Michael Guo, D.V.M., Ph.D.
Assistant Project Scientist
Division of Research
Department of Surgery
UC Davis Medical Center

My research focuses on molecular regulation of VE-cadherin-mediated cell-cell adhesion and microvascular barrier function. VE-cadherin is a Ca2+-depedent, endothelial-specific cadherin that plays a vital role in angiogenesis and microvascular barrier function. The extracellular domain forms homo- and heterophilic bonds with VE-cadherin on adjacent endothelial cells, and the highly conserved cytoplasmic domain is anchored to the actin cytoskeleton via -catenin and -catenin. Disruption of these multiprotein interactions leads to endothelial barrier dysfunction. Importantly, the VE-cadherin cytoplasmic domain serves not only as a structural linkage but also as a signaling molecule that coordinates VE-cadherin-cytoskeleton interactions and adherens junction reorganization. We aim to unravel molecular mechanisms underlying the disruption of endothelial adherens junction organization and microvascular barrier function under pathophysiological conditions.

Postcapillary venulars are the primary sites of blood-tissue exchange, angiogenesis, and inflammation. We use several approaches to examine the functions of these microvessels: 1) cultured endothelial cell monolayer, 2) isolated postcapillary venules, and 3) in situ venular network. Available techniques include: 1) molecular cloning, 2) real-time RT-PCR, 3) microarray gene expression profiling, 4) plasmid DNA transfection, 5) protein transfection, 6) siRNA, 7) Western blotting and immunohistochemistry, 8) electric cell-substrate impedance sensing, 9) confocal microscopy, and 10) intravital and time-lapse video microscopy.

Trache, A, JP Trzeciakowski, L Gardiner, Z Sun, M Muthuchamy, M Guo, SY Yuan, and GA Meininger. 2005. Histamine effects on endothelial cell fibronectin interaction studied by atomic force microscopy. Biophys J, 89: 2888-2898.

Guo, M, MH Wu, HJ Granger, and SY Yuan. 2005. Focal adhesion kinase in neutrophil-induced endothelial hyperpermeability. Microcirculation, 12:223-232.

Guo, M, MH Wu, EE Ustinova, W Xue, and SY Yuan. 2003. Transference of recombinant VE-cadherin cytoplasmic domain alters endothelial junctional integrity and microvascular permeability. J Physio, 554: 78-88.

Wu, M H, M Guo, SY Yuan, and HJ Granger. 2003. Focal adhesion kinase mediates venular hyperpermeability elicited by VEGF. J Physiol, 552:691-699.

Guo, M, MH Wu, F Korompai, and SY Yuan. 2003. Upregulation of protein kinase C enes and isozymes in the heart and aorta during early stages of diabetes. Physiol Genomics, 12:139-146.

Yuan, SY, MH Wu, EE Ustinova, M Guo, JH Tinsley, P De Lanerolle, and W Xu. 2002. Myosin light chain phosphorylation in neutrophil-stimulated coronary microvascular leakage. Circ Res, 90:1214-1221.