Ta-Yuan Chang, PhD
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Affiliation(s):
Geisel School of Medicine at Dartmouth
Areas of Interest:
Cholesterol metabolism in health and diseases
Biography & Research:
Structure-function analyses of ACAT1 in vitro and in vivo.
Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an integral membrane protein located in the endoplasmic reticulum. It catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acyl coenzyme A. This enzyme plays important roles in cellular cholesterol homeostasis. The first gene encoding the enzyme, designated as ACAT1, was identified in this laboratory. We have expressed ACAT1 as a recombinant protein in mammalian cells and have purified it to homogeneity. We are currently taking biochemical and biophysical approaches to identify the enzyme’s active and regulatory sites, and to determine the mechanisms of action of various ACAT inhibitors. Recent evidence has shown that ACAT1 is a drug target for treating neurodegenerative diseases including Alzheimer's disease, which is a major neurodegenerative disease in the developed countries. We are currently taking mouse genetic and cell biological approaches to determine the pathophysiological role of ACAT1 in multiple human diseases including Alzheimer's disease, atherosclerosis, and diet-induced obesity.
