Douglas G. Tilley, Ph.D.

Contact Dr. Tilley

Center for Translational Medicine
1025 Walnut St. Suite 402
Philadelphia, PA 19107

(215) 503-5615
(215) 503-9052 fax

Medical School

Residency

Fellowship
Duke University Medical Center, Department of Medicine, Cardiology, 2005-2008

Degree
Ph.D. Pharmacology and Toxicology, Queen's University at Kingston, ON, 2005

University Appointment
Assistant Professor of Pharmaceutical Sciences, 2008-current

Research and Clinical Interests
Diseases of the cardiovascular system such as heart failure, atherosclerosis and restenosis disrupt heart and blood vessel physiology. Progression of these diseases involves alterations in the cells that are responsible for normal cardiovascular function, including cardiomyocytes, vascular smooth muscle cells and endothelial cells. Receptors convert extracellular stimuli into intracellular signaling processes that mediate alterations in cell function. 7 transmembrane receptors (7TMRs) relay signals via G protein-dependent and -independent mechanisms, which include 2nd messenger generation and β-arrestin signaling, respectively. Stimulation of receptor tyrosine kinases (RTKs) induces autophosphorylation events and docking of scaffolding proteins that lead to activation of numerous downstream signaling cascades. Through the use of sensitive microscopy and molecular biology assays, my research focuses on understanding the interaction between 7TMRs and RTKs and how they regulate changes in cardiovascular function normally or in the progression of disease. Currently, the mechanism of interaction between the β1-adrenergic receptor and epidermal growth factor receptor is being investigated as well as how regulation of this receptor complex impacts cardiac function in the normal and failing heart. Discovery of novel receptor signaling complexes and how they are regulated will aid our understanding of how cardiovascular cells respond to various stimuli. These responses may confer signaling events that are protective, such as anti-apoptotic pathways, and/or detrimental, including hypertrophic and migratory pathways. Differential activation of receptor complexes may enable us to better inhibit adverse downstream signaling and promote protective pathways to treat diseases of the cardiovascular system.

Publications

Most Recent Peer-reviewed Publications

1. β-arrestin mediates β1-adrenergic receptor-epidermal growth factor receptor interaction and downstream signaling
2. Physiologic and cardiac roles of β-arrestins
3. Beta-arrestin-mediated signaling in the heart
4. β-Blockers alprenolol and carvedilol stimulate β-arrestin- mediated EGFR transactivation
5. β-Arrestin-mediated β1-adrenergic receptor transactivation of the EGFR confers cardioprotection
6. Role of β-adrenergic receptor signaling and desensitization in heart failure: New concepts and prospects for treatment
7. Vascular smooth muscle cell phenotype-dependent phosphodiesterase 4D short form expression: Role of differential histone acetylation on cAMP-regulated function
8. Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system
9. Vascular smooth muscle cell phosphodiesterase (PDE) 3 and PDE4 activities and levels are regulated by cyclic AMP in vivo
10. Reduced phosphodiesterase 3 activity and phosphodiesterase 3A level in synthetic vascular smooth muscle cells: Implications for use of phosphodiesterase 3 inhibitors in cardiovascular tissues
11. Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: Implications for diabetes-associated cardiovascular disease
12. Expression of phosphodiesterase 4D (PDE4D) is regulated by both the cyclic AMP-dependent protein kinase and mitogen-activated protein kinase signaling pathways: A potential mechanism allowing for the coordinated regulation of PDE4D activity and expression in cells