Research

Rao, L. Vijaya Mohan, Ph.D.

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Professor - Department of Cellular and Molecular Biology
(903)877-7332
Contact: vijay.rao@uthct.edu

Education:

M.S. , Genetics, Osmania University, Hyderabad, India
M.Phil., Life Sciences, Jawaharlal Nehru University, New Delhi, India
Ph.D., Life Sciences, Jawaharlal Nehru University, New Delhi, India
Post-doctoral Fellowship, University of California, San Diego, CA

Research Interest:

Hemostasis and Thrombosis, Membrane trafficking, Cell signaling

Research Synopsis:

Tissue factor (TF)-dependent blood coagulation plays a primary role in hemostasis after tissue injury and also in pathogenesis of many thrombotic events, including atherosclerosis, acute coronary syndrome, septicemia, and cancer. Tissue factor functions as the cellular receptor for plasma clotting factor VII(a) and the formation of TF/VII(a) complexes on cell surfaces triggers the coagulation cascade. The proper regulation of TF expression is critical not only for maintenance of the hemostatic balance but also health in general. Despite extensive information available on the protein biochemistry of TF and its interaction with FVIIa, how TF functional expression is regulated on cell surfaces remains poorly understood. Most TF on surfaces of resting cells exist in an encrypted state with very little procoagulant activity, and TF has to undergo decryption to become fully active. The cellular microenvironment on the plasma membrane that controls TF activity and cellular mechanisms that are responsible for TF decryption are poorly defined.

The endothelial cell lining constitutes the interface between vascular tissue and circulating blood. In their quiescent state, endothelial cells provide a non-thrombogenic surface and express proteins that participate in anticoagulant mechanisms, such as endothelial cell protein C receptor (EPCR), thrombomodulin (TM), tissue factor pathway inhibitor-1, and are devoid of procoagulant TF. Being at the interface between blood and the vessel wall, the endothelial cells are positioned optimally to interact with circulating clotting factors. Until recently, it is believed that FVII/FVIIa does not interact with the endothelium as native endothelial cells do not express TF, the only known cofactor/receptor for FVII/FVIIa. Our recent studies have established that FVII/FVIIa bind to EPCR in a true-ligand fashion. The physiological significance and importance of FVIIa interaction with EPCR are yet to be explored.


Both TF and EPCR, whose primary function is to regulate clotting, also affect various pathophysiological processes, ranging from embryo development to cancer. Studies from our laboratory and others have shown that FVIIa bound to either TF or EPCR induces protease-activated receptors (PAR)-mediated cell signaling. Understanding of FVIIa-TF and FVIIa-EPCR-induced cell signaling pathways and the resultant cellular alterations would help in understanding how the receptors and proteases involved in clotting process can influence pathogenesis of various diseases.

We are currently focusing on the following questions

  • Cellular dynamics that regulate TF activity at cell surfaces and molecular mechanisms responsible for TF decryption.
  • Establishing the pathophysiological significance of factor VIIa interaction with endothelial cell protein C receptor.
  • Mechanisms by which tissue factor and EPCR contribute or influence pathogenesis of various diseases, including cancer and inflammation.

Research Funding:

National Institute of Health, American Heart Association, Novo Nordisk

Selected Papers and Abstracts:

NOTICE: Protected health information is subject to electronic disclosure.