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Blood coagulation plays many important roles in health and disease. Aside from clotting blood, coagulation proteases also contribute to such processes as angiogenesis, cell proliferation, and cell migration. Currently, we are focused on two areas: I. Alternatively spliced Tissue Factor (asTF) as a therapeutic target in gastrointestinal malignancies. asTF is a soluble form of Tissue Factor (TF), the trigger of blood clotting. We discovered that asTF is elevated in the blood of patients suffering from pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. Mechanistically, asTF protein acts as a cell agonist promoting growth and spread of malignant cells. Our recently developed inhibitory antibody against asTF is currently being tested in animal models. II. Red blood cells (RBC) as novel contributors to vascular dysfunction in acute and chronic inflammatory states. We discovered that RBC can contribute to heightened clotting and obesity-related atherosclerosis, in large part because the levels of pro-inflammatory chemokines bound to RBC increase due to high-fat diet. We hope that these observations will improve our understanding of RBC biology, and help develop new diagnostic and/or therapeutic strategies aimed at ameliorating obesity-related chronic disorders.
University of CincinnatiDepartment of Internal Medicine Division of Hematology & Oncology 231 Albert Sabin Way, ML 0562 Cincinnati, OH 45267-0562
Phone: 513-558-2115 Fax: 513-558-2125 Email: thomp3tr@ucmail.uc.edu