Pendurthi, Usha, Ph.D.
Ph.D. in Biology - Osmania University, Hyderabad, India.
Post-doctoral Fellowship – Department of Medicine and Cancer Center, University of California, San Diego, CA.
Hemostasis and Thrombosis; Role of blood clotting proteases in pathogenesis of cancer, inflammation and other diseases.
Tissue factor (TF)-dependent blood coagulation plays primary role in hemostasis upon tissue injury but aberrant expression of TF leads to thrombotic disorders. The proper regulation of TF expression is critical not only for maintenance of the hemostatic balance but also health in general, and thus expression of TF activity on cell surfaces is tightly regulated. A part of our research focuses on understanding cellular mechanisms that regulate TF activity on cell surfaces.
Endothelial cell protein C receptor (EPCR) is a cellular receptor for protein C and activated protein C (APC). It is primarily localized on the endothelial cells of large blood vessels. Recent studies from our laboratory and others have shown that FVIIa, a clotting protease that binds to TF and initiates the activation of the coagulation cascade, also binds to endothelial cell protein C receptor (EPCR). FVIIa bound to EPCR on endothelial cells can activate PAR1-mediated cell signaling that provide barrier protective effect.
Both TF and EPCR, whose primary function is to regulate clotting, also affect various pathophysiological processes, including inflammation and cancer. Understanding of how TF-FVIIa- and EPCR-FVIIa-induced cell signaling pathways alters cellular functions and influence pathogenesis of cancer and inflammation is the primary focus of our research. Our recent studies show that introduction of EPCR expression to tumor cells through genetic engineering suppressed TF-driven tumor growth in malignant pleural mesothelioma. Studies are underway in identifying molecular mechanism by which EPCR suppresses tumor growth and evaluating therapeutic potential of EPCR-mediated pathway in curtailing tumor growth.
Selected Papers and Abstracts:
- Kothari H, Pendurthi UR, Rao LVM. Analysis of tissue factor expression in various cell model systems: cryptic vs. active. J Thromb Haemost 11: 1353-1363, 2013.
- Vatsyayan R, Kothari H, Pendurthi UR, Rao LVM. 4-Hydroxy-2-nonenal Enhances tissue actor activity in human monocytic cells via p38 MAPK activation-dependent phosphatidylserine exposure. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1601-11. doi: 10.1161/ATVBAHA.113.300972. Epub 2013 May 2.
- Keshava S, Sahoo S, Tucker TT, Idell S, Rao LVM, Pendurthi UR. Endothelial cell protein C receptor opposes mesothelioma growth driven by tissue factor. Cancer Res. 2013 Jul 1;73(13):3963-73. doi: 10.1158/0008-5472.CAN-12-1690. Epub 2013 Mar 28.
- Nayak RC, Keshava S, Esmon CT, Pendurthi UR, Rao LVM. Rab GTPases Regulate Endothelial Cell Protein C Receptor-mediated endocytosis and trafficking of factor VIIa. PLOS ONE 8: e59304, 2013.
- Rao LVM, Pendurthi UR. Regulation of tissue factor coagulant activity on cell surface. J Thromb Haemost 10: 2242-2253, 2012.
- Clark CA, Vatsyanan, Hedner U , Esmon CT, Pendurthi UR, Rao LVM. Endothelial cell protein C receptor-mediated redistribution and tissue-level accumulation of factor VIIa. J Thromb Haemost 10: 2383-2391, 2012.
- Kothari HK, Rao LVM, Vankayalapati R, Pendurthi UR. Mycobacterium tuberculosis infection and tissue factor expression in macrophages. PlosOne 7: e45700, 2012.
- Rao LVM, Kothari H, Pendurthi UR. Tissue factor encryption and decryption: Facts and controversies. Thromb Res 129 (suppl 2): 513-517, 2012.
- Williams L Tucker TA, Koenig K, Allen T, Rao LVM, Pendurthi UR, Idell SI. Tissue factor pathway inhibitor attenuates the progression of malignant pleural mesothelioma in nude mice. Am J Res Cell Mol Biol 46: 173-209, 2012.
- Gopalakrishnan R, Pendurthi UR, Hedner U, Agerso H, Esmon CT, Rao LVM. Influence of endothelial cell protein C receptor on plasma clearance of factor VIIa. J Thromb Haemost 10: 971-973, 2012.
- Sen P, Clark CA, Gopalakrishnan R, Hedner U, Esmon CT, Pendurthi UR, Rao LVM. Factor VIIa binding to endothelial cell protein C receptor: Differences between mouse and human systems. Thromb Haemost 107: 951-961, 2012 (cover photo).
- Rao LVM, Kothari H, Pendurthi UR. Tissue factor: Mechanisms of decryption. Frontiers in Bioscience E4: 1513-1527, 2012.
- Sen P, Nayak R, Clark C, Gopalakrishnan R, Esmon CT, Pendurthi UR, Rao LVM. Factor X binding to endothelial cell protein C receptor: A comparison with factor VIIa and activated protein C. Blood 118: 2635-2636, 2011.
- Kothari H, Rao LVM, Pendurthi UR. Glycosylation of tissue factor is not essential for its transport or functions. J Thromb Haemost 9: 1511-1520, 2011. (Commentary by J Morrissey, Low-carb tissue factor, J Thromb Haemost 9: 1508-1510, 2011).
- Sen P. Gopalakrishnan R, Kothari H, Clark C, Keshava S, Esmon CT, Pendurthi UR, Rao LVM. Factor VIIa bound to endothelial cell protein C receptor activates protease activated receptor-1 and mediates cell signaling and barrier protection. Blood 117, 3199-3208, 2011.
- Sen P, Komissarov AA, Florova G, Idell S, Pendurthi UR, Vijaya Mohan Rao L. Plasminogen activator inhibitor-1 inhibits factor VIIa bound to tissue factor. J Thromb Haemost 9, 531-539, 2011.
- Gopalakrishnan R, Hedner U, Clark C, Pendurthi UR, Rao LVM. rFVIIa transported from blood stream into tissues is functionally active. J Thromb Haemost 8, 2318-2321, 2010.
- Tucker T, Dean C, Komissarov AA, Koeing K, Mazar A, Pendurthi U, Allen T, Idell S. The urokinase receptor supports tumorigenesis of human pleural mesothelioma cells. Am J. Resp. Cell Mol. Biol 42: 685-696, 2010.