Biochemistry and Molecular Biology

University of Texas Medical Branch


Faculty

Darrell H. Carney, Ph.D., Professor

Computerized structure of Thrombin showing domains which interacts with different substrates and cell surface receptors.Understanding the molecular regulation of thrombin receptor expression, the signaling pathways used in thrombin-stimulated mitogenesis and chemotaxis, and the role of thrombin and thrombin receptors in the regulation of inflammation and wound healing are primary focuses of the Carney laboratories. In addition to its well characterized role in blood clotting, thrombin stimulates cell proliferation, migration, and/or differentiated functions in most cells (fibroblasts, endothelial cells, epithelial cells, neuronal cells, lymphocytes, etc.) which express one or more specific thrombin receptor component. Thus, thrombin is a potent growth factor and immune modulator.

High-affinity receptors for thrombin were first discovered and demonstrated to be involved in stimulation of cell proliferation by Dr. Carney almost 18 years ago. Since that time, this receptor and the signals that it generates have been extensively studied using biochemical and molecular biological techniques. It is now clear that the receptor has multiple components which are differentially expressed on specific cells. A major effort to clone one of these components is underway using differential display PCR, subtractive hybridization, and expression cloning.

Synthetic peptides that bind to the high-affinity receptor component have been identified and shown to act as agonists and antagonists of thrombin action. The agonist peptides accelerate wound healing in animal models. These peptides have allowed us to better understand the mechanisms by which thrombin initiates inflammation and wound healing and have been used to generate proprietary data for the development of cost effective thrombin peptide products to accelerate wound healing in several different major health care markets.

The development of normal, steroid-treated and diabetic animal models to study effects of thrombin in wound healing provides the opportunity to study the effects of thrombin both in vitro and in vivo. Skin capillary endothelial cells, epithelial cells, and neutrophils are now being used as models to dissect thrombin stimulated changes in expression of integrins, matrix components and cellular regulatory molecules.