Dr. Pandak's laboratory has been involved in the study of hepatocellular lipid and bile acid metabolism for 35 years. The laboratory is equipped with state-of-the-art lipid research equipment, and can provide the biochemical expertise to perform the required bile acid analysis.

More specifically, uncovered that microsomal levels of cholesterol participated in the transcription regulation of genes. The laboratory made first observations on the existence of "intestinal" bile acid mediated regulation (later determined as the FXR/FGF axis), that a gene could be transcriptionally upregulated by select cholesterol precursors, and the importance of sulfated oxysterols in intracellular lipid metabolism. More recently they have focused on the alternative pathway of bile acid synthesis; uncovering a new mitochondrial bile acid pathway to cholic acid, that CYP27A1 forms 3 vital regulatory oxysterols, the overlooked role of CYP7B1 in regulation/control of the levels and ratios of these regulatory oxysterols that control cholesterol and lipid metabolism through the regulation of SREBPs and nuclear receptors like LXR, and that chronic down regulation of CYP7B1 and the subsequent chronic elevation of oxysterols appears to be an initiating pathway in the progression of nonalcoholic fatty liver to inflammation; with likely implications in arterial inflammation.

Studies on intracellular movement of cholesterol developed as an offshoot of our hepatic studies with the START domain protein, StarD1. The laboratory has since become recognized in the START domain protein field. With studies on StarD5, have uncovered a novel pathway of cholesterol movement to the plasma membrane, and, its role as a rate-determining step of cholesterol efflux by determining StarD5's function, regulation, and possible clinical applicability in the treatment of colon cancer. With StarD4 we have demonstrated a protein involved in the

potentiation of membrane cholesterol exchange whose regulation is closely tied to the NPC's protein regulation. It is believed the proposed StarD5 & StarD4 studies will lay the ground work for a clearer understanding of intracellular cholesterol transport, cholesterol/triglyceride efflux, and role in cholesterol/lipid homeostasis. The study of intracellular cholesterol transport has been slow to develop based upon prior lack of clear cholesterol binding proteins and their ability to transport. The novel findings of our ongoing studies on the START domain proteins have opened unexpected doors which have clear implications for immediate translational relevance.