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Dr. Douglas Tilley

Event Start: Nov 21, 2018 1:00 pm
Location: Botterell Hall, Room B139

Douglas Tilley, PhD, FAHA

Associate Professor 
Center for Translational Medicine
Lewis Katz School of Medicine
Temple University
Philadelphia, PA

Cardiac and immune cell-specific β2-adrenergic receptor effects in ischemic injury

G protein-coupled receptors (GPCRs) constitute a large family of cell surface proteins that control an array of physiologic responses and remain the most prominent drug target class for numerous pathologic etiologies including heart failure (HF). GPCRs relay signals via both G protein-dependent and -independent mechanisms, which include 2nd messenger generation and GPCR kinase (GRK)/β-arrestin (βarr) signaling, respectively. Research in my laboratory focuses primarily upon aspects of GPCR regulation of cardiac function, inflammation and remodeling during HF or following acute cardiac injury. First, we are working to harness the next generation approach to βAR-targeted therapeutics: biased activation of cardioprotective β1AR signaling in the absence of cardiotoxic pathways. We are developing tools to allow the first gain-of-function assessment of the impact of βarr-biased β1AR-mediated epidermal growth factor receptor (EGFR) transactivation on signaling and survival outcomes in cardiomyocytes and to define the outcome of cell type-dependent EGFR deletion on cardiac function and survival under HF conditions. Second, we are investigating the impact of βarr-biased β2AR pepducins, small peptide fragments of the intracellular loops of β2AR, on cardiac function and remodeling following acute injury. Using genetically modified mice, we are also defining cardiomyocyte versus fibroblast-specific roles for biased β2AR signaling in the regulation of cardiac cell death, inflammation and fibrosis. Third, since β2AR are expressed on virtually all immune cell types, we are exploring the impact of β2AR signaling, via both G protein- and GRK/βarr-dependent mechanisms, on leukocyte release from hematopoietic organs and recruitment to sites of injury.

Wednesday November 21st, 2018
Botterell Hall, Room B139
1:00 - 2:00 pm