Alexander Staruschenko, Ph.D.
Phone: (414) 955-8475
M.S., Physiology, St. Petersburg State University, St. Petersburg, Russia, 1999
Ph.D., Cell Biology, Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia, 2003
D.Sci., Cell Biology, Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia, 2010
Postdoctoral Fellow, Physiology, University of Texas Health Science Center at San Antonio, 2003-2007
Alexander (Sasha) Staruschenko joined the Department of Physiology as an Assistant Professor in November 2007. Alexander is also a member of the Kidney Disease Center.
We are interested in the normal and pathophysiological regulation of epithelial ion channels. A particular emphasis is placed on the epithelial Na+ channel (ENaC). The long term control of blood pressure involves Na+ homeostasis through the precise regulation of ENaC in the aldosterone-sensitive distal nephron. ENaC is a member of the ENaC/Deg channel superfamily. ENaC/Deg channels are rather distinct in that they are non-voltage gated, highly Na-selective channels. ENaC activity is rate limiting for Na+ reabsorption in the distal nephron. Abnormalities in ENaC function have been linked to disorders of total body Na+ homeostasis, blood volume, blood pressure, and lung fluid balance. Gain of function mutations of both β and γ ENaC leading to channelhyperactivity (Liddle’s syndrome) are two the only known forms of monogenic hypertension. Most forms of monogenic hypertension, including apparent mineralocorticoid excess and glucocorticoid remediable aldosteronism, result from inappropriate regulation of ENaC activity and abnormal salt-water balance. Hyposecretion of aldosterone can be mimicked by loss of function mutations in ENaC subunits, which result in decreased channel activity and pseudohypoaldosteronism (PHA). PHA results in hypovolemia, hyperkalemia, salt wasting and in some instances hypotension. Recently, ENaC dysfunction has also been demonstrated in renal epithelial cells from animals and humans with Autosomal Recessive Polycystic Kidney Disease (ARPKD), which is a renal cystic disease confined to the distal nephron associated with improper handling of NaCl.
We use a number of contemporary methodologies, including electrophysiology, molecular biology, biochemistry, and fluorescence microscopy to investigate regulation of ENaC and aldosterone signaling. We routinely use reconstituted channels in mammalian expression systems, immortalized epithelial cell lines and freshly isolated rat collecting ducts in this regard. We perform real-time measurement of ion channel activity and fluorescence imaging, and perform biophysical analysis of ion channel activity and gating, create point mutations and chimeric proteins and genes, investigate cellular signal transduction, and study channels in heterologous expression systems as well as in native principal cells.
Currently we are working on projects including: 1) to determine the effects of small G proteins on ENaC activity and assign the cellular mechanism(s) of small G protein regulation of ENaC, 2) to identify the small G proteins responsible for trafficking of ENaC, 3) to identify cytoskeletal targets of small G proteins relevant to ENaC trafficking and their mechanism of action on the channel, 4) to determine which domains within ENaC subunits are necessary and modulatory for channel function, and 5)to identify which sequence tracts/domains within ENaC subunits are functional equivalent and which provide unique properties to the channel.
Research in our lab is supported by the National Heart, Lung, and Blood Institute, the American Heart Association, the American Society of Nephrology, and the American Diabetes Association.
- Staruschenko A. Regulation of transport in the connecting tubule and cortical collecting duct. Comprehensive Physiology 2(2): 1541‐1584, 2012.
- Mamenko M., Zaika O., Ilatovskaya D.V., Staruschenko A., Pochynyuk O. Angiotensin II increases activity of the Epithelial Na+ Channel (ENaC) in the distal nephron additively to aldosterone. Journal of Biological Chemistry. 287(1):660-71, 2012.
- Ilatovskaya D.V., Pavlov T.S., Negulyaev Y.A., Staruschenko A. Mechanisms of epithelial sodium channel (ENaC) regulation by cortactin: involvement of dynamin. Cell and Tissue Biology 6(1): 52–59, 2012.
- Pavlov T.S., Ilatovskaya D., Levchenko V., Mattson D.L., Roman R.J., Staruschenko A. Effects of cytochrome P450 metabolites of arachidonic acid on the epithelial sodium channel (ENaC). American Journal of Physiology: Renal Physiology 301(3): F672-F681, 2011.
- Karpushev A, Levchenko V, Ilatovskaya D, Pavlov T, Staruschenko A. Novel role of Rac1/WAVE signaling mechanism in regulation of the epithelial Na+ channel (ENaC). Hypertension. 57: 996-1002, 2011.
- Karpushev AV, Ilatovskaya DV, Staruschenko A. The actin cytoskeleton and small G protein RhoA are not involved in flow-dependent activation of ENaC. BMC Res Notes. 3:210, 2010.
- Pavlov TS, Imig JD, Staruschenko A. Regulation of ENaC-mediated sodium reabsorption by peroxisome proliferator-activated receptors. PPAR Research. 2010:703735, 2010.
- Pavlov T.S., Chahdi A., Ilatovskaya D.V., Levchenko V., Vandewalle A., Pochynyuk O., Sorokin A., Staruschenko A. Endothelin-1 regulates the epithelial Na+ channel via βPix/14-3-3/Nedd4-2 complex. Journal of the American Society of Nephrology. 21(5): 833-843, 2010.
- Staruschenko A., Jeske N.A., Akopian A. Contribution of TRPV1-TRPA1 interaction to the single-channel properties of the TRPA1 channel. Journal of Biological Chemistry. 285(20): 15167-15177, 2010.
- Levchenko V., Zheleznova N.N., Pavlov T.S., Vandewalle A., Wilson P.D. Staruschenko A. EGF and its related growth factors mediate sodium transport in mpkCCDc14 cells via ErbB2 (neu/HER-2) receptor. Journal of Cellular Physiology. 223(1): 252-259, 2010.
- Karpushev A., Vachugova D.V., Pavlov T.S., Negulyaev Y.A., Staruschenko A. Intact cytoskeleton is required for small G protein dependent activation of the epithelial Na+ channel. PLOS One. 5(1): e8827, 2010.
- Pavlov T.S., Levchenko V., Karpushev A., Vandewalle A., Staruschenko A. PPARγ antagonists decrease Na+ transport via the epithelial Na+ channel (ENaC). Molecular Pharmacology. 76(6): 1333-1340, 2009.
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