Andrey Sorokin, PhD
Microbiology and Molecular Genetics
Medical College of Wisconsin
Research Focus: Cell signaling as related to pathobiology of kidney diseases.
Institute of Cytology Academy of Sciences of Russia, (1981) Biochemistry
My research is primarily focused on characterizing the molecular mechanisms underlying the activation and termination of signaling pathways, as well as defining the cellular consequences of specific stimulation of these cascades in systems relevant for the signaling from G-protein coupled receptors. In renal mesangium endothelin-1 (ET-1) exerts excessive contraction, proliferation and extracellular matrix accumulation leading to glomerulosclerosis and kidney failure. We are studying ET-1 –induced signaling cascades underlying proliferation-associated and oxidative stress related renal glomerular diseases. We also investigate the posttranslational regulation of Cyclooxygenase-2 (COX-2), the key inducible enzyme in the production of prostaglandins. Our lab has demonstrated the anti-apoptotic effect of COX-2 in a number of cell systems and provided evidence that COX-2 promotes cell survival by a mechanism linking increased expression of pro-survival genes coupled to inhibition of NO- and superoxide-mediated apoptosis. The significance of ongoing studies is that new knowledge of mechanisms of posttranslational regulation of COX-2 activity will open novel strategies to inhibit COX-2 activity and combat glomerular renal diseases.
Another direction of my research is studying molecular mechanisms of infection of renal cells by BK virus (BKV), a non-enveloped double-stranded DNA polyomavirus. In recent years, nephritis induced by BKV has become a severe problem after renal transplantation. An objective of our studies is to identify the protein component of the BKV receptor and to develop pharmaceutical agents capable of mitigating BKV entry into human renal proximal tubular epithelial cells, considered to be one of the main natural targets of BKV.