Mingyao Liu , MD, MSc

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 high throughput drug screening 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 and tumourigenesis.

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 are developing 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 mechanims 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.

Additional Appointments

Full Professor, Department of Surgery, Medicine and Physiology, University of Toronto

Current Grant Support

Operating Grant, MOP-119514, Acute lung injury: from cellular mechanisms to molecular therapies, 2012-2017

Operating Grant, MOP-42546, Signal cross-talk in acute lung injury, Canadian Institutes of Health for Research, 2008-2013

Selected Publications

Cellular and Molecular Biology Studies

1. Lodyga M, De Falco V, Kapus A, Bai, XH, Melillo, RM, Santoro M and Liu M. XB130, a tissue specific adaptor protein that couples RET/PTC oncogenic kinase to PI3-kinase pathway. Oncogene 2009 Feb 19; 28(7):937-49.
2. Lodyga M, Bai X, Kapus A, and Liu M. Adaptor protein XB130 is a Rac-controlled component of lamellipodia that regulates cell motility and invasion. J Cell Sci 2010 Dec 1; 123(Pt 23):4156-69.
3. Xiao H, Bai XH, Kapus A, Lu WY, Mak AS, and Liu M. The protein kinase C cascade regulates recruitment of matrix metalloprotease 9 to podosomes and its release and activation. Mol Cell Biol. 2010 Dec; 30(23):5545-61.
4. Xiao H, Han B, Lodyga M, Bai XH, Wang Y, and Liu M. The actin-binding domain of actin filament associated protein is involved in the regulation of cytoskeletal structure. Cell Mol Life Sci 2012 Apr; 69(7):1137-51.
5. Xiao H, Li DX, and Liu M. Knowledge translation: airway epithelial cell migration and respiratory diseases. Cell Mol Life Sci 2012 Dec;69(24):4149-62.
6. Xiao H, Liu M. Atypical protein kinase C and cell motility. Cell Mol Life Sci 2012 Oct 25. [Epub ahead of print PMID: 23096778 DOI: 10.1007/s00018-012-1192-1
7. Xiao H, Eves R, Yeh C, Kan W, Xu F, Mak AS, Liu M. Phobol ester-induced podosomes in normal human bronchial epithelial cells. J Cell Physiol. 2009 Feb; 218(2):366-75.
8. Xiao H, Bai XH, Wang Y, Kim H, Mak AS, and Liu M. MEK/ERK pathway mediates PKC activation-induced recruitment of PKCζ and MMP-9 to podosomes. J Cell Physiol 2013 Feb;228(2):416-27.
9. Shiozaki A, Lodyga M, Bai X-H, Nadesalngam J, Oyaizu T, Winer D, Asa S, Keshavjee S, Liu M. XB130, a novel adaptor protein, promotes tumor growth. Am J Pathol 2011 Jan; 178:391-401.
10. Shiozaki A, Shen-Tu G, Bai X, Iitaka D, De Falco V, Santoro M, Keshavjee S, Liu M. XB130 mediates cancer cell proliferation and survival through multiple signal events downstream of Akt. PLoS One 2012; 7(8): e43646.
11. Shiozaki A, Bai X-H, Shen-tu G, Moodley S, Takeshita H, Fung S-Y, Wang Y, Keshavjee S, Liu M. Claudin 1 mediates TNFα-induced gene expression and cell migration in human lung carcinoma cells. PLoS ONE 7(5): e38049.
12. Shiozaki A and Liu M. Roles of XB130, a novel adaptor protein, in cancer. J Clin Bioinforma 2011, 1:10
13. Han B, Xiao H, Xu J, Lodyga M, Bai XH, Jin T, and Liu M. Actin filament associated protein mediates c-Src related SRE/AP-1 Transcriptional Activation. FEBS Lett 2011 Jan, 585:471-477.

Nanotechnology for lung injury and repair

14. Yang H, Fung S-Y, Liu M. Programming the cellular uptake of physiologically stable peptide-gold nanoparticle hybrids with single amino acid. Angew Chem Int Ed Engl 2011 Oct 4; 50 (41):9643-6. (IF: 12:73)
15. Fung S-Y, Oyaizu T, Yang H, Yuan Y, Han B, Keshavjee S, and Liu M. The potential of nanoscale combination of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury. Biomaterials 2011 Jun; 32(16):4000-8.
16. Bawa R, Fung S, Shiozaki A, Yang H, Zheng G, Keshavjee S, Liu M. Self-assembling peptide based nanoparticles enhance cellular delivery of the hydrophobic anticancer drug ellipticine through caveolin-dependent endocytosis. Nanomedicine 2012 Jul;8(5):647-54.
17. Mura M, Binnie M, Han B, Chen J, Andrade CF, Zhang Y, Ferrara, N. Hwang D, Waddell TK, Keshavjee S, and Liu M. Functions of type II pneumocyte-derived vascular endothelial growth factor in alveolar structure, acute inflammation and vascular permeability. Am J Pathol 2010 Apr, 176(4):1725-34.
18. dos Santos CC, Okutani D, Hu P, Han B, Crimi E, He X, Keshavjee S, Greenwood C, Slutsky AS, Zhang H, Liu M. Differential Gene Profiling in Acute Lung Injury Identifies Injury Specific Gene Expression. Crit Care Med. 2008 Mar; 36(3):855-65.
19. He X, Han B, Mura M, Li L, Cypel M, Soderman A, Picha K, Yang J and Liu M. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice. PLoS ONE. 2008 Jan 30;3(1):e1527.
20. He X, Han B, Bai XH, Zhang Y, Cypel M, Mura M, Keshavjee S, and Liu M. PTX3 as a potential biomarker of acute lung injury - supporting evidence from animal experimentation. Intensive Care Med 2010 Feb; 36(2):356-64.
21. Han B, Haitsma JJ, Zhang Y, Bai X, Rubacha M, Keshavjee S, Zhang H, Liu M. Long pentrxin PTX3 deficiency worsens LPS-induced acute lung injury. Intensive Care Med 2011; Feb; 37(2):334-342.
22. Han B, Ma X, Zhang J, Zhang Y, Bai X, Hwang DM, Keshavjee S, Levy GA, McGilvray I, and Liu M. Protective effects of long pentraxin PTX3 on lung injury in a severe acute respiratory syndrome model in mice. Lab Invest 2012 Sep; 92(9):1285-96. doi: 10.1038/labinvest.2012.92.
23. Tang P, Mura M, Seth R, and Liu M. Cell death and acute lung injury: how many ways cells can die? Am J Physiol Cell Mol Physiol 2008 Apr; 294(4):L632-41.
24. Sato M, Keshavjee S, and Liu M. Translational research: animal models for bronchialitis obliterans. Am J Transpl. 2009 Sep; 9(9):1981-7.
25. Oyaizu T, Fung S, Shiozaki A, Guan Z, Zhang Q, dos Santos CC, Han B, Mura M, Keshavjee S, Liu M. Src tyrosine kinase inhibition protects pulmonary ischemia-reperfusion-induced acute lung injury. Intensive Care Med. 2012 May;38(5):894-905.