University of Cincinnati Department of Pediatrics

Jay L. Degen, PhD

Title

Professor

Appointment

Professor of Pediatrics

Email

jay.degen@cchmc.org

Phone

513-636-4679

Fax

513-636-4317

Bio

Jay Degen's laboratory 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.

The molecular cloning of the genes encoding plasminogen, tPA, uPA, uPA-receptor, and PA-inhibitors has permitted the use of both gene-transfer and gene-targeting technologies to manipulate plasminogen activation both in vitro and in vivo.

The long-term objectives of this research program are to:

Define the role of key coagulation and fibrinolytic factors in development reproduction, hemostasis, inflammatory response, and wound repair and
Understand the relationship between hemostatic factors and the pathogenesis of disease, including cancer, atherosclerosis, and sickle cell disease.

An important experimental approach is the genetic manipulation of coagulation and
fibrinolytic factors in mice.

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.

Awards and Honors

Elected Membership in the American Chemical Society, 1978

Elected Membership in American Society for Biochemistry and Molecular Biology, 1989

Established Investigator of the American Heart Association, 1993-1998

"Creativity Award" XIII International Congress on Fibrinolysis and Thrombolysis, June 1996, Barcelona, Spain

Elected Chairman of the 2002 Gordon Conference on Thrombolysis

Elected as Member of the Council of the International Society for Fibrinolysis and Thrombolysis

Member, Council on Arteriosclerosis, Thrombosis and Vascular Biology July, 1998-June 2001

Scientific Advisory Board, Gladstone Intitute of Cardiovascular Disease, 1999-2000

Scientific Subcommittee on Hemostasis, American Society of Hematology, 1997-2000

Japanese Society for the Promotion of Science (JSPS) Fellow, July 1999

Chairman, 2001 Thrombolysis, Fibrinolysis and Extracellular Proteolysis Gordon Conference

Publications, Most Recent

Dr. Degen's publications as listed by PubMed.

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 α_Mβ₂ binding motif.J. Clin. Invest., In Press.

Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense.J. Thromb. Haemost. 5: 24-31, 2007.

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 110: 133-141, 2007.

Adams RA, Bauer J, Flick MJ, Sikorskil S, Nuriell T, Lassmann H, Degen JL, Akassoglou K. The fibrin-derived γ^377-395 peptide inhibits microglia activation and reverses relapsing paralysis in central nervous system autoimmune disease.J. Exp. Med. 204:571-582, 2007.

Zhang G, Kernan KA, Collins SJ, Cai X, Lopez-Guisa JM, Degen JL, Shvil Y, Eddy AA. Plasmin(ogen) Promotes Renal Interstitial Fibrosis by Promoting Epithelial-to-Mesenchymal Transition: Role of Plasmin-Activated Signals.J Am Soc Nephrol. 18: 846-859, 2007.

Shanmukhappa K, Sabla GE, Degen JL, Bezerra JA. Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor.BMC Gastroenterology 6: 40-48 2006.

Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, Lorenz JN, Dunn RS, Vorhees CV, Wills-Karp M, Degen JL, Davis RJ, Mizushima N, Rakic P, Dardzinski BJ, Holland SK, Sharp FR, Kuan C-Y. Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy.Am. J. Pathology 169: 566-583, 2006.

Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jiroušková M, and Degen JL. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer-mediated elimination of tumor cells.Blood 105: 178-185, 2005.

Shanmukhappa K, Mourya R, Sabla GE, Degen JL, and Bezerra JA. Hepatic to pancreatic switch defines a novel role of hemostatic factors in cellular plasticity in mice.Proc. Natl. Acad. Sci. USA, 102: 10182-10187, 2005.

Degen JL, Massari JV, Talmage KE, La Jeunesse CM, Kombrinck KW, Flick MJ, and Palumbo PS. Hemostatic factors support metastasis by impeding NK cell-mediated elimination of embolic tumor cells.Haematological Reports 1:21-23, 2005.

Cho J, Degen JL, Coller BS, and Mosher DF. Fibrin but not absorbed fibrinogen supports fibronectin assembly by spread platelets: effects of the interaction of alpha IIbbeta 3 with the C-terminus of the fibrinogen gamma-chain.J. Biol. Chem., 280: 35490-35498, 2005.

Jirouskova M, Chereshnev I, Vaananen H, Degen JL and Coller BS. Antibody blockade or mutation of the fibrinogen chain C-terminus are more effective in inhibiting murine arterial thrombus formation than complete absence of fibrinogen.Blood 103: 1995-2002, 2004.

Flick MJ, Du X, Witte DP, Jirouskova M, Soloviev DA, Busuttil SJ, Plow EF, and Degen JL. Leukocyte engagement of fibrinogen via the integrin receptor, α_Mß₂/Mac-1, is critical for host inflammatory response in vivo.J. Clin. Invest. 113: 1596-1606, 2004.

Palumbo JS, Zogg M, Talmage KE, Degen JL, Weiler H, and Isermann BH. Role of fibrinogen- and platelet-mediated haemostasis in mouse embryogenesis and reproduction.J. Thromb. Haemst. 2: 1368-1379, 2004.

Flick MJ, Du X, and Degen JL. Fibrin(ogen)- α_Mß₂ interactions regulate leukocyte function and innate immunity in vivo.Exp. Biol. & Med. 229: 1105-1110, 2004.

Tucker HM, Simpson J, Kihiko-Ehmann M, Younkin LH, McGillis JP, Younkin SG, Degen JL, and Estus S. Plasmin deficiency does not alter endogenous murine amyloid beta levels in mice.Neurosci Lett. 368: 285-289, 2004.

Currier AR, Sabla GE, Locaputo S, Melin-Aldana H, Degen JL, Bezerra JA. Plasminogen directs the pleiotropic effects of uPA in liver injury and repair.Am. J. Physiol. Gastrointest. Liver Physiol. 284: 508-515, 2003.

Isermann B, Sood R, Pawlinski R, Zogg M, Kalloway S, Degen JL, Mackman N, and Weiler H. The thrombomodulin-protein C system is essential for the maintenance of pregnancy.Nat. Med. 9: 331-337, 2003.

Kufrin D, Eslin DE, Bdeir K, Murciano JC, Kuo A, Kowalska M A, Degen JL, Sachais BS, Cines DB, Poncz M. Anti-thrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets. Blood 102: 926-933, 2003.

Palumbo JS, Talmage KE, Liu H, La Jeunesse CM, Witte DP, and Degen JL. Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patency.Blood 102: 2819-2827, 2003.

Ni H, Papalia JM, Degen JL, and Wagner DD. Control of thrombus embolization and fibronectin internalization by integrin αIIbβ3 engagement of the fibrinogen γ chain.Blood 102: 3609-3614, 2003.

Degen JL and Palumbo JS. Mechanisms linking hemostatic factors to tumor growth in mice.Pathophysiol Haemost Thromb. 33: 31-35, 2003.

View other representative publications.