The laboratory was founded in 1982.
Main research areas
Studies of the processes of reception of hormones, cytokines and growth factors and their intracellular signaling.
Elucidation of molecular mechanisms of regulation of tissue growth, migration, proliferation and differentiation of cells.
Studies of the components of fibrinolytic system and navigation receptors in the growth of blood vessels and nerves.
It was found that arterial injury leads to the expression in the vessel wall of urokinase and its receptor, which are the key participants of the migration of vascular and blood cells towards vessel lumen. Researchers of the Laboratory were the first, who determined the tertiary structure of urokinase and its complex with the urokinase receptor. The results obtained allowed to hypothesize that hydrogen peroxide acts as a secondary mediator and mediates the activating effect of growth factors, cytokines and urokinase on cell migration and proliferation.
Urokinase binding to the receptor is studied; it leads to the triggering of signaling cascades inside the cell, cytoskeleton rearrangement, redistribution of adhesive contacts, stimulation of cell adhesion, migration and proliferation. The role of the urokinase receptor in the selection of the growth trajectory and branching of the growing axon is clarified.
Biosensor technology and intravital microscopy of single cells are implemented in the laboratory.
The ongoing research in the laboratory is aimed to clarify the molecular mechanisms of cellular adipocytic differentiation and the development of insulin resistance. A new transcription factor Prep1, which controls the activity of PPARγ, the master regulator of adipogenesis and lipid metabolism, is described. At present, the mechanism of Prep1 action is being determined and its targets are investigated in the adipocyte genome.
The most significant results of the recent years
The mechanisms of vascular cell tolerance to the action of hormones and pharmacological substances are studied and the role of hypoxia in these processes was shown.
The interaction of urokinase with the extracellular matrix protein fibulinin-5 was established. Fibulin-5 was shown to affect the integrin-dependent urokinase effects on cell proliferation and migration and intracellular signaling.
A new urokinase signaling pathway regulating gene expression was identified; it is mediated by the rapid nucleoline-dependent translocation of urokinase into the nucleus, and is responsible for the phenotypic transdifferentiation of fibroblasts into myofibroblasts.
Based on the MRI analysis, a new mechanism for the interaction of urokinase with the urokinase receptor was described, according to which β-layers in the growth factor like domain of uPA are not necessary for the interaction with urokinase receptor.
Researchers of the laboratory identified and characterized mesenchymal stem cells (MSC) of human adipose tissue. The ability of these cells to stimulate tissue regeneration and to induce the growth of blood vessels and nerves was established. The mechanisms of that stimulation were revealed: it was established that the stimulating effect of MSCs is due to both the soluble secretion products (growth factors, cytokines and chemokines) as well as the generation of microvesicles. The effect of inflammation and hypoxia on the functional activity of these cells was evaluated. It was established that the rate of migration of mesenchymal cells is controlled by the receptor-dependent mechanism, including activation of NADPH oxidase (NOX), formation of reactive oxygen species and accumulation of hydrogen peroxide inside the cells.
A new transcription factor Prep1 and the mechanism of regulation of the activity of PPARγ, the master regulator of adipogenesis and lipid metabolism, are described. Prep1 was shown to belong to a family of homeobox-containing factors that are critical for cell differentiation, including adipocytic differentiation. Evidence was obtained that Prep1 can regulate the cells sensitivity to insulin action.
