Joel Meyer

Overview:

Dr. Meyer studies the effects of toxic agents and stressors on human and wildlife health. He is particularly interested in understanding the mechanisms by which environmental agents cause DNA damage, the molecular processes that organisms employ to protect prevent and repair DNA damage, and genetic differences that may lead to increased or decreased sensitivity to DNA damage. Mitochondrial DNA damage and repair, as well as mitochondrial function in general, are a particular focus. He studies these effects in the nematode Caenorhabditis elegans, in cell culture, and collaboratively in other laboratory model organisms as well as in human populations in the USA and globally.

Positions:

Truman and Nellie Semans/Alex Brown and Sons Associate Professor of Molecular Environmental Toxicology

Environmental Sciences and Policy
Nicholas School of the Environment

Associate Professor of Environmental Genomics in the Division of Environmental Sciences and Policy

Environmental Sciences and Policy
Nicholas School of the Environment

Faculty Network Member of The Energy Initiative

Nicholas Institute-Energy Initiative
Institutes and Provost's Academic Units

Affiliate, Duke Global Health Institute

Duke Global Health Institute
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1992

Juniata College

Ph.D. 2003

Duke University

Grants:

Center for Environmental Implications of Nanotechnology

Administered By
Pratt School of Engineering
Awarded By
National Science Foundation
Role
Investigator
Start Date
End Date

Fluoride and human health: Assessing novel biomarkers in detecting bone disorder

Administered By
Earth and Climate Sciences
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

COPAS BIOSORT Worm Sorter

Administered By
Neurology, Headache and Pain
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Are mitochondria a major target of antimicrobial silver nanoparticles?

Administered By
Environmental Sciences and Policy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

GW150184 Mitochondrial dysfunction and Gulf War Illness

Administered By
Environmental Sciences and Policy
Awarded By
United States Army Medical Research Acquisition Activity
Role
Principal Investigator
Start Date
End Date

Publications:

Mitochondrial DNA Mutagenesis: Feature of and Biomarker for Environmental Exposures and Aging.

PURPOSE OF REVIEW: Mitochondrial dysfunction is a hallmark of aging. Mitochondrial genome (mtDNA) instability contributes to mitochondrial dysfunction, and mtDNA mutagenesis may contribute to aging. However, the origin of mtDNA mutations remains somewhat controversial. The goals of this review are to introduce and review recent literature on mtDNA mutagenesis and aging, address recent animal and epidemiological evidence for the effects of chemicals on mtDNA damage and mutagenesis, propose hypotheses regarding the contribution of environmental toxicant exposure to mtDNA mutagenesis in the context of aging, and suggest future directions and approaches for environmental health researchers. RECENT FINDINGS: Stressors such as pollutants, pharmaceuticals, and ultraviolet radiation can damage the mitochondrial genome or disrupt mtDNA replication, repair, and organelle homeostatic processes, potentially influencing the rate of accumulation of mtDNA mutations. Accelerated mtDNA mutagenesis could contribute to aging, diseases of aging, and sensitize individuals with pathogenic mtDNA variants to stressors. We propose three potential mechanisms of toxicant-induced effects on mtDNA mutagenesis over lifespan: (1) increased de novo mtDNA mutations, (2) altered frequencies of mtDNA mutations, or (3) both. There are remarkably few studies that have investigated the impact of environmental chemical exposures on mtDNA instability and mutagenesis, and even fewer in the context of aging. More studies are warranted because people are exposed to tens of thousands of chemicals, and are living longer. Finally, we suggest that toxicant-induced mtDNA damage and mutational signatures may be a sensitive biomarker for some exposures.
Authors
Leuthner, TC; Meyer, JN
MLA Citation
Leuthner, Tess C., and Joel N. Meyer. “Mitochondrial DNA Mutagenesis: Feature of and Biomarker for Environmental Exposures and Aging.Curr Environ Health Rep, Nov. 2021. Pubmed, doi:10.1007/s40572-021-00329-1.
URI
https://scholars.duke.edu/individual/pub1501344
PMID
34761353
Source
pubmed
Published In
Current Environmental Health Reports
Published Date
DOI
10.1007/s40572-021-00329-1

Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling in Caenorhabditis elegans.

The consequences of damage to the mitochondrial genome (mtDNA) are poorly understood, although mtDNA is more susceptible to damage resulting from some genotoxicants than nuclear DNA (nucDNA), and many environmental toxicants target the mitochondria. Reports from the toxicological literature suggest that exposure to early-life mitochondrial damage could lead to deleterious consequences later in life (the "Developmental Origins of Health and Disease" paradigm), but reports from other fields often report beneficial ("mitohormetic") responses to such damage. Here, we tested the effects of low (causing no change in lifespan) levels of ultraviolet C (UVC)-induced, irreparable mtDNA damage during early development in Caenorhabditis elegans. This exposure led to life-long reductions in mtDNA copy number and steady-state ATP levels, accompanied by increased oxygen consumption and altered metabolite profiles, suggesting inefficient mitochondrial function. Exposed nematodes were also developmentally delayed, reached smaller adult size, and were rendered more susceptible to subsequent exposure to chemical mitotoxicants. Metabolomic and genetic analysis of key signaling and metabolic pathways supported redox and mitochondrial stress-response signaling during early development as a mechanism for establishing these persistent alterations. Our results highlight the importance of early-life exposures to environmental pollutants, especially in the context of exposure to chemicals that target mitochondria.
Authors
Hershberger, KA; Rooney, JP; Turner, EA; Donoghue, LJ; Bodhicharla, R; Maurer, LL; Ryde, IT; Kim, JJ; Joglekar, R; Hibshman, JD; Smith, LL; Bhatt, DP; Ilkayeva, OR; Hirschey, MD; Meyer, JN
MLA Citation
Hershberger, Kathleen A., et al. “Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling in Caenorhabditis elegans.Redox Biol, vol. 43, July 2021, p. 102000. Pubmed, doi:10.1016/j.redox.2021.102000.
URI
https://scholars.duke.edu/individual/pub1482924
PMID
33993056
Source
pubmed
Published In
Redox Biology
Volume
43
Published Date
Start Page
102000
DOI
10.1016/j.redox.2021.102000

PCR-Based Determination of Mitochondrial DNA Copy Number in Multiple Species.

Mitochondrial DNA (mtDNA) copy number is a critical component of overall mitochondrial health. In this chapter, we describe methods for simultaneous isolation of mtDNA and nuclear DNA (nucDNA), and measurement of their respective copy numbers using quantitative PCR. Methods differ depending on the species and cell type of the starting material, and availability of specific PCR reagents. We also briefly describe factors that affect mtDNA copy number and discuss caveats to its use as a biomarker.
Authors
Leuthner, TC; Hartman, JH; Ryde, IT; Meyer, JN
MLA Citation
Leuthner, Tess C., et al. “PCR-Based Determination of Mitochondrial DNA Copy Number in Multiple Species.Methods in Molecular Biology (Clifton, N.J.), vol. 2310, Jan. 2021, pp. 91–111. Epmc, doi:10.1007/978-1-0716-1433-4_8.
URI
https://scholars.duke.edu/individual/pub1484742
PMID
34096001
Source
epmc
Published In
Methods in Molecular Biology (Clifton, N.J.)
Volume
2310
Published Date
Start Page
91
End Page
111
DOI
10.1007/978-1-0716-1433-4_8

Xenobiotic metabolism and transport in <i>Caenorhabditis elegans</i>.

<i>Caenorhabditis elegans</i> has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology and pharmacology in <i>C. elegans</i> have been published, and this species has now been adopted by investigators in academic toxicology, pharmacology, and drug discovery labs. <i>C. elegans</i> has also attracted the interest of governmental regulatory agencies charged with evaluating the safety of chemicals. However, a major, fundamental aspect of toxicological science remains underdeveloped in <i>C. elegans</i>: xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species. The aim of this review was to initially briefly describe the history and trajectory of the use of <i>C. elegans</i> in toxicological and pharmacological studies. Subsequently, physical barriers to chemical uptake and the role of the worm microbiome in xenobiotic transformation were described. Then a review of what is and is not known regarding the classic Phase I, Phase II, and Phase III processes was performed. In addition, the following were discussed (1) regulation of xenobiotic metabolism; (2) review of published toxicokinetics for specific chemicals; and (3) genetic diversity of these processes in <i>C. elegans</i>. Finally, worm xenobiotic transport and metabolism was placed in an evolutionary context; key areas for future research highlighted; and implications for extrapolating <i>C. elegans</i> toxicity results to other species discussed.
Authors
Hartman, JH; Widmayer, SJ; Bergemann, CM; King, DE; Morton, KS; Romersi, RF; Jameson, LE; Leung, MCK; Andersen, EC; Taubert, S; Meyer, JN
MLA Citation
Hartman, Jessica H., et al. “Xenobiotic metabolism and transport in Caenorhabditis elegans.Journal of Toxicology and Environmental Health. Part B, Critical Reviews, vol. 24, no. 2, Feb. 2021, pp. 51–94. Epmc, doi:10.1080/10937404.2021.1884921.
URI
https://scholars.duke.edu/individual/pub1474866
PMID
33616007
Source
epmc
Published In
Journal of Toxicology and Environmental Health. Part B, Critical Reviews
Volume
24
Published Date
Start Page
51
End Page
94
DOI
10.1080/10937404.2021.1884921

Multiple metabolic changes mediate the response of Caenorhabditis elegans to the complex I inhibitor rotenone.

Rotenone, a mitochondrial complex I inhibitor, has been widely used to study the effects of mitochondrial dysfunction on dopaminergic neurons in the context of Parkinson's disease. Although the deleterious effects of rotenone are well documented, we found that young adult Caenorhabditis elegans showed resistance to 24 and 48 h rotenone exposures. To better understand the response to rotenone in C. elegans, we evaluated mitochondrial bioenergetic parameters after 24 and 48 h exposures to 1 μM or 5 μM rotenone. Results suggested upregulation of mitochondrial complexes II and V following rotenone exposure, without major changes in oxygen consumption or steady-state ATP levels after rotenone treatment at the tested concentrations. We found evidence that the glyoxylate pathway (an alternate pathway not present in higher metazoans) was induced by rotenone exposure; gene expression measurements showed increases in mRNA levels for two complex II subunits and for isocitrate lyase, the key glyoxylate pathway enzyme. Targeted metabolomics analyses showed alterations in the levels of organic acids, amino acids, and acylcarnitines, consistent with the metabolic restructuring of cellular bioenergetic pathways including activation of complex II, the glyoxylate pathway, glycolysis, and fatty acid oxidation. This expanded understanding of how C. elegans responds metabolically to complex I inhibition via multiple bioenergetic adaptations, including the glyoxylate pathway, will be useful in interrogating the effects of mitochondrial and bioenergetic stressors and toxicants.
Authors
Gonzalez-Hunt, CP; Luz, AL; Ryde, IT; Turner, EA; Ilkayeva, OR; Bhatt, DP; Hirschey, MD; Meyer, JN
MLA Citation
Gonzalez-Hunt, Claudia P., et al. “Multiple metabolic changes mediate the response of Caenorhabditis elegans to the complex I inhibitor rotenone.Toxicology, vol. 447, Jan. 2021, p. 152630. Pubmed, doi:10.1016/j.tox.2020.152630.
URI
https://scholars.duke.edu/individual/pub1465328
PMID
33188857
Source
pubmed
Published In
Toxicology
Volume
447
Published Date
Start Page
152630
DOI
10.1016/j.tox.2020.152630

Research Areas:

Abnormalities, Drug-Induced
Aldehydes
Benzopyrans
Calcium
Calibration
Cell Survival
DNA Replication
Dose-Response Relationship, Drug
Energy Metabolism
Fluorenes
Genotype
Half-Life
HeLa Cells
Heart
Heart Defects, Congenital
Humic Substances
Laboratories
Larva
Molecular Structure
Mutation
Neoplasm Proteins
Phosphorylation
Ponds
Proteolysis
Silver Nitrate
Solubility
Structure-Activity Relationship
Sulfides
Toxicity Tests
Transcriptome