The Shelden Lab at Washington State University




click image
Eric A. Shelden, Ph.D.
Associate Professor
School of Molecular Biosciences
Washington State University
Pullman, WA 99164-4660

Email: eshelden@wsu.edu
Phone: 509-335-2368
Fax: 509-335-1907

Links, Documents, Movies, Teaching,
MbioSci 401&501 Review Questions, School of Molecular Biosciences
SMB Graduate Program

Our Research:

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, development and exposure to environmental toxins.

Publications:

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.

Lee E, Shelden EA, Knecht DA. Changes in actin filament organization during pseudopod formation. 1997; Exp Cell Res 235: 295-9.

Leventhal PA, Shelden EA, Feldman EL. Tyrosine phosphorylation of paxillin and focal adhesion kinase during insulin-like growth factor-I-stimulated lamellipodial extension. 1997; J Biol Chem 272: 5214-18.

Shelden E, Knecht DA. Dictyostelium cell shape change requires myosin II. 1996; Cell Motil Cytoskeleton 35: 59-67.

Shelden E, Wadsworth P. Stimulation of microtubule dynamic turnover in living cells treated with okadaic acid. 1996; Cell Motil Cytoskeleton 35: 24-34.

Knecht DA, Shelden E. Three-dimensional localization of wild-type and myosin II mutant cells during morphogenesis of Dictyostelium. 1995; Dev Biol 170: 434-44.

Shelden E, Knecht DA. Mutants lacking myosin II cannot resist forces generated during multicellular morphogenesis. 1995; J Cell Sci 108: 1105-15.

Shelden E, Wadsworth P. Observation and quantification of individual microtubule behavior in vivo: Microtubule dynamics are cell type specific. 1993; J Cell Biol 120: 935-945.

Shelden E, Wadsworth P. Injection of biotin-tubulin into anaphase cells induces transient elongation of kinetochore microtubules and reversal of chromosome-to-pole motion. 1992; J Cell Biol 116: 1409-20.

Shelden E, Wadsworth P. Interzonal microtubules are dynamic during spindle elongation. J Cell Sci 1990; 97: 273-81.

Wadsworth P, Shelden E, Rupp J, Rieder CL. Biotin-tubulin incorporates into kinetochore fiber microtubules during early but not late anaphase. J Cell Biol 1989; 109: 2257-66.