M.D., Medicine, Second Military Medical University, 1984
Interdisciplinary and Emerging Signature Programs
Cardiovascular Sciences
Research Interests
My research interest lies in the molecular pathophysiology of barrier tissues, such as microvascular endothelium and intestinal epithelium, with a particular focus on their structure and function in trauma and inflammation. During the past two decades, my laboratory has conducted investigation in the following areas: 1) cell-specific mechanisms of leaky gut caused by trauma, burns and ischemia-reperfusion injury; 2) signal transduction in microvascular hyperpermeability during inflammation; and 3) focal adhesion kinase and integrin-mediated interactions between endothelial cells and extracellular matrices in the regulation of microvascular function and angiogenesis. We study these pathophysiological processes using in vivo, in situ and in vitro approaches that examine the microcirculatory dynamics, intact isolated microvessels, and cultured cells at molecular levels.
Recent Publications
Haines RJ, Beard RS, Chen L, Eitnier RA, Wu MH. Interleukin-1β Mediates β-Catenin-Driven Downregulation of Claudin-3 and Barrier Dysfunction in Caco2 Cells.Digestive Diseases and Sciences. 61(8) : 2252-61, 2016.
Haines RJ, Beard RS, Eitner RA, Chen L, Wu MH. TNFα/IFNγ Mediated Intestinal Epithelial Barrier Dysfunction Is Attenuated by MicroRNA-93 Downregulation of PTK6 in Mouse Colonic Epithelial Cells.PloS ONE. 11(4) : e0154351, 2016.
Breslin JW, Daines DA, Doggett TM, Kurtz KH, Souza-Smith FM, Zhang XE, Wu MH, Yuan SY. Rnd3 as a Novel Target to Ameliorate Microvascular Leakage.Journal of the American Heart Association. 5(4) : e003336, 2016.
Haines RJ, Beard RS, Wu MH. Protein tyrosine kinase 6 mediates TNFα-induced endothelial barrier dysfunction.Biochemical and Biophysical Research Communications. 456(1) : 190-6, 2015.
Trujillo AN Kesl SL Sherwood J Wu MH and Gould LJ. Demonstration of the Rat Ischemic Skin Wound Model.Journal of Visualized Experiments. 1(98) : e52637, 2015.
Chatterjee V, Beard RS, Reynolds JJ, Haines R, Guo M, Rubin M, Guido J, Wu MH, Yuan SY. MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.PloS ONE. 9(10) : e110286, 2014.
Beard RS Jr1 Haines RJ Wu KY Reynolds JJ Davis SM Elliott JE Malinin NL Chatterjee V Cha BJ Wu MH Yuan SY. Non-muscle Mlck is required for β-catenin- and FoxO1-dependent downregulation of Cldn5 in IL-1β-mediated barrier dysfunction in brain endothelial cells.J Cell Sci.. 127(8) : 1840-53, 2014.
Fujita M1 Ieguchi K Cedano-Prieto DM Fong A Wilkerson C Chen JQ Wu M Lo SH Cheung AT Wilson MD Cardiff RD Borowsky AD Takada YK Takada Y. An integrin binding-defective mutant of insulin-like growth factor-1 (R36E/R37E IGF1) acts as a dominant-negative antagonist of the IGF1 receptor (IGF1R) and suppresses tumorigenesis but still binds to IGF1R.J Biol Chem.. 288(27) : 19593-603, 2013.
Rigor RR Shen Q Pivetti CD Wu MH Yuan S. Myosin light chain kinase signaling in endothelial barrier dysfunction.Med Res Rev.. 33(5) : 911-33, 2013.
Sun C, Beard RS, McLean DL, Rigor RR, Konia T, Wu MH, Yuan SY. ADAM15 deficiency attenuates pulmonary hyperpermeability and acute lung injury in lipopolysaccharide-treated mice.American Journal of Physiology. Lung Cellular and Molecular Physiology. 304(3) : L135-42, 2013.
Guo M, Yuan SY, Frederich BJ, Sun C, Shen Q, McLean DL, Wu MH. Role of non-muscle myosin light chain kinase in neutrophil-mediated intestinal barrier dysfunction during thermal injury.Shock (Augusta, Ga.). 38(4) : 436-43, 2012.
Sun C, Wu MH, Lee ES, Yuan SY. A disintegrin and metalloproteinase 15 contributes to atherosclerosis by mediating endothelial barrier dysfunction via Src family kinase activity.Arteriosclerosis, Thrombosis, and Vascular Biology. 32(10) : 2444-51, 2012.
Lee ES, Van Spyk EN, Chun KC, Pitts RL, Wu MH, Yuan SY. Monocytic adhesion molecule expression and monocyte-endothelial cell dysfunction are increased in patients with peripheral vascular disease versus patients with abdominal aortic aneurysms.The Journal of Surgical Research. 177(2) : 373-81, 2012.
Sun C Wu MH and Yuan SY. nmMLCK deficiency ameliorates atherosclerosis in ApoE-deficient mice via reduced endothelial barrier dysfunction and monocyte migration.Circulation. 124: 48-57, 2011.
Lee ES, Shen Q, Pitts RL, Guo M, Wu MH, Sun SC, Yuan SY. Serum metalloproteinases MMP-2, MMP-9, and metalloproteinase tissue inhibitors in patients are associated with arteriovenous fistula maturation.Journal of Vascular Surgery. 54(2) : 454-9; discussion 459-60, 2011.
Shen Q, Lee ES, Pitts RL, Wu MH, Yuan SY. Tissue inhibitor of metalloproteinase-2 regulates matrix metalloproteinase-2-mediated endothelial barrier dysfunction and breast cancer cell transmigration through lung microvascular endothelial cells.Molecular Cancer Research : MCR. 8(7) : 939-51, 2010.
Lee ES Shen Q Pitts RL Guo M Wu MH and Yuan SY. Vein graft expression of matrix metalloproteinase as biomarker for hemodialysis arteriovenous fistula maturation.Vas Endovas Surg. 44: 674-79, 2010.
Sun C Wu MH Guo M Day ML Lee ES and Yuan SY. ADAM 15 regulates endothelial permeability and neutrophil migration viaSrc/ERK1/2 signaling.Cardiovasc Res. 15(87) : 348-55, 2010.
Shen Q Wu MH and Yuan SY. Endothelial contractile cytoskeleton and microvascular permeability.Cell Health and Cytoskeleton. 1: 43-50, 2009.