Kleiderer-Pezold Professor of Biochemistry, Director of the W.M. Keck Center for Transgene Research
University of Notre Dame
My laboratory studies the structure, function and activation of proteins that participate in blood coagulation and blood clot dissolution. The in vivo mechanisms of the roles of these proteins in these processes are being addressed through targeted gene-replacement approaches and corresponding in vitro structure-function studies of these proteins are being studied by the most modern biophysical techniques, e.g., X-ray crystallography, NMR, Cryo-EM. Most of these proteins exist in an inactive state in plasma and thus must be activated to enzymes to exhibit their functional properties. The molecular events involved in the activation and analysis of the concomitant structural changes that occur in the protein are investigated by modern biochemical techniques. Major tools of the laboratory involve cloning, mutagenesis and expression of variant recombinant proteins and individual protein domains, immunochemical studies of the proteins, as well as physical and chemical analysis of their solution structures. The properties of the proteins are then related to their functions. To determine the biological functions of genes encoding coagulation and clot-dissolving proteins in hemostasis, cancer, inflammation, bacterial invasion, wound healing, embryonic implantation and development, metastases, and atherosclerosis, gene deletion and other gene targeting experiments are being performed in mice, in conjunction with phenotyping of these animals. Such studies are expected to provide important information on the development and progression of these disease states.