References:
- Brown, R.C., L. Wu, K. Hicks, and R.G. O’Neil. Regulation of blood-brain barrier permeability by TRPC and TRPV calcium-permeable channels. Microcirculation. 2008 (In press).
- Wu, L., X. Gao, R.C. Brown, S. Stefan, R.G. O’Neil. 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, 2007.
- 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.
- 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.
- O’Neil, R.G., and S. Heller. The mechanosensitive nature of TRPV channels. Pflugers Archiv. 451:193-203, 2005.
- 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.
- Liu, X., M.I. Zhang, L.B. Peterson, and R.G. O’Neil. Osmomechanical stress selectively regulates translocation of protein kinase C isoforms. FEBS Lett. 538:101-106, 2003.
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 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:
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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.
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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.
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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).
