Wei-Yang Lu
Associate Professor
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M.D. Shandong University, China, 1983 |
Research in Dr. Lu's laboratory primarily focuses on cellular and molecular mechanisms through which cytokines and trophic factors regulate central synaptic transmission and plasticity under physiological and/or disease conditions. Acute cognitive impairment is commonly observed in elderly patients suffering with inflammations in peripheral organs. In addition, aging-related neurodegenerative diseases are often associated with ongoing innate immune responses in the brain. Studies have revealed that in chronic neurodegenerative illnesses, such as Alzheimer's disease, systemic inflammation can exacerbate symptoms of cognitive deficits and drive the progression of histological neurodegeneration. Currently, Dr. Lu and his colleagues are using animal models to study how acute and chronic visceral inflammations/injuries affect cognitive functions as well as the ultra-structure of synapses and glutamatergic synaptic transmission in the cortex and hippocampus, by means of multiple techniques including immunohistochemistry and patch-clamp recordings. On the other hand, Dr. Lu is studying γ-aminobutyric acid (GABA) signaling in non-neuronal cells. GABA is a primary inhibitory neurotransmitter in the adult brain. Interestingly, GABA exists in the circulating plasma and GABA receptors are expressed in some non-neuronal cells. For example, it is known that GABA regulates pancreatic islet α-cell excitability and glucagon release. Most recently, Dr. Lu and colleagues demonstrated that an autocrine GABA signaling system exists in airway epithelial cells. This airway epithelial GABA signaling is associated with asthmatic reactions by increasing airway goblet cell formation and mucus overproduction. Currently, Dr. Lu and his team are investigating the role of GABAergic signaling in the regulation of visceral-brain interaction. Key Research Issues:
1. Glutamatergic synaptic plasticity and apoptosis
2. GABA signaling in non-neuronal cells
3. Actions of non-steroidal anti-inflammatory drugs on ion channels.
Wei-Yang Lu and Mark Inman. GABA Nurtures Allergic Asthma. Clinical and Experimental Allergy (in press). Amy P Wong, Armand Keating, Wei-Yang Lu, Pascal Duchesneau, Xinghua Wang, Adrian Sacher, Jim Hu, Barry R Stripp, Thomas K Waddell. Identification of a novel epithelial-like bone marrow cell population that can repopulate the airway epithelium. Journal of Clinical Investigation 2009 Feb;119(2):336-48. Yun-Yan Xiang, Shuhe Wang, Mingyao Liu, Jeremy A Hirota, Jingxin Li, William Ju Yijun Fan, Margaret M Kelly, Bin Ye, Beverley Orser, Paul M O'Byrne, Mark D Inman, Xi Yang and Wei-Yang Lu. A GABAergic system in airway epithelium is essential for mucus overproduction in asthma. Nature Medicine 2007;13: 862 - 867. Yun-Yan Xiang, Haiheng Dong, Yudi Wan, Jingxin Li; Albert Yee, Burton B. Yang and Wei-Yang Lu. Versican G3 domain regulates neurite growth and synaptic transmission of hippocampal neurons by activation of epidermal growth factor receptor. Journal of Biological Chemistry 2006; 281:19358-19368. Haiheng Dong, Yunyan Xiang, Noa Farchi, William Ju, Yaojiong Wu, Liwen Chen, Yutian Wang, Binyamin Hochner, Burton Yang, Hermona Soreq and Wei-Yang Lu. Excess acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons. Journal of Neuroscience 2004; 24(41):8950-8960. H.Y. Man, Q.H. Wang, W.-Y. Lu, S.D. Souda, L. Liu, W. Ju, L.E. Becker, Wymann, J.F. MacDonald and Y.T. Wang. Selective activation of AMPA receptor-associated PI3-Kinase is required for LTP. Neuron, 2003; 38:611-624. Patrick Cossette, Lidong Liu, Katéri Brisebois, Haiheng Dong, Anne Lortie, Michel Vanasse, Jean-Marc Saint-Hilaire, Lionel Carmant, Andrei Verner, Wei-Yang Lu, Yu Tian Wang & Guy A. Rouleau. Mutation of GABA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nature Genetics 2002; 31:184-189. Wei-Yang Lu, Hengye Man, William Ju; William S. Trimble, John F. MacDonald and Yu Tian Wang. Activation of Synaptic NMDA Receptors Induces Membrane Insertion of AMPA Receptors and LTP in Cultured Hippocampal Neurons. Neuron 2001; 29:243-254.
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)Awards
