical Oncology), Oncological Sciences, and Pathology, at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. For his efforts, he recently won the Pershing Square Sohn Prize for Young Investigators in Cancer Research.

Dr. Greenbaum, a computational biologist, was among seven researchers to receive the award from the Pershing Square Sohn Cancer Research Alliance, a program of The Pershing Square Foundation. His laboratory will receive $200,000 yearly for the next three years. In a novel partnership, The Mark Foundation for Cancer Research will fully fund Dr. Greenbaum’s award, and has named him a Pershing Square Sohn Mark Foundation Fellow.

Dr. Greenbaum’s work “will be instrumental in understanding what types of T cells are required for generating effective anti-tumor immunity and how to design immune therapies that selectively induce their development,” says a longtime colleague and mentor, Nina Bhardwaj, MD, PhD, the Ward-Coleman Chair in Cancer Research, and Director of Cancer Immunotherapy, at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

Dr. Greenbaum began his career studying the evolution of viruses and later became interested in checkpoint blockade inhibitor immunotherapies, which help the body recognize and kill cancer cells, and for which the Nobel Prize was recently awarded. He led a group that created the first predictive mathematical model demonstrating how a set of melanoma and lung cancer patients would respond to certain immunotherapies, a finding described in November 2017 in the journal Nature. To further improve such models, “we work with clinicians, oncologists, immunologists, geneticists, and others to try to round out the full picture of how the immune system interacts with cancer,” Dr. Greenbaum says. “This is a very vibrant time in cancer immunotherapy.”

Watch the video from the Pershing Square Sohn Cancer Research Alliance

Harvard Business Review: How Mount Sinai Health System Fosters Collaboration to Fight Cancer

Oct 3, 2018 | Featured, Research

Samir Parekh, MD

In an article published in the Harvard Business Review, Joel Dudley, PhD, Mount Sinai Professor in Biomedical Data Science at the Icahn School of Medicine at Mount Sinai and Executive Vice President for Precision Health for the Mount Sinai Health System, and Samir Parekh, MD, Associate Professor, Medicine (Hematology and Medical Oncology), and Oncological Sciences, write about the unique partnership between researchers and doctors at Mount Sinai who are using advanced computer analytics to treat blood and bone marrow cancers.

Joel Dudley, PhD

“The Mount Sinai Health System is organized differently from most, as one integrated institution. Doctors from the seven Mount Sinai hospitals work side by side with researchers from the Icahn School of Medicine at Mount Sinai,” the authors write.

“Indeed, many clinicians also have Sinai research labs. If a clinician and a researcher devise a viable idea to solve a medical problem, they are free to join forces and pursue the project. This makes it possible to rapidly bring a finding from the lab bench to the patient bedside.”

Read the full article in the Harvard Business Review

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