Marion Cooley

Marion A. Cooley, Ph.D.
Research Assistant Professor

Email: cooleyma@musc.edu


BS University of South Carolina
PhD University of South Carolina
Postdoctoral Training: University of North Carolina (Chapel Hill) & Medical University of South Carolina



Research Interest:

The extracellular matrix (ECM) is a three-dimensional network of molecules that surrounds cells in tissues and can direct organ morphogenesis, tissue repair and disease progression. Cells receive information from the ECM by means of cell surface receptors. This information is then transmitted from the ECM-cell interface by signaling pathways to elicit cellular behaviors such as migration, proliferation and differentiation. My major research emphasis is to understand how this network of molecules stimulates specific cellular behaviors. In our research we use both mouse genetic models and cell-based assays to study the role of the ECM in:

  • Bmp-2-mediated bone formation and bone repair

The goal of this project is to identify ECM proteins that can induce Bmp-2 signaling in order to promote bone formation. We have recently identified the ECM protein, Fibulin-1 (Fbln1), the prototypical member of the Fibulin family, as a positive modulator of Bmp-2 signaling.  Studies are underway to determine the mechanisms by which this ECM protein promotes Bmp-2-mediated osteoblast differentiation and bone formation. We are also investigating whether Fbln1 is required for bone repair using a critical size calvarial defect model system.

Figure 1Figure 1. Fbln1 null neonates have reduced alizarin red staining of membranous bones and endochondral bones in the cranium. A and B show that alizarin red staining in the membranous frontal, parietal and interparietal bones from a P0 Fbln1 null neonate (B) is reduced as compared to P0 wild-type (A). Arrow in B points to the interfrontal bone in P0 Fbln1 null that is reduced compared to P0 wild-type. C and D are higher magnification views of the otic region in P0 wild-type and P0 Fbln1 null skull showing reduced ossification of the otic capsule and tympanic ring bone (T) in P0 Fbln1 null. Arrowhead in C points to a bone in P0 wild-type otic capsule that is absent in the P0 Fbln1 null otic capsule. As, alisphenoid bone; FB, frontal bone; Ib, interfrontal bone; Ip, interparietal bone; Oc, otic capsule; P, parietal bone; T, tympanic ring bone.

  • Pericyte adhesion to vascular networks

The integrity of the brain's vascular system is controlled in part by support cells referred to as pericytes. We are investigating how the ECM promotes pericyte attachment to blood vessel during the development of the cerebrovasculature.

  • Cardiac development

Recent findings suggest that the ECM protein, Fbln1, negatively regulates TGFβ2 signaling and endothelial to mesenchymal transition (EMT) during cardiac outflow tract (OFT) development. We are investigating the mechanism by which Fbln1 inhibits TGFβ2 activity to control EMT in the proximal OFT cushions.

Figure 2Figure 2. Fibulin-1 deficient embryos display hypercellular OFT cushions and blood cell accumulation in OFT cushions at E9.5. (A and B) H&E stained E9.5 sections of proximal OFT cushions from wild type and Fbln1 null embryos, respectively. Note the abundant cells present in the cushion of the Fbln1 null section compared to the wild type. C and D show AMIRA 3D reconstructions of wild type and Fbln1 null proximal OFT cushions at E9.5. C 3D reconstruction of wild type shows endocardial cell content but little mesenchymal cell content (blue) and no blood cell content in the cushion. D 3D reconstruction of Fbln1 null shows an increase in mesenchymal cell content (blue) and the presence of blood cells (red) in the proximal cushions. C, proximal OFT cushions; L, lumen of OFT.


  1. Thomas, J.W., Cooley, M.A., Broome, J.M., Salgia, R., Griffin, J.D., Lombardo, C.R. and Schaller,M.D. The Role of Focal Adhesion Kinase Binding in the Regulation of Tyrosine Phosphorylation of Paxillin.  Journal of Biological Chemistry 1999. 274: 36684-36692. PMID: 10593973.
  2. Shen, Y., Lyons, P., Cooley, M., Davidson, D., Veillette, A., Salgia, R., Griffin, J. and Schaller, M.D. The Noncatalytic Domain of Protein-Tyrosine Phosphatase-PEST Targets Paxillin for Dephosphorylation in Vivo. Journal of Biological Chemistry 2000. 275:1405-1413. PMID:10625692.
  3. Cooley, M.A., Broome, J., Ohngemach, C., Romer, L.H. and Schaller, M.D. Paxillin Binding is not the Sole Determinant of Focal Adhesion Localization or Dominant-Negative Activity of Focal Adhesion Kinase/Focal Adhesion Kinase-Related Nonkinase. Molecular Biology of the Cell 2000. 11:3247-3263. PMID: 10982414.
  4. Cooley, M. and Mishra, N.C. Genetic Analysis of the In Vivo Role of DNA Polymerases in Saccharomyces Cerevisiae. Current Genetics 2000. 5: 256-263. PMID: 11191209.
  5. Argraves W. S., Greene, L. M., Cooley, M. A. and Gallagher, W. M.  Fibulins: Physiological and Disease Perspectives. EMBO Rep. 2003 Dec;4(12):1127-1131. PMID: 14647206. PMC1326425.
  6. Cooley, M.A., Kern, C.B., Fresco, V.M., Wessels, A., Thompson, R.P., McQuinn, T.C., Twal, W.O., Mjaatvedt, C.H., Drake, C.J., Argraves, W.S. Fibulin-1 is required for morphogenesis of neural crest-derived structures. Dev Biol. 2008 Jul 15;319(2):336-45.. PMID: 18538758. PMC2965525.
  7. McCulloch, D.R., Nelson, C.M., Dixon, L.J., Silver, D.L., Wylie, J.D., Lindner, V., Sasaki, T., Cooley, M.A., Argraves, W.S., Apte, S.S. ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev Cell. 2009 Nov;17(5):687-98. PMID: 19922873. PMC2780442.
  8. Cooley, M.A. and Argraves, W.S. The Fibulins. Biology of Extracellular Matrix. Series Editor: Robert P. Mecham. Springer-Verlag Berlin Heidelberg. 2011 Chapter 10, page 337-67.
  9. Cooley M.A., Fresco V.M., Dorlon M.E., Twal W.O., Lee N.V., Barth J.L., Kern C.B., Iruela-Arispe M.L., Argraves W.S. Fibulin-1 is required during cardiac ventricular morphogenesis for versican cleavage, suppression of ErbB2 and Erk1/2 activation, and to attenuate trabecular cardiomyocyte proliferation. Dev Dyn. 2012 Feb;241(2):303-14. PMID: 22183742. PMC3489172.
  10. Cooley M.A., Harikrishnan, K., Oppel, J.A., Miler, S.F., Barth,  J.L., Haycraft, C.J.,  Reddy, S.V. and Argraves, W.S. Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix. Bone 2014.  PMID 25201465.
  11. Harikrishnan, K., Cooley M.A., Sugi, Y., Rasmussen, L.M., Kern, C. B, Argraves, K.M. and Argraves, W.S., Fibulin-1 suppresses proximal outflow tract endothelial to mesenchymal transition and blood cell infiltration.  Mech of Devel 2015. PMID 25575930
Last updated on 28-Dec-2017

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