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Edward F. Plow, Ph.D.Department ChairThe Robert C. Tarazi, M.D., Endowed Chair in Heart and Hypertension Research
Department of Molecular Cardiology
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Area of general research interest:
Cell adhesion and migration, integrins, platelets, protease receptors, plasminogen, fibronection.
Current program:
- Role of integrins in cell adhesion and migration
- Plasminogen receptors and pericellular proteolysis.
- Ligand recognition by platelet integrins.
- Mechanisms of integrin activation
- Utilization of transgenic mice to assess the functions of plasminogen in vivo.
Investigators:
- Bledzka, Kamila, Ph.D., Postdoctoral Fellow
- Chen, Qiuyun, Ph.D., Project Staff
- Das, Mitali, Ph.D., Postdoctoral Fellow
- Das, Riku, Ph.D., Postdoctoral Fellow
- Frolova, Ella, Ph.D., Postdoctoral Fellow
- Ma, Yan-Qing, Ph.D., Project Staff
- McCue, Brian, Research Technologist
- Pesho, Michelle, Ph.D., Postdoctoral Fellow
- Pluskota, Ela, M.D., Ph.D., Project Staff
- Sossey-Alaoui, Khalid, Ph.D., Project Staff
- Solovjov, Dmitry, Ph.D., Research Associate
- Stenina, Olga, Ph.D., Assistant Staff
- Ustinov, Valentin, Ph.D., Research Associate
- Young, Duprane Pedaci, Ph.D., Postdoctoral Fellow
Collaborators:
- Busuttil, Steve, M.D.
- Byzova, Tatiana, Ph.D.
- Degan Jay, Ph.D.
- Geng, Jian-Guo, Ph.D.
- Hoover-Plow, Jane, Ph.D.
- Penn, Marc, M.D., Ph.D.
- Qin, Jun, Ph.D.
- Simon, Dan, Ph.D.
- Swaisgood, Carmen, Ph.D.
- Topol, Eric, M.D.
- Ugarova, Tatiana, Ph.D.
- Vinogradova, Olga, Ph.D.
Brief Description:
Integrins are a large and broadly distributed family of adhesion receptors. Each member is a noncovalent heterodimer composed of an alpha and a beta subunit.
Key to the many functions of integrins is their capacity to rapidly modulate their affinity for ligands, recognize multiple and structurally unrelated ligands, engage these ligands in a divalent ion-dependent manner, and mediate intracellular signaling events.
Development of a molecular understanding of these central properties of integrins is a goal. Integrins of particular interest are αIIbβ3, which mediates platelet aggregation, and αMβ2, which plays a pivotal role in leukocyte transmigration during inflammatory responses. Mutagenesis, expression, biophysical, immunochemical and functional analyses are being employed in these studies.
Plasminogen is the zymogen form of the proteolytic enzyme plasmin. In addition to its central role in fibrinolysis, plasmin(ogen) is also involved in cell migration. This is evident from the reduction in inflammatory responses to a variety of stimuli in plasminogen-deficient mice. The participation of plasminogen in inflammation depends upon its interaction with cell surface receptors.
We are seeking to identify the repertoire of plasminogen receptors and to assess their functions in vitro and in vivo.
Key References:
Malinin, N.L., and L. Zhang, J. Choi, A. Ciocea, O.V. Razorenova, Y. Ma, E.A. Podrez, M. Tosi, D.P. Lennon, A.I. Caplan, S.B. Shurin, E.F. Plow, T.V. Byzova. “A point mutation in KINDLIN-3 ablates activation of three integrin subfamilies in humans.” Nature Medicine (Feb. 22, 2009): Epub. PMID: 19234460
- To download an ePrint of the Nature Medicine article, click here. To save the file to your desktop, click the “Save” button. Locate the file on your desktop and double click to open. Note: This download is for PC users only. Mac users should contact requestinfo@tsp.sheridan.com.
Ma YQ, et al. Regulation of integrin αIIbβ3 activation by distinct regions of its cytoplasmic tails. Biochemistry 2006;45:6656-62.
Solovjov DA, Pluskota E, Plow EF. Distinct roles for the alpha and beta subunits in the functions of integrin αMβ2. J Biol Chem 2005;280:1336-45.
Stenina OI, et al. Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites. FASEB J 2005;19:1893-5.
Pluskota E, et al. Mechanism and effect of thrombospondin-4 polymorphisms on neutrophil function. Blood 2005;106:3970-8.