Participating Faculty

Eric Shelden

Eric Shelden

Department:School of Molecular Biosciences, WSU
Credentials:1992~Ph.D., University of Massachusetts, Zoology
Office:Biotechnology Life Sciences 341
Phone:509-335-2368
Fax:509-335-4159
Mailing Address:School of Molecular Biosciences
PO Box 647520
Pullman, WA 99164-7520
E-mail:eshelden@wsu.edu


Research Interests

Protein biochemistry and biology of Hsp27.

Research Summary

Hsp27 is an abundant and widely distributed member of the small heat shock family of proteins and is of potential importance to normal and pathological development of reproductive tissue. Altered expression of Hsp27 has been demonstrated in ovarian, breast, and endometrial cancers and is correlated with increased tumor malignancy, altered estrogen receptor activities and enhanced resistance to chemotherapy. Normal, regulated expression of Hsp27 may be required for proper developments of male and female reproductive organs as well as spermatogenesis, and antisense inhibition of Hsp27 expression has been reported to induce redifferentiation of MCF-7 mammary carcinoma cells. The mechanism of Hsp27 function is still unclear, but proposed mechanisms include chaperone-like refolding of other denatured proteins, stabilization of contractile and structural protein complexes, altered apoptotic signaling, and reduction in cellular levels of reactive oxygen species. These activities are regulated by phosphorylation of up to three serines and s-thiolation of a single cysteine, but effects of these modifications on Hsp27 are not fully understood.

My laboratory is investigating the regulation and function of Hsp27 in developing zebrafish embryos using molecular and biochemical methods, as well as fluorescence microscopy. We recently reported that Hsp27 can associate with basolateral cell junctions in epithelial cell monolayers and co-localize with actin, at the level of the light microscope, in at epithelial cell-cell junctions and developing myofibrils. We are expressing Hsp27 mutants in zebrafish embryos and testing these mutants for their ability to interact with cytoskeletal complexes, promote survival and protect cell function from disruptions in embryos exposed to heat shock, reactive oxygen species, annoxia and a variety of environmental toxins. These studies employ fractionation followed by immunoblotting, as well as assays of apoptosis and cell survival using LDH release and fluorimetric quantification of nucleic acid content. In addition, we conduct fluorescence localization studies using immunofluorescence and analysis of expressed fluorescent fusion proteins in transiently and stably transformed fish lines. We also test interaction of Hsp27 with fluorescent fusion proteins of cytoskeletal proteins using Forster resonance energy transfer (FRET) methods.

Research Publications

2005-2009

Tucker, N.R. and E.A. Shelden, Hsp27 associates with the titin filament system in heat-shocked zebrafish cardiomyocytes. Exp Cell Res, 2009.

Tucker, N.R., A. Ustyugov, A.L. Bryantsev, M.E. Konkel, and E.A. Shelden, Hsp27 is persistently expressed in zebrafish skeletal and cardiac muscle tissues but dispensable for their morphogenesis. Cell Stress Chaperones, 2009. 14(5): p. 521-33.

Bryantsev, A.L., M.B. Chechenova, and E.A. Shelden, Recruitment of phosphorylated small heat shock protein Hsp27 to nuclear speckles without stress. Exp Cell Res, 2007. 313(1): p. 195-209.

Mao, L. and E.A. Shelden, Developmentally regulated gene expression of the small heat shock protein Hsp27 in zebrafish embryos. Gene Expr Patterns, 2006. 6(2): p. 127-33.

Mao, L., A.L. Bryantsev, M.B. Chechenova, and E.A. Shelden, Cloning, characterization, and heat stress-induced redistribution of a protein homologous to human hsp27 in the zebrafish Danio rerio. Exp Cell Res, 2005. 306(1): p. 230-41.

Hirano S, Sun X, DeGuzman CA, Ransom RF, McLeish KR, Smoyer WE, Shelden EA, Welsh MJ, Benndorf R. 2005 p38 MAPK/HSP25 signaling mediates cadmium-induced contraction of mesangial cells and renal glomeruli. Am J Physiol Renal Physiol. 288(6):F1133-43.

Washington State University