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James Ferrara

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Primary Appointment: Pediatrics-Hematology/Oncology
Other PIBS Depts.: Cancer Biology
PubMed Name: James L.M. Ferrara
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 DESCRIPTION OF RESEARCH
  My laboratory investigates the immunobiology of bone marrow transplantation (BMT). A major therapeutic benefit of allogeneic BMT resides in the graft versus leukemia (GVL) effect which is mediated by cytotoxic pathways of cytolytic T cells and natural killer cells. The GVL effect is tightly linked to graft versus host disease (GVHD), a major toxicity of BMT. Using well defined mouse models, our research has shown that cascades of inflammatory cytokines amplify GVHD and that blockade of cascade checkpoints can prevent GVHD. Furthermore, many of these anti-inflammatory strategies preserve cytolytic T lymphocyte function, permitting a separation of GVL and GVHD in well defined animal models.

We have recently determined that epithelial targets of GVHD are damaged primarily by cytokines and that neutralization of cytokines can suppress the inflammation of GVHD but preserve beneficial graft versus tumor effects. We have also shown that histone deacetylase inhibitors can prevent inflammatory cytokine release while preserving CTL function and GVL effects. We are investigating the mechanisms of these exciting new strategies with the intent of designing innovative clinical trials.