Michael C. Phillips, PhD, DSc
- Department: Pediatrics
- Division: GI/Nutrition
- Address:
34th & Civic Center Boulevard
Abramson, Room 1102D
Philadelphia, PA 19104 - Phone: (215)590-0587
- Email: phillipsmi@email.chop.edu
Research Summary:
My research interests are focused on lipoprotein metabolism and atherosclerosis. In particular, I aim to understand the molecular mechanisms underlying the protective action of high-density lipoprotein (HDL) against the development of atherosclerosis. Recent research has emphasized understanding the structural basis of the properties of apolipoprotein (apo) A-I that protect against the formation of plaques in arteries, the principal protein component of HDL, and of the HDL receptors known as scavenger receptor class B, type I (SR-BI) and ATP-binding cassette transporter AI (ABCA1). My laboratory focuses on understanding the molecular mechanisms by which these proteins mediate cholesterol transport at cell surfaces.
My laboratory employs protein engineering methods to create variants of apo A-I. We use these molecules to explore the effects of mutations on the ability of the protein to create HDL particles and transport cholesterol. Knowledge of the two-domain structure of apo A-I is allowing us to define the mechanisms by which apo A-I and ABCA1 interact to form HDL particles. We are collaborating with colleagues at the University of Pennsylvania to explore the effects of natural apo A-I mutations on HDL metabolism and cholesterol transport in vivo. In this project we alter apo A-I and HDL metabolism using adeno-associated virus-mediated gene transduction methods, and monitor the consequences for cholesterol transport and the incidence of atherosclerosis.
My long-term research goal is to gain sufficient molecular insight into the anti-atherogenic properties of apo A-I and HDL to permit the rational design of molecules that mimic these functions in order to reduce the risk of coronary heart disease.
