Exposure to environmental arsenicals has been linked to a number of human pathologies, include bladder and lung cancer. We hypothesize that arsenical-mediated perturbation of the epigenetic landscape is an important factor that drives malignant progression. Three integrated specific aims are described in this proposal will address this hypothesis from a gene to genome wide analysis, and from in vitro to """"""""real world"""""""" settings.
Aim 1 is designed to develop epigenetic targets as biomarkers of arsenical exposure. Preliminary epigenome-wide scanning studies of urine sediments from individuals with known exposure levels in their drinking water have identified candidate epigenetic biomarkers are correlated with arsenical exposure level. The utility of these candidate biomarkers will be evaluated using high sensitivity, high resolution technologies in a new cohort population.
Aim 2 will determine if arsenicals produce common perturbations to the epigenomic landscape in their distinct epithelial targets. Experimental strategies of arsenical exposure that caused malignant transformation of urothelial cells will be expanded to lung epithelial model systems. Results from these experiments will help determine if there are seminal epigenetic changes that are common to epithelial malignant transformation in general, as well as the epigenetic changes that display tissue-origin specificity.
Aim 3 will provide a detailed investigation of the phenotypic consequences of epigenetic gene inactivation of an arsenical target gene, G0S2, which is closely linked to the malignant transformation of urothelial cells. If our hypothesis is correct, then results from these studies will provide new insights into the mechanisms of their chronic arsenical exposure, as well as serve as a platform for inquiries into other, non-cancer, arsenic-induced human pathologies, such as diabetes and cardiovascular disease.
Environment - genome interactions are becoming more important in understanding pollutant associated diseases. Epigenetic studies will provide new insights into the mechanisms of arsenic-induced cancers, as well as serve as a platform for inquiries into other, non-cancer, arsenic-induced human pathologies, such as diabetes and cardiovascular disease. An important mechanism of arsenical toxicity is its ability to alter cellular phenotype through disruption of the normal epigenetic landscape.
|Mora, Marco; Braun, Rachel A; Shingler, Taylor et al. (2017) Analysis of remotely sensed and surface data of aerosols and meteorology for the Mexico Megalopolis Area between 2003 and 2015. J Geophys Res Atmos 122:8705-8723|
|Guo, Zhilin; Brusseau, Mark L (2017) The impact of well-field configuration and permeability heterogeneity on contaminant mass removal and plume persistence. J Hazard Mater 333:109-115|
|Zhang, Xiang; Gu, Xiaogang; Lu, Shuguang et al. (2017) Application of ascorbic acid to enhance trichloroethene degradation by Fe(III)-activated calcium peroxide. Chem Eng J 325:188-198|
|Danish, Muhammad; Gu, Xiaogang; Lu, Shuguang et al. (2017) An efficient catalytic degradation of trichloroethene in a percarbonate system catalyzed by ultra-fine heterogeneous zeolite supported zero valent iron-nickel bimetallic composite. Appl Catal A Gen 531:177-186|
|Ramos-Ruiz, Adriana; Sesma-Martin, Juan; Sierra-Alvarez, Reyes et al. (2017) Continuous reduction of tellurite to recoverable tellurium nanoparticles using an upflow anaerobic sludge bed (UASB) reactor. Water Res 108:189-196|
|Madeira, Camila L; Speet, Samuel A; Nieto, Cristina A et al. (2017) Sequential anaerobic-aerobic biodegradation of emerging insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO). Chemosphere 167:478-484|
|Honeker, Linnea K; Neilson, Julia W; Root, Robert A et al. (2017) Bacterial Rhizoplane Colonization Patterns of Buchloe dactyloides Growing in Metalliferous Mine Tailings Reflect Plant Status and Biogeochemical Conditions. Microb Ecol 74:853-867|
|Fu, Xiaori; Gu, Xiaogang; Lu, Shuguang et al. (2017) Benzene oxidation by Fe(III)-catalyzed sodium percarbonate: matrix constituent effects and degradation pathways. Chem Eng J 309:22-29|
|Olivares, Christopher I; Madeira, Camila L; Sierra-Alvarez, Reyes et al. (2017) Environmental Fate of 14C Radiolabeled 2,4-Dinitroanisole in Soil Microcosms. Environ Sci Technol 51:13327-13334|
|Soltani, Naghmeh; Keshavarzi, Behnam; Sorooshian, Armin et al. (2017) Oxidative potential (OP) and mineralogy of iron ore particulate matter at the Gol-E-Gohar Mining and Industrial Facility (Iran). Environ Geochem Health :|
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