Alexander G. Obukhov, Ph.D.
Education / Training
- 1983, M.S. in Chemistry, Samara State University, Samara, Russia
- 1988, Ph.D. in Biophysics, Bogomoletz Institute of Physiology, Kiev, Ukraine
- 1989, Postdoctoral Fellowship in Electrophysiology, Bogomoletz Institute of Physiology, Kiev, Ukraine
- 1992, Humboldt Postdoctoral Fellowship in Electrophysiology, Institute of Pharmacology, Berlin, Germany
Research Biography Summary
Contribution to Science
My laboratory investigates the functional roles and properties of TRP proteins. TRP proteins form Ca2+-permeable cation-selective channels in the plasma membrane. TRPs are widely expressed throughout our body. TRPs serve as “communication channels” between the environment and the cell. When the channels open, Ca2+ cations enter the cell to regulate gene expression, exocytosis, contractions, or to activate multiple Ca2+-dependent kinases, and phosphatases. Mammalian TRP channels have been subdivided into five groups: TRPC (Canonical TRP), TRPV (the Vanilloid subfamily), TRPM (the Melastatin subfamily), TRPA1 (the Ankyrin subfamily), TRPP (the Polycystin subfamily), and TRPML (the Mucolipin subfamily). TRPs are molecular sensors of various physical and chemical stimuli ranging from heat (TRPV1), cold (TRPM8), cell swelling (TRPV4), various ligands such as capsaicin (TRPV1), menthol (TRPM8), mustard oil (TRPA1), sweet compounds (TRPM5), or the hormones of G-protein coupled receptors (TRPCs). Currently, my laboratory focuses on investigating the functional role of TRPC channels in the adrenal chromaffin and vascular smooth muscle cells. We also perform structure-function studies to identify the amino acid residues responsible for specific biophysical characteristics of TRPC channels. We employ an array of techniques ranging from single-channel recording, cloning, site-directed mutagenesis, Western blots, and fluorescence imaging to in vivo gene transfer.
This research program is funded by an R01 NIH grant to A.G. Obukhov.
Xingjuan Chen, M.S., Ph.D. – Postdoctoral Appointee
Wennan Li, M.S., Ph.D. – Postdoctoral Appointee
Ashley Riley –Undergraduate Student
Sarah Flores – Undergraduate Student
S. Christopher Hiett – Undergraduate Student
Nicholas Gianaris, B.S., M.S. – Part time Research Technical Assistant
Christian L. Egly - LHSI Fellow, Undergraduate Student
Obukhov AG, Harteneck C, Zobel A, Harhammer R, Kalkbrenner F, Leopoldt D, Luckhoff A, Nurnberg B, Schultz G. (1996) Direct activation of trpl cation channels by G alpha11 subunits. EMBO J. 15(21):5833-5838.
Zitt C, Obukhov AG, Strubing C, Zobel A, Kalkbrenner F, Luckhoff A, Schultz G. (1997) Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion. J. Cell Biol. 138(6):1333-1341.
Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397 (6716):259-263.
Schaefer M, Plant TD, Obukhov AG, Hofmann T, Gudermann T, Schultz G. (2000) Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J. Biol. Chem. 275 (23):17517-17526.
Obukhov AG, Nowycky MC. (2002) TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca2+ to trigger exocytosis in neuroendocrine cells. J. Biol. Chem. 277(18):16172-16178.
Obukhov AG, Nowycky MC. (2004) TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin-binding phosphoprotein-50 (EBP50). J. Cell Physiol. 201(2):227-235.
Obukhov AG, Nowycky MC. (2005) A cytosolic residue mediates Mg2+ block and regulates inward current amplitude of a transient receptor potential channel. J. Neurosci. 25(5):1234-1239.
Lee D, Obukhov AG, Shen Q, Liu Y, Dhawan P, Nowycky MC, Christakos S. (2006) Calbindin-D28k decreases L-type calcium channel activity and modulates intracellular calcium homeostasis in response to K+ depolarization in a rat beta cell line RINr1046-38. Cell Calcium 39(6):475-485.
Liu CH, Wang T, Postma M, Obukhov AG, Montell C, Hardie RC. (2007) In Vivo Identification and Manipulation of the Ca2+ Selectivity Filter in the Drosophila Transient Receptor Potential Channel. J. Neurosci. 27(3):604-615.
Obukhov AG and Nowycky MC. (2008) TRPC5 channels undergo changes in gating properties during the activation-deactivation cycle. J Cell Physiol. 216(1):162-171.
Hu G, Oboukhova EA, Kumar S, Sturek M, and Obukhov AG. Canonical Transient Receptor Potential Channels Expression is Elevated in a Porcine Model of Metabolic Syndrome.
Mol Endocrinol, 23(5):689-699, May 2009. full text · PubMed
Edwards JM, Neeb ZP, Alloosh MA, Long X, Bratz IN, Peller CR, Byrd JP, Kumar S, Obukhov AG, and Sturek M. Exercise training decreases store-operated Ca2+ entry associated with metabolic syndrome and coronary atherosclerosis. Cardiovasc Res. 85(3):631-640, Feb 2010. PubMed
Grimm C, Jörs S, Saldanha SA, Obukhov AG, Pan B, Oshima K, Cuajungco MP, Chase P, Hodder P, Heller S. Small molecule activators of TRPML3. Chem Biol. 17(2):135-148, Feb 26, 2010. Free Full Text, PubMed
Chakraborty S, Berwick ZC, Bartlett PJ, Kumar S, Thomas AP, Sturek M, Tune JD, Obukhov AG. Bromoenol lactone inhibits voltage-gated Ca2+ and transient receptor potential canonical channels. J Pharmacol Exp Ther. 339(2):329-40, Nov 2011.
Kumar S, Chakraborty S, Barbosa C, Brustovetsky T, Brustovetsky N, Obukhov AG. Mechanisms controlling neurite outgrowth in a pheochromocytoma cell line: the role of TRPC channels. J Cell Physiol. 227(4):1408-19, Apr 2012. Epub: May 2011.
Grimm C, Jörs S, Guo Z, Obukhov AG, Heller S.Constitutive Activity of TRPML2 and TRPML3 Channels versus Activation by Low Extracellular Sodium and Small Molecules. J Biol Chem. 287(27):22701-22708, Jun 2012.
Additional References are located on the website of the National Center for Biotechnology Information.