Limitation of Asthma Therapy: The Black Box and the Paradox

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Raymond B. Penn, PhD

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/survival 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 and COPD. Moreover, GPCRs appear to mediate important mitogenic and survival signaling pathways in cells comprising the tumor microenvironment- including epithelia, fibroblasts, stem cells, and inflammatory cells- rendering them potentially important therapeutic targets in the treatment of cancer. Finally, many GPCR genes possess 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.



1. What is asthma and how is it treated?

2. Why beta-agonists are anti-asthma drugs.

3. How beta-agonists got a bad rap (and a black box), how a borrowed idea from the heart field was used to explore the paradoxical (beneficial) effect of beta-blockers explains paradoxical, thus paving the way for new generation of beta-adrenoceptor ligands in the treatment of asthma.

Presentation: 1 hour & 6 minutes