Alexander Staruschenko, PhD
Professor & Eminent Scholar
PhD, Cell Biology, Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia, 2003
Postdoctoral Fellow, Physiology, University of Texas Health Science Center at San Antonio, 2003-2007
MS, Physiology, St. Petersburg State University, 1999
Alexander (Sasha) Staruschenko joined the Department of Physiology as an Assistant Professor in November 2007 and was promoted to Associate Professor in 2012.
The Staruschenko Lab is interested in the normal and pathophysiological regulation of ion channels in the kidney. 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 channel hyperactivity (Liddle's syndrome) are two the only known forms of monogenic hypertension. 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 are specifically focused on the role of ENaC in the development of salt-sensitive hypertension and mechanisms involved in regulation of this channel in this disease setting.
Another area of interest is regulation of Transient Receptor Potential Canonical (TRPC) channels in podocytes. Glomerular podocytes are central components of the renal filtration barrier, and, at least in part, play a role in the pathogenesis of almost all proteinuric glomerulopathies. TRPC proteins, which belong to the larger TRP superfamily of channels, form Ca2+-permeable channels that are important players in the pathogenesis of renal and cardiovascular diseases. An association between altered TRPC channel function and/or expression with the development of various kidney diseases has garnered the attention of many investigators. TRPC6 is an essential component of the podocyte slit diaphragm, where it is integrated into a signaling complex that interacts with nephrin, podocin, alpha-actinin-4, calcineurin etc. Several independent laboratories have reported the identification of TRPC6 mutations associated with autosomal dominant FSGS. These genetic discoveries highlighted the critical importance of the podocyte and TRPC6 channel in the maintenance of the glomerular filtration and raised the possibility that abnormalities of the podocyte may also play a role in more common glomerular diseases such as diabetic nephropathy.
Additional emphasis is placed to the role of reactive oxygen species (ROS) and other paracrine signaling molecules (such as ATP) in the control of ion channels in the kidney and renal function, respectively. ROS, and specifically H2O2 in the kidney plays a critical role in the development of salt-sensitive hypertension. For example, chronic administration of H2O2 into the medullary interstitium of salt-resistant rats produces a salt-sensitive form of hypertension while medullary infusion of catalase to Dahl salt-sensitive rats reduces hypertension by nearly 50%. Purinergic signaling system intrinsic to the distal nephron similarly enables the kidney to dynamically match Na+ excretion to Na+ intake as a homeostatic mechanism to maintain blood pressure within a normal range despite broad changes in Na+ consumption. We recently developed a new approach based on enzymatic microelectrode biosensors allowing us to measure basal levels and real time endogenous substances release in the kidney in response to drug perfusion. Using this innovative approach in combination with microscopical analysis and electrophysiological measurements of ion channels in isolated glomeruli and nephron segments we are focused on the role of ROS and ATP in regulation of renal ion channels and control of blood pressure.
We use a number of contemporary methodologies, including electrophysiology, molecular biology, biochemistry, and fluorescence microscopy to investigate regulation of ENaC, TRPC, Kir and other ion channels in the kidney. We routinely use reconstituted channels in mammalian expression systems, immortalized epithelial cell lines and freshly isolated collecting ducts and glomeruli in this regard.
Currently we are working on a numerous projects related to ion channels in the kidney. Our main goals are: 1) To define mechanisms and relevance of ENaC regulation by members of the epidermal growth factors (EGF) family in salt-sensitive hypertension; 2) To identify the small G proteins responsible for trafficking of ENaC; 3) To define the cellular and molecular mechanism by which H2O2 modulates ENaC activity; 4) To determine mechanisms of regulation of TRPC channels in podocytes; 5) To determine mechanisms of the excessive calcium flux in podocytes in diabetic nephropathy; 6) To determine the relationship between ENaC activity and cystogenesis in PKD; and 7) To define specific role of Kcnj10/16 heteromeric channels in the kidney.
(Miller B, Palygin O, El-Meanawy A, Mattson DL, Geurts AM, Staruschenko A, Sorokin A.) Life Sci. 2021 Aug 15;279:119661 PMID: 34087282 PMCID: PMC8265215 SCOPUS ID: 2-s2.0-85107260373 06/05/2021
(Spires DR, Palygin O, Levchenko V, Isaeva E, Klemens CA, Khedr S, Nikolaienko O, Kriegel A, Cheng X, Yeo JY, Joe B, Staruschenko A.) Physiol Genomics. 2021 Jun 01;53(6):223-234 PMID: 33870721 SCOPUS ID: 2-s2.0-85108022875 04/20/2021
(Schlingmann KP, Renigunta A, Hoorn EJ, Forst AL, Renigunta V, Atanasov V, Mahendran S, Barakat TS, Gillion V, Godefroid N, Brooks AS, Lugtenberg D, Lake J, Debaix H, Rudin C, Knebelmann B, Tellier S, Rousset-Rouvière C, Viering D, de Baaij JHF, Weber S, Palygin O, Staruschenko A, Kleta R, Houillier P, Bockenhauer D, Devuyst O, Vargas-Poussou R, Warth R, Zdebik AA, Konrad M.) J Am Soc Nephrol. 2021 Jun 01;32(6):1498-1512 PMID: 33811157 SCOPUS ID: 2-s2.0-85107319220 04/04/2021
(Bohovyk R, Fedoriuk M, Isaeva E, Shevchuk A, Palygin O, Staruschenko A.) J Cell Mol Med. 2021 May;25(9):4216-4219 PMID: 33745233 PMCID: PMC8093965 SCOPUS ID: 2-s2.0-85102841283 03/22/2021
(Shalygin A, Shuyskiy LS, Bohovyk R, Palygin O, Staruschenko A, Kaznacheyeva E.) Int J Mol Sci. 2021 Apr 22;22(9) PMID: 33922367 PMCID: PMC8122765 SCOPUS ID: 2-s2.0-85104554043 05/01/2021
(Klemens CA, Chulkov EG, Wu J, Hye Khan MA, Levchenko V, Flister MJ, Imig JD, Kriegel AJ, Palygin O, Staruschenko A.) Hypertension. 2021 Feb;77(2):582-593 PMID: 33390052 PMCID: PMC7856014 SCOPUS ID: 2-s2.0-85100070512 01/05/2021
(Manis AD, Palygin O, Isaeva E, Levchenko V, LaViolette PS, Pavlov TS, Hodges MR, Staruschenko A.) JCI Insight. 2021 01 11;6(1) PMID: 33232300 PMCID: PMC7821607 SCOPUS ID: 2-s2.0-85099291307 11/25/2020
(Palygin O, Klemens CA, Isaeva E, Levchenko V, Spires DR, Dissanayake LV, Nikolaienko O, Ilatovskaya DV, Staruschenko A.) iScience. 2021 SCOPUS ID: 2-s2.0-85106559673 01/01/2021
(Klemens CA, Staruschenko A.) Am J Physiol Renal Physiol. 2020 12 01;319(6):F1001-F1002 PMID: 33166184 PMCID: PMC7792698 SCOPUS ID: 2-s2.0-85096815515 11/10/2020
(Staruschenko A, Brooks HL.) Am J Physiol Renal Physiol. 2020 12 01;319(6):F1042 PMID: 33166180 SCOPUS ID: 2-s2.0-85097003645 11/10/2020
(Nikolaienko O, Isaeva E, Levchenko V, Palygin O, Staruschenko A.) Am J Physiol Regul Integr Comp Physiol. 2020 12 01;319(6):R684-R689 PMID: 33052061 PMCID: PMC7792816 SCOPUS ID: 2-s2.0-85098454395 10/15/2020
(Golosova D, Palygin O, Bohovyk R, Klemens CA, Levchenko V, Spires DR, Isaeva E, El-Meanawy A, Staruschenko A.) Life Sci Alliance. 2020 12;3(12) PMID: 33046522 PMCID: PMC7556751 SCOPUS ID: 2-s2.0-85092887222 10/14/2020