Thomas C. Rich, Ph.D.
USA Department of Pharmacology
Ph.D.: Vanderbilt University
Post-doctoral: University of Colorado Health Sciences Center
Phone: (251) 460-6039
The overall goal of our lab is to understand the cellular mechanisms that underlie signaling specificity – in particular, understanding how second messenger signals differentially regulate a wide variety of cellular responses. We are focused on determining how the subcellular localization and kinetics of cAMP and cGMP signals contribute to the activation of specific downstream targets. These processes involve not only the localization of key signaling enzymes – receptors, cyclases, phophodiesterases, kinases, and phosphatases – to their cellular targets; it also involves the localization of cAMP and cGMP signals themselves. The following are ongoing projects in the lab:
- Elucidating the contributions of receptor desensitization and the regulation of cyclase and phosphodiesterase activities in shaping cAMP and cGMP signals in pulmonary endothelial and smooth muscle cells.
- Understanding the cellular mechanisms by which localized phosphodiesterase activity regulates endothelial barrier permeability.
- Determining the molecular mechanisms underlying synergistic effects of b2 adrenergic agonists and corticosteroids in the treatment of asthma.
- Measuring enzyme activity in discrete subcellular locations.
- Developing optical approaches for the real time measurement of cyclic nucleotide signals in intact tissue.
Rich, T.C., K.A. Fagan, H. Nakata, J. Schaack, D.M.F. Cooper, J.W. Karpen. 2000. Cyclic nucleotide-gated channels colocalize with adenylyl cyclase in regions of restricted cAMP diffusion. J. Gen. Physiol. 116:147-161. [see commentary: Pugh, E.N. 2000. J. Gen. Physiol. 116:143-146.]
Rich, T.C., T.E. Tse, J.G. Rohan, J. Schaack, J.W. Karpen. 2001. In vivo assessment of phosphodiesterase activity using tailored cyclic nucleotide-gated channels as cAMP sensors. J. Gen. Physiol. 118:63-77.
Rich, T.C., K.A. Fagan, T.E. Tse, J. Schaack, D.M.F. Cooper, J.W. Karpen. 2001. A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell. Proc. Natl. Acad. Sci. USA 98:13049-13054. [see commentary: Schwartz, J.H. 2001. Proc. Natl. Acad. Sci. USA 98:13482-13484.]
Rich, T.C., J.W. Karpen. 2002. Cyclic AMP sensors in living cells: what signals can they actually measure? Ann. Biomed. Eng. 30:1088-1099.
Clark, R.B., T.C. Rich. 2003. Probing the roles of protein kinases in G-protein-coupled receptor desensitization. Mol. Pharmacol. 64:1015-1017.
Brady, J.D., T.C. Rich, X. Le, K. Stafford, L. Lynch, J.W. Karpen, R.L. Brown, J.P. Martens. 2004 Functional role of lipid rafts in cyclic nucleotide-gated channel activation. Mol. Pharmacol. 65:503-511.
Piggott, L.A., K.A. Hassell, Z. Berkova, A.P. Morris, M. Silberbach, T.C. Rich. 2006. Natriuretic peptides and nitric oxide stimulate cGMP synthesis in different cellular compartments. J. Gen. Physiol. 128:3-14.
Rich, T.C., W. Xin, C. Mehats, K.A. Hassell, L.A. Piggott, X. Le, J.W. Karpen, and M. Conti. 2007. Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cells. Am. J. Physiol. 292:C319-C331.
Xin, W.K., T.M. Tran, W. Richter, R.B. Clark, T.C. Rich. 2008. Functional roles of GRK and PDE activities in the regulation of b2 adrenergic signaling. J. Gen. Physiol. 134:349-364.
Xie M., T.C. Rich, C. Scheitrum, M. Conti, and W. Richter. 2011. Inactivation of multidrug resistance proteins disrupts both cellular extrusion and intracellular degradation of cAMP. Mol. Pharmacol 80: 281-293.
Blackman B.E., J. Heimann, K. Horner, D. Wang, W. Richter, T.C. Rich, and M. Conti. 2011. PDE4D and PDE4B function in distinct subcellular compartments in mouse embryonic fibroblasts. J. Biol. Chem. 286:12590-12601.
Leavesley S.J., N. Annamdevula, J. Boni, S. Stocker, K. Grant, B. Troyanovsky, T.C. Rich, and D.F. Alvarez. 2012. Hyperspectral imaging microscopy for identification and quantitative analysis of fluorescently-labeled cells in highly autofluorescent tissue. J. Biophotonics. 5:67-84.
Feinstein W.P., B. Zhu, S.J. Leavesley, S.L. Sayner, and T.C. Rich. 2012. Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells. Am. J. Physiol. Cell Physiol. 302: C839-C852. [see commentary: Murray, F. 2012. Am. J. Physiol. Cell Physiol. 302:C837-C838.]
Horvat S.J., D.A. Deshpande, H. Yan, R.A. Panettieri, J. Codina, T.D. DuBose, W. Xin, T.C.* Rich, and R.B.* Penn. 2012. AKAPs regulate compartmentalized cAMP signaling in airway smooth muscle. FASEB J. in press. [*reflects equal contributions from the Rich and Penn laboratories.]
Henesy M.B., A.L. Britain, B. Zhu, L. Amable, R.E. Honkanen, J.D. Corbin, S.H. Francis, and T.C. Rich. 2012. Calcineurin regulates homologous desensitization of natriuretic peptide receptor-A and inhibits ANP-induced testosterone production in MA-10 cells. PLoS ONE. in press.