@article{starnes_jackson_rock_belcher_2024, title={Quantitative cross-species comparison of serum albumin binding of per- and polyfluoroalkyl substances from five structural classes}, volume={3}, ISSN={["1096-0929"]}, url={https://doi.org/10.1093/toxsci/kfae028}, DOI={10.1093/toxsci/kfae028}, abstractNote={Abstract}, journal={TOXICOLOGICAL SCIENCES}, author={Starnes, Hannah M. and Jackson, Thomas W. and Rock, Kylie D. and Belcher, Scott M.}, year={2024}, month={Mar} }
 @article{guillette_jackson_guillette_mccord_belcher_2022, title={Blood concentrations of per- and polyfluoroalkyl substances are associated with autoimmune-like effects in American alligators from Wilmington, North Carolina}, volume={4}, ISSN={["2673-3080"]}, url={http://dx.doi.org/10.3389/ftox.2022.1010185}, DOI={10.3389/ftox.2022.1010185}, abstractNote={Surface and groundwater of the Cape Fear River basin in central and coastal North Carolina is contaminated with high levels of per- and polyfluoroalkyl substances (PFAS). Elevated levels of PFAS have also been found in blood of fish and wildlife from the Cape Fear River, and in the blood of human populations reliant on contaminated well or surface water from the Cape Fear River basin as a source of drinking water. While the public and environmental health impacts of long-term PFAS exposures are poorly understood, elevated blood concentrations of some PFAS are linked with immunotoxicity and increased incidence of some chronic autoimmune diseases in human populations. The goal of this One Environmental Health study was to evaluate PFAS exposure and biomarkers related to immune health in populations of American alligators (Alligator mississippiensis), a protected and predictive sentinel species of adverse effects caused by persistent toxic pollutants. We found that serum PFAS concentrations in alligator populations from the Cape Fear River were increased compared to a reference population of alligators from the adjoining Lumber River basin. The elevated serum PFAS concentrations in the Cape Fear River alligators were associated with increased innate immune activities, and autoimmune-like phenotypes in this population. In addition to evidence of significantly higher double stranded-DNA binding autoantibodies in adult Cape Fear River alligators, our qRT-PCR analysis found remarkably high induction of Interferon-α signature genes implicated in the pathology of human autoimmune disease. We interpret the association of increased PFAS exposure with disrupted immune functions to suggest that PFAS broadly alters immune activities resulting in autoimmune-like pathology in American alligators. This work substantiates and extends evidence from experimental models and human epidemiology studies showing that some PFAS are immune toxicants.}, journal={FRONTIERS IN TOXICOLOGY}, publisher={Frontiers Media SA}, author={Guillette, T. C. and Jackson, Thomas W. and Guillette, Matthew and McCord, James and Belcher, Scott M.}, year={2022}, month={Oct} }
 @article{jackson_baars_belcher_2022, title={Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential Metal Ion Homeostasis}, volume={2}, ISSN={["1096-0929"]}, url={https://doi.org/10.1093/toxsci/kfac027}, DOI={10.1093/toxsci/kfac027}, abstractNote={Abstract}, journal={TOXICOLOGICAL SCIENCES}, publisher={Oxford University Press (OUP)}, author={Jackson, Thomas W. and Baars, Oliver and Belcher, Scott M.}, year={2022}, month={Feb} }
 @article{jackson_scheibly_polera_belcher_2021, title={Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry}, volume={55}, ISSN={["1520-5851"]}, url={https://doi.org/10.1021/acs.est.1c01200}, DOI={10.1021/acs.est.1c01200}, abstractNote={Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically based pharmacokinetic modeling approaches is currently limited by a lack of experimental data defining albumin-binding properties for most PFAS. A novel thermal denaturation assay was optimized to evaluate changes in the thermal stability of HSA in the presence of increasing concentrations of known ligands and a structurally diverse set of PFAS. Assay performance was initially evaluated for fatty acids and HSA-binding drugs ibuprofen and warfarin. Concentration-response relationships were determined and dissociation constants (Kd) for each compound were calculated using regression analysis of the dose-dependent changes in HSA melting temperature. Estimated Kd values for HSA binding of octanoic acid, decanoic acid, hexadecenoic acid, ibuprofen, and warfarin agreed with established values. The binding affinities for 24 PFAS that included perfluoroalkyl carboxylic acids (C4-C12), perfluoroalkyl sulfonic acids (C4-C8), mono- and polyether perfluoroalkyl ether acids, and polyfluoroalkyl fluorotelomer substances were determined. These results demonstrate the utility of this differential scanning fluorimetry assay as a rapid high-throughput approach for determining the relative protein-binding properties and identification of chemical structures involved in binding for large numbers of structurally diverse PFAS.}, number={18}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, publisher={American Chemical Society (ACS)}, author={Jackson, Thomas W. and Scheibly, Chris M. and Polera, M. E. and Belcher, Scott M.}, year={2021}, month={Sep}, pages={12291–12301} }
 @article{jackson_ryherd_scheibly_sasser_guillette_belcher_2020, title={Gestational Cd Exposure in the CD-1 Mouse Induces Sex-Specific Hepatic Insulin Insensitivity, Obesity, and Metabolic Syndrome in Adult Female Offspring}, volume={178}, ISSN={["1096-0929"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85097035964&partnerID=MN8TOARS}, DOI={10.1093/toxsci/kfaa154}, abstractNote={Abstract}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Jackson, Thomas W. and Ryherd, Garret L. and Scheibly, Chris M. and Sasser, Aubrey L. and Guillette, T. C. and Belcher, Scott M.}, year={2020}, month={Dec}, pages={264–280} }
 @article{jackson_bendfeldt_beam_rock_belcher_2020, title={Heterozygous mutation of sonic hedgehog receptor (Ptch1) drives cerebellar overgrowth and sex-specifically alters hippocampal and cortical layer structure, activity, and social behavior in female mice}, volume={78}, ISSN={["1872-9738"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85080064843&partnerID=MN8TOARS}, DOI={10.1016/j.ntt.2020.106866}, abstractNote={Sonic hedgehog (SHH) signaling is essential for the differentiation and migration of early stem cell populations during cerebellar development. Dysregulation of SHH-signaling can result in cerebellar overgrowth and the formation of the brain tumor medulloblastoma. Treatment for medulloblastoma is extremely aggressive and patients suffer life-long side effects including behavioral deficits. Considering that other behavioral disorders including autism spectrum disorders, holoprosencephaly, and basal cell nevus syndrome are known to present with cerebellar abnormalities, it is proposed that some behavioral abnormalities could be inherent to the medulloblastoma sequalae rather than treatment. Using a haploinsufficient SHH receptor knockout mouse model (Ptch1+/−), a partner preference task was used to explore activity, social behavior and neuroanatomical changes resulting from dysregulated SHH signaling. Compared to wild-type, Ptch1+/− females displayed increased activity by traveling a greater distance in both open-field and partner preference tasks. Social behavior was also sex-specifically modified in Ptch1+/− females that interacted more with both novel and familiar animals in the partner preference task compared to same-sex wild-type controls. Haploinsufficiency of PTCH1 resulted in cerebellar overgrowth in lobules IV/V and IX of both sexes, and female-specific decreases in hippocampal size and isocortical layer thickness. Taken together, neuroanatomical changes related to deficient SHH signaling may alter social behavior.}, journal={NEUROTOXICOLOGY AND TERATOLOGY}, author={Jackson, Thomas W. and Bendfeldt, Gabriel A. and Beam, Kelby A. and Rock, Kylie D. and Belcher, Scott M.}, year={2020} }
 @article{guillette_jackson_belcher_2018, title={Duality of estrogen receptor beta action in cancer progression}, volume={41}, ISSN={["1471-4973"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85047091078&partnerID=MN8TOARS}, DOI={10.1016/j.coph.2018.05.001}, abstractNote={The physiological actions of estrogens are primarily mediated by the nuclear hormone receptors estrogen receptor alpha (ERα) and beta (ERβ). Activities of these nuclear steroid hormone receptors in etiology and progression of many hormone-responsive cancers are well-established, yet the specific role of each receptor, and their various expressed isoforms, in estrogen-responsive cancers remains unclear. Recent advances in nuclear receptor profiling, characterization of expressed splice variants, and the availability of new experimental cancer models, has extended the understanding of the complex interplay between the differentially expressed nuclear estrogen receptors. In this review, we discuss proposed roles of ERβ in several subtypes of cancers that lack significant ERα expression and define current understanding of how different ERs collaborate to regulate cellular processes.}, journal={CURRENT OPINION IN PHARMACOLOGY}, author={Guillette, T. C. and Jackson, Thomas W. and Belcher, Scott M.}, year={2018}, month={Aug}, pages={66–73} }