Douglas Tilley, PhD

Research Interests

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).  Proximally, GPCRs engage both G protein- and (GRK)/β-arrestin-dependent signaling responses, which can relay divergent effects on functional outcomes, allosteric modulation of which may offer a refined approach to promote beneficial signaling outcomes during disease progression.  Research in my laboratory focuses primarily upon aspects of GPCR regulation of cardiac and immune cell function, inflammation and remodeling during HF or following acute cardiac injury.

Current Projects 

Structural determinants of EGFR effects on cardiac function and remodeling 

The epidermal growth factor receptor (EGFR) has long been implicated as a pro-hypertrophic signaling node downstream of neurohormone GPCRs, however we recently discovered that it also acts to maintain cardiac contractile homeostasis.  Understanding the specific molecular requirements controlling these processes could provide novel insight into how to dissociate EGFR-dependent hypertrophy from contractile homeostasis as a novel therapeutic strategy for chronic HF. 

βAR-dependent regulation of leukocytes in acute cardiac injury 

The goal of this project is to define how β2-adrenergic receptor (β2AR) regulates leukocyte function and survival, not only to attain a fundamental understanding of the mechanisms and influence of β2AR signaling on the early immune response to cardiac injury, but also to determine whether β2AR-selective therapeutics would offer fine-tuned strategies to regulate ischemic injury-induced remodeling and survival outcomes.  

Leukocyte-dependent regulation of cardiorenal syndrome 

Renal dysfunction is a strong independent predictor for poor prognosis in HF patients, which manifests as cardiorenal syndrome (CRS), therefore understanding how renal fibrosis and dysfunction are mediated during the development and progression of CRS is essential to designing therapeutic strategies to ameliorate this condition.  The goals of this project are to define the role of leukocytes in mediating CRS development and progression, characterize the molecular pathways by which they do so and test how their modulation impacts the development of renal fibrosis and dysfunction. 

Educational Background

• 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

Memberships

• American Society for Pharmacology and Experimental Therapeutics
• American Heart Association
• International Society for Heart Research, American Section

Digital Bibliography

View NCBI My Bibliography