Why I Became a Scientist
When I was a teenager I wanted to be a medical doctor. However, soon after obtaining a medical degree from Shandong University in China, I was obligated to take a junior position in the Department of Physiology at the same university. Many years after postgraduate studies on neurophysiology, I was gradually attracted into the area and eventually became a neuroscientist. I never regretted to pursue a career in science because my life is fulfilled with exciting and inspiring experiences. My colleagues and I are enjoying satisfactions from the journey in exploring the mysteries of biological mechanisms, which may not be relevant to our current day-to-day life, but will be beneficial for human life in the future. We enthusiastically welcome new members to join our research team. With the comprehensive training programs in the laboratory, many students have become scientists.
Our research engages two major topics.
The first theme focuses on cellular and molecular mechanisms through which cytokines regulate central synaptic transmission and plasticity under physiological and/or disease conditions. Specifically, we use animal models to study how acute and chronic visceral (e.g. pulmonary) inflammations/injuries affect the activity of microglia, the profile of neurogenesis and the ultra-structure of synapses, as well as glutamatergic synaptic transmission in the cortex and hippocampus.
The second theme is of γ-aminobutyric acid (GABA) signaling in non-neuronal cells. Besides its pivotal role in the brain, GABA is a common signaling molecule outside the central nervous system (CNS). Pioneer studies in our laboratory revealed autocrine GABA signaling systems in lung epithelial cells and alveolar macorphages. Results from our recent studies suggest that these GABA signaling systems balance the Th1/Th2 cell responses in the lung by modulating T-lymphocytes and macrophage functions, maintaining pulmonary homeostasis.
How systemic inflammations contribute to neurodegeneration and affect cognitive functions?
Acute impairment of cognition is commonly observed in elderly patients suffering with severe inflammations in peripheral organs, which frequently induce innate immune responses in the CNS being expressed as microglia activation. In addition, aging-related neurodegenerative diseases are often associated with ongoing inflammatory reactions in the brain. We are studying the influence of circulating Th1/Th2 cytokines on microglia polarization, neurogenesis and synaptic functions in the hippocampus of mice at differenct ages.
Does modification of GABA signaling in the peripheral affect inflammatory reactions in the CNS?
Besides its critical roles in the CNS, GABA is produced and secreted by several types of endocrine cells, e.g. pancreatic β-cells and adrenal chromaffin cells, thus GABA exists in the circulating plasma at low concentration. A large body of evidence indicates that GABA regulates activities of endocrine and immune cells producing anti-inflammatory actions. We are investigating whether modification of GABA signaling in the peripheral alleviates inflammatory reactions in the CNS and hence defer the process of neurodegeneration.
- MD Shandong University, China (1983)
- MSc Shandong University, China (1987)
- PhD Memorial University of Newfoundland, Canada (1996)
- Postdoctoral Fellow, Department of Physiology University of Toronto (1996 – 2000)
(Fellowships of Medical Research Council of Canada, Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada)
- NARSAD Essel Investigator, 2006
- New Investigator Award, 2002 Canadian Institutes of Health Research
- New Investigator Award, 2002 Heart and Stroke Foundation (declined)
- The Henry J.M. Barnett Research Scholarship Award, 2002 Heart and Stroke Foundation (declined).
- Research Fellowship, 2000 Canadian Institutes of Health Research
- Research Fellowship, 1999 Medical Research Council of Canada, (MRC, declined).
- Research Fellowship, 1999 Heart and Stroke Foundation of Canada (HSFC)
- Stroke Investigator Award, 1998 Heart and Stroke Foundation of Ontario
- Research Fellowship, 1996 NCE (Neuroscience)
Xiang YY, Dong H, Yang BB, MacDonald JF, Lu WY. Interaction of acetylcholinesterase with neuroexin-1β regulates glutamatergic synaptic stability in hippocampal neurons. Molecular Brain 2014 Mar; 7(1):15.
Wang S, Luo Y, Feng A, Li T, Yang X, Nofech-Mozes R, Yu M, Wang C, Li Z, Yi F, Liu C, Lu WY. Ethanol induced impairment of glucose metabolism involves alterations of GABAergic signaling in pancreatic β-cells. Toxicology 2014 Dec; 326:44-52.
Xiang YY, Chen X, Li J, Wang S, Faclier G, MacDonald JF, Hogg JC, Orser BA, Lu WY. Isoflurane regulates atypical type-A γ-aminobutyric acid receptors in alveolar type II epithelial cells. Anesthesiology 2013 May; 118(5):1065-1075.
Bansal P, Wang S, Liu S, Xiang YY, Lu WY*, Wang Q. GABA coordinates with insulin in regulating secretory function in pancreatic INS-1 β-cells. PLoS ONE 2011; 6(10):e26225. *Co-Corresponding Author.
Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proceedings of the National Academy of Sciences of the USA 2011 Jul; 108(28):11692-11697.
Wang S, Xiang YY, Ellis R, Wattie J, Feng M, Inman MD, Lu WY. Effects of furosemide on allergic asthmatic responses in mice. Clinical and Experimental Allergy 2011 Oct; 41(10):1456-1467.
Kimura T, Kawabe H, Jiang C, Zhang W, Xiang YY, Lu C, Salter MW, Brose N, Lu WY, Rotin D. Deletion of the ubiquitin ligase Nedd4-2 in lung epithelia causes cystic fibrosis-like disease. Proceedings of the National Academy of Sciences of the USA 2011 Feb; 108(8):3216-3221.
Wong AP, Keating A, Lu WY, Duchesneau P, Wang X, Sacher A, Hu J, Waddel TK. Identification of a bone marrow-derived epithelial-like population capable of repopulating injured mouse airway epithelium. The Journal of Clinical Investigation 2009 Feb; 119(2):336-348.
Xiang YY, Wang S, Liu M, Hirota JA, li J, Ju W, Fan Y, Kelly MM, Ye B, Orser B, O'Byrne PM, Inman MD, Yang W, Lu WY. A GABAergic system in airway epithelium is essential for mucus overproduction in asthma. Nature Medicine 2007 Jul; 13(7):862-867.
Contact InfoRobarts Research Institute, Room 7240
1151 Richmond St. N.
London, ON N6A 5B7
Phone: 519-931-5777 ext. 24282