- Identify OGR1 as the principal proton-sensing receptor in the airway, capable of regulating airway resistance via its function of airway smooth muscle.
- Identify inflammation, and microaspiration of acid, as two mediators of low pH in the airway lumen.
- List 2 specific drugs that can function as OGR1 activators and potential asthma therapeutics.
Presentation: PowerPoint slides only, no audio
Penn, PhD, Raymond B., "Proton-sensing receptors- therapeutic targets in the management of asthma?" (2014). Division of Pulmonary and Critical Care Medicine Presentations and Grand Rounds. Presentation 111.
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.