James Ferrara, MD, is Principal Investigator on a Program Project (P01) grant from the National Cancer Institute — Cellular and Molecular Studies of Bone Marrow Transplant — which has received continuous funding since 1997, with the most recent renewal extending through 2027. The goal of the P01 is to reduce graft-versus-host disease (GVHD), a major cause of morbidity and mortality after allogeneic stem cell transplant, by elucidating its basic biology, developing laboratory strategies to predict its long term outcomes, and translating findings into novel therapeutic strategies via Phase II clinical trials.
Using pioneering proteomic techniques, the Ferrara Bone Marrow Transplant Laboratory has identified and validated biomarkers for skin, gut, and steroid-resistant GVHD, and developed the first algorithm that predicts GVHD prior to symptom onset. The capacity of biomarkers to guide therapy led to the establishment in 2014 of MAGIC (Mount Sinai Acute GVHD International Consortium), comprising 25 bone marrow transplant centers across the U.S., Europe, and Asia that conduct clinical trials to prevent and treat acute GVHD.
Acute GVHD in the gastrointestinal (GI) tract accounts for the majority of non-relapse mortality. The mechanisms of damage to the GI crypt during GVHD and enhancing its regeneration are the focus of the current funding cycle across the three projects of the P01. Specifically, Project 1, led by Pavan Reddy, MD, at the University of Michigan, and Project 2, led by Dr. Ferrara, focus on the role of mitochondrial damage in intestinal stem cells and the role of the enzyme RIP1 that causes their death. Project 3, led by John Levine, MD, focuses on two risk adapted clinical trials that determine treatment based on GI damage as measured by serum biomarkers.
James L.M. Ferrara, MD, DSc Ward-Coleman Chair in Cancer Medicine Professor and Director, Hematologic Malignancies Translational Research Center The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai
John Levine, MD, MS Professor of Medicine (Hematology and Medical Oncology) and Pediatrics Louis Aledort Clinical Research Professor in Hematology Co-director, Mount Sinai Acute GVHD International Consortium Icahn School of Medicine at Mount Sinai