Education:

• BS (2002) Public Health. Fudan University; Shanghai, China.
• MS (2005) Toxicology. Fudan University; Shanghai, China.

Current Research:

Niemann-Pick C1-Like 1 (NPC1L1) has been recently found to be essential for normal absorption of intestinal cholesterol since disruption of NPC1L1 in mice causes a dramatic reduction in fractional absorption of dietary cholesterol. However, the molecular and cellular basis for this gene to control cholesterol absorption remains to be elucidated.

NPC1L1 protein is a polytopic transmembrane protein. It is predicted to have 13 transmembrane domains, five of which comprise the putative sterol-sensing domain (SSD). There are at least seven classes of proteins sharing SSD and playing important roles in different aspects of cholesterol homeostasis or cholesterol-linked signaling. Previous studies in our lab have found that acute cholesterol depletion induced by methyl-β-cyclodextrin stimulates relocation of NPC1L1 from the intracellular compartments to the cell surface in a hepatoma cell line, which is coupled to enhanced cellular uptake of free cholesterol from the medium. We hypothesize that SSD regulates intracellular trafficking and function of NPC1L1. By using stable cell lines expressing EGFP-tagged wildtype and SSD-mutated NPC1L1 proteins, intracellular itineraries of these proteins following cholesterol manipulation will be visualized. Also, ability of wildtype and mutant proteins in binding to free cholesterol and in mediating cellular uptake of free cholesterol will be assayed. In addition, in order to probe the signaling regulating translocation and function of NPC1L1, and to dissect the NPC1L1 pathway, immunoprecipitation and mass spectrometry (MS) will be used to identify NPC1L1 partners. Once these partners are confirmed in vitro, their physiological functions in vivo will be tested by transgenic approaches.