Walter Klimecki

Walter Klimecki

Associate Professor, Veterinary Medicine
Assistant Professor, Medicine - (Research Scholar Track)
Associate Professor, Pharmacology and Toxicology
Associate Professor, Public Health
Associate Professor, Genetics - GIDP
Adjunct Associate Professor, Nursing
Associate Professor, BIO5 Institute
Contact
(520) 626-7470

Work Summary

Walter Klimecki's research program involves the 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. The Klimecki lab studies diseases resulting from human exposure to arsenic, contributing to a better understanding of the inherited genetic differences between people that result in altered chemical processing of arsenic after it enters the body.

Research Interest

Walter T. Klimecki, DVM, PhD, is an Associate Professor in the Department of Pharmacology and Toxicology in the College of Pharmacy at the University of Arizona. Dr. Klimecki holds joint appointments in the College of Medicine, the College of Public Health, and the Arizona Respiratory Center. He is a Full Member of the Southwest Environmental Health Sciences Center (SWEHSC) where, together with BIO5 director Martinez and BIO5 Statistics Consulting Service director Billheimer, he leads the Integrative Health Sciences (IHS) Center at SWEHSC. The IHS is a translational research support core at SWEHSC, focused on lowering the “activation energy” for translational research.Dr. Klimecki’s research focuses on the toxicology of metals in the environment, an issue particularly relevant in our mining-intensive state. His research work has encompassed a wide range of experimental approaches, from epidemiological studies of arsenic-exposed human populations, to laboratory models including cell culture and rodents. Using cutting edge genetics tools, Dr. Klimecki’s group recently published the first report of an association between human ancestry and response to environmental toxicants. In this provocative work, his group found that individuals whose genomes were comprised of DNA with its origins in the indigenous American populations processed ingested arsenic in a less harmful manner than did individuals whose genomes had their origins in Europe. Using laboratory models his group made ground-breaking discoveries of the impact of arsenic exposure on a process known as autophagy, in which cells digest parts of their own machinery in a sort of “cash for clunkers” arrangement. The ability of arsenic to perturb this process is only now being appreciated by the toxicology community, thanks to the work of the Klimecki Lab. Dr. Klimecki was recently elected as a Vice President-elect to the Metals Specialty Section of the Society of Toxicology, the preeminent scientific toxicology organization in the world. Dr. Klimecki’s research is highly collaborative: his grants and publications have included many BIO5 members, including BIO5 director Fernando Martinez, and BIO5 members Donata Vercelli, Dean Billheimer, and Marilyn Halonen.

Publications

Zhao, F., Severson, P., Pacheco, S., Futscher, B. W., & Klimecki, W. T. (2013). Arsenic exposure induces the warburg effect in cultured human cells. Toxicology and Applied Pharmacology, 271(1), 72-77.
BIO5 Collaborators
Bernard W Futscher, Walter Klimecki

PMID: 23648393;PMCID: PMC3714307;Abstract:

Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75. ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. © 2013 Elsevier Inc.

Gomez-Rubio, P., Roberge, J., Arendell, L., Harris, R., O'Rourke, M., Chen, Z., Cantu-Soto, E., Meza-Montenegro, M., Billheimer, D., Lu, Z., & Klimecki, W. (2011). Association between body mass index and arsenic methylation efficiency in adult women from southwest U.S. and northwest Mexico. Toxicology Applied Pharmacology, 252(2), 176-182.
BIO5 Collaborators
Dean Billheimer, Walter Klimecki
Gomez-Rubio, P., Gomez-Rubio, P., Klimentidis, Y., Klimentidis, Y., Cantu-Soto, E., Cantu-Soto, E., Meza-Montenegro, M., Meza-Montenegro, M., Billheimer, D., Billheimer, D., Lu, Z., Lu, Z., Chen, Z., Chen, Z., Klimecki, W., & Klimecki, W. (2012). Indigenous American Ancestry is Associated with Arsenic Methylation Efficiency in an Admixed Population of Northwest Mexico. J Toxicol Environ Health A, 75(1), 36-49.
BIO5 Collaborators
Dean Billheimer, Walter Klimecki
Burgess, J. L., Fierro, M. A., Lantz, R. C., Hysong, T. A., Fleming, J. E., Gerkin, R., Hnizdo, E., Conley, S. M., & Klimecki, W. (2004). Longitudinal decline in lung function: Evaluation of interleukin-10 genetic polymorphisms in firefighters. Journal of Occupational and Environmental Medicine, 46(10), 1013-1022.
BIO5 Collaborators
Jefferey L Burgess, Walter Klimecki, Clark Lantz
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., Adhihetty, P. J., Adler, S. G., Agam, G., Agarwal, R., Aghi, M. K., Agnello, M., Agostinis, P., Aguilar, P. V., Aguirre-Ghiso, J., , Airoldi, E. M., et al. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1), 1-222.
BIO5 Collaborators
Yin Chen, Walter Klimecki