Dr. Mingyao Liu

University Appointments

Professor of Surgery, Medicine and Physiology
Director of International Research Relations, Faculty of Medicine
Full Member, Institute of Medical Science, School of Graduate Studies

Hospital Appointments

Senior Scientist, Division of Cellular and Molecular Biology,
Director, Center for Research Training and Education, University Health Network Toronto General Research Institute

Research Interests

One of the major interests of the laboratory is the cellular and molecular mechanisms of lung injury. We are focusing on the ischemia-reperfusion induced lung injury in lung transplantation. We are developing nano-particular based drug/siRNA delivery systems.

Another major research interest is lung repair and regeneration. We are exploring the role of PI3K/Akt pathway in lung tissue injury and repair using transgenic mice with deficiency of an adaptor protein cloned in my lab, XB130. We work on role of XB130 in cell proliferation, survival and migration.

Current Grant Support

CIHR
Ventilator-induced acute lung injury: from mechanotransduction to molecular therapies
2006-2011

CIHR
Signal cross-talk in acute lung injury
2008-2013/p>

Selected Recent Publications

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Research Laboratory

Project I. Ventilator-induced lung injury: from mechanotransduction to molecular therapy (CIHR, MT-13270)
Our recent work has demonstrated mechanical stretch stimulated cytokine production in lung cells through specific signal transduction pathways. Stretch-induced cytoskeletal deformation converts physical force into the biochemical reactions of signaling events through protein-protein interactions. We have used microarray-bioinformatics to determine genes related to acute lung injury. Using a conditional knockout technique, we identified that vascular endothelial growth factor (VEGF) produced in type II alveolar epithelial cells are important for pulmonary vascular permeability and survival of lung epithelial cells. During acute lung injury and endotoxin challenge, cells undergo caspase-independent death (oncosis) in multiple organs.

Currently, we are using animal models to determine the therapeutic effect of Src inhibitors on acute lung injury. In collaboration with scientists at the University of Waterloo, we are developing nano-particular based delivery systems for drugs and small interference RNA (siRNA). We are also studying the roles of tissue factor and PTX3 (a novel mediator in innate immunity and inflammation) in acute lung injury.

Project II. Signal cross-talk in acute lung injury (CIHR, MOP-42546)
We have recently 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. We have evidence that this adaptor protein is involved in the PI3K/Akt pathway. Using 3D confocal microscopic scanning and live cell imaging, we found that lung epithelial cells could form podosomes during migration and invasion. XB130 may be part of these cellular processes.

Currently, we are working on the role of XB130 in cell cycle progress, cell survival and cell migration. Cell proliferation, cell death and cell migration are important to maintain the normal physiological function and tissue repair. Transgenic mice with xb130 knocked out have been generated. We will further study the role of XB130 in the lung injury and repair with cellular and molecular approaches both in vitro and in vivo.