Cellular Metabolism of Sterols and Fatty Acids; Implications in Neurodegenerative diseases, obesity and diabetes

Work in the Yang lab focuses on two areas: the cellular dynamics of lipid droplets, adipocyte development, obesity and diabetes; and cholesterol trafficking in eukaryotic cells and its role in neurodegenerative disorders.:

Project 1: Oxysterol binding proteins, intracellular cholesterol trafficking and neurological diseases

Aberrant distribution of cholesterol causes neurodegenerative diseases such as Alzheimer’s disease. We have identified novel proteins that regulate cholesterol transport from late endosomes and lysosomes. We now aim to identify additional regulators of cellular cholesterol distribution, and to understand how these proteins may regulate heart and brain function. The students will learn many techniques in cell biology such as cell culture, fluorescence microscopy etc.

Selected References:

  • Du X, Kumar J, Ferguson C, Schulz TA, Ong YS, Hong W, Prinz WA, Parton RG, Brown AJ & Yang H, 2011, ‘A role for oxysterol-binding protein-related protein 5 in endosomal cholesterol trafficking’, Journal of Cell Biology, 192 (1): 121-135.
  • Du X, Brown AJ & Yang H, 2015, ‘Novel mechanisms of intracellular cholesterol transport: membrane contact sites and oxysterol binding proteins’, Current Opinion in Cell Biology, 35: 37-42.

Project 2: Seipin, lipid droplets, adipose tissue development and human obesity

Human obesity is, in essence, the accumulation of lipid droplets, which are storage granules of fat. We have identified many mutants that affect the size and number of lipid droplets, and have also uncovered a role for a human disease gene – SEIPIN – in lipid droplet formation. Our recent data suggest that Seipin may regulate the metabolism of fatty acids and phospholipids. Our current aim is to determine the molecular function of SEIPIN, and how it regulates lipid droplet morphology and adipocyte development. The students will learn techniques in lipids biochemistry and cell biology

Selected References:

  • Fei W, Shui G, Gaeta B, Du X, Kuerschner L, Li P, Brown AJ, Wenk MR, Parton RG & Yang H, 2008, ‘Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast’, Journal of Cell Biology, 180(3): 473-482.
  • Liu L, Jiang QQ, Wang, X, Zhang Y, Lin RC, Lan S, Shui, G, Zhou L, Li P, Wang Y, Cui X, Gao MM, Zhang L, Lv Y, Xu G, Liu G, Zhao D and Yang H, 2014, Adipose-specific knockout of seipin/BSCL2 results in progressive lipodystrophy’, Diabetes, 63:1–12.

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