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Bradshaw Research Lab

Amy Bradshaw, Ph.D.Amy Bradshaw, Ph.D.

Associate Professor
Division of Cardiology

The Bradshaw laboratory is focused on cellular mechanisms controlling procollagen processing and collagen deposition in cardiac fibrosis and in periodontal ligament repair.

A fundamental question in cell biology is how cells regulate the synthesis and construction of tissue-specific extracellular matrices (ECMs) in their environment and, in turn, how changes in the structure and composition of the ECM can influence cell behavior in response to injury and disease. In particular, we are interested in cellular mechanisms of collagen fibril assembly in the ECM and the function of matricellular proteins in the regulation of this process. Matricellular proteins are defined as proteins that associate with the ECM but do not contribute structurally to the ECM in contrast to classical ECM proteins such as collagen and laminin. We have established that one matricellular protein, SPARC (secreted protein acidic and rich in cysteine, osteonectin, BM-40), influences the formation of collagen I fibers in connective tissues of mice. For example, collagen accumulation associated with cardiac pressure-overload hypertrophy is significantly reduced in SPARC-null mice. Elucidation of pathways by which SPARC and other collagen binding proteins influence collagen incorporation and stability in the ECM can lead to the design of strategies to control fibrotic processes in the heart and in other tissues. Alternatively, in diseases in which collagenous tissue is degraded, such as in periodontal disease, factors that improve collagen assembly could be used as essential tools to restore damaged tissues.

Recently, my laboratory defined a novel role of SPARC in regulating the activity of transglutaminase in collagen fibril assembly. We reported that inhibition of transglutaminase activity altered collagen content, fibril diameter, and mechanical properties of tissue. As transglutaminase is highly expressed by macrophages, an interesting speculation is functional differences in collagen deposition might be tightly regulated by macrophage expression of transglutaminase and SPARC thus contributing to the disorganized fibrotic deposition of collagen in disease. The Bradshaw laboratory has been supported by grants from the National Heart, Lung and Blood Institute, the American Heart Association, the Medical University of South Carolina, and the US Department of Veterans Affairs.
 

Publications:

PubMed Collection