Sharon L. Ashworth
Assistant Research Professor of Biological Sciences
Degree: Ph.D. 1998 Purdue University
Phone: (207) 581-2820
Location: 151A Hitchner Hall
Cellular, biochemical, and molecular analysis of the actin cytoskeleton in response to renal ischemia.
My research focuses on the response of the actin cytoskeleton to ischemia induced acute renal failure (ARF). 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, 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 characterized by reduced blood flow to the kidney that results in cell injury and inflammation that leads to decreased urine production and increased toxic end products in the circulating blood. Reorganization of the actin cytoskeleton in kidney proximal tubule cells is one of the earliest observable signs of ischemia induced kidney cell injury. The bundled actin filaments present in the apical microvilli of these cells are severed and depolymerized and actin dependent cellular polarization is lost as well as 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. To understand better the actin cytoskeletal changes observed in response to ARF, my laboratory is investigating the interaction of actin with two competing actin binding proteins, cofilin (an actin severing and depolymerizing protein) and tropomyosin (an actin stabilizing protein). We are using immunofluorescence and confocal microscopy to visualize these changes in cell culture, rat, and mouse kidneys and in the zebrafish pronephros. To analyze regulation of these two proteins, cofilin and tropomyosin, we are using molecular and biochemical techniques under physiologic and ischemic conditions. A better understanding of how ischemic insults affect the actin cytoskeleton in kidney cells will lead to new treatment methods and improved survival rates for patients suffering from acute renal failure.
Marquis H, Bell EP, Miller EE, Gilman MS, Bond SK, Grimaldi R, Ashworth SL. 2009. Analysis of the Danio rerio cofilin mutant. MDIBL Bulletin: 48, 52-53.
Campos SB, Ashworth SL, Hosford M, Sandoval RM, Hallett MA, Atkinson SJ, Molitoris BA. 2009. Cytokine induced F-actin reorganization in endothelial cells involves RhoA activation. American Journal of Physiology- Renal Physiology: 296, F487-F495.
Ashworth SL, Sandoval RM, Tanner GA, Molitoris BA. 2007. Two-photon Microscopy: Visualization of Kidney Dynamics. Kidney International: 72, 416-421.
Ashworth SL and Tanner GL. 2006. Fluorescent labeling of renal cells in vivo. Nephron: 103, 91-96.Suurna MV, Ashworth SL, Hosford M, Sandoval RM, Wean SE, Shah BM, Bamburg JR, Molitoris BA. 2006. Cofilin mediates ATP Depletion-induced endothelial cell actin alternations. American Journal of Physiology- Renal Physiology: 290, F1398-1407.Tanner GA., Sandoval RM, Molitoris BA, Bamburg JR, Ashworth SL. 2005. Micropuncture gene delivery and intravital two-photon visualization of protein expression in rat kidney. American Journal of Physiology- Renal Physiology: 289(3), F638-643.
Ashworth SL, Wean SE, Campos SB, Temm-Grove CJ, Southgate EL, Vrhovski B, Gunning P, Weinberger RP and Molitoris BA. 2004. Renal ischemia induces tropomyosin dissociation-destabilizing microvilli microfilaments. American Journal of Physiology- Renal Physiology: 286, F988-F996.
Ashworth SL, Southgate EL, Sandoval RM, Meberg PJ, Bamburg JR, Molitoris BA. 2003. ADF/Cofilin mediates actin cytoskeleton alterations in LLC-PK cells during ATP depletion. American Journal of Physiology- Renal Physiology: 284, F852-F862.