Division of Pulmonary, Allergy & Critical Care

Research in my laboratory centers on uncovering the molecular and cellular mechanisms that contribute to organ dysfunction following pulmonary injury. A key focus is the interplay between cellular signaling pathways and the processes of injury and repair in critical lung cell types, including epithelial cells, endothelial cells, and alveolar macrophages. Through a range of experimental models, we examine how acute insults and chronic stressors impact cellular resilience and function. We are particularly interested in how genetic predisposition, aging, and environmental exposures shape the lung's metabolic capacity to adapt and recover from injury. As a practicing physician, my goal is to translate these insights into clinical practice by identifying the molecular drivers of diseases such as pulmonary fibrosis and acute respiratory distress syndrome, ultimately leading to the development of more effective therapies for these severe lung conditions.

“G protein-coupled receptor (GPCR) signaling in airway smooth muscle."
Studies focus on understanding the mechanisms by which PKA mediates both contractile inhibition and negative feedback regulation of the β2AR in human airway smooth muscle. Protocols include: 1) development of human airway smooth muscle cultures using airway tissue harvested from asthmatic or non-asthmatic subjects; 2) biochemical analysis of pro- and anti- contractile signaling in airway smooth muscle cultures; 3) cloning of recombinant PKA inhibitory constructs and expressing them in cells or tissue; and 4) analysis of regulation of airway smooth muscle contraction using murine trachea or 4th generation human airways ex vivo.

“Arrestin selectivity for GPCRs in airway smooth muscle.”
Studies focus on detailing the role arrestin isoforms play in regulating the signaling capacity and function of different pro- and anti- contractile GPCRs in airway smooth muscle. Protocols include: 1) development of human airway smooth muscle cultures using airway tissue harvested from asthmatic or non-asthmatic subjects, and murine airway smooth muscle cultures derived for airways from beta-arrestin1 and beta-arrestin2 subtype knockout mice ; and 2) characterization of effect of arrestin subtype knockout (mice) or knockdown (human) on signaling and function of pro- and anti- contractile GPCRs. 

“OGR1 is a proton-sensing GPCR in airway smooth muscle.”
Studies focus on characterizing the signaling events elicited by reduced extracellular pH in human airway smooth muscle cells, their dependence on the G protein-coupled receptor OGR1, and associated functional consequences. Protocols involve: 1) assessing signaling by OGR1 in artificial systems (recombinant OGR1 expressed in HEK293 cells) or primary human airway smooth muscle (endogenous OGR1 in cells in culture or 4th generation human airways) by reduced extracellular pH or novel putative OGR1 ligands; 2) effect of reduced extracellular pH or novel putative OGR1 ligands on single cell or human airway smooth muscle tissue contraction both ex vivo (mouse and human) or in vivo (in mice expressing or lacking OGR1).

“Optimizing beta-adrenoceptor signaling bias in asthma.”
Studies explore the capacity of different ligands of the beta-2-adrenoceptor (b2AR) to promote Gs and arrestin-dependent signaling, and regulate the asthma phenotype in murine models of allergic lung inflammation, based on the observation that certain types of b2AR antagonists (“beta-blockers), when administered chronically in mice, strong inhibit the development of allergen-induced inflammation and airway hyperreactivity. Protocols include: 1) characterization of ligand “bias” (the ability to promote Gs- or arrestin-dependent signaling) in multiple cell types (including airway epithelium and smooth muscle); 2)  the effect of these ligands on mucin production in murine and human airway epithelial cultures; and 3) the effect of chronic ligand treatment on the asthma phenotype induced by allergic lung inflammation in wild type mice and mice deficient in beta-arrestin expression in specific cell types.