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Project Publications: Duke University: Mechanisms and Consequences of Evolved Adaptation to Environmental Pollution

Superfund Research Program

Mechanisms and Consequences of Evolved Adaptation to Environmental Pollution

Project Leader: Richard T. Di Giulio
Co-Investigator: David E. Hinton
Grant Number: P42ES010356
Funding Period: 2011-2022

Project-Specific Links




  • Boyda J, Hawkey AB, Holloway Z, Trevisan R, Di Giulio RT, Levin ED. 2021. The organophosphate insecticide diazinon and aging: Neurobehavioral and mitochondrial effects in zebrafish exposed as embryos or during aging. Neurotoxicol Teratol 87:doi:10.1016/ PMID:34224825 PMCID:PMC8440393
  • Bozinovic G, Shea D, Feng Z, Hinton DE, Sit TL, Oleksiak MF. 2021. PAH-pollution effects on sensitive and resistant embryos: Integrating structure and function with gene expression. PLoS One 16(4):e0249432. doi:10.1371/journal.pone.0249432 PMID:33822796 PMCID:PMC8023486
  • Chernick M, Lieberman N, Brown DR, Di Giulio RT, Hinton DE, Burke T. 2021. Heart development in two populations of Atlantic killifish (Fundulus heteroclitus) following exposure to a polycyclic aromatic hydrocarbon mixture. Ecotoxicol Environ Saf 208:111580. doi:10.1016/j.ecoenv.2020.111580 PMID:33396103
  • Redfern L, Jayasundara N, Singleton D, Di Giulio RT, Carlson J, Sumner SJ, Gunsch C. 2021. The role of gut microbial community and metabolomic shifts in adaptive resistance of Atlantic killifish (Fundulus heteroclitus) to polycyclic aromatic hydrocarbons. Sci Total Environ 776:145955. doi:10.1016/j.scitotenv.2021.145955 PMID:33647645 PMCID:PMC8294123
  • Silva RA, Di Giulio RT, Rice CD. 2021. The in vitro proinflammatory properties of water accommodated sediment extracts from a creosote-contaminated US Environmental Protection Agency Superfund Site. Environ Toxicol Chem 40(6):1576-1585. doi:10.1002/etc.5001 PMID:33512033


  • Baldwin WS, Bain LJ, Di Giulio RT, Kullman SW, Rice CD, Ringwood AH, van den Hurk P. 2020. 20th Pollutant Responses in Marine Organisms (PRIMO 20): Global issues and fundamental mechanisms caused by pollutant stress in marine and freshwater organisms. Aquat Toxicol 227:doi:10.1016/j.aquatox.2020.105620 PMID:32932042
  • Trevisan R, Uzochukwu D, Di Giulio RT. 2020. PAH sorption to nanoplastics and the Trojan Horse Effect as drivers of mitochondrial toxicity and PAH localization in zebrafish. front environ sci 8:doi:10.3389/fenvs.2020.00078


  • Di Giulio RT, Newman MC. 2019. Ecotoxicology. Chapter 30 in: Casarett & Doull's Toxicology: The Basic Science of Poisons, 9th Edition. McGraw Hill Education,
  • Haschek-Hock WM, Berenbaum M, Hinton DE, Cora MC, Chernoff N, Travios G, Liu C, Lu K, Law M. 2019. Pathology in ecological research with implications for one health: session summary. Toxicol Pathol 47:1072-1075. doi:10.1177/0192623319880530 PMID:31645202 PMCID:PMC6910945
  • Lindberg C, Di Giulio RT. 2019. Polycyclic aromatic hydrocarbon and hypoxia exposures result in mitochondrial dysfunction in zebrafish. Aquat Toxicol 216:doi:10.1016/j.aquatox.2019.105298 PMID:31586484 PMCID:PMC6917040
  • Trevisan R, Voy C, Chen S, Di Giulio RT. 2019. Nanoplastics decrease the toxicity of a complex PAH mixture but impair mitochondrial energy production in developing zebrafish. Environ Sci Technol 53:8405-8415. doi:10.1021/acs.est.9b02003 PMID:31259535 PMCID:PMC6660138
  • Volkoff SJ, Osterberg JS, Jayasundara N, Cooper EM, Hsu-Kim H, Rogers LA, Gehrke GE, Jayaraman S, Di Giulio RT. 2019. Embryonic fundulus heteroclitus responses to sediment extracts from differentially contaminated sites in the Elizabeth River, VA. Ecotoxicology 28:9:1126-1135. doi:10.1007/s10646-019-02116-z PMID:31620948 PMCID:PMC7768734


  • Gearhart-Serna LM, Jayasundara N, Tacam M, Di Giulio RT, Devi GR. 2018. Assessing cancer risk associated with aquatic polycyclic aromatic hydrocarbon pollution reveals dietary routes of exposure and vulnerable populations. J Environ Public Health 2018:5610462. doi:10.1155/2018/5610462 PMID:30327676 PMCID:PMC6169233
  • Osterberg JS, Cammen KM, Schultz TF, Clark BW, Di Giulio RT. 2018. Genome-wide scan reveals signatures of selection related to pollution adaptation in non-model estuarine Atlantic killifish (Fundulus heteroclitus). Aquat Toxicol 200:73-82. doi:10.1016/j.aquatox.2018.04.017 PMID:29727773 PMCID:PMC6957077
  • Pitt JA, Kozal JS, Jayasundara N, Massarsky A, Trevisan R, Geiter N, Wiesner MR, Levin ED, Di Giulio RT. 2018. Uptake, tissue distribution, and toxicity of polystyrene nanoparticles in developing zebrafish (Danio rerio). Aquat Toxicol 194:185-194. doi:10.1016/j.aquatox.2017.11.017 PMID:29197232
  • Pitt JA, Trevisan R, Massarsky A, Kozal JS, Levin ED, Di Giulio RT. 2018. Maternal transfer of nanoplastics to offspring in zebrafish (Danio rerio): A case study with nanopolystyrene. Sci Total Environ 643:324-334. doi:10.1016/j.scitotenv.2018.06.186 PMID:29940444
  • Wang F, Fang M, Hinton DE, Chernick M, Jia S, Zhang Y, Xie L, Dong W, Dong W. 2018. Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47. Chemosphere 198:342-350. doi:10.1016/j.chemosphere.2018.01.081 PMID:29421749


  • Brown DR, Thompson J, Chernick M, Hinton DE, Di Giulio RT. 2017. Later life swimming performance and persistent heart damage following subteratogenic PAH mixture exposure in the Atlantic killifish (Fundulus heteroclitus). Environ Toxicol Chem 36:3246-3253. doi:10.1002/etc.3877 PMID:28585726
  • Hartman JH, Kozal JS, Di Giulio RT, Meyer JN. 2017. Zebrafish have an ethanol-inducible hepatic 4-nitrophenol hydroxylase that is not CYP2E1-like. Environ Toxicol Pharmacol 54:142-145. doi:10.1016/j.etap.2017.07.004 PMID:28728133 PMCID:PMC5563387
  • Jayasundara N, Fernando PW, Osterberg JS, Cammen KM, Schultz TF, Di Giulio RT. 2017. Cost of tolerance: Physiological consequences of evolved resistance to inhabit a polluted environmental in Teleost fish Fundulus heteroclitus. Environ Sci Technol 51:8763-8772. doi:10.1021/acs.est.7b01913 PMID:28682633
  • Lindberg C, Jayasundara N, Kozal JS, Leuthner T, Di Giulio RT. 2017. Resistance to polycyclic aromatic hydrocarbon toxicity and associated bioenergetic consequences in a population of Fundulus heteroclitus. Ecotoxicology 26(3):435-448. doi:10.1007/s10646-017-1775-6 PMID:28213827
  • Luz AL, Godebo TR, Smith LL, Leuthner T, Maurer LL, Meyer JN. 2017. Deficiencies in mitochondrial dynamics sensitize Caenorhabditis elegans to arsenite and other mitochondrial toxicants by reducing mitochondrial adaptability. Toxicology 387:81-94. doi:10.1016/j.tox.2017.05.018 PMID:28602540
  • Macaulay LJ, Chernick M, Chen A, Hinton DE, Bailey JM, Kullman SW, Levin ED, Stapleton HM. 2017. Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development. Environ Toxicol Chem 36(1):36-48. doi:10.1002/etc.3535 PMID:27329031
  • Massarsky A, Kozal JS, Di Giulio RT. 2017. Glutathione and zebrafish: old assays to address a current issue. Chemosphere 168:707-715. doi:10.1016/j.chemosphere.2016.11.004 PMID:27836271 PMCID:PMC5182135
  • Mu J, Chernick M, Dong W, Di Giulio RT, Hinton DE. 2017. Early life co-exposures to a real-world PAH mixture and hypoxia result in later life and next generation consequences in medaka (Oryzias latipes). Aquat Toxicol 190:162-173. doi:10.1016/j.aquatox.2017.06.026 PMID:28728047 PMCID:PMC5584607
  • Raftery TD, Jayasundara N, Di Giulio RT. 2017. A bioenergetics assay for studying the effects of environmental stressors on mitochondrial function in vivo in zebrafish larvae. Comp Biochem Physiol C Toxicol Pharmacol 192:23-32. doi:10.1016/j.cbpc.2016.12.001 PMID:27939721 PMCID:PMC5218841
  • Slotkin TA, Skavicus S, Card JA, Di Giulio RT, Seidler FJ. 2017. In vitro models reveal differences in the developmental neurotoxicity of an environmental polycylic aromatic hydrocarbon mixture compared to benzo[a]pyrene: Neuronotypic PC12 Cells and embryonic neural stem cells. Toxicology 377:49-56. doi:10.1016/j.tox.2016.12.008 PMID:28049045 PMCID:PMC5250555


  • Brown DR, Bailey JM, Oliveri A, Levin ED, Di Giulio RT. 2016. Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish. Neurotoxicol Teratol 53:55-63. doi:10.1016/ PMID:26548404 PMCID:PMC4803068
  • Brown DR, Clark BW, Garner LV, Di Giulio RT. 2016. Embryonic cardiotoxicity of weak aryl hydrocarbon receptor agonists and CYP1A inhibitor fluoranthene in the Atlantic killifish (Fundulus heteroclitus). Comp Biochem Physiol C Toxicol Pharmacol 188:45-51. doi:10.1016/j.cbpc.2016.05.005 PMID:27211013
  • Gonzalez-Hunt CP, Rooney JP, Ryde IT, Anbalagan C, Joglekar R, Meyer JN. 2016. PCR-based analysis of mitochondrial DNA copy number, mitochondrial DNA damage, and nuclear DNA damage. Curr Protoc Toxicol 67:20.11.1-20.11.25. doi:10.1002/0471140856.tx2011s67 PMID:26828332 PMCID:PMC4928199
  • Luz AL, Godebo TR, Bhatt DP, Ilkayeva OR, Maurer LL, Hirschey MD, Meyer JN. 2016. From the cover: arsenite uncouples mitochondrial respiration and induces a Warburg-like effect in Caenorhabditis elegans. Toxicol Sci 152(2):349-362. doi:10.1093/toxsci/kfw093 PMID:27208080 PMCID:PMC4960910
  • Luz AL, Lagido C, Hirschey MD, Meyer JN. 2016. In vivo determination of mitochondrial function using luciferase-expressing Caenorhabditis elegans: contribution of oxidative phosphorylation, glycolysis, and fatty acid oxidation to toxicant-induced dysfunction. Curr Protoc Toxicol 69:25.8.1-25.8.22. doi:10.1002/cptx.10 PMID:27479364 PMCID:PMC5002950
  • Riley AK, Chernick M, Brown DR, Hinton DE, Di Giulio RT. 2016. Hepatic responses of juvenile Fundulus heteroclitus from pollution-adapted and nonadapted populations exposed to Elizabeth River sediment extract. Toxicol Pathol 44(5):738-748. doi:10.1177/0192623316636717 PMID:26992886 PMCID:PMC4912431
  • Santa-Gonzalez GA, Gomez-Molina A, Arcos-Burgos M, Meyer JN, Camargo M. 2016. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest. Redox Biol 9:124-133. doi:10.1016/j.redox.2016.07.004 PMID:27479053 PMCID:PMC4971155
  • Van Houten B, Hunter SE, Meyer JN. 2016. Mitochondrial DNA damage induced autophagy, cell death, and disease. Front Biosci (Landmark Ed) 21:42-54. PMID:26709760 PMCID:PMC4750375


  • Brown DR, Clark BW, Garner LV, Di Giulio RT. 2015. Zebrafish cardiotoxicity: the effects of CYP1A inhibition and AHR2 knockdown following exposure to weak aryl hydrocarbon receptor agonists. Environ Sci Pollut Res Int 22(11):8329-8338. doi:10.1007/s11356-014-3969-2 PMID:25532870 PMCID:PMC4442063
  • Di Giulio RT, Clark BW. 2015. The Elizabeth River story: a case study in evolutionary toxicology. J Toxicol Environ Health B Crit Rev 18(6):259-298. doi:10.1080/15320383.2015.1074841 PMID:26505693 PMCID:PMC4733656
  • Jayasundara N, Garner LV, Meyer JN, Erwin K, Di Giulio RT. 2015. AHR2-Mediated transcriptomic responses underlying the synergistic cardiac developmental toxicity of PAHs. Toxicol Sci 143(2):469-481. doi:10.1093/toxsci/kfu245 PMID:25412620 PMCID:PMC4306723
  • Jayasundara N, Kozal JS, Arnold MC, Chan SS, Di Giulio RT. 2015. High-throughput tissue bioenergetics analysis reveals identical metabolic allometric scaling for teleost hearts and whole organisms. PLoS One 10(9):e0137710. doi:10.1371/journal.pone.0137710 PMID:26368567 PMCID:PMC4569437
  • Luz AL, Rooney JP, Kubik L, Gonzalez C, Song DH, Meyer JN. 2015. Mitochondrial morphology and fundamental parameters of the mitochondrial respiratory chain are altered in Caenorhabditis elegans strains deficient in mitochondrial dynamics and homeostasis processes. PLoS One 10(6):e0130940. doi:10.1371/journal.pone.0130940 PMID:26106885 PMCID:PMC4480853
  • Luz AL, Smith LL, Meyer JN, Rooney JP. 2015. Seahorse Xfe 24 extracellular flux analyzer-based analysis of cellular respiration in Caenorhabditis elegans. Curr Protoc Toxicol 66:25.7.1-15. doi:10.1002/0471140856.tx2507s66 PMID:26523474 PMCID:PMC4632645
  • Macaulay LJ, Chen A, Rock KD, Dishaw L, Dong W, Hinton DE, Stapleton HM. 2015. Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor β. Aquat Toxicol 168:38-47. doi:10.1016/j.aquatox.2015.09.007 PMID:26433919 PMCID:PMC4618599
  • Robey R, Weisz J, Kuemmerle NB, Salzberg AC, Berg A, Brown DG, Kubik L, Palorini R, Al-Mulla F, Al-Temaimi R, Colacci A, Mondello C, Raju J, Woodrick J, Scovassi A, Singh N, Vaccari M, Roy R, Forte S, Memeo L, Salem HK, Amedei A, Hamid RA, Williams GP, Lowe L, Meyer JN, Martin FL, Bisson WH, Chiaradonna F, Ryan EP. 2015. Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?. Carcinogenesis 36Suppl1:S203-S231. doi:10.1093/carcin/bgv037 PMID:26106140 PMCID:PMC4565609
  • Rooney JP, Ryde IT, Saunders LH, Howlett EH, Colton MD, Germ KE, Mayer GD, Greenamyre JT, Meyer JN. 2015. PCR based determination of mitochondrial DNA copy number in multiple species. Methods Mol Biol 1241:23-38. doi:10.1007/978-1-4939-1875-1_3 PMID:25308485 PMCID:PMC4312664


  • Colton MD, Kwok KW, Brandon JA, Warren IH, Ryde IT, Cooper EM, Hinton DE, Rittschof D, Meyer JN. 2014. Developmental toxicity and DNA damage from exposure to parking lot runoff retention pond samples in the Japanese medaka (Oryzias latipes). Mar Environ Res 99:117-124. doi:10.1016/j.marenvres.2014.04.007 PMID:24816191 PMCID:PMC4309550
  • Fang M, Getzinger GJ, Cooper EM, Clark BW, Garner LV, Di Giulio RT, Ferguson PL, Stapleton HM. 2014. Effect-directed analysis of Elizabeth River porewater: developmental toxicity in zebrafish (Danio rerio). Environ Toxicol Chem 33(12):2767-2774. doi:10.1002/etc.2738 PMID:25196082 PMCID:PMC4393830
  • Shaughnessy DT, McAllister KA, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli A, Begley T, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. 2014. Mitochondria, energetics, epigenetics, and cellular responses to stress. Environ Health Perspect 122(12):1271-1278. doi:10.1289/ehp.1408418 PMID:25127496 PMCID:PMC4256704


  • Bess AS, Ryde IT, Hinton DE, Meyer JN. 2013. UVC-induced mitochondrial degradation via autophagy correlates with mtDNA damage removal in primary human fibroblasts. J Biochem Mol Toxicol 27(1):28-41. doi:10.1002/jbt.21440 PMID:23132756 PMCID:PMC3640456
  • Bozinovic G, Sit TL, Di Giulio RT, Wills LF, Oleksiak MF. 2013. Genomic and physiological responses to strong selective pressure during late organogenesis: Few gene expression changes found despite striking morphological differences. BMC Genomics 14:779. doi:10.1186/1471-2164-14-779 PMID:24215130 PMCID:PMC3835409
  • Clark BW, Bone AJ, Di Giulio RT. 2013. Resistance to teratogenesis by F1 and F2 embryos of PAH-adapted Fundulus heteroclitus is strongly inherited despite reduced recalcitrance of the AHR pathway. Environ Sci Pollut Res Int doi:10.1007/s11356-013-2446-7 PMID:24374617 PMCID:PMC4074458
  • Clark BW, Cooper EM, Stapleton HM, Di Giulio RT. 2013. Compound- and mixture-specific differences in resistance to polycyclic aromatic hydrocarbons and PCB-126 among Fundulus heteroclitus subpopulations throughout the Elizabeth River Estuary (Virginia, USA). Environ Sci Technol 47(18):10556-10566. doi:10.1021/es401604b PMID:24003986 PMCID:PMC4079253
  • Dong W, Macaulay LJ, Kwok KW, Hinton DE, Stapleton HM. 2013. Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: a tool for examining OH-BDE toxicity to early life stages. Aquat Toxicol 132-133:190-199. doi:10.1016/j.aquatox.2013.02.008 PMID:23531416 PMCID:PMC3642849
  • Garner LV, Brown DR, Di Giulio RT. 2013. Knockdown of AHR1A but not AHR1B exacerbates PAH and PCB-126 toxicity in zebrafish (Danio rerio) embryos. Aquat Toxicol 142-143:336-346. doi:10.1016/j.aquatox.2013.09.007 PMID:24084256 PMCID:PMC3837554
  • Meyer JN, Leung MC, Rooney JP, Sendoel A, Hengartner MO, Kisby GE, Bess AS. 2013. Mitochondria as a target of environmental toxicants. Toxicol Sci 134:1-17. doi:10.1093/toxsci/kft102 PMID:23629515 PMCID:PMC3693132
  • Van Wettere AJ, Hinton DE, Kullman SW, Law JM. 2013. Anchoring hepatic gene expression with development of fibrosis and neoplasia in a toxicant-induced fish model of liver injury. Toxicol Pathol 41(5):744-760. doi:10.1177/0192623312464308 PMID:23197195 PMCID:PMC4096295
  • Zhao B, Bohonowych JE, Timme-Laragy AR, Jung D, Affatato AA, Rice RH, Di Giulio RT, Denison MS. 2013. Common commercial and consumer products contain activators of the aryl hydrocarbon (dioxin) receptor. PLoS One 8(2):e56860. doi:10.1371/journal.pone.0056860 PMID:23441220 PMCID:PMC3575475



  • Fleming CR, Di Giulio RT. 2011. The role of CYP1A inhibition in the embryotoxic interactions between hypoxia and polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures in zebrafish (Danio rerio). Ecotoxicology 20:1300-1314. doi:10.1007/s10646-011-0686-1 PMID:21706407 PMCID:PMC4018733
  • Jung D, Matson CW, Collins LB, Laban G, Stapleton HM, Bickham JW, Swenberg JA, Di Giulio RT. 2011. Genotoxicity in Atlantic killifish (Fundulus heteroclitus) from a PAH-contaminated Superfund site on the Elizabeth River, Virginia. Ecotoxicology 20:1890-1899. doi:10.1007/s10646-011-0727-9 PMID:21706406 PMCID:PMC3203518
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