Shelden, Eric A.
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MBioS 401/501

Research Interests

Cytoskeletal regulation in cell division, motility and differentiation.

Cell morphology, motility and polarity are intimately dependent on the normal function of the microtubule and actin microfilament cytoskeletal systems. These systems comprise a dynamic equilibrium in which assembly of monomeric subunits into filaments, and their subsequent disassembly, is regulated in a spatially complex, energy dependent manner. Reorganization of the cytoskeleton, through the action of proteins effecting the assembly, disassembly, cross linking and sequestration of cytoskeletal proteins, is widely recognized as critical to normal cell division, development and differentiation, and has been correlated with changes in cell behavior accompanying abnormal development or disease progression, such as oncogenesis and metastasis.

Cytoskeletal and heat shock protein (hsp) regulation during cellular injury.

It is becoming increasingly appreciated that the cytoskeleton is a specific target of agents inducing cellular injury, such as thermal and oxidative stress, anoxia or ischemia, and a variety of environmental and pharmacologic toxins. In general, cells respond to a sublethal injury by altering their protein expression patterns. So-called housekeeping and cell-type specific protein expression is reduced, while expression of heat shock or stress response proteins is enhanced, often in an injury and cell-type specific manner. One class of these proteins, small heat shock proteins less than 40 kDa in molecular weight, is thought to regulate the stability of the cytoskeleton through mechanisms which are still poorly understood. My laboratory is currently funded by grants from the NIH National Institute of Environmental Health Science and National Institute on Aging to study the putative roles of the small heat shock protein hsp27 in the regulation of actin cytoskeletal stability during cellular injury. I am particularly interested in understanding how hsp27 might stabilize actin filaments in cells during ATP depletion and during exposure to environmental toxins.

Publications (1998-Current)

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

Mao, L. and Shelden, E.A. Developmentally regulated gene expression of the small heat shock protein Hsp27 in zebrafish embryos. 2006. Gene Expr Patterns 6(2):127-133.

Mao, L., Bryantsev, A.L., Chechenova, M.B. and Shelden, E.A. Cloning,
characterization and heat stress-induced redistribution of a protein homologous to human hsp27 in the zebrafish Danio rerio. 2005. Exp Cell Res 306 (1):230-241.

Yancy, S. L., Shelden, E. A., Gilmont, R. R. , and Welsh, M. J. Sub-lethal sodium arsenite exposure inhibits cell adhesion and migration, alters focal adhesion location and number, and decreases phosphorylation of T397 of focal adhesion kinase (FAK) in H9C2 myoblasts. 2004. Toxicological Sciences 84(2): 278-286.

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

Hirano, S, Shelden, E, Gilmont, R.R. Hsp27 regulates fibroblast adhesion motility and matrix contraction. 2004; Cell Stress & Chaperone. 9:29-37.

Sun X, Fontaine JM, Rest JS, Shelden EA, Welsh MJ, Benndorf R. Interaction of human HSP22 (HSPB8) with other small heat shock proteins. 2004; J Biol Chem. 279(4):2394-402.

Bonham RT, Fine MR, Pollock FM, Shelden EA. Hsp27, hsp70 and
metallothionein in renal epithelial cells: effects of prolonged, sublethal exposure to cadmium. 2003; Toxicol Appl Pharmacol. 191:63-73.

Kaplan MJ, Lewis EE, Shelden EA, Somers E, Pavlic R, McCune WJ, Richardson BC. The apoptotic ligands TRAIL, TWEAK and FASL mediate monocyte death induced by autologous lupus T cells. 2002; J Immunol. 169:6020-6029

Shelden EA, Weinberg JM, Sorenson DR, Edwards CA, Pollock FM. Site specific alteration of actin assembly visualized in living renal epithelial cells during ATP depletion. 2002; J Am Soc Nephrol. 13: 2667-2680.

Shelden EA, Borrelli MJ, Pollock FM, Bonham, R. Heat shock protein 27 associates with basolateral cell boundaries in heat shocked and ATP depleted epithelial cells. 2002; J Am Soc Nephrol 13: 332-41.

Richards N, Schaner P, Shelden E, Diaz A, Stuckey J, Wadhwa A, Gumucio DL. Interaction between pyrin and apoptosis speck protein modulates ASC-induced apoptosis. 2001; J Biol Chem 276: 39320-29.

Meyer GE, Shelden E, Kim B, Feldman EL. IGF-I promotes neuroblastoma cell motility. 2001; Oncogene 20: 7542-50.

Morita Y, Yang J, Gupta R, Shimizu K, Shelden EA, Endres J, Mule JJ, McDonagh KT, Fox DA. Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis. 2001; J Clin Invest 107: 1257-1284.

Johns LM, Levitan ES, Shelden EA, Holz RW, Axelrod D. Restriction of secretory granule motion near the plasma membrane of chromaffin cells. 2001; J Cell Biol 153: 177-90.

Shelden EA, Feldman EL. Automated difference image analysis of lamellar ruffling: effect of temperature change on human SH-SY5Y neuroblastoma cells. 2000; J Neurosci Methods 102: 145-54.

Yamamura Y, Shelden E, Fox DA. Interactions of T cells and synovial fibroblasts. 2000; Mod Rheumatol 10: 16-18.

Shu L, Shelden E, Lee S, Chang Y, Holzman L, Shayman J. Independence of glycosphingolipid formation and caveolar protein sorting. 1999; Arch Biochem Biophys 373: 83-90.

Zhu W, TomHon C, Mason M, Campbell T, Shelden E, Richards N, Goodman M, Gumucio DL. Analysis of linked human e and g transgenes: Effect of locus control region hypersensitive sites 2 and 3 or a distal YY1 mutation on stage-specific expression patterns. 1999; Blood 93: 3540-49.

Shelden E. Major role for active extension in process formation by ras-transformed fibroblasts. Cell Motil Cytoskeleton 1999; 42: 12-26.

Shelden E, Knecht DA. Reconstruction and display of curvilinear objects from optical section data using 3D curve fitting algorithms. 1998; J Microsc 191: 97-107.

Lee E, Shelden EA, Knecht DA. Formation of F-actin aggregates in cells treated with actin stabilizing drugs. 1998; Cell Motil Cytoskeleton 39: 122-33.

Otteson DC, Shelden E, Jones J, Kameoka J, Hitchcock PF. Pax2 expression and retinal morphogenesis in the normal and Krd mouse. 1998; Dev Biol 193: 209-224.