RESEARCH INTERESTS

Inflammation and Neutrophil Biology Atherosclerosis, Vascular and Leukocyte Adhesion Molecules, MechanoBiology and Signal Transduction. Technology development in fluorescence microscopy, flow cytometry, microfluidics to image leukocyte function on vascular mimetic models of vascular diseases.

RESEARCH SYNOPSIS

We study the process of inflammation and its relation to chronic diseases. The onset of vascular inflammation is the interaction between circulating leukocytes and endothelial cells. In order to fight infection, leukocytes must attach to the wall of a blood vessel and migrate through the endothethial lining. This process is tightly regulated by adhesion molecules and molecular signals produced at the vascular endothelium. When leukocyte recruitment becomes chronically disregulated, a number of human diseases result including atherosclerosis, sepsis, and autoimmune diseases. We are currently exploring the mechanisms by which endothelial cells selectively produce adhesion molecules in response to inflammatory stimuli, and how leukocytes integrate these endothelial signals in order to arrest and migrate on the blood vessel wall. Development of novel means of imaging the process of inflammation on cells and in animal models is also a focus of the lab.

SELECTED PUBLICATIONS

2006 Green CE, Schaff UY, Sarantos MR, Lum AF, Staunton DE, and SI Simon. Dynamic shifts in LFA-1 affinity regulate neutrophil rolling, arrest, and transmigration on inflamed endothelium. Blood. 107:2101-2111.

2006 Zhang H, Schaff UY, Green CE, Chen H, Sarantos MR, Huy, Warad, Simon SI, and CA Lowell. Impaired integrin- dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils. Immunity. 25:285-295.

2007 Ting HJ, Stice J, Schaff UY, Hui DY, Rutledge JC, Knowlton AA, Passerini AG, and SI Simon. Triglyceride-rich lipoproteins prime aortic endothelium for an enhanced inflammatory response to TNF-. Circulation Research. 7(4):448-56.

2007 Simon SI, Nyunt T, Florine-Casteel K, Ritchie K, Ting-Beall HP, Evans E, and D Needham. Dynamics of Neutrophil Membrane Compliance and Microstructure probed with a Micropipet-based Piconewton Force Transducer. Annals of Biomed Eng. 35(4):595-604.

2007 Schaff UY, Xing MQ, Lin KK, Pan N, Jeon NL, and SI Simon Vascular mimetics based on soft lithography for imaging the leukocyte-endothelial inflammatory response. Lab on a Chip. 7: 448-456

2007 Schaff UY, Sarantos MR, Ting HJ, and SI Simon Optical and fluorescence detection of integrin activation supporting neutrophil recruitment on inflamed endothelium. Methods in Molecular Biology vol. 138:

2007 Sadhu C, Lipsky B, Garcia L, Schaff, UY, Lin KK, Simon SI, and DE Staunton. Binding of CD11c/CD18 to VCAM-1 supports its role in delayed hypersensitivity response. Journal Leukocyte Biology Apr;7(4):448-56.

2007 Lin L, Kim SC, Wang Y, Gupta S, Davis B, Simon SI, Torre-Amione G, Knowlton AA. HSP60 in Heart Failure: Abnormal Distribution and Role in Cardiac Myocyte Apoptosis. Am J Physiol Heart Circ Physiol. 293(4):H2238-47.

2007 Tsou JK, Gower RM, Schaff UY, Ting HJ, Insana MF, Passerini AG, and SI Simon. Spatial regulation of adhesion molecule expression and monocyte recruitment to human aortic endothelial cells under shear flow. Microcirculation

2007 Kim MNH, Liu W, Liu FT, Borjesson DL, Curry FE, and SI Simon. Dynamics of neutrophil infiltration and vascular permeability during cutaneous wound healing using fluorescence imaging. Journal of Investigative Dermatology

2007 Schaff U, Mattila P.E., Simon SI, and Walcheck B. Neutrophil adhesion to E-selectin under shear promotes the redistribution and coclustering of ADAM17 and its proteolytic substrate L-selectin. 2007 J. Leukocyte Biology

2007 Schaff UY, Shih HH, Lorenz M, Sako D, Bridges K, Kriz R, Shaw GD, and SI Simon SLIC-1: A novel sorting nexin that directs subcellular distribution of PSGL-1. European J. Immunology.

2007 Schaff UY, Yamayoshi I, Tse T, Griffin D, Kibathi L, and SI Simon Calcium flux in neutrophils synchronizes b₂-integrin adhesive and signaling events that guide inflammatory recruitment. Annals Biomedical Engineering.