Research interests

Dynamic interactions of actin and actin associated proteins • acute kidney failure • confocal and 2-photon microscopy imaging • 3D image reconstruction • fluorescent probes • rat, mouse and zebrafish model systems • cell culture

 Acute renal failure (ARF) occurs at a high frequency in the American adult population with the nation wide cost for patient care estimated at over twelve billion dollars a year.  Although the occurrence of ARF is high and leads to significant mortality rates in intensive care units, very little progress has been made in the last thirty years to overcome these statistics.  In addition, very expensive medical procedures such as long term dialysis or renal transplantation often follow an occurrence of ARF.  Ischemic ARF is not a simple disease.  It is characterized by altered blood flow to the kidney that results in cell injury and inflammation which leads to decreased urine production and increased toxic end products in the circulating blood.  Although no one causal explanation has been described to account for these changes, alterations to the actin cytoskeleton has been demonstrated within multiple cell types in the kidney in response to ischemic acute renal failure.  Several structural changes in kidney epithelial cells during ischemia and subsequent recovery support a role for the actin cytoskeleton in this disease process.  These changes include: 1) breakdown of the apical microvilli; 2) loss of cell to cell junctions; 3) loss of polarization of the cells; and 4) loss of cell to cell and cell to substrate adhesion.  The extent of damage to these cellular structures depends on the severity and length of the ischemic event.  These changes also lead to functional changes in the cell and can be directly related to disruption of the normal architecture of the actin cytoskeleton, both spatially and temporally. To better understand actin cytoskeletal changes in response to kidney failure, my studies will analyze the dynamic interaction of actin and the actin associated proteins, actin depolymerizing factor (ADF)/cofilin (actin destabilizing proteins) and tropomyosin (an actin stabilizing protein), under physiological and ischemic conditions biochemically, in cell culture, in rat and mouse kidneys and also in the zebrafish nephros

Publications

• Ashworth, S. L., R. M. Sandoval, G. A. Tanner and B. A. Molitoris. 2007. Two-photon Microscopy: Visualization of Kidney Dynamics. 72, 416-421.
• Suurna, M. V., S. L. Ashworth, M. Hosford, R. M. Sandoval, S. E. Wean, B. M. Shah, J. R. Bamburg, B. A. Molitoris. 2006. Cofilin mediates ATP depletion-induced endothelial cell actin alterations. Am. J. Physiol. Renal Physiol., 290, F1398-1407.
• Ashworth, S. L. and G.A. Tanner. 2006. Fluorescent labeling of renal cells in vivo. Nephron 103, 91-96.
• Tanner, G. A., R. M. Sandoval, B. A. Molitoris, J. R. Bamburg, S. L. Ashworth. 2005. Micropuncture gene delivery and intravital two-photon visualization of protein expression in rat kidney. Am. J. Physiol. Renal Physiol. 289(3), F638-643.
• Ashworth, S. L., S. E. Wean, S. B. Campos, C. J. Temm-Grove, E. L. Southgate, B. Vrhovski, P. Gunning, R. P. Weinberger and B. A. Molitoris. 2004. Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments. Am. J. Physiol. Renal Physiol., 286, F988-F996.
• Ashworth, S. L., E. L. Southgate, R. M. Sandoval, P. J. Meberg, J. R. Bamburg and B. A. Molitoris. 2003. ADF/Cofilin mediates actin cytoskeletal alterations in LLC-PK cells during ATP depletion. Am. J. Physiol Renal Physiol. 284, F852-F862.
• Yang, Y., Pares-Matos, E. I., Tesmer, V. M., Dai, C., Ashworth, S., Huai, J. and M. Bina. 2002. Organization of the promoter region of the human NF-IL6 gene. Biochimica et Biophysica Acta. 1577:102-108.
• Ashworth, S. L., R. M. Sandoval, M. Hosford, J. R. Bamburg and B.A. Molitoris. 2001. Ischemic injury induces ADF relocalization to the apical domain of rat proximal tubule cells. Am. J Physiol Renal Physiol. 280, F886-F894.
• Molitoris, B. M., S. L. Ashworth, T. A. Sutton. 2001. Ischemia-induced derangements in the actin cytoskeleton: mechanisms and functional significance. In: Update in Intensive Care and Emergency Medicine: Mechanism of Organ Dysfunction in Critical Illness. Springer-Verlag, Berlin 38:227-238.
• Ashworth, S. L., and B. A. Molitoris. 1999. Pathophysiology and functional significance of apical membrane disruption during ischemia. Curr. Opin. Neph. Hyper. Vol. 8, 449-458.
• Ren, H., B. Gibbon, S. Ashworth, D. Sherman, M. Yuan, and C.J. Staiger. 1997. Actin purified from maize pollen functions in living plant cells. Plant Cell. Vol. 9, 1445-1457.