Our laboratory focuses on G-protein coupled receptor (GPCR) signaling in the heart, with two main areas of emphasis.
1. Free fatty acid receptor 4 (Ffar4). Ffar4 is a G-protein coupled receptor for long chain fatty acids (Carbon chains 14-24) including omega-3 polyunsaturated fatty acids (omega 3-PUFAs). Clinically, omega 3-PUFAs improve outcomes in heart failure, but the mechanism is unclear. We previously demonstrated that eicosapentaenoic acid, or EPA an omega 3-PUFA, prevents heart failure in a mouse model but not through the traditional mechanism of membrane incorporation. Alternatively, we found that the cardioprotective effects of EPA might be mediated through Ffar4, an entirely novel molecular mechanism to explain the benefits of omega 3-PUFAs in the heart. Currently, our research is focused on understanding this novel role for Ffar4 as a cardioprotective nutrient sensor in the heart that responds to fatty acid composition to protect the heart from pathologic stress.
2. alpha 1-Adrenergic receptors (alpha 1-AR): alpha 1-ARs are receptors activated by the endogenous sympathetic catecholamines norepinephrine (produced in sympathetic nerve terminals) and epinephrine (produced in the adrenal gland). Clinically, alpha 1-ARs were originally used for the treatment of hypertension (HTN) and are currently used to treat benign prostatic hyperplasia (BPH). Clinical trials demonstrated that alpha 1-AR antagonists (doxazosin) worsened outcomes in patients with HTN, significantly increasing cardiac events and doubling the risk of heart failure. Our work has provided a mechanistic basis to explain the failure of alpha 1-blockers in patients with HTN, demonstrating that alpha 1-ARs in cardiac myocytes protect the heart from pathologic stress. Currently, our research is focused on understanding the molecular basis for the cardioprotective effects of alpha 1-ARs focusing on how differential subcellular compartmentalization of receptors affects their function. Further, based on our work on alpha 1-AR subcellular compartmentalization, we are developing a next-generation alpha 1-blocker for HTN without cardiac side-effects.
2231 6th Street SE
Minneapolis, MN 55455