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 Gazes Cardiac Research Institute | faculty | Amy D. Bradshaw, Ph.D.

Amy D. Bradshaw, Ph.D.

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 pressure-overload hypertrophy is significantly reduced in SPARC-null mice. Elucidation of pathways by which SPARC and other collagen binding proteins influences 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 are useful tools to improve strategies to restore damaged tissues.

Dr Bradshaw's Lab
Laboratory Members
Erik Eadie
Jessica Trombetta-esilva
Yuhua Zhang

 
Publications

1.      Harris, B.H., Zhang, Y., Card, L., Rivera, L., Brekken, R.A., and Bradshaw, A.D. (2011) SPARC Regulates Collagen I Interaction with Cardiac Fibroblast Cell Surfaces. Am J Physiol Heart Circ. Res, 301:H841-847. PMCID: PMC3191098

2.      McCurdy, S.M., Dai, Q., Zhang, J., Zamilpa, R., Ramirez, T.A., Dayah, T., Nguyen, N., Jin, Y., Bradshaw, A.D., Lindsey, M.L. (2011) SPARC Mediates Early Extracellular Matrix Remodeling Following Myocardial Infarction. Am J Physiol Heart Circ. Res, 301:H497-505. PMCID: PMC3154667

3.      Nie, J., Bradshaw, A.D., Delany, A.M., Sage, E.H. (2011) Inactivation of SPARC enhances high fat diet-induced obesity in mice. Conn Tiss Res., 52: 99-108. PMID: 20615096 PMCID, in progress.

4.      Trombetta, J., Bradshaw A.D. (2010) The absence of SPARC compromises structural integrity of the periodontal ligament in mice. J. Histochem. Cytochem. 58: 871-9. PMCID: PMC2942740.

5.      Bradshaw, A.D. (2010) The Role of SPARC in Extracellular Matrix Assembly. J. Cell Commun. Signal. 3: 239-246. PMCID: PMC2778582

6.      Card, L., Henderson, N., Zhang, Y., Bornstein, P., Bradshaw, A.D. (2010) Expression in SPARC-null Mice of Collagen type I lacking the Globular Domain of the a1(I) N-propeptide Results in Abdominal Hernias and Loss of Dermal Collagen. Matrix Biology 29, 559-64. PMCID: PMC2957371.

7.      McCurdy, S., Baicu, C.F., Heyman, S., and Bradshaw, A.D. (2010) Cardiac Extracellular Matrix Remodeling: Fibrillar Collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC) J. Mol Cell Cardiol. 48: 544-549. PMCID: PMC2823826

8.      Trombetta, J.M., Yu, H., Arias, D.N., Rossa, C. Jr, Kirkwood, K.L., Bradshaw, A.D. (2010) SPARC/Osteonectin-Null Mice have Increased Bone Loss and Decreased Periodontal Ligament Collagen Content in Response to LPS-Induced Periodontitis. J. Dent. Res. 90:477-82. PMCID: PMC2942740.

9.      Bradshaw, A.D., Baicu, C.F., Rentz, T.J., Derienzo, C., Van Laer, A., Boggs, J., and Zile, M.R. (2010) Age-dependent alterations in fibrillar collagen content and myocardial diastiolic function: role of SPARC in post-synthetic procollagen processing. Am J Physiol Heart Circ. Res, 298: H614-622, PMCID: PMC2822576.

10.       Bradshaw, A.D., Baicu, C.F., Rentz, T.J., Derienzo, C., Boggs, J., Van Laer, A., Lacy, J., and Zile, M.R. (2009) Pressure-Overload Induced Alterations in Myocardial Hypertrophy and Extracellular Collagen Content: Role of SPARC-Dependent Post-Synthetic Collagen Processing. Circulation 119, 269-280. PMCID: PMC2734276

Pubmed Listings

Amy D. Bradshaw, Ph.D.

Amy D. Bradshaw, Ph.D.
Principal Investigator at the Gazes Cardiac Research Institute
Associate Professor of Medicine

Dr. Bradshaw's Contact Information

Room 223, Gazes/Thurmond Building
114 Doughty St.
Charleston, SC 29425

Phone: (843)792-4549

Lab:(843)792-4962
Fax:
(843)876-5068
Email: bradshad@musc.edu

Dr. Bradshaw's Education
1986 B.A. University of California, San Diego
1995 Ph.D. University of California, Santa Barbara
1996-2002 Postgraduate Education at University of Washington and the Hope Heart Institute, Seattle, WA Dr. Helene Sage