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

Meza-Montenegro, M. M., Gandolfi, A. J., Santana-Alcántar, M. E., Klimecki, W. T., Aguilar-Apodaca, M. G., Del Río-Salas, R., De la O-Villanueva, M., Gómez-Alvarez, A., Mendivil-Quijada, H., Valencia, M., & Meza-Figueroa, D. (2012). Metals in residential soils and cumulative risk assessment in Yaqui and Mayo agricultural valleys, northern Mexico. The Science of the total environment, 433, 472-81.

This investigation examines the extent of soil metal pollution associated with the Green Revolution, relative to agricultural activities and associated risks to health in the most important agricultural region of Mexico. Metal contents in bulk soil samples are commonly used to assess contamination, and metal accumulations in soils are usually assumed to increase with decreasing particle size. This study profiled the spatial distribution of metals (Ni, Cr, Pb, Cu, Fe, Cd, V, Hg, Co, P, Se, and Mn) in bulk soil and fine-grained fractions (soil-derived dust) from 22 towns and cities. The contamination of soil was assessed through the use of a geoaccumulation index (Igeo) and pollution index (PI). The results of this study indicated that a number of towns and cities are moderately to highly polluted by soil containing Be, Co, Hg, P, S, V, Zn, Se, Cr, and Pb in both size fractions (coarse and fine). Hazard index in fine fraction (HI(children)=2.1) shows that risk assessment based on Co, Mn, V, and Ni spatially related to power plants, have the potential to pose health risks to local residents, especially children. This study shows that risk assessment based on metal content in bulk soil could be overestimated when compared to fine-grained fraction. Our results provide important information that could be valuable in establishing risk assessment associated with residential soils within agricultural areas, where children can ingest and inhale dust.

Loh, M. M., Sugeng, A., Lothrop, N., Klimecki, W. -., Wilkinson, S., & Beamer, P. -. (2014). Multimedia Exposures to Arsenic and Lead for Children in a Community Near a Former Mine Tailings and Smelter Site. Environmental Research.
Bieli, C., Eder, W., Frei, R., Braun-Fahrländer, C., Klimecki, W., Waser, M., Riedler, J., Mutius, E. v., Scheynius, A., Pershagen, G., Doekes, G., Lauener, R., & Martinez, F. D. (2007). A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. Journal of Allergy and Clinical Immunology, 120(6), 1308-1315.

PMID: 17919709;Abstract:

Background: Consumption of farm milk in early life is associated with less asthma and allergies. Objective: We hypothesized that genetic variation in the innate immunity receptor CD14 might modify the association between farm milk consumption and asthma and atopy. Methods: Questionnaire data, serum IgE levels, and genotypes for 4 single nucleotide polymorphisms in CD14 were assessed in farmers' and nonfarmers' children from 2 European populations (Allergy and Endotoxin study, n = 576; Prevention of Allergy Risk factors for Sensitization in children related to Farming and Anthroposophic Lifestyle study, n = 1539). In a subsample (n = 222) CD14 gene expression was measured in peripheral blood leukocytes. The effects of farm milk and CD14 genotypes on asthma, allergies, and CD14 expression and their interactions were investigated. Results: We found a significant interaction between genetic variation in CD14/-1721 and farm milk consumption. Adjusted odds ratios for the association between farm milk and asthma varied between the genotypes: AA, 0.18 (95% CI, 0.07-0.47); AG, 0.47 (95% CI, 0.26-0.86); and GG, 0.98 (95% CI, 0.46-2.08). Similar patterns were observed for symptoms of allergic rhinoconjunctivitis and pollen sensitization. CD14/-1721 also modified the association between farm milk and CD14 gene expression (adjusted geometric means ratios: AA, 1.61 (95% CI, 0.98-2.66); AG, 1.11 (95% CI, 0.71-1.72); and GG, 0.76 (95% CI, 0.39-1.48). Conclusion: The protective effect of farm milk consumption on allergic diseases is stronger in children carrying the A allele in CD14/-1721 than in children homozygous for the G allele. This might be mediated through farm milk-induced upregulated CD14 gene expression. Clinical implications: Our results support the hypothesis that the inverse association between farm milk consumption and allergic diseases is mediated by CD14-activated innate immune mechanisms. © 2007 American Academy of Allergy, Asthma & Immunology.

Oshiro, M. M., Futscher, B. W., Lisberg, A., Wozniak, R. J., Klimecki, W. T., Domann, F. E., & Cress, A. E. (2005). Epigenetic regulation of the cell type-specific gene 14-3-3sigma. Neoplasia (New York, N.Y.), 7(9), 799-808.

Epigenetic control participates in processes crucial in mammalian development, such as X-chromosome inactivation, gene imprinting, and cell type-specific gene expression. We provide evidence that the p53-inducible gene 14-3-3sigma is a new example of a gene important to human cancer, where epigenetic mechanisms participate in the control of normal cell type-specific expression, as well as aberrant gene silencing in cancer cells. Like a previously identified cell type-specific gene maspin, 14-3-3sigma is a p53-inducible gene; however, it participates in G2/M arrest in response to DNA-damaging agents. 14-3-3Sigma expression is restricted to certain epithelial cell types, including breast and prostate, whereas expression is absent in nonepithelial tissues such as fibroblasts and lymphocytes. In this report, we show that in normal cells expressing 14-3-3sigma, the 14-3-3sigma CpG island is unmethylated; associated with acetylated histones, unmethylated histone H3 lysine 9; and an accessible chromatin structure. By contrast, normal cells that do not express 14-3-3sigma have a methylated 14-3-3sigma CpG island with hypoacetylated histones, methylated histone H3 lysine 9, and an inaccessible chromatin structure. These findings extend the spectrum of cell type-specific genes controlled, partly, by normal epigenetic mechanisms, and suggest that this subset of genes may represent important targets of epigenetic dysregulation in human cancer.

Kripke, D. F., Rex, K. M., Ancoli-Israel, S., Nievergelt, C. M., Klimecki, W., & Kelsoe, J. R. (2008). Delayed sleep phase cases and controls. Journal of circadian rhythms, 6, 6.

Delayed sleep phase disorder (DSPD) is a condition in which patients have difficulty falling asleep before the early morning hours and commonly have trouble awakening before late morning or even early afternoon. Several studies have suggested that variations in habitual bedtime are 40-50% heritable.