Molecular Recognition in Biological Systems and Bioinformatics

Endothelial cell migration; wound repair; tissue remodeling; fluorescence microscopy; cytoskeletal dynamics and regulation; cellular response to hemodynamics.

My primary research interest is the behavior of endothelial cells, which form the inner lining of blood vessels and are key players in the remodeling events that occur during wound healing, aneurysm formation, tumor growth, and a wide variety of disease conditions. There are two questions about endothelial behavior that drive most of the research in my laboratory:

(1) How does an endothelial cell migrate during wound healing and blood-vessel remodeling? We are particularly interested in the motor protein, myosin II, and how it exerts force within the cytoskeleton to push or pull the cell as it moves. In order to study the organization and movements of cytoskeletal proteins - and not just their biochemical properties - we use a variety of light microscopic methods to examine the dynamics and biochemistry of cytoskeletal proteins in living migrating endothelial cells. We also use conventional biochemical, genetic, and pharmacological manipulations to investigate the regulatory events that control myosin II behavior in situ.

(2) How do endothelial cells sense and respond to their mechanical environment?
Blood vessels remodel to accommodate long-term changes in blood flow. Certain flow environments can cause destructive remodeling that leads to cerebral aneurysms (local "ballooning" of vessels). Working with biomedical engineers in the laboratory of Dr. Hui Meng at the Toshiba Stroke Research Center, we use cell culture and whole animal systems to examine how endothelial cells respond to specific hemodynamic micro-environments in order to understand the mechanism and regulation of flow-induced remodeling, especially as it relates to cerebral aneurysms.

A third interest is understanding the response of cultured endothelial cells to electrical fields, which have been shown to orient endothelial migration in vitro and to suppress edema in vivo by enhancing the endothelial permeability barrier.

• Live-cell fluorescence microscopy workstation
• Continuous-flow microinjection
• Chambers for cell culture under fluid flow

• Rabbit
• Cow
• Dog

• Myosin
• Myosin light chain kinase
• Rho kinase
• Nitric oxide
• Nitric oxide synthase

• Wound healing
• Angiogenesis
• Cerebral aneurysm
• Tissue remodeling

• Cell culture
• Live-cell time-lapse imaging
• Immunofluorescence
• SDS-PAGE and isoelectric focusing
• Western blotting
• Immunoadsorption

Primary cultures of bovine aortic endothelial cells

Cerebral aneurysms, solid tumors, wounds

Brain, blood vessels

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