Research Bio
I earned Ph.D. from Institute of Medical Genetics (Moscow, Russia). My research there was focused on studying changes in genome which are associated with schizophrenia.
During my work in Molecular Neurobiology Branch in NIDA/NIH I analyzed the effect of amphetamine on mouse brain using expression microarrays, and participated in the large-scale SNP genotyping project of multisubstance abuse patients which led to identification of several genomic loci responsible for increased drug abuse vulnerability.
My postdoctoral research in George Mason University (Virginia) was related to the biology of drug abuse, focusing on the expression changes caused in brain of adolescent rats by exposure to nicotine.
My current research focuses on neurological complications of HIV-1 infection. These complications include cognitive, motor and behavioral abnormalities. It is thought that the cause of these complications is a low-grade inflammation going on in central nervous system (CNS).
Clinical observation had shown that use of addictive drugs, especially methamphetamine, is associated with accelerated progression of neurological complications of AIDS. We hypothesize that both maladies affect brain vasculature and change cerebral blood flow therefore aggravating the toxic effect of each other. We use mouse model of neuroAIDS to study the effect of MA on brain vasculature.
The data obtained in Dewhurst lab and in other labs suggested that mixed lineage kinase 3 (MLK3) mediates different aspects of HIV-1-related neuroinflammation, and that blockage of MLK3 may reduce both microglila activation and neuronal damage. I work on further characterization of role of MLK3 in neuroinflammation and on developing new pharmacological inhibitors of MLK3 aiming to create a drug which could curb the neurological complications of AIDS.
2012
Polesskaya O, Sun A, Salahura G, Silva JN, Dewhurst S, Kasischke K. "Detection of microregional hypoxia in mouse cerebral cortex by two-photon imaging of endogenous NADH fluorescence." Journal of visualized experiments : JoVE. 2012 (60)Epub 2012 Feb 21. |
2012
Silva J, Polesskaya O, Knight W, Zheng JT, Granger M, Lopez T, Ontiveros F, Feng C, Yan C, Kasischke KA, Dewhurst S. "Transient hypercapnia reveals an underlying cerebrovascular pathology in a murine model for HIV-1 associated neuroinflammation: role of NO-cGMP signaling and normalization by inhibition of cyclic nucleotide phosphodiesterase-5." Journal of neuroinflammation. 2012 9:253. Epub 2012 Nov 20. |
2011 Feb 10
Polesskaya O, Silva J, Sanfilippo C, Desrosiers T, Sun A, Shen J, Feng C, Polesskiy A, Deane R, Zlokovic B, Kasischke K, Dewhurst S. "Methamphetamine causes sustained depression in cerebral blood flow." Brain research. 2011 Feb 10; 1373:91-100. Epub 2010 Dec 13. |
2010 Oct 20
Perry SW, Barbieri J, Tong N, Polesskaya O, Pudasaini S, Stout A, Lu R, Kiebala M, Maggirwar SB, Gelbard HA. "Human immunodeficiency virus-1 Tat activates calpain proteases via the ryanodine receptor to enhance surface dopamine transporter levels and increase transporter-specific uptake and Vmax." The Journal of neuroscience : the official journal of the Society for
Neuroscience. 2010 Oct 20; 30(42):14153-64. |
2010 Oct
Gelbard HA, Dewhurst S, Maggirwar SB, Kiebala M, Polesskaya O, Gendelman HE. "Rebuilding synaptic architecture in HIV-1 associated neurocognitive disease: a therapeutic strategy based on modulation of mixed lineage kinase." Neurotherapeutics : the journal of the American Society for
Experimental NeuroTherapeutics. 2010 Oct 0; 7(4):392-8. |
