Faculty
| J. Stacey Klutts, M.D., Ph.D. Assistant Professor and Staff Clinical Pathologist Veterans Administration Medical Center Pathology - 113 VAMC (Room BW17) Highway 6 West, Iowa City, IA 52246 B.S., Missouri State University, 1995 Ph.D., University of Arkansas for Medical Sciences, 2002 M.D. University of Arkansas for Medical Sciences, 2002 Laboratory Medicine Residency, Washington University School of Medicine/Barnes-Jewish Hospital, 2002-2007 Postdoctoral Fellow, Washington University , 2003-2006 Chief Resident, Laboratory Medicine, Washington University/Barnes-Jewish Hospital, 2006-2007 |
Research Program Description:
My laboratory primarily focuses on the human pathogenic fungus Aspergillus fumigatus. This is a ubiquitous environmental mold that can cause a variety of diseases in humans, including a life-threatening invasive infection in the setting of immune compromise. Treatment options exist for invasive aspergillosis, but therapeutic failures are common with mortality rates as high as 85% in some patient populations. This high mortality rate is partially due to a paucity of effective anti-fungal drugs to treat advanced infections. My laboratory is interested in identifying new anti-fungal drug targets.
Currently, the main focus of the laboratory is to better understand the process of cell wall synthesis in A. fumigatus. Pathogenicity and survival of A. fumigatus in vivo requires a number of virulence factors, with the ability to generate a rigid cell wall being one of the most important. Targeting cell wall synthesis with anti-fungal therapy has been successful in the treatment of a number of fungal infections. However, identification of additional drug targets in the pathway of cell wall assembly is hindered by our limited knowledge of these synthetic mechanisms. My laboratory is taking three parallel and complementary approaches to identify enzymes/proteins involved in cell wall synthesis. One aim is to develop enzymatic assays for monitoring the activity of glycosyltransferase enzymes likely involved in cell wall synthesis and to use these assays to purify/identify the corresponding proteins. Second, we are deleting enzymes that we hypothesize are involved in cell wall synthesis and studying the resulting deletion strains in detail. Lastly, we are taking a forward genetic approach with the development of an insertional mutagenesis library in A. fumigatus that is being screened for strains containing cell wall defects.
Combined, these approaches are aimed at deciphering pathways involved in Aspergillus cell wall synthesis and identification of plausible anti-fungal drug targets within those pathways.
Selected Publications:
Klutts, J.S. and Robinson-Dunn, B. "A Critical Appraisal of the Role of the Clinical Microbiology Laboratory in Diagnosis of Invasive Fungal Infections" J. Clin Micro. 2011 49: S39-S42.
Reilly MC, Levery SB, Castle SA, Klutts JS, Doering TL. "A Novel Xylosylphosphotransferase Activity Discovered in Cryptococcus neoformans". J. Biol. Chem. 2009. 284: 36118-27.
Klutts, J.S. and Doering, T.L. "Cryptococcal Xylosyltransferase 1 (Cxt1p) from Cryptococcus neoformans Plays a Direct Role in the Synthesis of Capsule Polysaccharides". J.Biol. Chem. 2008. 283: 14327-34.
Klutts JS, Levery SB, Doering TL. A beta-1,2-xylosyltransferase from Cryptococcus neoformans defines a new family of glycosyltransferases. J Biol Chem. 2007 Jun 15;282(24):17890-9.
Klutts JS, Yoneda A, Reilly MC, Bose I, Doering TL. Glycosyltransferases and their products: cryptococcal variations on fungal themes. FEMS Yeast Res. 2006 Jun;6(4):499-512. (Review)
Klutts JS, Liao RS, Dunne WM Jr, Gronowski AM. Evaluation of a multiplexed bead assay for assessment of Epstein-Barr virus immunologic status. J Clin Microbiol. 2004 Nov;42(11):4996-5000.
Griffith CL, Klutts JS, Zhang L, Levery SB, Doering TL. UDP-glucose dehydrogenase plays multiple roles in the biology of the pathogenic fungus Cryptococcus neoformans. J Biol Chem. 2004 Dec 3;279(49):51669-76.
Klutts S, Pastuszak I, Edavana VK, Thampi P, Pan YT, Abraham EC, Carroll JD, Elbein AD. Purification, cloning, expression, and properties of mycobacterial trehalose-phosphate phosphatase. J Biol Chem. 2003 Jan 24;278(4):2093-100.