Research Program Overview
The unifying theme of the research program in Miller’s laboratory is the role of cholesterol metabolism and lipid oxidation in fundamental biologic processes and in the development of human disease. The discovery of an oxidized lipoprotein function in activating toll-like receptors (TLRs), made in our lab, has connected lipoprotein metabolism with inflammation in atherosclerosis. We pioneered the use of zebrafish in studying vascular lipid accumulation and inflammation and created new transgenic zebrafish lines with lipid abnormalities and with genetic reporters to detect oxidized lipids. This work led to discoveries of novel functions of lipid and cholesterol metabolism in regulation of vascular and neuro inflammation, neuropathic pain and angiogenesis.
The current projects in the lab revolve around the concept of inflammarafts and the protective role of apolipoprotein A-I binding protein (AIBP, read A-one-BP) in chronic inflammatory diseases and in pain states. Inflammarafts are enlarged, cholesterol-rich, liquid-ordered domains in the plasma membrane (often called lipid rafts) serving as an assembly platform for functional receptor complexes in inflammatory cells. AIBP facilitates selective depletion of cholesterol from inflammaraft-expressing cells, which leads to the disassembly of inflammatory receptor complexes and the overall protective effect in the context of chronic inflammatory diseases. The active (and highly collaborative) projects in the lab explore the inflammaraft related biology and its implications, using cellular and animal models of atherosclerosis, neuropathic pain, Alzheimer’s disease, and asthma.