Beamer, P. -., Sugeng, A. J., Kelly, M. D., Lothrop, N., Klimecki, W. -., Wilkinson, S. T., & Loh, M. M. (2014). Use of dust fall filters as passive samplers for metal concentrations in air for communities near contaminated mine taillings.. Environmental Science:Processes and Impacts.
Bolt, A. M., Douglas, R. M., & Klimecki, W. T. (2010). Arsenite exposure in human lymphoblastoid cell lines induces autophagy and coordinated induction of lysosomal genes. Toxicology Letters, 199(2), 153-159.
PMID: 20816728;PMCID: PMC2956852;Abstract:
Chronic exposure to inorganic arsenic is associated with diverse, complex diseases, making the identification of the mechanism underlying arsenic-induced toxicity a challenge. An increasing body of literature from epidemiological and in vitro studies has demonstrated that arsenic is an immunotoxicant, but the mechanism driving arsenic-induced immunotoxicity is not well established. We have previously demonstrated that in human lymphoblastoid cell lines (LCLs), arsenic-induced cell death is strongly associated with the induction of autophagy. In this study we utilized genome-wide gene expression analysis and functional assays to characterize arsenic-induced effects in seven LCLs that were exposed to an environmentally relevant, minimally cytotoxic, concentration of arsenite (0.75 μM) over an eight-day time course. Arsenic exposure resulted in inhibition of cellular growth and induction of autophagy (measured by expansion of acidic vesicles) over the eight-day exposure duration. Gene expression analysis revealed that arsenic exposure increased global lysosomal gene expression, which was associated with increased functional activity of the lysosome protease, cathepsin D. The arsenic-induced expansion of the lysosomal compartment in LCL represents a novel target that may offer insight into the immunotoxic effects of arsenic. © 2010 Elsevier Ireland Ltd.
Palmer, S. M., Klimecki, W., Yu, L., Reinsmoen, N. L., Snyder, L. D., Ganous, T. M., Burch, L., & Schwartz, D. A. (2007). Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. American Journal of Transplantation, 7(3), 693-699.
PMID: 17217435;Abstract:
We have developed the hypothesis that genetic polymorphisms which alter the expression or function of innate immune receptors contribute to the marked interindividual differences in the onset and severity of lung transplant rejection. In this analysis, we considered the effects of a common promotor polymorphism of the lipopolysaccharide receptor CD14 associated with increased transcriptional activity upon the development of posttransplant rejection and graft survival. Genotyping was performed in 226 lung transplant recipients well characterized with regards to clinical outcomes. An earlier onset of acute rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft survival due to greater BOS related deaths was evident in patients with the CD14 -159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95% CI, 1.03-2.64, p-value = 0.04) after adjusting for other important covariates. Furthermore, TT patients have significantly greater sCD14, TNF-α and IFN-γ in the peripheral blood implying a heightened state of innate immune activation drives the development of increased post-transplant rejection. Inhibition of innate immune activation through CD14 represents a novel and potentially important therapeutic target to prevent post-transplant rejection and improve outcomes after human lung transplantation. © 2007 The Authors.
Martínez, M. E., Thompson, P., Jacobs, E. T., Giovannucci, E., Jiang, R., Klimecki, W., & Alberts, D. S. (2006). Dietary factors and biomarkers involved in the methylenetetrahydrofolate reductase genotype-colorectal adenoma pathway. Gastroenterology, 131(6), 1706-16.
Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate homeostasis and metabolism. We assessed 2 polymorphisms in the MTHFR gene (C677T and A1298C) in relation to colorectal adenoma recurrence and conducted analyses to investigate their joint effects with plasma and dietary markers of folate status.
Beamer, P., Klimecki, W., Loh, M., Van Horne, Y. O., Sugeng, A., Lothrop, N., Billheimer, D., Guerra, S., Lantz, R. C., & Martinez, F. (2016). Association of Children’s Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. International Journal of Environmental Research and Public Health, 13(5), E521. doi:10.3390/ijerph13050521
BIO5 Collaborators
Walter Klimecki, Clark Lantz