UCLA / Orthopaedic Hospital Department of Orthopaedic Surgery
David Geffen School of Medicine at UCLA
Rehabilitation Center A3-21
1000 Veteran Avenue
Los Angeles, CA 90095
- B.S., Biochemistry, Punjab Agriculture University, India (1967)
- M.S., Biochemistry, Punjab Agriculture University (1969)
- Ph. D., Biological Chemistry, University of Minnesota (1975)
Proteases in Hemostasis and Thrombosis: Our laboratory is investigating specificity of protein:protein and protein:ligand interactions involved in human hemostasis and thrombosis as well as plasmin and TFPI-2 (tissue factor pathway inhibitor-2). In particular, we are working on the functions of the γ-carboxyglutamic acid (Gla) domains, EGF-like domains and the serine protease modules of vitamin k-dependent proteins. The primary focus is to determine the structural bases for these domains in binding to their respective protein cofactors, metal ions, and macromolecular substrates with high degree of specificity. Interaction of factor IXa (Hemophilia B) with factor VIIIa (hemophilia A), and of factor VIIa with tissue factor and TFPI-1 remains the primary focus of the laboratory. The plasminogen-plasmin system is essential for rheumatoid arthritis and bone remodeling, and we are evaluating the role of TFPI-2 in this context. We use molecular biology, enzymology, molecular modeling and crystallography approaches to study these important biological problems that have relevance to human diseases.
AWARDS / RECOGNITION
- American Heart Association, Established Investigator Award (1983-1988)
- Advisory Board, Thrombosis and Haemostasis (2000-2009)
- Editorial Board, Journal of Biological Chemistry (2001-2006)
- Cochairman TFPI Nomenclature Subcommittee of ISTH (1992-1996)
- NIH Hematology-2 Study Section Member (1998-2002)
- Schmidt, A..E., Ogawa, T., Gailani, D., and Bajaj, S.P. Structural Role of Gly193 in Serine Proteases: Investigations of Gly555Glu (Gly193 in chymotrypsin) Mutant of Blood Coagulation Factor XIa. J. Biol. Chem. 279:29485-29492, 2004.
- Ndonwi, M., Broze, G.J., and Bajaj, S.P. The First Epidermal Growth Factor-like Domains of Factor Xa and IXa are Important for the Activation of the Factor VII-Tissue Factor Complex. J. Thromb. Haemost. 1:112-118, 2005.
- Schmidt, A.E., Stewart, J.E., Mathur, A., Krishnaswamy, S., and Bajaj, S.P. Structural Role of Factor IXa Na+-Site and Protease Domain Ca2+-Site in Catalysis and Factor VIIIa Binding. J.Mol. Biol. 350:78-91, 2005.
- Schmidt, A.E., Chand, H., Cascio, D., Kisiel, W., and Bajaj, S.P. Crystal structure of Kunitz Domain 1 of Tissue Factor Pathway Inhibitor-2 Complexed to Trypsin: Implications for KD1 Specificity of Inhibition. J. Biol. Chem. 280:27832-27838, 2005.
- Bajaj, S.P., and Thompson., A.R. Molecular and Structural Biology of Factor IX. Ed. R.W. Colman, J. Hirsh, V.J. Marder, A.W. Clowes, and J.N. George. Hemostasis and Thrombosis: Basic Principles & Clinical Practice. 5th Edition. Lippincott, Williams & Wilkins; Philadelphia: 2005, pages 131-150.
- Bajaj, S.P., Schmidt, A.E., Agah, S., Bajaj, M.S., and Padmanabhan, K. High Resolution Crystal Structures of p-aminobenzamidine- and benzamidine-VIIa/soluble tissue factor: Unpredicted conformation of the 192-193 peptide bond and mapping of Ca2+, Mg2+, Na+, and Zn2+ sites in factor VIIa. J. Biol. Chem. 281:24873-24888, 2006.
- Gailani, D., Schmidt, A., Sun, M.F., Bolton-Maggs, P.H., Bajaj, S.P. A cross-reactive material positive variant of coagulation factor XI (FXIP520L) with a catalytic defect. J Thromb Haemost. 5:781-787, 2007
- Ndonwi, M., Broze, G.J. Jr., Agah, S., Schmidt, A.E., and Bajaj, S.P. Substitution of the GLA domain in factor X by that of protein C impairs its interaction with factor VIIa/tissue factor: Lack of comparable effect by similar substitution in factor IX. J. Biol. Chem. 282:15632-15644, 2007
- Bajaj, M.S., Ghosh, M., and Bajaj, S.P. Fibronectin-adherent monocytes express tissue factor and tissue factor pathway inhibitor whereas endotoxin-stimulated monocytes primarily express tissue factor: Physiologic and pathologic implications. J Thromb Haemost. 5:1493-1499, 2007
- Schmidt, A.E., Sun, M.F., Ogawa, T., Bajaj, S.P., and Gailani, D. Functional role of residue 193 (chymotrypsin numbering) in serine proteases: Influence of side chain length and ?-branching on the catalytic activity of blood coagulation factor XIa. Biochemistry. 47:1326-1335, 2008.
- Agah, S; and Bajaj, S.P. Role of magnesium in factor XIa catalyzed activation of factor IX: calcium binding to factor IX under physiologic magnesium. J Thromb Haemost. 7:1426-1428, 2009.
Messer, AS; Velander, W,H; and Bajaj, S.P. Contribution of magnesium in binding of factor IXa to the phospholipid surface: implications for vitamin K-dependent coagulation proteins. J Thromb Haemost. 2009, Oct 8. [Epub ahead of print]
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