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 an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the “Honor Roll” of best hospitals in America, ranked No. 15 nationally in the 2016-2017 “Best Hospitals” issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation’s top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai’s Kravis Children’s Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals."
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