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College of Medicine

Research Area(s)

  • The role of intracellular signaling molecules in leukocyte recruitment and transendothelial migration

About

Associate Professor

Department of Pharmacology
College of Medicine
University of Saskatchewan

Academic Credentials

B.M.Sc.(MD), Faculty of Medicine, Soochow University School of Medicine, China
M.M.Sc., Soochow University School of Medicine, China
Ph.D., Uppsala University, Sweden

PhD Position available in Dr. Liu's lab

Posting

Research Interests

  • The role of intracellular signaling molecules in leukocyte recruitment and transendothelial migration.

The recruitment of leukocytes from the flowing bloodstream into inflamed tissues is of key importance in inflammation. This recruitment involves complex interactions between leukocytes and vascular endothelial cells, characterized as firstly the tethering and rolling of leukocytes along the endothelium followed by leukocyte activation and firm adhesion to the endothelium, the transmigration of leukocytes across the endothelium (diapedesis), and finally the chemotactic migration of emigrated leukocytes toward the site of infection or injury (chemotaxis). These dynamic processes involve sophisticated cellular and molecular interactions and multiple signaling events among cell adhesion molecules, chemotactic signals, and intracellular signaling pathways. The cellular and molecular mechanisms and the role of intracellular signaling molecules in both leukocytes and endothelial cells involved in the leukocyte recruitment are our research interests in the lab.

Professional Affiliations

Member, Cardiovascular Research Group
http://www.usask.ca/cardiovascular

Member, The American Association of Immunologists (AAI)
http://www.aai.org/

Member, Society of Leukocyte Biology (SLB)
http://leukocytebiology.org/

Member, The Canadian Society of Pharmacology and Therapeutics (CSPT)
http://www.pharmacologycanada.org/

 

Current Trainees
Graduate students:

  • Musstafa Smeir: LSP1 and eNOS protein interactions
  • Li Hao: The role of Bam32, TAPP1 and TAPP2 in neutrophil recruitment

Undergraduate Research Students:

  • Hammad Kazani: The role of LSP1 in ROS production and microvascular hyperpermeability

Previous Members

  • Xi Lei
  • Najia Xu (Jennifer)
  • Jiannan Huang
  • Yang Su
  • Syed M. Qadri
  • Entesar Omran
  • Mokarram Hossain

Selected Publications

  1. Cao K, Liao X, Lu J, Yao S, Wu F, Zhu X, Shi D, Wen S, Liu L, Zhou H. IL-33/ST2 plays a critical role in endothelial cell activation and microglia-mediated neuroinflammation modulation. J Neuroinflammation. 2018 May 4;15(1):136.
  2. Zhao Y, Shi D, Cao K, Wu F, Zhu X, Wen S, You Q, Zhang K, Liu L, Zhou H. Fingolimod targets cerebral endothelial activation to block leukocyte recruitment in the central nervous system. J Leukoc Biol. 2018;103(1):107-118.
  3. Li X, Wang Y, Wei P, Shi D, Wen S, Wu F, Liu L, Ye N, Zhou H. Bisphenol A affects trophoblast invasion by inhibiting CXCL8 expression in decidual stromal cells. Molecular and Cellular Endocrinology. 2018(7):07.016.
  4. Hossain M, Omran E, Xu N, Liu L. The Specific Mitogen- and Stress-Activated Protein Kinase MSK1 Inhibitor SB-747651A Modulates Chemokine-Induced Neutrophil Recruitment. International Journal of Molecular Sciences. 2017 Oct 17;18(10):2163.
  5. Wu F, Liu L, Zhou H. Endothelial Cell Activation in Central Nervous System Inflammation. J Leukoc Biol 2017;101(5):1119-1132.
  6. Wu F, Zou Q, Ding X, Shi D, Zhu X, Hu W, Liu L, Zhou H. Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain. J Neuroinflammation 2016;13(1):23.
  7. Zhu X, Shi D, Li X, Gong W, Wu F, Guo X, Xiao H, Liu L, Zhou H. TLR signalling affects sperm mitochondrial function and motility via phosphatidylinositol 3-kinase and glycogen synthase kinase-3α. Cellular Signalling 2015;28(3):148-156.
  8. Khanh LNP, Channabasappa S, Hossain M, Liu L, Singh B. Leukocyte-specific protein 1 (LSP1) regulates neutrophil recruitment in acute lung inflammation. Am J Physiol-Lung Cell Mol Physiol 2015;309(9):L995-L1008.
  9. Hossain M, Qadri SM, Xu N, Su Y, Cayabyab FS, Heit B, Liu L. Endothelial LSP1 Modulates Extravascular Neutrophil Chemotaxis by Regulating Nonhematopoietic Vascular PECAM-1 Expression. J Immunol 2015;195(5):2408-2416.
  10. Syed M Qadri, Yang Su, Francisco S Cayabyab and Lixin Liu. Endothelial Na+/H+ exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal. Cardiovasc Diabetol. 2014 Sep 30;13(1):134.
  11. Yang Su, Syed M Qadri, Francisco S Cayabyab, Lingyun Wu and Lixin Liu. Regulation of methylglyoxal-elicited leukocyte recruitment by endothelial SGK1/GSK3 signaling. Biochim Biophys Acta-Mol Cell Res. 2014 Nov; 1843(11):2481-2491.
  12. Yang Su, Syed M Qadri, Mokarram Hossain, Lingyun Wu and Lixin Liu. Uncoupling of eNOS contributes to redox-sensitive leukocyte recruitment and microvascular leakage elicited by methylglyoxal. Biochem Pharmacol 2013 Dec 15;86(12):1762-1774.
  13. Gurpreet K. Aulakh, Yadu Balachandran, Lixin Liu and Baljit Singh. Angiostatin inhibits activation and migration of neutrophils. Cell Tissue Res. 2014 Feb;355(2):375-396.
  14. Yang Su, Syed M Qadri, Lingyun Wu and Lixin Liu. Methylglyoxal modulates endothelial nitric oxide synthase-associated functions in EA.hy926 endothelial cells. Cardiovasc Diabetol 2013 Sep 19; 12(1):134.
  15. Mokarram Hossain, Syed M. Qadri, Yang Su and Lixin Liu. ICAM-1-mediated leukocyte adhesion is critical for the activation of endothelial LSP1. Am J Physiol Cell Physiol 2013; 304: C895–C904.
  16. Najia Xu, Mokarram Hossain and Lixin Liu. Pharmacological inhibition of p38 mitogen-activated protein kinases affects KC/CXCL1-induced intraluminal crawling, transendothelial migration, and chemotaxis of neutrophils in vivo. Mediators Inflamm. 2013;2013: 290565. doi: 10.1155/2013/290565.
  17. Jianxin Lu, Jingzhang Ji, Howard Meng, David Wang, Bo Jiang, Lixin Liu, Edward Randell, Khosrow Adeli and Qing H Meng. The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats. Cardiovasc Diabetol. 2013 Apr 5;12:58. doi: 10.1186/1475-2840-12-58.
  18. Yang Su, Xi Lei, Lingyun Wu and Lixin Liu. The role of endothelial cell adhesion molecules P-selectin, E-selectin and intercellular adhesion molecule-1 in leukocyte recruitment induced by exogenous methylglyoxal.Immunology. 2012; 137(1): 65-79.
  19. Mokarram Hossain, Syed M Qadri and Lixin Liu. Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature. J Inflamm (Lond). 2012;9(1):28. doi: 10.1186/1476-9255-9-28.
  20. Xi Lei, Mokarram Hossain, Syed M Qadri and Lixin Liu*. Different microvascular permeability responses elicited by the CXC chemokines MIP-2 and KC during leukocyte recruitment: Role of LSP1. Biochem Biophys Res Commun. 2012;423(3): 484-489.
  21. Najia Xu, Xi Lei and Lixin Liu. Tracking neutrophil intraluminal crawling, transendothelial migration and chemotaxis in tissue by intravital video microscopy. J Vis Exp. 2011;(55). pii: 3296. doi: 10.3791/3296.
  22. Steven M. Kerfoot, Claudine Bonder, Graciela Andonegui and Lixin Liu. Exogenous stromal cell-derived factor-1 induces subtle leukocyte recruitment in vivo. Am J Physiol Heart Circ Physiol 2008;294(6): H2524-H2534.
  23. Bryan Heit, Lixin Liu, Pina Colarusso, Kamal Puri and Paul Kubes. PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J Cell Sci 2008; 121(Pt 2): 205-214.
  24. Lixin Liu and Paul Kubes. What is the appropriate surgical intervention when imaging? Blood 2008; 111(9):4828.
  25. Lixin Liu, K.D. Puri, J.M. Penninger and Paul Kubes. Leukocyte PI3Kg and PI3Kd have temporally distinct roles for leukocyte recruitment in vivo. Blood 2007; 110(4): 1191-1198.
  26. Mia Phillipson, Bryan Heit, Pina Colarusso, Lixin Liu, Christie M. Ballantyne and Paul Kubes.  Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 2006; 203(12):2569-2575.
  27. Lixin Liu and Paul Kubes. Chemokines in leukocyte transendothelial migration. Chemokine Biology: Basic Research and Clinical Application (Editors: Bernhard Moser, Gordon L. Letts, Kuldeep Neote). 2006, p109-122.
  28. Lixin Liu, Denise C. Cara, Jaswinder Jaur, Eko Raharjo, Sarah C. Mullaly, Jenny Jongstra-Bilen, Jan Jongstra and Paul Kubes.  LSP1 is an endothelial gate keeper of leukocyte transendothelial migration. J Exp Med 2005; 201(3): 409-418.
  29. Adil I. Khan, Steven M. Kerfoot, Bryan Heit, Lixin Liu, Graciela Andonegui, Brian Ruffell, Pauline Johnson and Paul Kubes.  Role of CD44 and hyaluronan in neutrophil recruitment. J Immunol 2004; 173: 7594-7601.
  30. Renata C.O. Zanardo, Claudine S. Bonder, John M. Hwang, Graciela Andonegui, Lixin Liu, Dietmar Vestweber, Lori Zbytnuik and Paul Kubes. A down regulatable E-selectin ligand is functionally important for PSGL-1-independent leukocyte-endothelial cell interactions. Blood  2004; 104(12): 3766-3773.
  31. Lixin Liu and Paul Kubes.  Molecular mechanisms of leukocyte recruitment: organ-specific mechanisms of action.Thromb Haemost 2003; 89(2): 213-220.
  32. Lixin Liu, Lena Håkansson, Peter Ridefelt, Rodolfo C. Garcia and Per Venge. Priming of eosinophil migration across lung epithelial cell monolayers and upregulation of CD11b/CD18 are elicited by extracellular Ca2+. Am J Respir Cell  Mol Biol 2003; 28: 713-721.
  33. Astrid E.M. Zuurbier, Lixin Liu, Frederik P.J. Mul, Arthur J. Verhoeven, Edward F. Knol and Dirk Roos.  Neutrophils enhance eosinophil migration across monolayers of lung epithelial cells. Clin Exp Allergy2001; 31: 444-452.
  34. Lixin Liu, Peter Ridefelt, Lena Håkansson and Per Venge.  Regulation of human eosinophil migration across lung epithelial monolayers by distinct calcium signaling mechanisms in the two cell types. J Immunol 1999; 163: 5649-5655.
  35. Lixin Liu, Astrid E.M. Zuurbier, Frederik P.J. Mul, Arthur J. Verhoeven, René Lutter, Edward F. Knol and Dirk Roos.  Triple role of platelet-activating factor in eosinophil transmigration across monolayers of lung epithelial cells: eosinophil chemoattractant and priming agent and epithelial cell activator. J Immunol 1998; 161: 3064-3070.
  36. Lixin Liu, Frederik P.J. Mul, René Lutter, Dirk Roos and Edward F. Knol. Transmigration of human neutrophils across airway epithelial cell monolayers is preferentially in the physiologic basolateral-to-apical direction. Am J Respir Cell Mol Biol1996; 15(6): 771-780.
  37. Lixin Liu, Frederik P.J. Mul, Taco W. Kuijpers, René Lutter, Dirk Roos and Edward F. Knol.  Neutrophil transmigration across monolayers of endothelial cells and airway epithelial cells is regulated by different mechanisms.  Ann N Y Acad Sci 1996; 796: 21-29.