References:
- Gao, X., L. Wu, R.G. O’Neil. Temperature-modulated diversity of TRPV4 channel gating: Activation by physical stresses and phorbol ester derivatives through protein kinase C-dependent and -independent pathways. J. Biol. Chem. 278:27129-27137, 2003.
- O’Neil, R.G., and R.C. Brown. The vanilloid receptor family of calcium-permeable channels (TRPV): Molecular integrators of microenvironmental stimuli. News Physiol. Sci. 18:226-231, 2003.
- O’Neil, R.G., L. Wu, N. Mullani. Uptake of a fluorescent deoxyglucose analogue (2-NBDG) in tumor cells. Molecul. Imag. Biol. 7:388-392, 2005.
- O’Neil, R.G., and S. Heller. The mechanosensitive nature of TRPV channels. Pflugers Archiv. 451:193-203, 2005.
- Morrelli, S.P., R.G. O’Neil, R.C. Brown, and R.M. Bryan, Jr. PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries. Am. J. Physiol. Heart Circ. Physiol. 292:H1390-H1397, 2006.
- Brown, R.C., A.P. Morris, and R.G. O’Neil. Tight junction protein expression and barrier properties of immortialized mouse brain microvessel endothelial cells. Brain Res. 1130:17-30, 2007.
- Wu, L., X. Gao, R.C. Brown, S. Stefan, R.G. O’Neil. Role of the TRPV4 channel as a molecular sensor of flow in renal cells. Am. J. Physiol. 2007 (in press).
Roger G. O'Neil, Ph.D.
Professor
UTHSC-Medical School, (713) 500 - 6316
Roger.G.ONeil@uth.tmc.edu
Calcium signaling and ion channels
Research in our laboratory is broadly focused on cell signaling and the mechanisms by which cells sense and transducer extracellular signals (stimuli) into chemical changes within the cell. We are particularly interested in calcium signaling and the regulation of intracellular calcium levels in physiological and pathophysiological (hypertension, diabetes mellitus, and renal failure). Intracellular calcium is a major second messenger in animal cells that controls a myriad of calcium-dependent processes and functions ranging from cell shape and contractility to gene expression and cell proliferation. Our primary focus is on the mechanisms but which mechanical stimuli (shear stress, membrane stretch, cell swelling, etc.) and vasoactive peptides/inflammatory mediators (angiotensin II, endothelin 1, bradykinin, thrombin, etc.) induce calcium signaling and the control of calcium-dependent functions (transcellular fluid and solute transport, cell shape, cytoskeletal structure, etc.) in vascular endothelial cells and renal epithelial cells. We would like to elucidate the mechanistic basis of normal and dysfunctional regulation of calcium signaling associated with altered pathophysiological states (hypertension, diabetes mellitus, and renal failure). Our most recent work is directed at understanding the function and structure of the emerging new super family of calcium – permeable ion channels, the “transient receptor potential” ion channels, or TRP channels in these processes. Emphasis is on elucidating the function/dysfunction of specific TRP channels, the channel structure and the channel associations with key accessory proteins that may function as an integrated calcium signallingplex. Because of the broad nature of these studies, eclectic investigative techniques are employed in the laboratory ranging from molecular biology assays to single channel function measurements. The techniques include electrophysiological techniques (singles-channel patch clamp, two-electrode voltage clamp), confocal and fluorescence imaging (fluorescence spectroscopy, fluorescence energy transfer, fluorescence polarization, 3-D reconstruction), biochemical assessment of protein expression and transduction pathways (immunocytochemistry, biochemical assays, mass spectroscopy), and molecular assessment of channel expression, structure and function (cloning, RT-PCR, Q-PCR, Northern blotting, gene silencing and RNA interference, heterologous expression systems).
