Michael A. Gimbrone, Jr., MD


Department of Pathology
Brigham and Women's Hospital
Center for Excellence in Vascular Biology
New Research Building, Room 752
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: (617) 732-7514
Fax: (617) 732-7513
Email: mgimbrone@rics.bwh.harvard.edu
Web Page: The Gimbrone Lab Page
1 postdoctoral fellow, 1 research associate


The focus of our laboratory’s studies is the vascular endothelial cell, the single-cell-thick lining of the cardiovascular system. Using a combination of cell and molecular biological approaches, in both in vitro and in vivo model systems, we are attempting to define the role(s) of this dynamic and vital cell in health and disease.

 

In the mid-1980’s, our research group described the process of activation of vascular endothelium by humoral stimuli, such as proinflammatory cytokines (IL-1, TNF). This led to the discovery of “endothelial-leukocyte adhesion molecule” (ELAM-1, now designated E-selectin), the first example of an endothelial-specific, inducible leukocyte adhesion molecule important in inflammation. Molecular cloning of ELAM-1 revealed a new family of adhesion molecules – the Selectins – which are actively being explored as targets for anti-inflammatory therapies. Our laboratory also identified VCAM-1, as a mononuclear leukocyte-selective adhesion molecule that is induced, in arterial endothelial cells, by cytokines and components of oxidized lipoproteins, and marks the earliest lesions of atherosclerosis in vivo. Ongoing studies focus on the role of the activated endothelial cell in various disease processes.

 

In collaboration with bioengineering colleagues at MIT, our laboratory has developed in vitro fluid mechanical systems to examine the cellular and molecular responses induced in vascular endothelial cells by hemodynamic forces. Utilizing these in vitro model systems, we have previously characterized a “shear-stress-response element” (SSRE) in the promoter of the human PDGF-B gene, the first example of a cis-acting transcriptional regulator of endothelial gene expression by biomechanical forces. The subsequent characterization of additional SSREs, in other biomechanically regulated endothelial genes, has validated this mechanism of endothelial activation. Utilizing a differential display strategy, we also have described the induction of “atheroprotective genes” in endothelium by steady laminar shear stresses, which may be responsible for the resistance of certain vascular geometries to atherosclerotic lesion development.

 

We are currently applying high-thru-put transcriptional profiling and bioinformatic strategies to analyze the functional phenotypes of vascular endothelial cells in a variety of (patho)physiologic settings relevant to human disease pathogenesis. (see Website).

 

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BBS webpage updated 12/02/2009