2019 Mount Sinai Health Hackathon Winners

The three team finalists were: George:  Katie Depue, David Koellhofer, and Brendan Reilly.  Deliberate: Marc Aafjes, Michael Balangue, Do Hyung Kwon, Hansaim Lim, and Paulo Serodio. Deep Brain Precision: John Di Capua, Taylor Miller, Ashley So, and Danielle Soldin.

One hundred eighty medical and graduate students, and others, formed 19 teams to participate in the fourth annual Mount Sinai Health Hackathon in October. The 48-hour competition, held over the weekend leading up to the SinaInnovations Conference, challenged the participants to create novel health care solutions that would expand the limits of human performance.

Three teams each received checks totaling $2,500 and will have the opportunity to pitch their ideas again in 2020 at Mount Sinai’s Innovation Showcase before a group of entrepreneurs and venture capitalists. They will be joined by a fourth wild-card team chosen from the non-finalists.

Scott L. Friedman, MD, Dean for Therapeutic Discovery, and Chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, told the participants, “We started this event four years ago as part of a larger effort to spur innovation. This is really the embodiment of our values about teamwork and doing great things.”

The three team finalists were:

Deliberate: Improving the quality of care in psychotherapy through confidential recording and analysis. Team members: Marc Aafjes, Michael Balangue, Do Hyung Kwon, Hansaim Lim, and Paulo Serodio.

George: An artificial intelligence application that allows dialysis providers to optimize scheduling and improve a clinic’s efficiency. Team members: Katie Depue, David Koellhofer, and Brendan Reilly.

 Deep Brain Precision: An app that would allow physicians to monitor a patient’s progress after receiving deep brain stimulation for Parkinson’s disease and other motor disorders. Team members: John Di Capua, Taylor Miller, Ashley So, and Danielle Soldin.

Sponsors and partners: Accenture; Altice Business; Cisco; Farmer’s Fridge; Kitware; PepsiCo; Persistent Systems; the National Center for Advancing Translational Sciences, National Institutes of Health; and the Christopher & Dana Reeve Foundation.

Annual Gala Champions Prostate Cancer Research

Ash Tewari, MBBS, MCh, left, and Arthur Blank

The Milton and Carroll Petrie Department of Urology at the Icahn School of Medicine at Mount Sinai raised more than $1 million at its Fourth Annual Prostate Cancer Research Gala on Wednesday, November 6, to support patient care, research, prevention, and education. Roger Goodell, Commissioner of the National Football League (NFL), and Don Garber, Commissioner of Major League Soccer (MLS), were Co-Chairs of the event, held at Cipriani 42nd Street. Television host Seth Meyers was the emcee.

The gala honored Arthur Blank, owner of the NFL’s Atlanta Falcons and MLS’s Atlanta United; and Nina Bhardwaj, MD, PhD, Professor of Medicine (Hematology and Medical Oncology) and Director of Immunotherapy at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

“We’re grateful to Mr. Blank and Dr. Bhardwaj for their support in advancing our understanding of prostate cancer,” said Ash Tewari, MBBS, MCh, Chair of the Department of Urology at the Mount Sinai Health System and the Kyung Hyun Kim, MD Professor of Urology at the Icahn School of Medicine, who spearheaded the gala.

Nina Bhardwaj, MD, PhD

Mr. Blank, owner and Chairman of the Blank Family Businesses and a member of The Milton and Carroll Petrie Department of Urology Chairman’s Board, said, “The work being done by Mount Sinai has forever changed the course of research and medicine. I feel beyond fortunate to have been one of the lives saved because of their work and will continue to be a champion for their efforts.”

The gala kicked off the three-day 2019 International Prostate Cancer and Urology Symposium at The Mount Sinai Hospital, which featured in-depth training and lectures from more than 100 urologists, surgeons, oncologists, and other providers. Guest speaker Deepak Chopra, MD, FACP, a renowned pioneer in integrative medicine and personal transformation, discussed the mind/body cancer connection.

Fifth Annual Mount Sinai Innovation Awards

Erik Lium, PhD, Executive Vice President, Mount Sinai Innovation Partners, center, presents the Mount Sinai Inventor of the Year Award  to Edward Schuchman, PhD, and Calogera Simonaro, PhD

Individuals and teams from the Mount Sinai Health System were honored for significant advances in biomedical research, technology, and medicine at the fifth annual Mount Sinai Innovation Awards ceremony, which was held Monday, October 14, in conjunction with the SinaInnovations conference.

Two faculty members from the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, Edward Schuchman, PhD, Professor, and Calogera Simonaro, PhD, Research Professor, received the Mount Sinai Inventor of the Year Award for their discovery of the drug pentosane polysulfate sodium for the treatment of mucopolysaccharidosis (MPS), a rare and potentially fatal disease that affects the skeletal system, skin, heart, brain, and other organs. Their work has led to exclusive licenses with Paradigm Biopharmaceuticals, Ltd, and ReqMed Company, Ltd.

The Mount Sinai Deal of the Year Award for RenalytixAI was given to Barbara Murphy, MD, Murray M. Rosenberg Professor of Medicine and Dean for Clinical Integration and Population Health; Steven Coca, DO, Associate Professor of Medicine (Nephrology); and Girish Nadkarni, MD, Assistant Professor of Medicine (Nephrology). RenalytixAI is the first AI-enabled diagnostic for kidney disease to be publicly announced as a Breakthrough Device designation by the U.S. Food and Drug Administration. Dirk Hubmacher, PhD, Assistant Professor of Orthopedics, and Tim Ahfeldt, PhD, Assistant Professor of Neuroscience, and Neurology, received the Faculty Idea Prize for their work with disorders that involve dysregulation of the extracellular matrix (ECM).

Seventeen innovators received the 4D Technology Development Program Award for four projects:

  • Novel inhibitors via an unexplored epigenetic strategy in cancer treatment: Emily Bernstein, PhD; Robert DeVita, PhD; Chiara Vardabasso, PhD; and Roberto Sanchez, PhD.
  • Detachable balloon-sheath microcatheter for improved flow control in transvenous and transarterial liquid embolization: Anthony Costa, PhD; Kurt Yaeger, MD; Thomas Oxley, MD, PhD; Alejandro Berenstein, MD; and Peter Backeris, ME.
  • Novel phase-shifting retinal tamponade: Avnish Deobhakta, MD; Richard Rosen, MD; Sean Ianchulev, MD, MPH; and Christopher Frenz, PhD.
  • Multitasking deep neural nets for improving breast cancer diagnosis from digital screening mammography: Li Shen, PhD; Weiva Sieh, MD, PhD; Laurie R. Margolies, MD; and Joseph H. Rothstein, MS.

The Annual Dean’s Healthcare System Award went to Laurie Keefer, PhD; Ksenia Gorbenko, PhD; Marla C. Dubinsky, MD; Stacy Tse, PharmD; Laura Manning, MPH, RD; and Jordyn Feingold, MAPP, on behalf of the GRITT-IBD Team (Gaining Resilience Through Transitions for patients with Inflammatory Bowel Diseases) and its interdisciplinary collaboration in service of optimal patient care.

Five individuals received Trainee Innovation Idea Awards:

MD student Daniel Ranti: Automated generation of discharge summaries using deep learning.

PhD student Arpit Dave: PatchAid, a possible treatment for vitiligo, a skin disease.

Postdoctoral fellows Eugenie Martineau, PhD, and Enrica Piras, PhD: Vaginal Lactobacillus spray for infants delivered by C-section.

House staff physician Kurt Yaeger, MD: Arteriovenous malformation microcatheter.

 Jones Day was the premier sponsor.

Ten Renowned Mount Sinai Faculty Members Honored at Convocation

Front row, from left: Florian Krammer, PhD; Sundar Jagannath, MBBS; Fred R. Hirsch, MD, PhD; Lakshmi A. Devi, PhD; Joshua B. Bederson, MD; and Dennis S. Charney, MD. Back row, from left: James S. Tisch; Sarah E. Millar, PhD; Roxana Mehran, MD; Avi Ma’ayan, PhD; Daniel M. Labow, MD; and Nathalie Jette, MD, MSc.

 

The 2019 Convocation Ceremony honored 10 renowned faculty members at the Icahn School of Medicine at Mount Sinai who have advanced the fields of neurosurgery, molecular pharmacology, oncology, bioinformatics, vaccinology, population health, cardiovascular clinical research, and gene and cell medicine:

JOSHUA B. BEDERSON, MD
Leonard I. Malis, MD/Corinne and Joseph Graber Professor of Neurosurgery

Joshua B. Bederson, MD, Professor and System Chair of the Mount Sinai Health System’s Department of Neurosurgery, is widely recognized as one of his generation’s leading skull base and cerebrovascular surgeons. He is a world leader in developing advanced intraoperative applications of digital visualization technologies, augmented reality, and microscope integration. As System Chair, he has led the department through a period of extraordinary growth to become one of the largest and most respected neurosurgery programs in the nation. Dr. Bederson serves as Co-Director of the Skull Base Surgery Center and Pituitary Care and Research Center, and has performed more than 4,000 neurosurgical operations at Mount Sinai.

He joined Mount Sinai and founded the Cerebrovascular Disorders Clinical Program in 1992, where he established the first basic science laboratory in the Department of Neurosurgery. Dr. Bederson developed models of stroke and subarachnoid hemorrhage and became the first Mount Sinai neurosurgeon to receive an NIH-RO1 as principal investigator. His academic activities have led to more than 130 peer-reviewed publications. He was appointed Vice Chair of the Department of Neurosurgery and Neurosurgery Residency Director in 2001. An advocate for cross-department cooperation, he fostered collaborative efforts with Mount Sinai’s Neurology Stroke Program, Otolaryngology Skull Base and Otology programs, The Tisch Cancer Institute, and Translational Neuroscience Center. He was appointed Chair of Neurosurgery in 2008.

Dr. Bederson is a leader in neurosurgical technology development. In 2015, in partnership with Anthony B. Costa, PhD, he co-founded the Neurosurgery Simulation Core, a digital technology research group dedicated to developing augmented and virtual reality for clinical neurosurgery application. His successful innovation leadership has led to the creation of Sinai BioDesign, a neuroscience-driven medical device incubator, and AISINAI, a group of scientists, physicians, and researchers dedicated to developing artificial intelligence platforms that enhance patient care. Dr. Bederson’s fostering of neurosurgical innovation contributed to the development of a new biomedical engineering and imaging institute, launching in 2021.

LAKSHMI A. DEVI, PhD
Mount Sinai Professor in Molecular Pharmacology

Lakshmi A. Devi, PhD, is Dean of the Office of Academic Development and Enrichment, and a Professor in the Departments of Pharmacological Sciences, Neuroscience, and Psychiatry. She is an internationally recognized leader in molecular neurobiology and pharmacology. Among her ground-breaking scientific discoveries are the demonstration that membrane proteins such as G protein-coupled receptors form interacting complexes and these serve as novel therapeutic targets. Dr. Devi’s group has identified compounds targeting these complexes; efforts are currently underway to develop these as drugs for the treatment of chronic pain, substance abuse and addiction. Dr. Devi’s recent projects include identifying and characterizing novel brain receptor systems involved in the regulation of feeding and reward-related behaviors.

Dr. Devi is the author of more than 200 papers and review articles in the areas of molecular neurobiology and drug discovery, as well as the editor of seven books. Among her honors and awards are the Senior Scientist Research and Mentorship Award, the Gaisman Frontiers in Biomedical Research Award, NIH MERIT Award, International Narcotics Research Conference Founder Award and Winter Conference of Brain Research Pioneer Award. Dr. Devi is an elected Fellow of the American Association for the Advancement of Science and a member of the Advisory Council of National Institute on Drug Abuse, National Institutes of Health (NIH).

Dr. Devi became Dean of the Office of Academic Development and Enrichment in 2014. In this role, she established a school-wide mentoring program which helps each faculty member clarify their aspirations for research, education, and leadership and connects them with the resources to strengthen and accomplish their goals. This is achieved through workshops, seminars, and panel discussions that connect faculty across the Mount Sinai Health System, thereby promoting mentorship, collaboration and leadership development.

A native of India, Dr. Devi received her Bachelor’s and Master’s degrees from the University of Mysore, India, and her PhD degree from the University of Windsor, Canada. She obtained post-doctorate training in Neurochemistry at the Addiction Research Foundation in Palo Alto, California and in Molecular Neurobiology at the Vollum Institute, Oregon. Dr. Devi joined the faculty of Pharmacology at New York University School of Medicine and in 2002 moved to the Icahn School of Medicine at Mount Sinai as a Professor of Pharmacology and Systems Therapeutics.

FRED R. HIRSCH, MD, PhD
Joe Lowe and Louis Price Professor of Medicine

Fred R. Hirsch, MD, PhD, is Executive Director of the newly created Center for Thoracic Oncology at the Icahn School of Medicine at Mount Sinai, which is a multidisciplinary center focusing on development of translational and clinical science within lung cancer and mesotheliomas, including development of innovative clinical trials. A focus for the Center is screening, early detection, and management of early stage lung cancer. Dr. Hirsch is also Associate Director of Biomarker Discovery at The Tisch Cancer Institute; and Professor of Medicine at the Icahn School of Medicine of Mount Sinai.

Dr. Hirsch has worked in clinical and translational research in lung cancer for more than 25 years. His current research has helped to identify and validate prognostic markers for lung cancer outcomes and biomarkers for personalized lung cancer therapies that illustrate how these therapies work and who will likely benefit from such treatment.

Prior to joining Mount Sinai in 2019, Dr. Hirsch spent 18 years as Professor of Medicine and Pathology at the University of Colorado and five years as CEO of the International Association for the Study of Lung Cancer. He has been the recipient of awards and honors, including the Wuan Ki Hong Lectureship Award, the Addario Foundation Lecture Award, the Japanese Lung Cancer Society Merit Award, and the IASLC Mary Matthews Award for Translational Research in Lung Cancer. Dr. Hirsch has contributed to more than 400 publications in peer-reviewed journals.

Dr. Hirsch earned his medical and doctorate degrees from the University of Copenhagen, Denmark.

SUNDAR JAGANNATH, MD
Mount Sinai Professor in Multiple Myeloma

A renowned expert in the research and treatment of multiple myeloma and bone marrow transplantation, Sundar Jagannath, MD, is Director of the Multiple Myeloma Program at The Tisch Cancer Institute and Professor of Medicine, Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai.

The Multiple Myeloma Program is a leader in patient care and translational research for this relatively rare cancer of the bone marrow and is the largest of its kind in New York City and one of the largest in the country. Dr. Jagannath and his team treat a high volume of patients, including more than 400 new patients each year, providing novel, precision medicine therapies that offer the best chance for good outcomes with a high quality of life.

Dr. Jagannath has published more than 180 peer-reviewed articles in top publications, including the New England Journal of Medicine, Blood, the Journal of Clinical Oncology and Cancer. He has presented more than 150 abstracts and authored nearly 30 book chapters. He is editor-in-chief of Clinical Lymphoma, Myeloma & Leukemia and a board member for the Society of Hematologic Oncology. He is the recipient of the distinguished 2018 Fellow of the American Society of Clinical Oncology Award (FASCO) for his extraordinary volunteer service, dedication, and commitment to the American Society of Oncology, the practice of clinical oncology, and people with cancer. In 2003, he received the Humanitarian Award from the Multiple Myeloma Research Foundation.

A board-certified specialist in internal medicine and medical oncology, Dr. Jagannath received his medical degree at Maharaja Sayajirao University Medical Center in Baroda, India, and continued his medical training with a fellowship in immunovirology at McMaster University Medical Center in Hamilton, Ontario, Canada.

NATHALIE JETTE, MD, MSc, FRCPC
Bluhdorn Professor of International Medicine

Nathalie Jette, MD, MSc, FRCPC, is a Professor of Neurology and Population Health Science and Policy at the Icahn School of Medicine at Mount Sinai. She is a health services researcher, epileptologist, Vice Chair for Clinical Research Neurology, and Chief of the Division of Health Outcomes and Knowledge Translation Research across the Mount Sinai Health System.

As part of her research program, Dr. Jette studies appropriateness and quality-of-care, disparities in care, health outcomes (especially surgical) and psychiatric comorbidities, and determines how best to optimize these outcomes in persons living with epilepsy and other neurological conditions. She is seeking to improve quality of life in those living with neurological conditions regionally, nationally and internationally, through her strong international collaborations with academic researchers, patient advocacy groups and organizations such as the International League Against Epilepsy, the International Bureau for Epilepsy, and the World Health Organization. Her team uses a variety of data sources (e.g. electronic health records, administrative data, registry data) and statistical approaches to study neurological outcomes and to develop prediction tools and decision models to help clinicians provide the best possible care to persons living with neurological conditions. She is also involved in knowledge translation research, including development of e-tools and apps, to enhance the dissemination of evidence-based practice to improve epilepsy and other neurological outcomes.

Dr. Jette earned her medical degree from the University of Ottawa Faculty of Medicine, where she also completed her residency in Neurology. She followed with a fellowship at Columbia University. She has been the recipient of more than 50 research, teaching and clinical awards, including the International League Against Epilepsy Ambassador for Epilepsy Award in 2017. She also maintains an active epilepsy practice within the Mount Sinai Health System.

FLORIAN KRAMMER, PhD
Mount Sinai Professor in Vaccinology

Florian Krammer, PhD, is a Professor of Microbiology at the Icahn School of Medicine at Mount Sinai whose work focuses on understanding the mechanisms of interactions between antibodies and viral surface glycoproteins and on translating this work into novel, broadly protective vaccines and therapeutics. The Krammer Laboratory, which is part of the NIH-funded Centers for Excellence in Influenza Research and Surveillance (CEIRS), is focused mainly on the influenza virus, but is also working on the Zika virus, hantaviruses, filoviruses, and arenaviruses.

Dr. Krammer received his training in biotechnology and applied virology at the University of Natural Resources and Life Sciences in his native Austria, where he established various expression systems for antigens using insect cells/baculovirus, mammalian cells, bacteria, yeast, and plants. His post-doctoral work with Peter Palese, PhD, Chair of the Department of Microbiology, focused on the development of broadly neutralizing anti-hemagglutinin stalk antibodies and the design of a universal influenza virus vaccine. The results of these studies have been very promising: after successful testing in animal models, clinical testing with this universal influenza virus vaccine is currently ongoing.

Dr. Krammer has published more than 160 papers, is a member of the editorial boards of the Journal of Virology, Plos One, Vaccine, MDPI Vaccines and Heliyon, and is a prolific peer reviewer for more than 50 journals. He is also a former member of the Edward Jenner Society Young Investigator Program, and is scientific advisor for PathSensors and a Distinguished Scientific Advisor for the Trudeau Institute. Finally, Dr. Krammer is on the organizing committee of the Vaccine Technology and ESWI conference series.

DANIEL M. LABOW, MD
Eugene W. Friedman, MD Professor of Surgical Oncology

Daniel M. Labow, MD, Chair of Surgery at Mount Sinai West and Mount Sinai St. Luke’s, is a board-certified surgeon with a specialty in surgical oncology. He established himself at The Mount Sinai Hospital in 2004 after studying medicine at a unique combined medical school, the Dartmouth-Brown Medical Program. He completed his general surgery residency at the University of Chicago, and conducted two years of research during that time at Memorial Sloan Kettering Thoracic Oncology Lab. He returned to Sloan Kettering for his fellowship training in surgical oncology.

Dr. Labow continuously designs processes to facilitate unprecedented patient care and instills this practice on the new generation of physicians while working tirelessly to advance the educational program at Mount Sinai. He established the Surgical Oncology Fellowship in 2007, which is now one of the only two ACGME-approved fellowships in Surgical Oncology in New York City, and has served as Program Director throughout this time.

Dr. Labow’s clinical and research interests include the diagnosis and treatment of a broad range of both primary and metastatic malignancies, including gastric and esophageal cancer, pancreatic neoplasms, primary and metastatic liver malignancies, biliary tract disease, colon and rectal cancer, sarcoma, and melanoma. Dr. Labow’s devotion to research and training allows him to understand the entire spectrum of treatments for these cancers, including investigational approaches to help guide each individual patient along the appropriate treatment’s unique pathway. Moreover, he concentrates on the application of minimally invasive techniques and their role in cancer care.

Initially at The Mount Sinai Hospital and now throughout the Mount Sinai Health System, Dr. Labow established and continues to direct one of the busiest Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) programs in the country. This technique, which combines surgery with intraoperative chemotherapy, has revolutionized the treatment of cancers in the abdominal (peritoneal) lining that stem from colon, gastric, ovarian, and appendiceal cancers, as well as mesothelioma and pseudomyxoma peritonei. Dr. Labow, who has performed more than 500 HIPEC procedures since 2007, recognized the effect the combination procedure has in significantly extending patient survival rates whilst minimizing the known side effects of chemotherapy that are normally administered intravenously.

Dr. Labow’s rapport with his patients, his medical knowledge, and his dedication as a physician contribute to his reputation with patients as well as other physicians.

AVI MA’AYAN, PhD
Mount Sinai Professor in Bioinformatics

Avi Ma’ayan, PhD, is the Director of the Mount Sinai Center for Bioinformatics and a Professor in the Department of Pharmacological Sciences. His laboratory applies computational and mathematical methods to study the complexity of regulatory networks in mammalian cells, and develops algorithms and software to analyze and visualize how intracellular regulatory systems function as networks to control cellular processes such as differentiation, de-differentiation, apoptosis and proliferation. The laboratory’s main focus is in developing methods that link changes in genome-wide gene expression to transcriptional regulators and cell signaling pathways.

The Ma’ayan Lab has developed several popular web-based bioinformatics software tools and databases that enable biologists to perform enrichment analyses, network analysis, and machine learning to find new knowledge about single genes and gene sets. Using these tools and databases, the Ma’ayan Lab works closely with experimentalists on projects that utilize high-throughput experiments to understand cell regulation at the global scale. Thus far, more than 850,000 unique users have accessed the databases and tools developed by the Ma’ayan Lab.

Dr. Ma’ayan was born and raised on a kibbutz in northern Israel. In 1993, he won the Israeli national championship in the 3000 steeplechase, an Olympic track and field event. This achievement earned him a full athletic scholarship at Fairleigh Dickinson University in Teaneck, New Jersey, where he majored in Computer Science and competed in NCAA Division I athletics. After graduation, he worked as a software engineer for five years in two mid-size companies, earned his PhD at Mount Sinai, and joined the faculty. Since then, Dr. Ma’ayan and members of his laboratory published over 160 peer reviewed articles and Dr. Ma’ayan has served as the lead principal investigator on NIH grants that have totaled more than $30 million in the past 10 years.

ROXANA MEHRAN, MD
Mount Sinai Professor in Cardiovascular Clinical Research and Outcomes

Roxana Mehran, MD, is an internationally renowned interventional cardiologist and clinical research expert in the field of cardiovascular disease. As Director of the Center for Interventional Cardiovascular Research and Clinical Trials at Mount Sinai, she has built a globally respected academic research center focused on developing randomized clinical trials, outcomes research projects and high impact academic publications.

A prolific researcher, Dr. Mehran has served as principal investigator for numerous global studies, developed risk scores for bleeding and acute kidney injury, participates regularly in developing clinical guidelines, and has authored more than 900 peer-reviewed articles. She has been honored by Clarivate Analytics as one of the most influential scientific minds and highly cited researchers for several consecutive years.

She is a founder and Chief Scientific Officer of the Cardiovascular Research Foundation (CRF) and recently founded Women as One, an independent nonprofit organization dedicated to advancing opportunities for women in medicine. Very active within professional organizations, Dr. Mehran has been the Chair of the Interventional Council for the American College of Cardiology (ACC); Program Chair of the 2016 Annual Scientific Sessions of the Society for Cardiovascular Angiography and Interventions (SCAI), where she is also a co-founder of the Women in Innovations (WIN) Committee; and is a member of the American Heart Association’s (AHA) Go Red for Women Scientific Advisory Group.

Dr. Mehran earned her medical degree from St. George’s University School of Medicine and completed fellowships in cardiovascular disease and interventional cardiology at Mount Sinai. Prior to joining Mount Sinai in 2010, Dr. Mehran held appointments at Columbia University Medical Center, Lenox Hill Hospital, and Washington Hospital Center. She is a recipient of several awards, including the 2016 American College of Cardiology Bernadine Healy Leadership in Cardiovascular Disease award, the 2018 Nanette Wenger Award from Women’s Heart for excellence in research and education, and the 2019 Ellis Island Medal of Honor.

SARAH E. MILLAR, PhD
Lillian and Henry M. Stratton Professor of Gene and Cell Medicine

Sarah E. Millar, PhD, is Director of the Black Family Stem Cell Institute and a Professor in the Department of Cell, Developmental and Regenerative Biology and The Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai. Her research focuses on cell-cell signaling and epigenetic mechanisms controlling development, stem cell function and regeneration of epithelial organs including the skin epidermis and ectodermal appendages such as hair follicles, mammary glands, taste papillae, and teeth.

Dr. Millar and her co-workers identified Wnt/beta-catenin signaling as a key pathway required for initiating the formation of ectodermal appendages from multipotent cells in mammalian embryos. By analyzing genetic mouse models and tissues from human patients carrying mutations in the WNT10A gene, they showed that Wnt signaling plays key roles in regulating the functions of a wide variety of adult epithelial stem cells, as well as controlling specialized differentiation programs in palmoplantar skin. They are currently using patient-derived and gene edited iPS cells to model human genetic skin disease in vitro and test novel therapeutic approaches.

Dr. Millar is an Editorial Board member for Developmental Cell and Experimental Dermatology, and Deputy Editor for the Journal of Investigative Dermatology. She has received several awards in recognition of her research, including an NIH MERIT Award for her work on Wnt signaling in the skin, and the 2017 William Montagna Lectureship Award of the Society for Investigative Dermatology.

After graduating from Cambridge University, Dr. Millar received her PhD from the University of London and then trained as a postdoctoral fellow at the National Institutes of Health and at Stanford University. Before joining Mount Sinai in 2019, Dr. Millar was The Albert M. Kligman Professor of Dermatology, Vice Chair for Basic Research in the Department of Dermatology, and Director of the Skin Biology and Diseases Resource-based Center at the University of Pennsylvania’s Perelman School of Medicine.

 

Pioneering Discoveries in Inflammatory Bowel Disease

Precise cell types that correlate with a patient’s resistance to the standard therapy for Crohn’s disease—anti-inflammatory drugs called TNF inhibitors—have been identified for the first time by researchers at the Icahn School of Medicine at Mount Sinai and published in the September 5, 2019, issue of Cell. TNF inhibitors are used in Crohn’s disease to stop inflammation, but as many as 30 percent of patients do not respond to this treatment and require surgical intervention within 10 years after diagnosis. The new discovery could open the door to identifying biomarkers and tailoring better therapeutic options for these patients.

At the same time, two studies in the September 26, 2019, issue of The New England Journal of Medicine validate effective therapies for patients with treatment-resistant ulcerative colitis (UC), a chronic inflammatory disease of the large intestine. Both of these studies were led by Bruce E. Sands, MD, the Dr. Burrill B. Crohn Professor of Medicine and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai.

The results of Dr. Sands’ first clinical trial validated ustekinumab as a UC therapy. In the phase lll clinical trial, Dr. Sands and his team tested more than 900 patients with moderate-to-severe UC who were unable to tolerate or had an inadequate response to TNF inhibitors. The results from this trial led the U.S. Food and Drug Administration in October to approve ustekinumab for adult patients with moderately to severely active ulcerative colitis. Ustekinumab had previously been approved for treating patients with Crohn’s disease.

The second study was the first ever head-to-head comparison of two biologic therapies for inflammatory bowel disease: vedolizumab and adalimumab. In total, 769 participants with moderate to severe UC were recruited for this randomized phase 3b study, with 383 patients receiving 300 mg of vedolizumab intravenously at weeks 0, 2, and 6, then every 8 weeks, and with subcutaneous placebo injections, and 386 receiving placebo intravenously and adalimumab subcutaneously (160 mg week 1, 80 mg week 2, and then 40 mg every 2 weeks).

Researchers found that patients who received vedolizumab achieved significantly higher week 52 clinical remission rates than patients who received adalimumab (31.3% versus 22.5%) and endoscopic improvement (39.7% versus 27.7%). The remission rates for both therapies were similar among the 20% of participants who had previous exposure to TNF inhibitors.

In the study in Cell, Mount Sinai researchers used single-cell RNA sequencing and CyTOF technology to examine inflamed and noninflamed small intestine tissue samples as soon as they were removed from Crohn’s disease patients. Looking at the lesions in real time on a single-cell level, the investigators identified the immune cells and the circulating blood cells and their interactions, and mapped a landscape of thousands of cells in the lesion.

“Single-cell profiling provides unprecedented information on the make-up of the disease,” says co-corresponding author Miriam Merad, MD, PhD, Director of the Precision Immunology Institute and the Human Immune Monitoring Center at the Icahn School of Medicine at Mount Sinai. “This type of analysis will help us understand why patients respond to or resist specific treatment and what else we could
be targeting.”

Co-corresponding author Judy H. Cho, MD, Director of The Charles Bronfman Institute for Personalized Medicine, and Ward-Coleman Professor of Translational Genetics and Medicine at the Icahn School of Medicine at Mount Sinai, says, “We designed this study in a way that defines inflammation with unprecedented precision using immunology and computational biology to get a better understanding of this disease.”

Computational biologist Ephraim Kenigsberg, PhD, Assistant Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, and co-corresponding author of the Cell study, says, “Single-cell analysis revealed different cellular signatures, and when we integrated this with larger data sets, including clinical trials, we were able to make our findings clinically relevant.”

Landmark Study on Aspirin for High-Risk Heart Patients Is Led by Mount Sinai

Roxana Mehran, MD, center, principal investigator of the TWILIGHT study, with leading collaborators in the study, from left, Annapoorna S. Kini, MD; Valentin Fuster, MD, PhD; Juan J. Badimon, PhD; George Dangas, MD, PhD; Usman Baber, MD, MS; and Samin K. Sharma, MD.

High-risk patients who have undergone a coronary stent procedure may not require long-term aspirin, according to a groundbreaking global study led by Roxana Mehran, MD, Director of the Center for Interventional Cardiovascular Research and Clinical Trials, Mount Sinai Heart, and the Mount Sinai Professor in Cardiovascular Clinical Research and Outcomes, Icahn School of Medicine at Mount Sinai.

“We showed that withdrawal of aspirin after three months in patients already on ticagrelor, a potent antiplatelet regimen, reduced bleeding significantly without the harm of increasing death or heart attacks,” says Dr. Mehran, global principal investigator of “Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention” (TWILIGHT), which was published in September 2019 in The New England Journal of Medicine.

Says Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, “I am proud of our team for achieving such great success with our collaborators in the United States and around the world on this pioneering clinical trial.”

The study addresses long-standing questions about the treatment of high-risk patients after percutaneous coronary intervention (PCI), also known as angioplasty, which opens blocked arteries and restores normal blood flow to the heart. “The same patients who are at high risk for ischemic events—such as heart attack or stroke caused by blocked blood vessels—are also at high risk for bleeding events,” says Dr. Mehran. “You have to find the right balance in therapies, and it is not easily found.”

In the current standard of care, high-risk patients who have received a cardiac stent are advised to take dual-antiplatelet therapy (DAPT)—both aspirin and a drug from a class of strong antiplatelet medications called P2Y12 inhibitors, of which ticagrelor is one. These two medications prevent heart attack or stroke by reducing the risk of blood clots. DAPT combines two drugs with similar effects, Dr. Mehran says, like using both “a shotgun and slingshot” for self-defense. TWILIGHT examined the impact of taking ticagrelor alone versus ticagrelor plus aspirin on clinically relevant bleeding among high-risk patients.

Investigators enrolled 9,006 patients at 187 sites in the United States, Canada, Europe, and Asia. They were high risk, meaning they met criteria such as having long or complex lesions in coronary arteries, or disorders such as diabetes or chronic kidney disease. All patients had undergone PCI with at least one drug-eluting stent and were prescribed aspirin and ticagrelor. After a three-month course of DAPT, the 7,119 patients without major adverse events were randomized to take either DAPT or ticagrelor with a placebo for 12 months. Among patients who took DAPT, 7.1 percent had major bleeding, compared with 4 percent of those who took ticagrelor and a placebo, and there was no difference in the risk for heart attack, death, or stroke between the groups. “This simpler approach saved many bleeding events and preserved the benefit of the single potent blood thinner,” says Usman Baber, MD, MS, Assistant Professor of Medicine (Cardiology), Icahn School of Medicine, who was lead author of the study with Dr. Mehran, and Chair of the TWILIGHT Clinical Coordinating Center.

The results were corroborated by a sub-study led by Juan J. Badimon, PhD, Professor of Medicine (Cardiology), and Director of Atherothrombosis Research at Mount Sinai Heart. Using a tool he is renowned for developing, the Badimon Chamber, researchers measured the thrombogenicity or “stickiness” of the blood in a group of 42 TWILIGHT patients, testing samples taken before and after they completed the 12-month treatment. Like the clinical study, the study of blood samples found that withdrawing aspirin caused no additional clot formation.

“The findings are particularly important and have the potential to change PCI practice,” says a co-author of the TWILIGHT study, Samin K. Sharma, MD, Director of Clinical and Interventional Cardiology at The Mount Sinai Hospital, and Anandi Lal Sharma Professor of Medicine in Cardiology.

Dr. Mehran expressed profound gratitude to Mount Sinai, which was the global sponsoring organization of TWILIGHT. “This study gives you an idea of the things we are able to do as an institution,” she says, “bringing together all of our resources to answer important questions for physicians and enhance the outcome for patients.”

The drug ticagrelor is made by AstraZeneca, which provided Mount Sinai with an unrestricted grant to perform the investigator-initiated study. Dr. Mehran has received financial compensation as an advisory board member for AstraZeneca in the past, and she and Dr. Baber have received consulting fees from AstraZeneca in the past.

Pin It on Pinterest