My long term area of interest is to understand the role of cholesterol metabolites in vascular-related diseases, such as atherosclerosis, cancer and metabolic diseases. Previously, we discovered that the most abundantly circulating oxysterol 27-hydroxycholesterol (27HC) directly binds to estrogen receptor (ER) and alters the ER function in a tissue- specific manner. Importantly, 27HC is the first identified endogenous selective ER modulator (SERM), and has an adverse impact on the cardiovascular protection afforded by estrogen. 27HC also promotes breast tumor progression and decreases bone mineral density through the modification of ER activity. Since serum 27HC levels closely correlate with circulating cholesterol levels, hypercholesterolemia may also alter the estrogen-mediated homeostasis through 27HC. In addition, recently we found that Liver X Receptor (LXR), which also belongs to the nuclear receptor superfamily and has oxysterols as its ligands, has a novel function in the vascular endothelial cells through non-transcriptional (non-nuclear) actions that are mediated by crosstalk between LXR and ER.
