Education

Postdoctoral Fellow
Yale University, 1979
Ph.D.
University of Illinois, 1976
M.S.
University of Illinois, 1974
M.A.
Walla Walla College, 1972

Areas of Interest

Research Interests

Calcium signaling and ion channels

Research Information

Calcium signaling and ion channels

Research in our laboratory is broadly focused on cell signaling and the mechanisms by which cells sense and transduce extracellular signals (stimuli) into chemical changes within the cell. We are particularly interested in calcium signaling and the structure and function of calcium-permeable channels and their assembly into calcium signalingplexes with a special focus on the superfamily of “transient receptor potential” channels (TRP channels). TRP channels are a relatively new class of calcium-permeable channels that are widely expressed in numerous tissue/cell types, ranging from renal epithelia to neuronal sensory cells, and are highly sensitive to numerous microenvironmental stimuli (mechanical stresses, noxious agents, inflammatory mediators, etc). As a consequence, they are emerging as playing critical roles in the control of intracellular calcium levels and calcium signaling networks in both physiological and pathophysiological states in a broad range of tissues. We have two main areas of interest relating to calcium signaling a third relating to application of optical probes in biology:

  1. TRP channels/signalingplexes in renal cell function: Our focus is on determining the role of TRP channels and calcium signalingplexes (Ca-sensitive potassium channels, kinases/phosphatases, cytoskeletal components) in sensing and responding to mechanical stresses (tubular fluid flow/shear stress, pressure, cell swelling) in renal tubular epithelial and glomerular mesangial cells during pathophysiological states that directly impact renal function (hypertension, hyponatremia, diabetes mellitus, renal failure). Emphasis is on eludicating how altered mechanical stresses in various dysfunctional states leads to altered fluid and electrolyte balance.
  2. Calcium signaling networks and function of the blood-brain barrier: Our interest is in the role of calcium signaling entities (TRP channels, Na:Ca exchangers, calcium storage sites) and underlying calcium signalingplexes in controlling the function/dysfunction of brain microvascular endothelial cells. Emphasis is on elucidating the role of calcium signalingplexes and calcium signaling networks in regulating the function of the neurovascular unit (the cells associated with the blood-brain barrier) with a special emphasis on the calcium-dependent mechanism controlling the integrity of the endothelial cell barrier, the blood-brain barrier, in pathophysiological states associated with stroke/cerebral ischemia, hypertension, and inflammation.
  3. Optical probe markers: Our interest is directed at the identification/development and application of optical markers as reporters of cellular processes and/or cell/tissue status. Emphasis is on the application of optical methods (fluorescence imaging, confocal microscopy, surface plasmon resonance, and multiparametric spectral techniques) to identify and/or modulate dysfunctional states in various pathophysiological settings (e.g., cancerous cells, dysfunctional calcium signaling networks).

Because of the broad nature of investigative studies in our laboratory, eclectic investigative techniques are employed in the laboratory ranging from molecular biology assays/methods (cloning/expression, RT-PCR, Northern blotting, RNAi interference), to electrophysiological techniques (single channel- and whole-cell patch clamp), to advanced imaging techniques (fluorescence/confocal microscopy, fluorescence energy transfer, total internal reflectance fluorescence, multiparametric spectral imaging, 3-D reconstruction).

O'Neil Lab Model

Publications

Publication Information

  • Mamenko M, Zaika OL, Boukelmoune N, Berrout J, O’Neil RG, Pochynyuk O. (2013). Discrete control of TRPV4 channel function in the distal nephron by protein kinases A and C. J Biol Chem., 288:20306-2014.
  • Zaika O, Mamenko M, Berrout J, Boukelmoune N, O’Neil RG, Pochynyuk O. (2013). TRPV4 dysfunction promotes renal cystogenesis in autosomal recessive polycystic kidney disease. J Am Soc Nephrol., 24:604-616.
  • Berrout J, Jin M, Mamenko M, Zaika O, Pochynyuk O, O’Neil RG. (2012). Function of TRPV4 as a mechanical transducer in flow-sensitive segments of the renal collecting duct system. J Biol Chem., 287: 8782-8791.
  • Berrout J, Jin M, O’Neil RG. (2012). Critical role of TRPP2 and TRPC1 channels in stretch-induced injury of blood brain barrier endothelial cells. Brain Research, 1436:1-12.
  • Jin M, Berrout J, Chen L, and O’Neil RG. (2012). Hypotonicity-induced TRPV4 function in renal collecting duct cells: modulation by progressive cross-talk with Ca2+-activated K+ channels. Cell Calcium, 51:131-139.
  • Lichtenberger LM, Zhou Y, Jayaraman V, Doyen JR, O’Neil RG, Dial EJ, Volk DE, Gorenstein DG, Boggara MB, Krishnamoorti R. (2012). Insight into NSAID-induced membrane alterations: pathogenesis and therapeutics: Characterization of interaction of NSAIDs with phosphatidylcholine. Biochim Biophysica Acta., 1821: 994-1002.
  • Mamenko M, Zaika O, O’Neil RG, and Pochynyuk O. (2012). Ca2+ imaging as a tool to assess TRP channel function in murine distal nephrons. IN: Ion Channels. Methods and Protocols, N. Gamper, ed, (In Press).
  • Pochynyuk O, Zaika O, O’Neil RG, Mamenko M. (2012). Novel insights into TRPV4 function in the kidney. Pflugers Arch. (In Press)
  • Zaika O, Mamenko M, Berrout J, Boukelmoune N, O’Neil R, and Pochynyuk O. (2012). TRPV4 dysfunction determines renal cystogenesis in a rat model of autosomal recessive polycystic kidney disease. J Am Soc Nephrol., (accepted).
  • Jin M, Berrout J, O’Neil RG. (2011). Regulation of TRP channels by osmomechanical stress. IN: TRP Channels (Methods in Signal Transduction Series), editor Michael Xi Zhu. CRC Press, New York, pp 353-373.
  • Jin M, Wu Z, Chen L, James J, Collins D, Walters ET, and O’Neil RG. (2011). Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A. PLoS ONE, 6(2):e16713.
  • Mamenko N, Zaika O, Jin M, O’Neil RG, and Pochynyuk O. (2011). Purinergic activation of Ca2+-permeable TRPV4 channels is essential for mechano-sensitivity in the aldosterone-sensitive distal nephron. PLoS ONE, 6:e22824.
  • Ma X, Cheng KT, Wong CO, O’Neil RG, Birnbaumer L, Ambudkar IS, and Yao X. (2011). Hetermomeric TRPV4-C1 channels contribute to store-operated Ca2+ entry in vascular endothelial cells. Cell Calcium, 50:502-509.
  • Zaika O, Mamenko M, O’Neil RG, and Pochynyuk O. (2011). Bradykinin acutely inhibits activity of the epithelial Na+ channels (ENaC) in mammalian aldosterone-sensitive distal nephron. Am J Physiol Renal Physiol., 300:F1105-F1115.
  • Hicks K, O’Neil RG, Dubinsky WS, and Brown RC. (2010). TRPC-mediated actin-myosin Jin contraction is critical for BBB disruption following hypoxic stress. Am J Physiol Cell Physiol., 298, C1583-C1593.
  • Kunjilwar KK, Fishman HM, Englot DJ, O’Neil RG, and Walters ET. (2010). Long-lasting hyperexcitability induced by depolarization in the absence of detectable Ca2+ signals. J Neurophysiol., 101, 1351-1360.
  • Brown RC, Wu L, Hicks K, and RG O’Neil. (2008). Regulation of blood-brain barrier permeability by TRPC and TRPV calcium-permeable channels. Microcirculation, 152 359-371.
  • Wu L, Gao X, Brown RC, Stefan S, O’Neil RG. (2007). Dual role of the TRPV4 channel as a sensor of flow and osmolality in renal epithelial cells. Am J Physiol Renal Physiol., 293:F1699-F1713.
  • Brown RC, Morris AP, and O’Neil RG. (2007). Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells. Brain Res., 1130:17-30.
  • Morrelli SP, O’Neil RG, Brown RC, and Bryan RM, Jr. (2006). PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries. Am J Physiol Heart Circ Physiol., 292:H1390-H1397.
  • O’Neil RG, and Heller S. (2005). The mechanosensitive nature of TRPV channels. Pflugers Archiv., 451:193-203.
  • O’Neil RG, Wu L, Mullani N. (2005). Uptake of a fluorescent deoxyglucose analogue (2-NBDG) in tumor cells. Molecul Imag Biol., 7:388-392.
  • Liu X, Zhang MI, Peterson LB, and O’Neil RG. (2003). Osmomechanical stress selectively regulates translocation of protein kinase C isoforms. FEBS Lett., 538:101-106.