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Your Environment. Your Health.

Project Publications: University of North Carolina-Chapel Hill: Molecular Drivers of Arsenic-Induced Diabetes

Superfund Research Program

Molecular Drivers of Arsenic-Induced Diabetes

Project Leader: Praveen Sethupathy (Cornell University)
Co-Investigators: Miroslav Styblo, Rebecca C. Fry, Fei Zou
Grant Number: P42ES031007
Funding Period: 2020-2025
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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  • Carberry C, Bangma J, Koval L, Keshava D, Hartwell HJ, Sokolsky M, Fry RC, Rager JE. 2023. Extracellular vesicles altered by a per- and polyfluoroalkyl substance mixture: in vitro dose-dependent release, chemical content, and MicroRNA signatures involved in liver health. Toxicol Sci doi:10.1093/toxsci/kfad108 PMID:37851381
  • Douillet C, Miller M, Cable PH, Shi Q, El-Masri HA, Matousek T, Koller BH, Thomas DJ, Styblo M. 2023. Fate of arsenicals in mice carrying the human AS3MT gene exposed to environmentally relevant levels of arsenite in drinking water. Sci Rep 13(1):3660. doi:10.1038/s41598-023-30723-8 PMID:36871058 PMCID:PMC9985638
  • Eaves LA, Choi G, Hall EM, Sille FC, Fry RC, Buckley JP, Keil AP. 2023. Prenatal exposure to toxic metals and neural tube defects: a systematic review of the epidemiologic evidence. Environ Health Perspect 131(8):86002. doi:10.1289/EHP11872 PMID:37647124 PMCID:PMC10467818
  • Eaves LA, Keil AP, Jukic AM, Dhingra R, Brooks JL, Manuck TA, Rager JE, Fry RC. 2023. Toxic metal mixtures in private well water and increased risk for preterm birth in North Carolina. Environmental Health 22(1):69. doi:10.1186/s12940-023-01021-7 PMID:37845729 PMCID:PMC10577978
  • Freedman AN, Clark J, Eaves LA, Roell K, Oran A, Koval L, Rager JE, Santos HP, Kuban K, Joseph RM, Frazier JA, Marsit CJ, Burt AA, O'Shea TM, Fry RC. 2023. A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm. Autism Res 16(5):918-934. doi:10.1002/aur.2915 PMID:36938998 PMCID:PMC10192070
  • Shang B, Venkatratnam A, Liu T, Douillet C, Shi Q, Miller M, Cable P, Zou F, Ideraabdullah FY, Fry RC, Styblo M. 2023. Sex-specific transgenerational effects of preconception exposure to arsenite: metabolic phenotypes of C57BL/6 offspring. Arch Toxicol doi:10.1007/s00204-023-03582-5 PMID:37615676
  • Soares MB, Duckworth O, Styblo M, Cable PH, Alleoni LR. 2023. Pyrolysis temperature and biochar redox activity on arsenic availability and speciation in a sediment. J Hazard Mater 460:132308. doi:10.1016/j.jhazmat.2023.132308 PMID:37639794


  • Bulka C, Enggasser AE, Fry RC. 2022. Epigenetics at the intersection of COVID-19 risk and environmental chemical exposures. Curr Environ Health Rep doi:10.1007/s40572-022-00353-9 PMID:35648356 PMCID:PMC9157479
  • Carberry C, Ferguson SS, Beltran AS, Fry RC, Rager JE. 2022. Using liver models generated from human-induced pluripotent stem cells (iPSCs) for evaluating chemical-induced modifications and disease across liver developmental stages. Toxicol Vitro 83:doi:10.1016/j.tiv.2022.105412 PMID:35688329
  • Carberry C, Turla T, Koval L, Hartwell HJ, Fry RC, Rager JE. 2022. Chemical mixtures in household environments: In silico prediction and in vitro testing of potential join action on PPARy in human liver cells. Toxics 10(5):199. doi:10.3390/toxics10050199 PMID:35622613 PMCID:PMC9146550
  • Clark J, Bommarito P, Styblo M, Rubio-Andrade M, Garcia-Vargas GG, Gamble MV, Fry RC. 2022. Maternal serum concentrations of one-carbon metabolism factors modify the association between biomarkers of arsenic methylation efficiency and birth weight. Environmental Health 21(1):68. doi:10.1186/s12940-022-00875-7 PMID:35836250 PMCID:PMC9281096
  • Shang B, Venkatratnam A, Hartwell HJ, Douillet C, Cable P, Liu T, Zou F, Ideraabdullah FY, Fry RC, Styblo M. 2022. Ex vivo exposures to arsenite and its methylated trivalent metabolites alter gene transcription in mouse sperm cells. Toxicol Appl Pharmacol 455:116266. doi:10.1016/j.taap.2022.116266 PMID:36209798
  • Todero JE, Koch-Laskowski K, Shi Q, Kanke M, Hung Y, Beck R, Styblo M, Sethupathy P. 2022. Candidate master microRNA regulator of arsenic-induced pancreatic beta cell impairment revealed by multi-omics analysis. Arch Toxicol 96(6):1685-1699. doi:10.1007/s00204-022-03263-9 PMID:35314868 PMCID:PMC9095563


  • Clark J, Avula V, Ring C, Eaves LA, Howard T, Santos HP, Smeester L, Bangma J, O'Shea TM, Fry RC, Rager JE. 2021. Comparing the predictivity of human placental gene, microRNA, and CpG methylation signatures in relation to perinatal outcomes. Toxicol Sci 183(2):269-284. doi:10.1093/toxsci/kfab089 PMID:34255065 PMCID:PMC8478332
  • Douillet C, Ji J, Meenakshi IL, Lu K, Pardo-Manuel de Villena F, Fry RC, Styblo M. 2021. Diverse genetic backgrounds play a prominent role in the metabolic phenotype of CC021/Unc and CC027/GeniUNC mice exposed to inorganic arsenic. Toxicology 452:152696. doi:10.1016/j.tox.2021.152696 PMID:33524430 PMCID:PMC7914223
  • Ghiuzeli CM, Styblo M, Saunders RJ, Calabro A, Budman D, Allen S, Devoe C, Dhingra R. 2021. The pharmacokinetics of therapeutic arsenic trioxide in acute promyelocytic leukemia patients. Leuk Lymphoma 63:653-663. doi:10.1080/10428194.2021.1978084 PMID:34689693 PMCID:PMC8891048
  • Hung Y, Huang S, Dame MK, Yu Q, Yu QC, Zeng Y, Camp JG, Spence JR, Sethupathy P. 2021. Chromatin regulatory dynamics of early human small intestinal development using a directed differentiation model. Nucleic Acids Res 49(2):726-744. doi:10.1093/nar/gkaa1204 PMID:33406262 PMCID:PMC7826262
  • Hutch CR, Stelmak D, Kanke M, Koch-Laskowski K, Cummings B, Griffin C, Leix K, Sethupathy P, Singer K, Sandoval DA. 2021. Diet-dependent sex differences in the response to vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab 321(1):E11-E23. doi:10.1152/ajpendo.00060.2021 PMID:33998293 PMCID:PMC8321822
  • O'Connor S, Murphy EA, Szwed SK, Kanke M, Marchildon F, Sethupathy P, Darnell RB, Cohen P. 2021. AGO HITS-CLIP reveals distinct miRNA regulation of white and brown adipose tissue identity. Genes Dev 35(9-10):771-781. doi:10.1101/gad.345447.120 PMID:33832988 PMCID:PMC8091975
  • Oyesola OO, Shanahan MT, Kanke M, Mooney BM, Webb LM, Smita S, Matheson MK, Campioli P, Pham D, Fruh SP, McGinty JW, Churchill MJ, Cahoon JL, Sundaravaradan P, Flitter B, Mouli K, Nadjsombati MS, Kamynina E, Peng SA, Cubitt R, Gronert K, Lord JD, Rauch I, von Moltke J, Sethupathy P, Tait-Wojno ED. 2021. PGD2 and CRTH2 counteract Type 2 cytokine-elicited intestinal epithelial responses during helminth infection. J Exp Med 218(9):e20202178. doi:10.1084/jem.20202178 PMID:34283207 PMCID:PMC8294949
  • Shanahan MT, Kanke M, Oyesola OO, Hung Y, Koch-Laskowski K, Singh AP, Peck BC, Biraud M, Sheahan B, Cortes JE, Gong H, Sahoo DK, Cubitt R, Kurpios NA, Mochel JP, Allenspach K, McElroy SJ, Ding S, von Moltke J, Dekaney CM, Tait-Wojno ED, Sethupathy P. 2021. Multiomic analysis defines the first microRNA atlas across all small intestinal epithelial lineages and reveals novel markers of almost all major cell types. Am J Physiol Gastrointest Liver Physiol 321:doi:10.1152/ajpgi.00222.2021 PMID:34643097 PMCID:PMC8887887
  • Smith GJ, Tovar A, Kanke M, Wang Y, Deshane J, Sethupathy P, Kelada SN. 2021. Ozone-induced changes in the murine lung extracellular vesicle small RNA landscape. Physiol Rep 9(18):doi:10.14814/phy2.15054 PMID:34558223 PMCID:PMC8461034
  • Styblo M, Venkatratnam A, Fry RC, Thomas DJ. 2021. Origins, fate, and actions of methylated trivalent metabolites of inorganic arsenic: progress and prospects. Arch Toxicol 95(5):doi:10.1007/s00204-021-03028-w PMID:33768354 (ahead of print)
  • Swahari V, Nakamura A, Hollville E, Stroud H, Simon JM, Ptacek TS, Beck MV, Flowers C, Guo J, Plestant C, Liang J, Kurtz CL, Kanke M, Hammond SM, He Y, Anton E, Sethupathy P, Moy SS, Greenberg ME, Deshmukh M. 2021. MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation. Cell Rep 35(1):doi:10.1016/j.celrep.2021.108946 PMID:33826889 PMCID:PMC8103628
  • Toyonaga T, Araba KC, Kennedy MM, Keith BP, Wolber EA, Beasley C, Steinbach EC, Schaner MR, Jain A, Long MD, Barnes EL, Herfarth HH, Isaacs KL, Hansen JJ, Kapadia MR, Guillem JG, Gulati AS, Sethupathy P, Furey TS, Ehre C, Sheikh SZ. 2021. Increased colonic expression of ACE2 associates with poor prognosis in Crohn's disease. Sci Rep 11(1):13533. doi:10.1038/s41598-021-92979-2 PMID:34188154 PMCID:PMC8241995
  • Wang X, Zhang W, Yang Y, Wang J, Qiu H, Liao L, Oikawa T, Wauthier E, Sethupathy P, Reid LM, Liu Z, He Z. 2021. A microRNA-based network provides potential predictive signatures and reveals the crucial role of PI3K/AKT signaling for hepatic lineage maturation. Front Cell Dev Biol 9:670059. doi:10.3389/fcell.2021.670059 PMID:34141708 PMCID:PMC8204022
  • Zhang W, Lanzoni G, Hani H, Overi D, Cardinale V, Simpson S, Pitman W, Allen A, Yi X, Wang X, Gerber D, Prestwich G, Lozoya O, Gaudio E, Alvaro D, Tokaz D, Dominguez-Bendala J, Adin C, Piedrahita JA, Mathews K, Sethupathy P, Carpino G, He Z, Wauthier E, Reid LM. 2021. Patch grafting, strategies for transplantation of organoids into solid organs such as liver. Biomaterials 277:121067. doi:10.1016/j.biomaterials.2021.121067 PMID:34517276


  • Douillet C, Koller BH, Styblo M. 2020. Metabolism of inorganic arsenic in mice lacking genes encoding GST-P, GST-M, and GST-T. Chem Res Toxicol 33(8):2043-2046. doi:10.1021/acs.chemrestox.0c00273 PMID:32700902 PMCID:PMC7802361
  • Koller BH, Snouwaert JN, Douillet C, Jania LA, El-Masri HA, Thomas DJ, Styblo M. 2020. Arsenic metabolism in mice carrying a BORCS7/AS3MT locus humanized by syntenic replacement. Environ Health Perspect 128(8):87003. doi:10.1289/EHP6943 PMID:32779937 PMCID:PMC7418654
  • Li Y, Douillet C, Huang MC, Beck R, Sumner SJ, Styblo M. 2020. Exposure to inorganic arsenic and its methylated metabolites alters metabolomics profiles in INS-1 832/13 insulinoma cells and isolated pancreatic islets. Arch Toxicol 94(6):1955-1972. doi:10.1007/s00204-020-02729-y PMID:32277266
  • Styblo M, Schmidt S. 2020. Matching rodents to people: A humanized mouse model of iAs methylation. Environ Health Perspect 128(10):104003. doi:10.1289/EHP8093 PMID:33054428 PMCID:PMC7560904
  • Venkatratnam A, Douillet C, Topping BC, Shi Q, Addo KA, Ideraabdullah FY, Fry RC, Styblo M. 2020. Sex-dependent effects of preconception exposure to arsenite on gene transcription in parental germ cells and on transcriptomic profiles and diabetic phenotype of offspring. Arch Toxicol doi:10.1007/s00204-020-02941-w PMID:33145626
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