Research/Areas of Interest: While most extracellular proteins have a signal peptide required for their export through endoplasmic reticulum and Golgi, a large group of secreted proteins lack this peptide and are exported through insufficiently studied nonclassical mechanisms. Our laboratory studies the stress-induced nonclassical export of FGF1 and IL1., two ubiquitous pro-angiogenic and pro-inflammatory molecules. We hope to understand how multi-protein release complexes are formed, the protein transport mechanisms and how these proteins exit to the extracellular compartment. This knowledge will facilitate the development of new clinical approaches to the regulation of angiogenesis, inflammation and tumor growth. We also study the interactions between FGF/FGFR, Jagged(Delta)/Notch and thrombin/PAR1 signaling, three major regulatory systems involved in practically all of the aspects of organism development and organ formation. Thrombin stimulation and downregulation of Notch signaling induce FGF1 expression and release, and the acquisition of the angiogenic phenotype by the cells. We hope to unravel the molecular cross-talk involving these molecules and use this knowledge for treatment of cardiovascular and oncological disorders. Our approaches include transgenic mouse models with conditional expression of FGF1 in endothelial cells and monocytes/macrophages that are being used to study the regulation of FGF1 export in vivo and its effects on tumor formation and tissue repair after ischemia. We also study the cell proliferative response to individual growth factors, including FGFs. We discovered that non-malignant cells respond to FGF by just one proliferative cycle and then indefinitely reside in the G1 phase of the second cycle. Apparently, the limitation of proliferative response to growth factors may be needed in the organism to prevent tissue hyperplasia, and we are exploring the molecular processes underlying this limitation.
- PhD, Cell & Molecular Biology, Engelhardt Inst of Mol Bio, Russian Federation, 1979
- MS, Cellular Biology, Moscow University, Russian Federation, 1975