Kenneth R. Cooke, MD
Year elected: 2008
Current membership category: Senior
Johns Hopkins University
The Bunting-Blaustein Cancer Research Building (CRB 1)
1650 Orleans Street, Room 207
Baltimore, MD 21287
United States of America
My scientific interests have centered on understanding the immunologic mechanisms that contribute to the development of idiopathic pneumonia syndrome (IPS) and acute graft-versus-host disease (GVHD), the two most common and life threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT). Data generated using mouse models of human disease support the hypothesis that the lung is a target organ of acute GVHD and is susceptible to two distinct, but inter-related pathways of immune-mediated injury. The first depends upon interactions between donor T cells and host antigen presenting cells and the generation of allo-antigen specific cellular effectors which home to the lung and cause damage and dysfunction. The second involves elements of the innate immune response including donor accessory cells and the effects of inflammatory mediators like TNFalpha and endogenous endotoxin as they interact via a “gut-liver-lung” axis of inflammation. These findings support a paradigm shift away from identifying lung injury after HSCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process involving two distinct, but inter-related pathways of immune mediated injury. Although a role for both lymphoid and myeloid cellular effectors in the development of IPS and GVHD has been established, the mechanisms by which donor leukocytes traffic to GVHD target organs are poorly defined. Current research is focused on determining the roles of endovascular injury and activation, chemokines and adhesion molecules in this context. Importantly, laboratory insights have lead to the development of national, multi-center trials in both adult and pediatric patients with IPS and GVHD.
Johns Hopkins University School of Medicine (Primary)
Stuart C. Ray, MD is the representative at this institution.