Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Biochemistry and Molecular Biology
Location:
BIOPARK 1 - 218
Phone (Primary):
410-706-8065
Phone (Secondary):
301-996-1994
Fax:
410-706-8121
Education and Training
M.S., Biophysics, T. Shevchenko National University of Kyiv, Ukraine (1977)
Ph.D., Biochemistry, Institute of Biochemistry, Natl. Acad. Sci. Ukraine, Kyiv, Ukraine (1980)
D.Sc., Biochemistry, Institute of Biochemistry, Natl. Acad. Sci. Ukraine, Kyiv, Ukraine (1991)
Biosketch
Dr. Medved graduated from Taras Shevchenko National University of Kyiv, Ukraine, and earned his Ph.D. and then D.Sc. degrees in Biochemistry from the Institute of Biochemistry, Kyiv, Ukraine. Starting in 1980, he worked at the same Institute, progressing from Junior Scientist to Senior Scientist, and eventually became the Head of the Department of Protein Structure and Function. In 1997, Dr. Medved joined the Department of Biochemistry at the American Red Cross J. Holland Laboratory, Rockville, MD, initially as a Scientist II and later as a Senior Scientist. In 2000, while conducting research at the J. Holland Laboratory, he became involved in teaching at the George Washington University, Washington, DC, first as an Associate Professor and then as a full Professor. Dr. Medved joined the University of Maryland Baltimore School of Medicine (UMB SOM) as a Professor in the Department of Biochemistry and Molecular Biology in 2004, and he has been working at the UMB SOM Center for Vascular and Inflammatory Diseases since then.
Dr. Medved’s primary research interests are in the field of blood coagulation and fibrinolysis, with a particular interest in the structure and interactions of blood coagulation and fibrinolytic proteins, with the emphasis on fibrinogen and fibrin and their roles in various (patho)physiological processes. His major contributions to this field include establishing multidomain structure of the fibrinogen molecule, elucidation of the molecular mechanism of fibrinogen to fibrin conversion, establishing the molecular mechanism initiating fibrinolysis, discovering a novel fibrin-VLDL receptor-dependent pathway of transendothelial migration of leukocytes that promotes inflammation. His current research focuses on establishing the molecular mechanisms underlying this and other fibrin-dependent inflammatory pathways of leukocyte transmigration and identifying specific antagonists of such pathways that may be developed as potent therapeutics for the treatment of inflammation-related cardiovascular disorders.
Dr. Medved has been continuously funded by the National Institutes of Health as a principal investigator since 1998 and has also received several grants from other funding agencies. His current research is funded by R01 grant from NIH/NHLBI. During his scientific career, Dr. Medved has published more than 110 scientific articles in peer-reviewed journals, obtained four US patents, and presented his research at numerous national and international scientific meetings. He has also received several awards for his scientific achievements, including Outstanding Investigator award from the International Fibrinogen Research Society (IFRS). Dr. Medved is a member of several scientific societies and has served as Vice Chairman and later as President of IFRS. He also has served as a grant reviewer for various national and international funding agencies, and as an editorial board member and reviewer for several international scientific journals.
Research/Clinical Keywords
Blood Coagulation, Fibrinolysis, Plasma Proteins Structure and Interaction, Fibrinogen, Fibrin, Fibrin(ogen) Receptors, Fibrin-Dependent Inflammation.
Highlighted Publications
- Yakovlev, S., Strickland, D.K., and Medved, L. (2022) Current view on the molecular mechanisms underlying fibrin(ogen)-dependent inflammation. Haemost. 122:1858-1868.
- Yakovlev, S., Cao, C., Galisteo, R., Zhang, L., Strickland, D.K., and Medved, L. (2019) Fibrin-VLDL receptor-dependent pathway promotes leukocyte transmigration by inhibiting Src kinase Fyn and is a target for fibrin β15-42 peptide. Haemost. 119: 1816-1826.
- 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. Haemost. 116: 1122-1130.
- Yakovlev, S., Mikhailenko, I., Cao, C., Zhang, L., Strickland, D., 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.
- Medved, L., and Nieuwenhuizen, W. (2003) Molecular mechanisms of initiation of fibrinolysis by fibrin. Haemost. 89: 409-419.
Complete List of my Publication in MyBibliography:
http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40856804/?sort=date&direction=ascending
Additional Publication Citations
1. Privalov, P.L., and Medved, L.V. (1982) Domains in the fibrinogen molecule. Mol. Biol., 159: 665-683.
2. Medved, L., Ugarova, T., Veklich Yu., Lukinova, N., and Weisel, J. (1990) Electron microscope investigation of the early stages of fibrin assembly: twisted protofibrils and fibers. J. Mol. Biol. 216: 503-509.
2. Novokhatny, V.V., Ingham, K.C., and Medved, L.V. (1991) Domain structure and domain-domain interactions of recombinant tissue plasminogen activator. Biol. Chem. 266: 12994-13002.
3. Medved, L.V., Vysotchin, A. and Ingham, K.C. (1994) Ca2+-dependent Interactions between Gla and EGF domains in human coagulation factor IX. Biochemistry 33: 478-485.
4. Medved, L.V., Orthner, C.L., Lubon, H., Lee, T.K., Drohan, W.N., and Ingham, K.C. (1995) Thermal stability and domain-domain interactions in natural and recombinant protein C. Biol. Chem. 270: 13652-13659.
5. Kurochkin, I.V., Procyk R., Bishop, P.D., Yee, V.C., Teller, D.C., Ingham, K.C., and Medved, L.V. (1995) Domain structure, stability, and domain-domain interactions in recombinant factor XIII. Mol. Biol. 248: 414-430.
6. Medved, L.V., Solovjov, D.A., and Ingham, K.C. (1996) Domain structure, stability and interactions in streptokinase. Eur. J. Biochem. 239: 333-339.
7. Medved, L., Litvinovich, S., Ugarova, T., Matsuka, Y, and Ingham, K. (1997) Domain structure, stability and functional activity of the recombinant human fibrinogen g-module (g148-411). Biochemistry 36: 4685-4693.
8. Yakovlev, S., Makogonenko, E., Kurochkina, N., Nieuwenhuizen, W., Ingham, K., and Medved, L. (2000) Conversion of fibrinogen to fibrin: Mechanism of exposure of tPA- and plasminogen-binding sites. Biochemistry 39: 15730-15741.
9. Tsurupa, G., and Medved, L. (2001) Identification and characterization of novel tPA- and plasminogen-binding sites within fibrin(ogen) αC-domains. Biochemistry 40: 801-808.
10. Medved, L., Tsurupa, G., and Yakovlev, S. (2001) Conformational changes upon conversion of fibrinogen into fibrin. The mechanisms of exposure of cryptic sites. N. Y. Acad. Sci. 936: 185-204.
11. Gorlatov, S., and Medved, L. (2002) Interaction of fibrin(ogen) with the endothelial cell receptor VE-cadherin: mapping of the receptor-binding site in the NH2-terminal portions of the fibrin b chains. Biochemistry 41: 4107-4116.
12. Tsurupa, G., Ho-Tin-Noe, B., Loyau, S., Angles-Cano, E., and Medved, L. (2003) Identification and characterization of novel Lys-independent apo(a)-binding sites within fibrinogen aC-domains. J. Biol. Chem. 278: 37154-37159.
13. Pechik, I., Madrazo, J., Mosesson, M.W., Hernandez, I., Gilliland, G.L., and Medved, L. (2004) Crystal structure of the complex between thrombin and the central ‘E’ region of fibrin. Natl. Acad. Sci. U.S.A. 101: 2718-2723.
14. Pechik, I., Yakovlev, S., Mosesson M.W., Gilliland, G.L., and Medved, L. (2006) Structural basis for the sequential cleavage of fibrinopeptides upon fibrin assembly. Biochemistry 45: 3588-3597.
15. Burton, R.A., Tsurupa, G., Hantgan, R., Tjandra, N., and Medved, L. (2007) NMR solution structure, stability, and interaction of the recombinant bovine fibrinogen αC-domain fragment. Biochemistry 46: 8550-8560.
16. Yakovlev, S., and Medved, L. (2009) Interaction of fibrin(ogen) with endothelial cell receptor VE-cadherin: localization of the fibrin-binding site within the third extracellular VE-cadherin domain. Biochemistry 48: 5171-5179.
17. Tsurupa, G., Yakovlev, S., McKee, P., and Medved, L. (2010) Non-covalent interaction of a2-antiplasmin with fibrin(ogen): Localization of a2-antiplasmin binding sites. Biochemistry 49: 7643-7651.
18. Yakovlev, S., Gao, Y., Cao, C., Chen, L., Strickland, D., 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.
19. Tsurupa, G., Mahid, A., Veklich, Y., Weisel, J.W., and Medved, L. (2011) Structure, stability, and interaction of fibrin aC-domain polymers. Biochemistry 50: 8028-8037.
20. Tsurupa, G., Pechik, I., Litvinov, R., Hantgan, R.R., Tjandra, N., Weisel, J.W., and Medved, L. (2012) On the mechanism of aC polymer formation in fibrin. Biochemistry 51: 2526-2538.
21. Yakovlev, S., Mikhailenko, I., Tsurupa, G., Belkin, A.M., and Medved, L. (2014) Polymerization of fibrin aC-domains promotes endothelial cell migration and proliferation. Thromb. Haemost. 112: 1244-1256.
22. 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 bN-domains. Biochemistry 56: 2518-2528.
23. Yakovlev, S., and Medved, L. (2018) Effect of fibrinogen, fibrin, and fibrin degradation products on transendothelial migration of leukocytes. Thromb. Res. 162: 93-100.
24. Yakovlev, S., and Medved, L. (2022) Dual functions of the fibrin βN-domains in the VLDL receptor-dependent pathway of transendothelial migration of leukocytes. Thromb. Res.214: 1-7.
25. Medved, L., and Weisel, J.W. (2022) The story of the fibrinogen αC-domains: evolution of our view on their structure and interactions. Haemost. 122:1265-1278.
Grants and Contracts
National Institutes of Health R01 Grant HL056051