About

Miroslav Styblo is a professor at the University of North Carolina Gillings School of Global Public Health. His research interests involve the metabolic interactions of essential microelements, especially trace metals, with toxic metals and metalloids that contaminate the food chain and drinking water reservoirs. His work includes studying the interactions between selenium, an essential micronutrient, and arsenic, an environmental contaminant and human carcinogen. He investigates the enzymes and co-factors involved in the metabolism of arsenic and selenium, as well as the mechanisms of arsenic-induced diabetes. Additionally, his research explores the role of nutritional antioxidants and antioxidant enzymes in responses to oxidative stress caused by environmental toxins, viral infections, or nutritional deficiencies.

Research topics

• Biochemistry
• Biology
• Chemistry
• Medicine
• Internal medicine
• Bioinformatics
• Genetics
• Endocrinology

Selected publications

• Dietary folate supplementation modifies effects of arsenic exposure on DNA methylation profiles in sperm of mice expressing the human AS3MT

  Archives of Toxicology · 2026-03-10

  articleSenior author
  PublisherDOI

• Transgenerational diabetogenic effects of preconception exposure to inorganic arsenic in C57BL/6 mice are associated with dysregulation of DNA methylation and gene expression in G1 and G2 offspring

  Archives of Toxicology · 2025-06-12 · 2 citations

  articleSenior author
  PublisherDOI

• Maternal one carbon metabolism and arsenic methylation in a pregnancy cohort in Mexico

  UNC Libraries · 2025-08-09

  articleOpen access
  PublisherDOI

• Heritable dysregulation of DNA methylation may underlie the diabetogenic effects of paternal preconception exposure to inorganic arsenic in C57BL/6J mice

  Toxicology and Applied Pharmacology · 2025-02-01 · 4 citations

  articleOpen accessCorresponding
  PublisherOA PDFDOI

• Correction to: Maternal one carbon metabolism and arsenic methylation in a pregnancy cohort in Mexico

  UNC Libraries · 2025-08-09

  articleOpen access1st authorCorresponding
  PublisherDOI

• A Novel Arsenic Methyltransferase Splice Variant Expressed in Human Keratinocytes

  ThinkIR: The University of Louisville's Institutional Repository (University of Louisville) · 2024-11-23

  articleOpen access

  Chronic inorganic arsenic (iAs) exposure from contaminated drinking water is a global issue that impacts over 220 million people worldwide. iAs is a Group 1 human carcinogen. Skin lesions, including skin cancer, are hallmarks of arsenic toxicity. Arsenic methyltransferase (AS3MT) is required for the biotransformation of iAs to monomethyl-As (MMAV and MMAIII) and MMA to dimethyl-As (DMAV and DMAIII), and the iAs:MMA:DMA ratio determines arsenic clearance and toxicity. Both trivalent MMA (MMAIII) and DMA (DMAIII) are exceedingly more toxic compared to iAs and may promote toxic and carcinogenic effects associated with chronic iAs exposure. HaCaT cells exposed to 100 nM iAs for 28 weeks undergo malignant transformation and represent an important tool to study iAs-induced skin carcinogenesis. However, whether these cells can metabolize iAs remains unknown. Our hypothesis is that HaCaT cells methylate iAs to promote malignant transformation. Human keratinocytes (HaCaT, Ker-CT, and HEKn) cells and a liver cell line (HepG2) were exposed to sodium arsenite (0 or 100 nM) for 24 h. iAs speciation within cells and media from 100 nM exposed cultures was determined by hydride-generation inductively coupled plasma mass spectrometry coupled with a cryotrap (HG-CT-ICP-MS). Total RNA and genomic DNA was isolated from 0 or 100 nM exposed cells. RNA was treated with DNAseI (-/+) and RNAseA (-/+) and AS3MT mRNA expression was determined by RT-PCR. Overall, human keratinocytes are poor iAs methylators compared to HepG2 cells. Among human keratinocytes, HaCaT cells contained the least amount of iAs metabolites compared to Ker-CT and HEKn cells. HaCaT cells also expressed the least amount of canonical AS3MT mRNA. In addition, we discovered a novel alternatively spliced AS3MT mRNA isoform that is expressed predominantly in human keratinocytes. Our conclusion is that arsenic-induced malignant transformation in HaCaT cells chronically exposed to iAs is likely driven by iAs rather than iAs metabolites. The novel AS3MT splice variant retains intron 2 of the AS3MT gene and this may promote nonsense-mediated mRNA decay of this transcript. Future work will determine whether chronic iAs exposure in human keratinocytes promotes upregulation of the canonical AS3MT mRNA and/or the novel AS3MT splice variant, and whether the new AS3MT splice variant is degraded by nonsense-mediated decay preventing translation of a truncated, non-functional AS3MT protein.

  PublisherOA PDF

• Geologic predictors of drinking water well contamination in North Carolina

  PLOS Water · 2024-01-11 · 2 citations

  articleOpen access

  More than 200 million people worldwide, including 11 million in the US, are estimated to consume water containing arsenic (As) concentrations that exceed World Health Organization and US EPA standards. In most cases, the As found in drinking water wells results from interactions between groundwater and geologic materials (geogenic contamination). To that end, we used the NCWELL database, which contains chemical information for 117,960 private drinking wells across North Carolina, to determine the spatial distribution of wells containing As contaminated water within geologic units. Specific geologic units had large percentages (up to 1 in 3) of wells with water exceeding the EPA As maximum contaminant level (MCL, 10 μg/L), both revealing significant variation within areas that have been previously associated with As contamination and identifying as yet unidentified problematic geologic units. For the 19 geologic units that have >5% of wells that contain water with As concentrations in exceedance of 10 μg/L, 12 (63%) are lithogenically related to the Albemarle arc, remnants of an ancient volcanic island, indicating the importance of volcanogenic materials, as well as recycled (eroded and deposited) and metamorphosed volcanogenic material. Within geologic units, wells that have As concentrations exceeding 10 μg/L tended to have pH values greater than wells with As concentrations less than 10 μg/L, emphasizing the importance of the extent of interaction between groundwater and geologic materials. Using census information with the geologic-based exceedance percentages revealed the importance of regional geology on estimates of population at risk compared to estimates based on county boundaries. Results illustrate that relating As contamination to geologic units not only helps explain sources of geogenic contamination but sharpens the identification of communities at risk for exposure and further illuminates problematic areas through geologic interpretation.

  PublisherOA PDFDOI

• Metabolic Phenotype of Wild-Type and As3mt-Knockout C57BL/6J Mice Exposed to Inorganic Arsenic: The Role of Dietary Fat and Folate Intake

  UNC Libraries · 2024-06-29 · 1 citations

  articleOpen access

  BACKGROUND: Inorganic arsenic (iAs) is a diabetogen. Interindividual differences in iAs metabolism have been linked to susceptibility to diabetes in iAs-exposed populations. Dietary folate intake has been shown to influence iAs metabolism, but to our knowledge its role in iAs-associated diabetes has not been studied. OBJECTIVE: The goal of this study was to assess how folate intake, combined with low-fat (LFD) and high-fat diets (HFD), affects the metabolism and diabetogenic effects of iAs in wild-type (WT) mice and in As3mt-knockout (KO) mice that have limited capacity for iAs detoxification. METHODS: Male and female WT and KO mice were exposed to 0 or [Formula: see text] iAs in drinking water. Mice were fed the LFD containing [Formula: see text] or [Formula: see text] folate for 24 weeks, followed by the HFD with the same folate levels for 13 weeks. Metabolic phenotype and iAs metabolism were examined before and after switching to the HFD. RESULTS: iAs exposure had little effect on the phenotype of mice fed LFD regardless of folate intake. High folate intake stimulated iAs metabolism, but only in WT females. KO mice accumulated more fat than WT mice and were insulin resistant, with males more insulin resistant than females despite similar %fat mass. Feeding the HFD increased adiposity and insulin resistance in all mice. However, iAs-exposed male and female WT mice with low folate intake were more insulin resistant than unexposed controls. High folate intake alleviated insulin resistance in both sexes, but stimulated iAs metabolism only in female mice. CONCLUSIONS: Exposure to [Formula: see text] iAs in drinking water resulted in insulin resistance in WT mice only when combined with a HFD and low folate intake. The protective effect of high folate intake may be independent of iAs metabolism, at least in male mice. KO mice were more prone to developing insulin resistance, possibly due to the accumulation of iAs in tissues. https://doi.org/10.1289/EHP3951.

  PublisherDOI

• Geologic predictors of drinking water well contamination in North Carolina

  UNC Libraries · 2024-02-02

  articleOpen access1st authorCorresponding

  More than 200 million people worldwide, including 11 million in the US, are estimated to consume water containing arsenic (As) concentrations that exceed World Health Organization and US EPA standards. In most cases, the As found in drinking water wells results from interactions between groundwater and geologic materials (geogenic contamination). To that end, we used the NCWELL database, which contains chemical information for 117,960 private drinking wells across North Carolina, to determine the spatial distribution of wells containing As contaminated water within geologic units. Specific geologic units had large percentages (up to 1 in 3) of wells with water exceeding the EPA As maximum contaminant level (MCL, 10 μg/L), both revealing significant variation within areas that have been previously associated with As contamination and identifying as yet unidentified problematic geologic units. For the 19 geologic units that have >5% of wells that contain water with As concentrations in exceedance of 10 μg/L, 12 (63%) are lithogenically related to the Albemarle arc, remnants of an ancient volcanic island, indicating the importance of volcanogenic materials, as well as recycled (eroded and deposited) and metamorphosed volcanogenic material. Within geologic units, wells that have As concentrations exceeding 10 μg/L tended to have pH values greater than wells with As concentrations less than 10 μg/L, emphasizing the importance of the extent of interaction between groundwater and geologic materials. Using census information with the geologic-based exceedance percentages revealed the importance of regional geology on estimates of population at risk compared to estimates based on county boundaries. Results illustrate that relating As contamination to geologic units not only helps explain sources of geogenic contamination but sharpens the identification of communities at risk for exposure and further illuminates problematic areas through geologic interpretation.

  PublisherDOI

• Erratum to: Phase I and pharmacokinetic evaluation of the anti-telomerase agent KML-001 with cisplatin in advanced solid tumors

  UNC Libraries · 2024-07-26

  erratumOpen access
  PublisherDOI

Recent grants

• Mechanisms of Arsenic-Induced Diabetes Mellitus

  NIH · $1.4M · 2013–2018

• Genetic underpinning of diabetes associated with arsenic exposure

  NIH · $3.3M · 2019–2024

• Developmental windows for arsenic-associated diabetes

  NIH · $456k · 2018–2023

• Humanized mouse models for arsenic toxicology

  NIH · $439k · 2021–2026

• A humanized mouse model for arsenic toxicology

  NIH · $428k · 2017–2020

Frequent coauthors

• David J. Thomas

  159 shared

• Zuzana Drobná

  North Carolina State University

  128 shared

• Luz M. Del Razo

  Center for Research and Advanced Studies of the National Polytechnic Institute

  71 shared

• Rebecca C. Fry

  55 shared

• Gonzalo G. Garcı́a-Vargas

  54 shared

• Christelle Douillet

  University of North Carolina at Chapel Hill

  46 shared

• Walter Cullen

  37 shared

• Michael P. Waalkes

  28 shared

Labs

• Curriculum in Toxicology & Environmental MedicinePI

Education

• Ph.D., Toxicology

  University of North Carolina at Chapel Hill

  1990

• M.S., Toxicology

  University of North Carolina at Chapel Hill

  1986

• B.S., Toxicology

  University of North Carolina at Chapel Hill

  1983