Xiaohui Zha, Ph.D.

xzha@ohri.ca
Phone: 798-5555 ext. 19828
Fax: 761-5036

Scientist, Chronic Disease, Ottawa Hospital Research Institute
Associate Professor, Department of Medicine, University of Ottawa
Associate Professor, Department of Biochemistry, Microbiology and Immunology, University of Ottawa

Training

Post-Doctoral Fellow ­-- Columbia University, (New York, NY, United States)
Ph.D. -- Cornell University (Ithaca, NY, United States)
B.Sc. -- Wuhan University (Wuhan, China)

Research Interest

Quantitative fluorescent microscopy
Membrane domains and trafficking
Cholesterol transport
ATP-binding cassette transporter proteins
Atherosclerosis

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 and pathological conditions, such as these relevant to atherosclerosis.

We hope to gain insight into the functional role 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.

Selected Publications

  1. J. Y. Lee, J. Karwatsky, L. Ma and X. Zha. “ABCA1 increases extracellular ATP to mediate cholesterol efflux to apoA-I”. Am J Physiol Cell Physiol. 2011 30, C886-94

  2. L. T. Ma, F. Dong, M. Denis, Y. Feng, M.D. Wang and X. Zha.  “Ht31, a PKA anchoring inhibitor, induces robust cholesterol efflux and reverses macrophage foam cell formation through ABCA1”. J. Biol. Chem., 2011, 286, 3370-3378.

  3. J. Karwatsky, L. T. Ma, F. Dong and X. Zha; “Cholesterol efflux to apoA-I in ABCA1-expressing cells is regulated by Ca2+ dependent-calcineurin signaling”. J. Lipid Research, 2010, 51:1144-56

  4. S. Nandi, L. Ma, M. Denis, J. Karwatsky, Z. Li and X. C. Jiang and X. Zha; “ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity”. J. Lipid Research2009, 50, 456-466. 

  5. 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, 16178-86.

  6. Y. Landry, M. Denis, S. Nandi, S. Bell, A. M. Vaughan and X. Zha; “ABCA1 expression disrupts raft membrane microdomains through its ATPase fueled functions”.  J. Biol. Chem., 2006, 281, 36091-101.

  7. 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, 1593-605.