Raymond Penn, M.D., Associate Professor
Dr. Penn received his B.A. in History and M.S. in Education from The University of Pennsylvania in 1980. After four years of teaching secondary school and working a consultant to the health club industry, he matriculated to Temple School of Medicine and worked on tissue mechanics of developmentally immature airways under Dr. Thomas Shaffer, culminating in a Ph.D. in Physiology in 1988. After a brief postdoctoral position studying organ system function in premature baboons at the Southwest Research Biomedical Research Institute in San Antonio, he took another postdoctoral position in 1990 with Dr. Jeffrey Benovic at Thomas Jefferson University to study regulation of G protein-coupled receptor (GPCR) signal transduction. In 1995 he became a faculty member at Thomas Jefferson University; became Associate Professor in 2002; and in 2003 relocated to the Wake Forest University School of Medicine, Department of Internal Medicine. He is currently Director of the Tinsley R. Harrison Translational Research Training Institute and with Stephen Peters, M.D., Ph.D., leads the Functional Genomics group in the Center for Human Genomics.

SYNOPSIS OF AREA OF INTEREST: Research focuses on regulation of GPCR signal transduction in physiologically relevant systems and development of model systems for assessing biologic significance of gene variation.

DETAILED AREA OF INTEREST: 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 cells. Aberrant GPCR signaling or exaggerated presentation of GPCR stimuli can promote cell hypercontractility, airway remodeling, and airway cell hyperplasia/hypertrophy, all of which contribute to the pathogenesis of asthma.

The long range goal of my research is to elucidate regulatory features of signaling in airway cells that may be targeted (either pharmacologically or via gene therapy) in the management of airway diseases. Toward this end my lab has established novel approaches in the application of molecular biology techniques in primary cultures of airway cells. For example, we have generated, through the use of fluorescence-activated cell sorting, homogeneous populations of ASM cells that express green fluorescent protein (GFP) chimeras of key signaling intermediates. Sorting of cells expressing GFP chimeras overcomes limitations imposed by low transfection efficiency of primary cell cultures, thus enabling us to examine the role of GPCR expression (Mundell et al. Am J Respir Cell Mol Biol, 2001) as well as disrupted GPCR-G protein coupling (Penn et al., J Biol Chem, 2001) on receptor signaling and trafficking outcomes. These studies are the first of their kind in primary airway cells and represent a significant advancement in the study of airway cell biology. Importantly, this methodology can be applied to study a myriad of signaling events and their relevance to virtually any primary cell function, including mesenchymal cells and blood cells. Ongoing studies include: 1) defining the mechanisms of GPCR crosstalk with other receptor-mediated signaling pathways; 2) genotype effects on both ASM and T cell signaling and function; and 3) regulation of cytokine-mediated effects on smooth muscle contraction and growth, and the modulatory effect of therapeutics.

PUBLICATIONS:

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 (in press)

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 ?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. Desphande, 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.

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