Douglas Tilley, PhD
Associate Professor, Pharmacology
Associate Professor, Center for Translational Medicine
- Contact Information
- About Me
During heart failure, alterations in cardiomyocyte receptor signaling mediate changes in hypertrophy, survival and contractile function that contribute to the progression of the disease. G protein-coupled receptors (GPCR) relay signals via both G protein-dependent and -independent mechanisms, which include 2nd messenger generation and β-arrestin signalling, respectively. Depending on the GPCR, either signaling branch may lead to the transactivation of receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR). Stimulation of EGFR has been shown to induce a vast network of downstream events however the impact of GPCR-mediated EGFR transactivation in the heart is still relatively unexplored. Recently, β1-adrenergic receptor (β1AR)-mediated EGFR transactivation was demonstrated to provide a protective role in the heart through unknown mechanisms.
Through the use of sensitive microscopy and molecular biology assays, my research focuses on understanding the interaction between GPCR and EGFR and how they regulate changes in cardiovascular function normally or in the progression of disease. Currently, the mechanism of interaction between the β1AR and EGFR 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 signalling complexes and how they are regulated will aid our understanding of how cardiovascular cells respond to various stimuli. These responses may confer signalling events that are either protective or maladaptive, providing a roadmap for the development of strategies to differentially activate receptor complexes to better inhibit adverse downstream signalling and promote protective pathways in the treatment of heart failure.
- Education, Training & Credentials
- Postdoctoral Fellowship, Duke University Medical Center, Division of Cardiology, Durham, NC, 2008
- PhD, Queen's University at Kingston, Ontario, Canada, 2005
- BScH, Life Sciences SSP, Queen's University at Kingston, Ontario, Canada, 1999
- American Society for Pharmacology and Experimental Therapeutics
- American Heart Association
- International Society for Heart Research, American Section
Maurice DH and Tilley DG (2007). Regulation of PDE Expression in Arteries: Role in Controlling Vascular Cyclic Nucleotide Signaling. (Beavo JA, Francis SH, Houslay MD, eds), Cyclic Nucleotide Phosphodiesterases in Health and Disease, CRC Press: Taylor and Francis Group, 22: 441-463.