Platelets are anucleate cells released from megakaryocytes that circulate in the vascular system. Their importance and function in hemostasis is well known. Our (Drs. Neil Blumberg, Richard Phipps and myself) research interests lie in the emerging concept that platelets have a significant role in the mediation of inflammation and immunoregulation. Of particular interest is the nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), part of a superfamily of ligand-activated receptors involved in transcriptional regulation of genes in energy metabolism and adipocyte differentiation. Several cell types including lymphocytes, fibroblasts, and endothelial cells express PPARgamma. Interestingly, our laboratory has recently demonstrated that human platelets also express PPARgamma and receptor binding of PPARgamma by PPARgamma agonists reduces platelet release of proinflammatory mediators. This is of major significance as platelet activation is linked to several diseases including atherosclerosis, insulin resistance in type II diabetes, and cancer. My goal is to understand the role of platelet PPARgamma in inflammation. This research is conducted in collaboration with the laboratory of Dr. Richard Phipps.
Platelet transfusion can cause a life-threatening inflammatory response. Upon activation, platelets undergo rapid morphological changes, and release bioactive mediators including chemokines, prostaglandins and growth factors that elicit a variety of responses. We will investigate the role of platelet-released proinflammatory mediators in transfusion-associated inflammation and multi-organ failure. Our goal is to develop a therapeutic strategy to reduce the risk of inflammatory responses in patients transfused with platelets.