Cellular and Structural Biology | Faculty
Department of Cellular & Structural Biology

CSB Faculty

 

Dr. Pierce Anson Pierce, Ph.D.
Assistant Professor/Research

 

University of North Texas Health Science Center at Fort Worth, 2004

 

210-562-6016
piercea2@uthscsa.edu

 

I received my Ph.D. in Biochemistry in 2004 based on the characterization of a novel allele for the antioxidant enzyme extracellular superoxide dismutase (SOD3) in atherosclerotic mice. Based on my graduate studies, I became interested in the role of oxidative stress in disease and aging, and joined Arlan Richardson's lab as a postdoc in 2004. Since then, I have been utilizing proteomics as a technique to address this research question in aging and the neurodegenerative disease ALS. Through this work, I developed a novel proteomics-compatible assay to monitor changes in protein conformation considering the role that protein oxidation has in protein unfolding and aggregation. In 2008, I was appointed to the Department of Veterans Affairs as a Research Health Scientist to study the role of heat shock factor 1 in delaying ALS symptoms and mortality.

 

Proteins play an essential role in carrying out almost every function within a cell or tissue, and are able to carry out these functions based on their unique three dimensional structures. During disease conditions, protein structures can be altered in several ways especially by protein oxidation, which can cause them to lose their function or impart them with toxic properties. In order to keep proteins folded in their proper structures and from forming irreversible aggregates, the cell produces heat shock proteins (HSPs) which can recognize misfolded proteins and properly fold them or direct them to proteolytic pathways. The major transcription factors responsible for expression of HSPs are heat shock factor 1 (HSF1) and HSF2. When levels of unfolded proteins rise in the cell caused by heat or oxidative stress, HSFs become activated and lead to production of more HSPs. Protein unfolding and aggregation are common features of Lou Gehrig's Disease or amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. ALS is characterized by a progressive loss of motorneurons and muscle atrophy, which eventually leads to paralysis and death. There is no known cure for this disease, and its cause is unknown. However, a small subset of patients (2%) are known to inherit the disease due to a number of possible mutations in the SOD1 gene. Using mice that overexpress HSFs, I am interested in understanding more about the role of protein unfolding in ALS and other age-related protein unfolding diseases, and learning more about the role of HSF1 and HSPs in protecting protein structure.

 

Dr. Pierce Research Image Two-dimensional gel separation of charge variants of mutant SOD1 protein (white arrows) in ALS mouse spinal chord.

 

Proteins were labelled for hydrophobicity (yellow fluorescence), separated, and subsequently stained for total protein (red fluorescence).
The dual-channel image demonstrates that various charged isoforms of mutant SOD1display heterogeneity in their exposure of hydrophobic domains which overall is considerably higher than non-mutant forms of SOD1.

 

Research Techniques:

  • 2D Gel Electrophoresis

  • HPLC/FPLC

  • Immunoblotting

  • MALDI-TOF Mass Spectrometry

  • Mammalian cell culture

  • Transgenic animal development and Microsurgical Techniques and manipulations in mice

  • PCR/qPCR

  • Protein Derivatization

  • Spectrophotometric/Fluorometric Assays

  • Tissue Cryotomy

 

PUBLICATIONS:
Pierce A, Mirzaei H, Muller F, De Waal E, Taylor AB, Leonard S, Van Remmen H, Regnier F, Richardson A, Chaudhuri A. (2008) GAPDH is conformationally and functionally altered in association with oxidative stress in mouse models of amyotrophic lateral sclerosis. J Mol Biol. 2008 Oct 24;382(5):1195-210. Epub 2008 Aug 6.

 

Pierce AP, de Waal E, McManus LM, Shireman PK, Chaudhuri AR. (2007) Oxidation and structural perturbation of redox-sensitive enzymes in injured skeletal muscle. Free Radic Biol Med. 2007 Dec 15;43(12):1584-93. Epub 2007 Sep 4.

 

Chaudhuri AR, de Waal EM, Pierce A, Van Remmen H, Ward WF, Richardson A. (2006) Detection of protein carbonyls in aging liver tissue: A fluorescence-based proteomic approach. Mech Ageing Dev. 2006 Nov;127(11):849-61. Epub 2006 Sep 26.

 

Pierce A, deWaal E, Van Remmen H, Richardson A, Chaudhuri A. (2006) A novel approach for screening the proteome for changes in protein conformation. Biochemistry. 2006 Mar 7;45(9):3077-85.

 

Pierce A, Whitlark J, Dory L. (2003) Extracellular superoxide dismutase polymorphism in mice. Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1820-5. Epub 2003 Jul 31.