I received my Ph.D. in Physiology from the Institute of Normal Physiology, Moscow, Russia. Then, from 1983-1991 I worked in the laboratory of Dr. L. Rosenshtraukh in the Institute of Experimental Cardiology, Moscow, Russia. With the goal of learning the digital fluorescence imaging technique, in October 1992, I joined the laboratory of Professor Mordecai P. Blaustein in the Department of Physiology of the University of Maryland School of Medicine. I was promoted to Assistant Professor in 2000. My research is funded by grants from the NIH, the Alzheimer’s Association and the American Heart Association.
My research program focuses on understanding the mechanisms of regulation of Ca2+ signaling in glial and vascular smooth muscle cells and its role in physiological and pathophysiological processes. There are two major areas of active research.
Altered glial calcium signaling in neurodegeneration.
A common feature of Alzheimer’s disease and Down’s syndrome is a cascading microglia/astrocyte activation, characterized by the abundant production of proinflammatory cytokines, such as interleukin-1beta (IL-1beta). IL-1beta stimulates astrocytes to synthesize and release neuroactive agents such as S100beta, a cytokine that fosters neuronal dysfunction and death by raising intracellular free Ca2+ concentration ([Ca2+]cyt). IL-1beta also upregulates expression and processing of b-amyloid precursor protein (bAPP) leading to increased production of amyloid b-protein (Ab) that is thought to play a major role in the pathogenesis of Alzheimer’s disease. Both, IL-1beta and Abeta increase [Ca2+]cyt in astrocytes by augmenting Ca2+ influx. The mechanisms underlying Ca2+ disregulation, although unknown, may be causally implicated in reactive changes of astrocytes leading to neurotoxicity. They may involve activation of store- and/or receptor-operated Ca2+ entry (SOCE and ROCE, respectively) through TRPC-encoded store- and receptor-operated Ca2+ channels (SOCs, ROCs).
Current work is examining these Ca2+ transport mechanisms and their contribution to changes in Ca2+ that occur under conditions of Ca2+ dysregulation as exemplified in IL-1beta- and Abeta-treated cells and in astrocytes from the trisomy 16 (Ts16) mouse, an animal model of Down syndrome and Alzheimer’s disease.
Store-operated Ca2+ entry in arterial smooth muscle cells and hypertension.
Chronic hypertension is typically associated with increased peripheral vascular resistance. This is due, in part, to enhanced arterial smooth muscle contractility, which is regulated by intracellular Ca2+. Recent findings reveal that Ca2+ influx through TRPC-encoded store-operated Ca2+ channels (SOCs) in the plasma membrane (PM), along with voltage-gated Ca2+ channels may play a role in regulating myogenic tone and vasoconstriction. The role of store-operated Ca2+ entry (SOCE) in smooth muscle contraction and myogenic tone, however, depends on the precise location of SOCs in the PM with respect to the underlying sarcoplasmic reticulum (SR) and its Ca2+ transporters and receptors.
The research project focuses on the function and localization of SOCE in freshly isolated smooth muscle cells from rat and mouse mesenteric arteries. In addition, the role of SOCE in the dysregulation of Ca2+ homeostasis under conditions of chronic in vivo ouabain treatment (manifested as ouabain-induced hypertension, an animal model of human essential hypertension) is being explored.
Lab Techniques and Equipment: