Biochemistry and Molecular Biology
800 W Baltimore St.
Education and Training
M.S., Biochemistry, Dnipropetrovsk State University, Ukraine (1991)
Ph.D., Biochemistry, Institute of Biochemistry, Natl. Acad. Sci. Ukraine, Kyiv, Ukraine (1997)
Postdoctoral Training in Biochemistry of Blood Coagulation and Fibrinolysis at Jerome H. Holland Laboratory of the American Red Cross, Rockville, MD (Mentor: Dr. L. Medved, 1998-2004)
I joined the Faculty at the University of Maryland Baltimore, School of Medicine, as a Research Associate in Dr. Medved’s laboratory in 2005. My current research focuses on the interactions of fibrin(ogen) with the VLDL receptor and VE-cadherin and their role in fibrin-dependent inflammation. In addition to its hemostatic function, fibrin(ogen), by interacting with different cell types through their various receptors and proteoglycans, also plays a prominent role in numerous (patho)physiological processes including inflammation. We have identified the VLDL receptor as a new receptor for fibrin and proposed a novel fibrin-VLDLR-dependent pathway of leukocyte transmigration which is a potential therapeutic target. Our further study localized fibrin-binding site within the VLDL receptor and identified two monoclonal antibodies whose epitopes overlap with this site. In our in vitro experiments, these antibodies efficiently inhibited leukocyte transmigration and exhibited significant anti-inflammatory properties and cardioprotective effect in the in vivo mouse models. They, together with the fibrin βN-domain-derived fragments, may be developed as potent therapeutics for treatment of fibrin-dependent inflammation-related cardiovascular disorders.
Fibrinogen, Fibrin, VLDL receptor, Endothelial cells, Leukocyte transmigration, Inflammation
Yakovlev, S., Gao, Y., Cao, C., Chen, L., Strickland, D.K., Zhang, L., and Medved, L. (2011) Interaction of fibrin with VE-cadherin and anti-inflammatory effect of fibrin-derived fragments. J. Thromb. Haemost. 9: 1847-1855.
Yakovlev, S., Mikhailenko, I., Cao, C., Zhang L., Strickland, D.K., and Medved, L. (2012) Identification of VLDLR as a novel endothelial cell receptor for fibrin that modulates fibrin-dependent transendothelial migration of leukocytes. Blood 119: 637-644.
Yakovlev, S., and Medved, L. (2015) Interaction of fibrin with the very low density lipoprotein receptor: Further characterization and localization of the fibrin-binding site. Biochemistry 54: 4751-4761.
Yakovlev, S., Belkin, A.M., Chen, L., Cao, C., Zhang, L., Strickland, D.K., and Medved, L. (2016) Anti-VLDL receptor monoclonal antibodies inhibit fibrin-VLDL receptor interaction and reduce fibrin-dependent leukocyte transmigration. Thromb. Haemost. 116: 1122-1130.
Yakovlev, S., and Medved, L. (2017) Interaction of fibrin with the very low density lipoprotein receptor: Further characterization and localization of the VLDL receptor-binding site in fibrin βN-domains. Biochemistry 56: 2518-2528.