Director of the BMT Program
Professor of Oncology and Pediatrics
Dr. Cooke joined the faculty of the Sidney Kimmel Cancer Center in 2013. He was recruited as the Herman and Walter Samuelson Professor in Oncology to serve as the overall director of Pediatric BMT Program. Dr. Cooke’s scientific and clinical interests have been directed toward understanding the immunologic mechanisms that contribute to the development of graft-versus-host disease (GVHD) and non-infectious lung injury both in the acute and chronic settings.
His laboratory focuses on four major areas: First, we are studying the role of endovascular injury and activation in the recruitment of donor myeloid and lymphoid effector cells to sites of target organ injury, specifically the lung. We also have demonstrated that TNFα functions as both an effector and facilitator of lung inflammation in experimental IPS, and that inflammation can be mitigated with TNFα neutralization. These observations led to the development of clinical trials, wherein neutralization of TNFα has been shown to provide a therapeutic benefit in pediatric transplant recipients with IPS.
Second, we are exploring physiologic mechanisms responsible for chronic inflammation, dysregulated repair and collagen deposition during the development of fibrotic lung injury after BMT. Third, in collaboration with investigators from Case Western, the laboratory has uncovered a heretofore unknown role for Cdk5, a ubiquitously expressed serine/threonine kinase, in T cell activation, migration and the generation of memory. Using novel chimeric and T cell-restricted Cdk5 gene deleted mice, we are currently exploring the contribution of Cdk5 in the induction of GVHD and graft-versus-leukemia activity following BMT. Finally, subsets of non-blood forming but bone marrow-derived stem cells called mesenchymal stem cells or MSCs have recently been discovered and can be expanded ex vivo while retaining their pluripotency. These cells have the capacity to both suppress the immune system and repair damaged tissue. While the co-administration of such cells has shown promise in optimizing transplantation outcomes in early phase clinical studies, the mechanisms by which these cells are protective remain enigmatic. The laboratory is using established animal models to identify the key points in the pathogenesis of GVHD and lung dysfunction where MSCs are operative.