Mount Sinai Receives $10 Million Grant to Study Graft vs. Host Disease
Researchers from the Icahn School of Medicine at Mount Sinai have been awarded a $10 million from the National Cancer Institute to explore the cellular and molecular mechanisms of acute graft-versus-host disease (GVHD), a common side effect that occurs after allogeneic bone marrow transplantation (BMT), and to develop novel therapeutic strategies for BMT patients with cancer that begin in the cells of blood-forming tissue or hematologic malignancies. James Ferrara, MD, DSc, Ward-Coleman Professor of Cancer Medicine and Director of the Center for Translational Research in Hematological Malignancies at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, will lead the collaborative project which includes research teams at University of Michigan-Ann Arbor, and Baylor College of Medicine in Texas, as well as a consortium of 20 transplant centers that will conduct trials in GVHD.
GVHD develops when the donor's immune cells attack the patient's normal cells after transplant. Nearly 6,000 patients develop acute GVHD each year and up to 50 percent of these patients will die from the disease. GVHD is the primary cause of transplant-related death.
Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to GVHD, and this grant will fund unique research projects this intestinal environment and the role that it plays in GVHD. The studies seek to understand the ability of microbial metabolites to influence the resistance of intestinal epithelial cells to donor T-cell-mediated damage and the role of the antimicrobial peptide regenerative 3 alpha in protecting intestinal stem cells. Researchers will also design a clinical trial of biomarker-guided therapy to prevent the development of steroid-refractory gastrointestinal GVHD.
“My colleagues and I have developed an exciting prognostic tool to identify those who will get GVHD and those who will not,” explained Dr. Ferrara. “In doing so, we will design treatment to respond to each patient’s disease progression and possibly stop its escalation. The studies are highly significant and translational, and have the potential to impact patients’ care.”
The study will also look at how the microbiome affects immune responses, and the proposed studies will likely have implications not only in gastrointestinal GVHD but in cancer immunotherapy in general. The projects all interact, and the study is highly integrated around a strong central theme of exploring the cellular and molecular mechanisms of GVHD to improve the care for the BMT patients.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.