Wei-Yang Lu
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Professor MD Shandong University Office: Robarts Research Institute, Room 7240 |
Why Science?
When I was young, I wanted to pursue medicine as a career, and so, I obtained my medical degree at Shandong University in China. After graduation from medical school, I was offered a position as junior faculty member in the Department of Physiology at the University, where I carried out in vivo electrophysiological studies on neurons in the brainstem of rodents exploring how they control respiration. It was during that time that I really fell in love with science and the curiosity of discovering new things. Following that, I completed my PhD program at Memorial University of Newfoundland and post-doc fellowships at the University of Toronto before joining as a faculty member in the Department of Anaesthesia. Later, I moved to Western for the opportunity to do collaborative research with a group of talented neuroscientists.
Research Goals
Research in my lab aims to address two scientific issues: 1) Mechanisms through which inflammatory factors regulate glutamatergic synaptic transmission and plasticity; and 2) Cellular and molecular mechanisms of GABA singling in non neuronal cells.
Specific Research Interests
1. Glutamatergic Synaptic Plasticity and Apoptosis
Currently, my lab uses animal models to study how visceral inflammations/injuries affect the ultra-structure and function of glutamatergic synapses in the cortex and cerebellum, by means of multiple techniques including immunohistochemistry and patch-clamp recordings. A synapse is sophisticated cell-cell contact that allows a neuron to pass electrical or chemical signals to target neurons or effector cells. The ultra-structure and function of a synapse are dynamically changing during development in response to various factors within its micro-environment. Aging related neurodegenerative diseases are often associated with ongoing innate immune responses in the brain. Results from our studies show that the inflammation related factors, such as nitric oxide, critically control the expression and activity of glutamate transporters in astrocytes and the cytosolic calcium dynamics of microglia, thus regulates the synaptic structure and transmission of neurons. Results from these studies may lead to a better understanding of neurodegeneration and potential treatments for neurological diseases.
2. GABA Signaling in Non-Neuronal Cells
GABA is a primary inhibitory neurotransmitter in the adult brain. In collaboration with colleagues and with funding from CIHR, we demonstrated that the GABAAR mediated autocrine signaling exist in many endocrine cells, immune cells, and epithelial cells. Specifically, we found that GABAAR regulates the proliferation and insulin secretion of pancreatic β cells, and the structure and function of airway epithelial cells. Moreover, autocrine GABA controls phenotypic transformation of macrophages. Given that GABA does not pass the blood-brain barrier, there is potential for GABA to be used to treat chronic visceral inflammations hence reduce neuronal apoptosis in the brain.
Most Rewarding Moments
One of the most rewarding moments as a professor and researcher is when a novel scientific finding is confirmed. I enjoy the happiness of discoveries together with students and research fellows who are the driving force of breakthroughs. In addition, it is an exciting movement when a new research fund is granted because sustained funding is gratifying allowing the research team to continue exploring various topics of interest. Furthermore, it is extremely motivating to publish a new study and to share the scientific knowledge with the world and add to all the scientific information available.
| 1996 |
Research Fellowship, Networks of Centres of Excellence (NCE), Neuroscience
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| 1998 |
Stroke Investigator Award, Heart and Stroke Foundation of Ontario (HSFO)
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| 1999 |
Research Fellowship, Heart and Stroke Foundation of Canada (HSFC)
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| 2000 |
Research Fellowship, Canadian Institutes of Health Research (CIHR)
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| 2002 |
The Henry J.M. Barnett Research Scholarship from HSFC
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| 2002 |
New Investigator Award, Canadian Institutes of Health Research
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| 2006 |
NARSAD Essel Investigator
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Publications:
See all my publications on PubMed.
Highlighted Publications
Tellios, V., Maksoud, M. J. E., Xiang, Y.-Y., & Lu, W.-Y. (2020). Nitric Oxide Critically Regulates Purkinje Neuron Dendritic Development Through a Metabotropic Glutamate Receptor Type 1-Mediated Mechanism. Cerebellum (London, England), 19(4), 510–526.
Maksoud, M. J. E., Tellios, V., An, D., Xiang, Y.-Y., & Lu, W.-Y. (2019). Nitric oxide upregulates microglia phagocytosis and increases transient receptor potential vanilloid type 2 channel expression on the plasma membrane. Glia, 67(12), 2294–2311.
Feng, A. L., Xiang, Y.-Y., Gui, L., Kaltsidis, G., Feng, Q., & Lu, W.-Y. (2017). Paracrine GABA and insulin regulate pancreatic alpha cell proliferation in a mouse model of type 1 diabetes. Diabetologia, 60(6), 1033–1042.
Xiang, Y.-Y., Chen, X., Li, J., Wang, S., Faclier, G., Macdonald, J. F., Hogg, J. C., Orser, B. A., & Lu, W.-Y. (2013). Isoflurane regulates atypical type-A γ-aminobutyric acid receptors in alveolar type II epithelial cells. Anesthesiology,118(5), 1065–1075.
Li, J., Xiang, Y.-Y., Ye, L., Tsui, L.-C., Macdonald, J. F., Hu, J., & Lu, W.-Y. (2008). Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR. The European Respiratory Journal, 32(2), 334–343.
Xiang, Y.-Y., Wang, S., Liu, M., Hirota, J. A., Li, J., Ju, W., Fan, Y., Kelly, M. M., Ye, B., Orser, B., O’Byrne, P. M., Inman,
M. D., Yang, X., & Lu, W.-Y. (2007). A GABAergic system in airway epithelium is essential for mucus overproduction in asthma. Nature Medicine, 13(7), 862–867.
Dong, H., Xiang, Y.-Y., Farchi, N., Ju, W., Wu, Y., Chen, L., Wang, Y., Hochner, B., Yang, B., Soreq, H., & Lu, W.-Y.(2004). Excessive Expression of Acetylcholinesterase Impairs Glutamatergic Synaptogenesis in Hippocampal Neurons. Journal of Neuroscience, 24(41), 8950–8960.
