Raymond B. Penn
The major focus of my research is to identify cellular and molecular mechanisms by which G protein-coupled receptors (GPCRs) mediate important functions in airway cells. GPCR signaling regulates contractile function, synthesis and release of autocrine factors, and cell growth in various airway cells, including airway smooth muscle (ASM), airway epithelium, lung fibroblasts, and T lymphocytes. Aberrant GPCR signaling or exaggerated presentation of GPCR stimuli can promote ASM hypercontractility, airway remodeling, and ASM hyperplasia/hypertrophy, all of which contribute to the pathogenesis of asthma. Moreover, many GPCR genes possees mutations that alter their expression or function; we are particularly interested in characterizing such altered function and its contribution to disease state or disease therapy.
Penn, R.B. Agonizing over Agonism: Should asthmatics turn their beta-receptors on or off? Proc Natl Acad Sci U S A. 106:2095-6, 2009.
Misior, A.M., D.A. Deshpande, M.J. Loza, R.M. Pascual, J.D. Hipp, and R.B. Penn. Glucocorticoid- and PKA- dependent transcriptome regulation in airway smooth muscle. Am J Respir Cell Mol Biol (in press)
Kong, K.C., U. Gandhi, T.J. Martin, C.B. Anz, H. Yan, A. M. Misior, R. M. Pascual, D. A. Deshpande, and R. B. Penn. Endogenous Gs-coupled receptors in smooth muscle exhibit differential susceptibility to GRK2/3-mediated desensitization. Biochemistry 47:9279-88, 2008.
Deshpande, D.A., B.S. Theriot, R.B. Penn, and J.K.L. Walker. Î²-arrestins specifically constrain Î²2-adrenergic receptor signaling and function in airway smooth muscle. FASEB J 22:2134-41, 2008.
Penn, R.B. Embracing emerging paradigms of G protein-coupled receptor agonism and signaling to address airway smooth muscle pathobiology in asthma. Naunyn Schmied Arch Pharmacol 378:149-69, 2008 .
Misior, A.M., H. Yan, D.A. Deshpande, R.M. Pascual, R.A. Panettieri Jr., and R.B. Penn. Mitogenic effects of cytokines on smooth muscle are critically dependent on protein kinase A and are unmasked by steroids and cyclooxygenase inhibitors. Mol Pharmacol 73:566-674, 2008.
Loza, M.J., S. Foster, S.P. Peters, and R.B. Penn. Interactive effects of steroid and beta-agonist on accumulation of type 2 T cells. J Allergy Clin Immunol 121:750.e1-5.e3, 2008.
Deshpande, D.A., R.M. Pascual, S. Wang, D.M. Eckman, E.C. Riemer, C.D. Funk, and R.B. Penn. PKC-dependent regulation of the receptor locus dominates functional consequences of Cysteinyl Leukotriene Type 1 receptor activation. FASEB J 21:2335-42, 2007.
Penn, R.B, V.E. Ortega, and E.R. Bleecker. A Roadmap to Functional Genomics. Physiol Genomics 119:235-44, 2007.
Sastry K.S., Y. Karpova, S. Prokopovich, A. J. Smith, B. Essau, A. Gersappe, J.P. Carson, M.J. Weber, T.C. Register, Y.Q. Chen, R.B. Penn, and G. Kulik. Epinephrine protects cancer cells from apoptosis via activation of PKA and BAD phosphorylation. J Biol Chem 282:14094-14100, 2007.
Loza, M.J., S.P. Peters, S. Foster, I.U. Khan, and R.B. Penn. Beta-agonist enhances type 2 T cell survival and accumulation. J Allergy Clin Immunol 119:235-44, 2007.
Codina, J., J. Liu, R.B. Penn, and T.D. DuBose Jr. Phosphorylation of S955 at the PKA consensus site promotes maturation of the ï¡-subunit of the colonic H+,K+-ATPase. J Am Soc Nephrol 17:1833-40, 2006.
Pascual, R.M., E. Dial, M.C. Seeds, M. Guo, R.A. Panettieri Jr., S.P. Peters, and R.B. Penn. Multiple regulatory elements influence interleukin-1beta-mediated prostaglandin E2 synthesis in airway smooth muscle. Am J Physiol (Lung Cell Mol Physiol) 290:L501-508, 2006.
Loza, M.J., S. Foster, S.P. Peters, and R.B. Penn. Beta-agonists modulate T cell functions via direct actions on type 1 and type 2 cells. Blood 107:2052-60, 2006.
Billington, C.K., K.C. Kong, R. Bhattacharyya, R.A. Panettieri Jr., P. Wedegaertner, T.O. Chan, and R.B. Penn. Cooperative regulation of p70S6 kinase by receptor tyrosine kinases and G protein-coupled receptors augments airway smooth muscle growth. Biochemistry 44:14595-14605, 2005.
Guo, M., S. Wang, M.F. Fontana, C.A. Valancius, R.M. Pascual, R.A. Panettieri, Jr., S.L. Tilley, B.H. Koller, and R.B. Penn. Cytokines regulate ï¢2AR responsiveness in airway smooth muscle via multiple PKA- and EP2 receptor- dependent mechanisms. Biochemistry 44:13771-13782, 2005.
Naik, S.U., C. K. Billington, R.M. Pascual, D.A. Deshpande, F. P. Stefano, T.A. Kohout, D.M. Eckman, J.L. Benovic, and R. B. Penn. Regulation of Cysteinyl Leukotriene Type 1 Receptor internalization and signaling. J Biol Chem 280:8722-8732, 2005.
Billington, C.K., and R.B. Penn. Signaling and regulation of G protein-coupled receptors in airway smooth muscle. Respir Res 4:2, 2003.
Penn, R.B., R.M. Pascual, Y.M. Kim, V.P. Krymskaya, R.A. Panettieri Jr., and J.L. Benovic. Arrestin specificity for GPCRs in human airway smooth muscle. J Biol Chem 276:32648-56, 2001.
Krymskaya, V.P., M.J. Orsini, A. Eszterhas, J.L. Benovic, R.A. Panettieri Jr., and R.B. Penn. Potentiation of human airway smooth muscle proliferation by Receptor Tyrosine Kinase and G protein-coupled receptor activation. Am. J. Resp. Cell Mol. Biol 23:546-554, 2000.
Goodman, O.B., J.G. Krupnick, F. Santini, V.V. Gurevich, R.B. Penn, A. Gagnon, J.H. Keen, and J.L. Benovic. ï¢-arrestin functions as a novel clathrin adaptor protein to promote agonist-specific G protein-coupled receptor internalization. Nature 383:447-450, 1996.
Penn, R.B., and J.L. Benovic. Structure of the human gene encoding beta-adrenergic receptor kinase. J. Biol. Chem. 269:14924-149390, 1994.