Grant: CIHR Clinician Scientist - Phase 2

Proper function of the immune system is essential for protection against infectious disease and maintaining human health. During the onset of infection, white blood cells and platelets release signaling molecules known as cytokines, which orchestrate a protective inflammatory response. When cytokine release is de-regulated, excessive inflammation results that causes cell and tissue death and loss of function. This is seen in periodontitis (gum disease), which is characterized by gingival (gum) inflammation and destruction of tooth-supporting connective tissues and bone. The purpose of this grant application is to study the mechanisms and identify the proteins responsible for maintaining the health of periodontal tissues. In addition to regulating blood coagulation (clotting), platelets are emerging as pivotal components of the host inflammatory response. We will study in human and mouse platelets, how infection causes cytokine release. The current project will focus on two major questions. First, we will identify the molecular signals that operate during periodontal infection and learn how these signals affect platelet function. We will also test the hypothesis that a group of proteins known as filamins mediate the release of cytokines from platelets. In this context, an improved understanding of platelet function could have important implications for rational treatment of inflammatory diseases, including periodontitis.