Amy D. Bradshaw, Ph.D.
Principal Investigator at the Gazes Cardiac Research Institute
Assistant Professor of Medicine
Room 223, Gazes / Thurmond Building
114 Doughty St., Charleston, SC 29425
Phone: (843) 792 - 4958 / Fax: (843) 876 - 5068
E-mail: bradshad@musc.edu
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EDUCATION:
1986 B.A. University of California, San Diego
1995 Ph.D. University of California, Santa Barbara
Postgraduate Education
1996-2002, University of Washington and The Hope Heart Institute, Seattle WA
Dr. Helene Sage
Research Interest:
 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. One focus of our laboratory is the mechanisms of matrix remodeling that take place in response to cardiac hypertrophy. Using different models of hypertrophy (e.g. pressure versus volume overload) we hope to discern how cardiac cells respond to injury in terms of matrix turnover and deposition. We employ cell culture models that involve both cardiocytes and cardiac fibroblasts to better understand the relationship between matrix deposition and accumulation (fibrosis) in the heart and cardiac function. A related area of study in our laboratory is the regulation of collagen fibril formation. We have established that SPARC (secreted protein acidic and rich in cysteine/osteonectin/BM-40), influences the formation of collagen I fibers in the skin of mice. A variety of factors are known to contribute to the regulation of collagen fibers including the presence (or absence) of proteoglycans such as decorin, lumican, fibromodulin, the processing of procollagens at both amino- and carboxyl-terminal prodomains, and the incorporation of other collagen types within collagen I fibers. We are currently investigating the mechanism(s) by which SPARC affects the size and stability of collagen I fibers.
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Recent Publications:
1. Bassuk, J.A., Birkebak, T., Rothmier, J.D., Clark, J.M., Bradshaw, A., Muchowski, P.J., Howe, C.C., Clark, J.I., and Sage, E.H. (1999) Disruption of the Sparc locus in mice alters the differentiation of lenticular epithelial cells and leads to cataract formation. Exp. Eye Res., 68, 321-331
2. Bradshaw, A.D., Francki, A.F., Motamed, K., Howe, C. and Sage, E.H. (1999) Primary mesenchymal cells isolated from SPARC-null mice exhibit altered morphology and rates of proliferation. Mol. Biol. Cell, 10, 1569-1579.
3. Francki, A.F., Bradshaw, A.D., Bassuk, J., Vernon, R.B., Howe, C. and Sage, E.H. (1999) SPARC regulates the expression of collagen type I and transforming growth factor-_ in mesangial cells. J. Biol. Chem. 274, 32145-32152.
4. Bassuk, J.A., Pichler, R., Rothmier, J.D., Pippen, J., Gordon, K., Meek, R.L., Bradshaw, A.D., Lombardi, D., Strandjord, T.P., Reed, M., Sage, E.H., Couser, W.G., and Johnson, R. (2000) Induction of TGF-_1 by the matricellular protein SPARC in a rat model of glomerulonephritis. Kid. Int. 57, 117-128.
5. Bradshaw, A.D., Bassuk, J., Francki, A., and Sage, E.H. (2000) Expression and purification of recombinant human SPARC produced by baculovirus. Mol. Cell Biol. Res. Comm. 3, 345-351.
6. Bradshaw, A.D. and Sage, E.H. (2001) SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J. Clin. Invest. 107, 1049-1054.
7. Bradshaw, A.D., Reed, M.J., Carbon, J.G., Pinney, E., Brekken, R.A., and Sage, E.H. (2001) Increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges in SPARC-null mice. Wound Repair Regen. 9, 522-530.
8. Bradshaw, A.D., Reed, M.J., and Sage, E.H. (2002) SPARC-Null mice exhibit accelerated cutaneous wound closure. J. Histochem. Cytochem. 50, 1-10.
9. Puolakkainen, P., Bradshaw, A.D., Kyriakides, T.R., Reed, M., Brekken, R., Wight, T., Bornstein, P., Ratner, B., and Sage, E.H. (2002) Mice that lack the matricellular protein SPARC exhibit a reduced foreign body reaction to implanted materials. Am. J. Pathol. 162, 627-35.
J. Invest. Dermatol. 120, 949-55
11. Bradshaw, A.D., Graves, D.C., and Sage, E.H. (2003) SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc. Natl. Acad. Sci USA , 100, 6045-6050.
12. Delaney, A.M., Kalajzic, I., Bradshaw, A.D., Sage, E.H., and Canalis, E. (2003) Osteonectin-null mutation compromises osteoblast formation, maturation, and survival. Endocrinol. 144, 2588-2596.
Endowment