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Scientist, Chronic Disease, Ottawa Hospital Research Institute
Assistant Professor, Department of Medicine and, Department of Biochemistry, Microbiology and Immunology, University of Ottawa
Research Interest
Quantitative fluorescent microscopy
Membrane domains and trafficking
Cholesterol transport
ATP-binding cassette transporter proteins
Research Activities
The focus of this laboratory is the study of cholesterol and membrane trafficking in mammalian cells. We use biophysical tools, mainly based on quantitative fluorescent microscopy, to characterize cholesterol and membrane dynamics under variety of physiological conditions.
We hope to gain insight into the roles of cholesterol at the cellular level. In addition to serving as a necessary building block for mammalian cell membranes, cholesterol plays a critical role in many protein/protein interactions. Cellular cholesterol homeostasis and transport are under stringent regulation. Disturbances to this regulation are implicated in numerous human disorders, such as coronary heart disease. Cellular cholesterol homeostasis is maintained through active cholesterol transport in and out of, as well as within cells. Deficiencies in cholesterol transport, due to mutations in key proteins, lead to human diseases. One of the proteins we study is the ATP-binding cassette protein A1 (ABCA1 - whose mutation gives rise to Tangier disease). Defective ABCA1 causes retardation in cholesterol trafficking from intracellular compartments to the cell surface. The molecular mechanism is not known at present. We are currently characterizing the function of ABCA1, and its impact on cholesterol distribution and membrane trafficking.
In addition, we are beginning to develop novel imaging-based biophysical techniques to probe the lipid-lipid interactions in cell membranes.
Grant Support
New Investigator Award, Heart & Stroke Foundation of Canada
New Opportunity Fund, Canadian Innovation Foundation
Grant-in-Aid, Heart & Stroke Foundation of Ontario
Operating grant, Canadian Institutes of Health Research
Selected Publications
1. M. Denis, Y. D. Landry, and X. Zha; "ATP-binding cassette A1-mediated lipidation of apolipoprotein A-I occurs at the plasma membrane and not in the endocytic compartments". J. Biol. Chem, 2008, 283, 16178-16186.
2. Y. D. Landry, M. Denis, S. Nandi, S. Bell, A.M.Vaughan and X. Zha; "ABCA1 Expression Disrupts Raft Membrane Microdomains through its ATPase-Related Functions". J. Biol. Chem, 2006, 281, 36091-36101.
3. A. Ridsdale, M. Denis, P. Gougeon, J. K. Ngsee, J.F. Presley and X. Zha; "Cholesterol is required for efficient ER-Golgi transport of secretory membrane proteins". Mol Biol Cell. 2006, 17, 1593-1605.
4. X. Zha, A. Gauthier, J. Genest, and R. McPherson; " Secretory vesicular transport from the Golgi is altered during ATP-binding cassette protein A1 (ABCA1) mediated cholesterol efflux" J. Biol. Chem, 2003, 278, 10002-10005.
5. X. Zha, J. Genest Jr. and R. McPherson; "Endocytosis is upregulated in Tangier fibroblasts: possible role of ABCA1 in endosomal vesicular transport." J. Biol. Chem, 2001, 276, 39476-39483.
6. S. Mukherjee*, X. Zha*, I. Tabas, and F. R. Maxfield; "Cholesterol distribution in living cells: fluorescence imaging using dehydroergosterol as a fluorescent cholesterol analog". Biophys. J., 1998, 75, 1915-1925. *shared first authorship.
7. X. Zha, L. M. Pierini, P. L. Leopold, P. J. Skiba, I. Tabas, and F. R. Maxfield; "ATP-independent endocytosis induced by sphingomyelinase treatment". J. Cell Biol., 1998, 140, 39-47.
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