Research Interests: We are focusing on the ischemia-reperfusion induced lung injury in lung transplantation, and the cellular and molecular mechanisms of acute lung injury. We have developed nano-particular based drug delivery systems for hydrophobic drugs/chemicals. We are developing a drug discovery pipeline for ischemia-reperfusion induced lung injury.
Another major research interest is the role of adaptor proteins in signal transduction. We have cloned an adaptor protein, XB130 (AFAP1L2), which can couple protein tyrosine kinase to the PI3K pathway in cells. We have generated xb130 knockout mice through collaboration. We are exploring the role of XB130/PI3K/Akt pathway in lung tissue injury/repair, tumourigenesis and thyroid function.
Project I. Acute lung injury: from cellular mechanisms to molecular therapy
We have developed a cell culture model to simulate hypothermic preservation and reperfusion in lung transplantation. Using this model, we are exploring the mechanisms of lung injury at the cellular and molecular levels. We also use this system for drug screening and discovery. We have a rat lung transplantation model to test the therapeutic effects of potential drugs in vivo. In collaboration with Dr. Shaf Keshavjee, we also have access to pig lung transplantation and human ex vivo lung perfusion system for pre-clinical studies. With this pipeline, we are exploring multiple therapeutic reagents.
We have developed a self-assembly peptide-based nano-particle delivery system for hydrophobic drugs. We have developed a gold nano-particle/peptide hybrid system for drug delivery as well.
Project II. Signal cross-talk in acute lung injury
We have cloned a novel human gene, xb130, which encodes a novel adaptor type protein. This protein can directly activate Src and subsequently activate AP-1/SRE. This adaptor protein is involved in the PI3K/Akt pathway. XB130 is part of Rac-induced lamillipodia for cell migration. Using 3D confocal microscopic scanning and live cell imaging, we found that human airway epithelial cells could form podosomes during migration and invasion. Currently, we are working on the molecular mechanisms of XB130 in cell signaling. Cell proliferation, cell death and cell migration are important to maintain the normal physiological function and tissue repair. Transgenic mice with XB130 knocked out will be used to further study the role of XB130 in the lung injury and repair and in tumourigenesis. We also found that XB130 is important for postnatal growth through its role in the regulation of thyroid functions.
We believe that translational medicine requires collaboration between basic scientists and clinicians. Our first project focuses on the knowledge translation. A drug discovery pipeline has been developed. The second project continues our journey in discovery of the nature of physiology and development of diseases.
Cell and tissue culture: Endothelial cells, epithelial cells, fibroblasts.
Procedures: Adenovirus, Elisa, gene expression analysis, immunohistochemistry, immunocytochemistry, mass spectrometry, microarrays, proteomics, qRT-PCR, RT-PCR, signal transduction characterization, siRNA, western blot, metabolomics.
Benchtop centrifuge, blotting apparatus, confocal microscope (core facility), culture hood, culture incubators, deconvolution fluorescence microscope, digital microscope, fluorescence microscope, low- and high-speed centrifuge, low and ultralow freezers, mass spectrometer, microwave oven, mini vortexer, plate reader, real-time/thermocycler, setups for electropherosis, stirrer/hot plate, water baths.
Mitsuteru Yoshida (visiting scientist)
Within the Department of Physiology:
Outside the Department of Physiology:
Shaf Keshavjee, Surgery, University of Toronto
Marcelo Cypel, Surgery, University of Toronto
Tom Waddell, Surgery, UofT
Gail Darling, Surgery, UofT
Shanna Kelley, Pharmacy, UofT
Gang Zheng, Medical Biophysics, UofT
Andras Kapus, Surgery, UofT
Burton Yang, LMP, UofT
Warren Chen, IBBME, UofT
Hartmut Grasemann ,Pediatrics, UofT
Committee member/Officer of national or international scientific organization:
Membership Committee, Society of Chinese Bio-Scientist in America Member, July 1, 2007- present
Editorial Board Member, Chinese Journal of Contemporary PediatricsNovember 2003 - present
World Journal of Transplantation, 2011 - 2015
World Journal of Critical Care Medicine, 2011 - 2015