Molecular genetics of plasminogen activation in development, hemostasis, and tumor progression; molecular genetics and biological role of plasminogen activation in development, hemostasis, wound repair, and disease
Jay L. Degen, PhD, is studying the regulation and biological roles of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), the two mammalian enzymes that convert plasminogen to the active serine protease, plasmin.
The PA/plasmin system of proteases is of particular interest because of its apparent dual function in the lysis of vascular fibrin clots (fibrinolysis) and the degradation of extracellular matrix in tissue remodeling and cell migration events.
Over the last few years, Dr. Degen's lab has generated and characterized gene-targeted mouse lines with deficits in the factors that are the foundation of the coagulation and fibrinolytic cascades, including fibrinogen-, plasminogen-, plasminogen activator-, and plasminogen activator receptor-deficient mouse lines.
These unique experimental animals are being intensively analyzed with regard to a wide range of phenotypic properties, including hemostasis, wound healing, angiogenesis and tumor biology.
Education and Training
PhD: University of Washington, 1983.
View PubMed Publications
Palumbo JS, Degen JL. Mechanisms coupling the hemostatic system to colitis-associated cancer. Thromb Res. 2010 Apr;125 Suppl 2:S39-43.
Shanmukhappa K, Matte U, Degen JL, Bezerra JA. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem. 2009 May 8;284(19):12917-23.
Mullins ES, Kombrinck KW, Talmage KE, Shaw MA, Witte DP, Ullman JM, Degen SJ, Sun W, Flick MJ, Degen JL. Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain. Blood. 2009 Jan 15;113(3):696-704.
Adhami F, Yu D, Yin W, Schloemer A, Burns KA, Liao G, Degen JL, Chen J, Kuan CY. Deleterious effects of plasminogen activators in neonatal cerebral hypoxia-ischemia. Am J Pathol. 2008 Jun;172(6):1704-16.
Palumbo JS, Barney KA, Blevins EA, Shaw MA, Mishra A, Flick MJ, Kombrinck KW, Talmage KE, Souri M, Ichinose A, Degen JL. Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function. J Thromb Haemost. 2008 May;6(5):812-9.
Palumbo JS, Degen JL. Mechanisms linking tumor cell-associated procoagulant function to tumor metastasis. Thromb Res. 2007;120 Suppl 2:S22-8.
Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD, Thornton S, Degen JL. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest. 2007 Nov;117(11):3224-35.
Roszell NJ, Danton MJ, Jiang M, Witte D, Daugherty C, Grimes T, Girdler B, Anderson KP, Franco RS, Degen JL, Joiner CH. Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice. Am J Hematol. 2007 Dec;82(12):1044-8.
Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost. 2007 Jul;5 Suppl 1:24-31. Review.
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Hu Z, Barney KA, Degen JL. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood. 2007 Jul 1;110(1):133-41.
Hemostatic factors as determinants of bacterial virulence and host defense. Principal Investigator. National Heart, Lung and Blood Institute. Sep 2006 – Aug 2011. #R01 HL085357.
Thrombin-mediated proteolysis in neuroinflammatory disease. Principal Investigator. National Heart, Lung and Blood Institute. Jul 2009 – Jun 2014. #R01 HL096126.