CVI Program Unit(s):
Thrombosis / Hemostasis
CVI Research Description:
The Krishnaswamy Lab focuses on the biochemistry, enzymology and physical biochemistry of the proteolytic reactions of blood coagulation. Our main interests lie in understanding how protein-protein interactions involved in the assembly of the coagulation complexes on membranes modulates enzymic function and how the coagulation enzymes achieve narrow and defined specificity.
- Associate Professor of Pediatrics at University of Pennsylvania School of Medicine (1998 – 2011)
- Associate Professor of Pharmacology at University of Pennsylvania School of Medicine (1998 – 2006)
- Professor of Pediatrics at University of Pennsylvania School of Medicine (2011– present)
- Ph.D., Biochemistry, Syracuse University (1984)
- BS, Biology, Syracuse University (1979)
- Krishnaswamy, S.. Exosite-Driven Substrate Specificity and Function in Coagulation.. J. Thromb. Haemost.. Vol 3. 2005:54-67.
- Lu, G., Chhum, S. and Krishnaswamy, S.. The affinity of protein C for the thrombin-thrombomodulin complex is determined in a primary way by active site-dependent interactions.. J. Biol. Chem.. Vol 280. 2005:15471-15478.
- Bianchini, E.P., Orcutt, S.J., Panizzi, P., Bock, P.E. and Krishnaswamy, S.. Ratcheting of the Substrate from the Zymogen to Proteinase Conformations Directs Sequential Cleavage of Prothrombin by Prothrombinase.. Proc. Natl. Acad. Sci. U.S.A.. Vol 102. 2005:10099-10104.
- Hacisalihoglu, A., Panizzi, P., Bock, P.E., Camire, R.M. and Krishnaswamy, S.. Restricted Active Site Docking by Enzyme-Bound Substrate Enforces the Ordered Cleavage of Prothrombin by Prothrombinase.. J. Biol. Chem.. Vol 282. 2007:32974 ? 32982.
- Kamath, P. and Krishnaswamy, S.. Fate of Membrane-Bound Reactants and Products during the Activation of Human Prothrombin by Prothrombinase.. J. Biol. Chem.. Vol 283. 2008:30164-30173.
- Cao, W., Krishnaswamy, S., Camire, R.M., Lenting, P.J. and Zheng, X.L.. Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13.. Proc. Natl. Acad. Sci. U.S.A.. Vol 105. 2008:7416-7421.
- Bradford, H.N., Miccuci, J.A. and Krishnaswamy, S.. Regulated Cleavage of Prothrombin by Prothrombinase. Repositioning a cleavage site reveals the unique kinetic behavior of the action of prothrombinase on its compound substrate.. J. Biol. Chem.. Vol 285. 2010:328-338.
- Buddai, S.K., Lu, G., Layzer, J., Rusconi, C.P., Sullenger, B.A., Monroe, D. and Krishnaswamy, S.. An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase.. J. Biol. Chem.. Vol 285. 2010:5212-5223.
- Kamath, P., Huntington, J.A. and Krishnaswamy, S.. Ligand binding shuttles thrombin along a continuum of zymogen-like and proteinase-like states.. J. Biol. Chem.. Vol 285. 2010:28651-28658.
- Kroh, H.K., Panizzi, P., Tchaikovski, S., Wei, N., Krishnaswamy, S. , Tans, G., Rosing, J., Furie, B., Furie, B.C. and Bock, P.E.. Active site-labeled prothrombin inhibits prothrombinase in vitro and thrombosis in vivo.. J. Biol. Chem.. Vol 286. 2011:23345-23356.
- Bradford, H.N. and Krishnaswamy, S.. Meizothrombin is an Unexpectedly Zymogen-Like Variant of Thrombin.. J. Biol.Chem.. Vol 287. 2012:30914-30925.
- Vadivel, K., Agah, S., Messer, A.S., Cascio, D., Bajaj, M.S., Krishnaswamy, S., Esmon, C.T., Padmanabhan, K. and Bajaj, S.P.. Structural and Functional Studies of ?-Carboxyglutamic Acid Domains of Factor VIIa and Activated Protein C: Role of Magnesium at Physiological Calcium.. J. Mol. Biol.. Vol 425. 2013:1961-1981.
- Krishnaswamy, S.. The Transition of Prothrombin to Thrombin.. J. Thromb. Hemostas.. Vol 11. 2013:265-276.
- Bradford, H.N., Orcutt, S.J. and Krishnaswamy, S.. Membrane Binding by Prothrombin Mediates its Constrained Presentation to Prothrombinase For Cleavage.. J. Biol.Chem.. Vol in press. 2013.