Sarah Y. Yuan, M.D., Ph.D.
Pearl Stamps Stewart Professor
Director, Division of Research
Department of Surgery
UC Davis Medical Center

The goal of our research is to better understand the cellular and molecular regulation of cardiovascular function in health and disease. We investigate the signaling mechanisms of cell-cell and cell-matrix interactions in the microcirculation during inflammation, trauma, infection, sepsis, atherosclerosis, diabetes, and metastatic tumor development. A unique aspect of our studies is the emphasis on translating novel molecular mechanisms into systemic pathophysiology via integrative analyses of human, animal, and cell models of diseases. Techniques utilized in these studies include intravital microscopy, 3D fluorescence imaging, fluorescence resonance energy transfer, electric cell-substrate impedance sensor, cell isometric tension, and state-of-the-art molecular approaches including gene knockout and mutation. Our group has been internationally recognized for developing innovative experimental models, such as the isolated microvessel preparation for quantification of permeability, and protein/peptide transfection to intact tissues for identification and characterization of specific therapeutic targets.  Our research has been continuously supported by the National Institutes of Health.

1. Signal transduction in leukocyte-endothelial cell-cell and cell-matrix adhesion.
2. Molelcular control of microcirculatory function in trauma, sepsis, and inflammation.
3. Gene regulation and molecular pathogenesis of diabetic complications and atherosclerosis.
4. Endothelial mechanisms of tumor angiogenesis and metastatic migration.
5. Development of biomarkers and therapeutic targets for diagnosis and treatment of inflammation.
6. Cerebral microcirculation and BBB structure and function in traumatic brain injury.

Tinsley JH et. al.  Activated neutrophils induce hyperpermeability and phosphorylation of adherence junction
proteins in endothelial cells. J Biol Chem 274: 24930-24934, 1999. 

Yuan SY et. al.  PKC activation contributes to microvascular barrier dysfunction in the heart at early stages of
diabetes.  Circ Res 87: 412-417, 2000.

Yuan SY et. al.  Myosin light chain phosphorylation in neutrophil-stimulated coronary microvascular leakage.
Circ Res 90: 1214-1221, 2002.

Yuan SY.  Protein kinase signaling in the modulation of microvascular permeability.  Vasc Pharmacology
39: 213-223, 2003.

Tinsley JH et. al.  Isoform specific knockout of endothelial myosin light chain kinase: closing the gap on
inflammatory disease.  Trends in Pharmacol Sci.  25: 64-66, 2004.

Gaudreault N et. al.  Counter-regulatory effects of PKCβ and PKCd on coronary endothelial permeability.
Arterioscler Thromb Vasc Biol.  28: 1527-1533, 2008.

Guo M et. al. Fibrinogen-g fragments induce endothelial barrier dysfunction and microvascular leak via
integrin-mediated and RhoA-dependent mechanism. Arterioscler Thromb Vasc Biol  29:3940-400, 2009.

Kumar P et. al. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Exp
Rev Mol Med 11: 1-20, 2009.

Sun C et. al. ADAM15 regulates endothelial permeability and neutrophil migration via Src/ERK1/2 signaling.
Cardiovas Res 87: 348-355, 2010.

Shen Q et. al. TIMP2 regulates MMP2-mediated endothelial barrier dysfunction and breast cancer cell
transmigration through lung microvascular endothelial cells.  Mol Cancer Res 8:939-951, 2010.