Josephine C. Adams, Ph.D.

Staff

Department of Cell Biology, Lerner Research Institute
The Cleveland Clinic Foundation
9500 Euclid Avenue NC-10
Cleveland, Ohio 44195
Telephone: (216) 444-3050
Fax: (216) 444-9404
adamsj@ccf.org

The Adams Laboratory:

  • Dae Joong Kim, Ph.D., Fellow
  • David Loftis, Technician
  • Tony Vehovec, Student

CCF Collaborators:

  • Martha Cathcart, PhD, Dept of Cell Biology
  • Marc Penn, MD, PhD, Dept of Cell Biology
  • Edward Plow, PhD, Dept of Molecular Cardiology
  • Mary Bronner, M.D., Dept of Anatomic Pathology
  • David Hicks, M.D., Dept of Anatomic Pathology
  • Marek Skacel, M.D., Dept of Anatomic Pathology
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Research Description

The research interest of our laboratory is in the responses of cells to extracellular matrix (ECM). ECM is fundamental to cell interactions in tissue organization and, by forming adhesive contacts with cells, regulates cell function through effects on the cytoskeleton, cell signaling processes and gene expression. Changes in the expression or function of adhesion molecules have causal roles in numerous genetic and acquired human diseases, with particular relevance to cancer and cardiovascular disease.

We have focused on the ECM component thrombospondin-1 (TSP-1), which is highly associated with tissue remodeling and repair. Cell adhesion to TSP1 induces cells to form cell protrusions supported by the actin-bundling protein fascin. Fascin is emerging as a target of many extracellular cues. We have established intracellular molecular mechanisms that regulate the assembly of fascin protrusions and are studying the role of fascin in migration and metastasis of colon- and breast-cancer cells, where fascin expression correlates with poor prognosis. Based on new structural knowledge of TSP proteins, we are working with recombinant domain proteins to understand the mechanisms by which TSPs are retained in ECM. We are also defining the role of a novel intracellular protein, muskelin, which affects cell spreading. Muskelin is a member of the kelch-repeat superfamily of proteins, many of which act as components of large protein complexes. Understanding these cellular processes should identify new candidate targets for translational applications.

Key References

Hashimoto Y, Parsons M, Adams JC.  Dual actin-bundling and protein kinase c-binding activities of fascin regulate carcinoma cell migration downstream of Rac and contribute to metastasis. Mol Biol Cell  2007; 18, 4591-4602.

Hashimoto Y, et al. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas. BMC Cancer  2006;6:241.

McKenzie P, et al. Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific paralogues, ancestral gene relationships and a tetrapod innovation. BMC Evol Biol  2006;6:33.

Kvansakul M, Adams JC, Hohenester E. Structure of a thrombospondin C-terminal fragment reveals a novel calcium core in the type 3 repeats. EMBO J.  2004;23:1223-33.

Anilkumar N, et al. Interaction of fascin and protein kinase Calpha: a novel intersection in cell adhesion and motility. EMBO J  2003;22:5390-402.