Walter Klimecki, DVM, PhD
Associate Department Head
Pharmacology & Toxicology
Dr. Klimecki received his Doctorate in Veterinary Medicine from Ohio State University in 1984, and his PhD in Pharmacology and Toxicology from the University of Arizona in 1994. Following his postdoctoral work, he was one of the founding members of a biotech company started within Motorola in Tempe, Ariz. He returned to the University of Arizona in 2000, where he has been a human genetics and toxicology researcher. He currently holds appointments in the College of Pharmacy, the College of Medicine and the College of Public Health, and he is a member of the Arizona Respiratory Center and the BIO5 Institute.
The focus of Dr. Klimecki's research program is the complicated balance between the particular DNA sequence “versions” of genes that we inherit from our ancestors, and the particular environmental exposures that we experience throughout our lives. Viewed broadly, those environmental exposures include many chemicals, some (like prescription drugs) with intentional exposures and some (like environmental toxicants) with unintended exposures. Toxicity resulting from these exposures is often a combination of the particular versions of genes that we inherit that produce our own unique biological systems, together with the underlying mechanisms by which chemicals can damage biological systems. The Klimecki research group studies this complex problem from both vantage points, which Dr. Klimecki summarizes below:
“Because of our interest in diseases resulting from human exposure to arsenic, a toxic exposure important in Arizona, our research has contributed to a better understanding of the inherited genetic differences between people that result in altered chemical processing of arsenic after it enters the body. In all likelihood, much of the arsenic-induced damage happens from chemical forms of arsenic that our bodies create, not the original chemical form that we find in drinking water. Understanding how human genetics determines our particular ways of creating modified chemical forms of arsenic is important to understand how arsenic causes disease, and who is most likely to be particularly sensitive to arsenic.
"At the same time, we are also studying the biological systems that are damaged by arsenic, leading to disease. In particular our recent work has established a novel pathway called autophagy as a target for arsenic-induced damage. Autophagy is a 'cash for clunkers' program in the cell. Components of the cell that are old and targeted for disposal are delivered to an organelle called the lysosome, where they are broken down to their component parts, and those parts are then recycled to build newer cellular structures that the cell needs. Disruption of this process has been linked to a diverse array of diseases, including cancer, diabetes, and cardiovascular disease. The ability of arsenic to disrupt autophagy offers new explanations of how arsenic makes people sick.”
Doctorate in Veterinary Medicine, Ohio State University, 1984
PhD in Pharmacology and Toxicology, University of Arizona, 1994
Bolt AM, Zhao F, Pacheco S, Klimecki WT. Arsenite-induced autophagy is associated with proteotoxicity in human lymphoblastoid cells. Toxicol. Appl. Pharmacol. 2012 Oct 15;264(2):255-61.
Bolt AM, Klimecki WT. Autophagy in toxicology: self-consumption in times of stress and plenty. J Appl. Toxicol. 2012 Jul;32(7):465-79.
Gomez-Rubio P, Klimentidis YC, Cantu-Soto E, Meza-Montenegro MM, Billheimer D, Lu Z, Chen Z, Klimecki WT. Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico. J. Toxicol Environ Health A. 2012;75(1):36-49. PMID: 22047162.
Gomez-Rubio P, Roberge J, Arendell L, Harris RB, O'Rourke MK, Chen Z, Cantu-Soto E, Meza-Montenegro MM, Billheimer D, Lu Z, Klimecki WT. Association between body mass index and arsenic methylation efficiency in adult women from southwest U.S. and northwest Mexico. Toxicol. Appl. Pharmacol. 2011 Apr15;252(2):176-82. PMID: 21320519; PMCID: PMC3075343.
Bolt A, Douglas RM, Klimecki WT. Arsenite exposure in human lymphoblastoid cell lines induces autophagy and coordinated induction of lysosomal genes. Toxicol. Letters 199(2): 153-159, 2010.
Bolt A, Byrd R, Klimecki WT. Autophagy is the predominant process induced by arsenite in human lymphoblastoid cell lines. Toxicol. Appl. Pharmacol. 244(3): 366-373, 2010.
Gomez-Rubio P, Meza-Montenegro MM, Cantu-Soto E, Klimecki WT. Genetic association between intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage disequilibrium cluster in chromosome 10. J Appl Toxicol. 30(3): 260-270, 2010. PMCID: PMC2862143
Meza MM, Yu L, Rodriguez YY, Guild M, Thompson D, Gandolfi AJ, Klimecki WT. Developmentally restricted genetic determinants of arsenic metabolism: Association between urinary methylated arsenic and CYT19 polymorphisms in children. Environmental Health Perspectives 113(6): 775-781, 2005