Joseph Stokes Research Institute / CHOP 310 Abramson 3516 Civic Center Blvd.
(215) 590-3346

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.

Enzymology, protein chemistry and physical biochemistry of blood coagulation. With relevance to the mission of ITMAT, we frequently work on novel inhibitors of coagulation that exploit the complexity of macromolecular interactions to achieve specificity for the coagulation enzymes.

Professor of Biochemistry and Biophysics at University of Pennsylvania School of Medicine (2014– present)
Professor of Pediatrics at University of Pennsylvania School of Medicine (2011– present)
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– present)
Ph.D., Biochemistry, Syracuse University (1984)
BS, Biology, Syracuse University (1979)
Selected Publications
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.