@article {225, title = {Building the Environmental Chemical-Protein Interaction Network (eCPIN): An Exposome-Wide Strategy for Bioactive Chemical Contaminant Identification}, journal = {Environmental Science and Technology}, year = {2023}, chapter = {in press}, author = {Gong, YF and Yang, DW and Barrett, H and Yang, DW and Peng, H} } @article {228, title = {Per- and Polyfluoroalkyl Substances in Canadian Fast Food Packaging}, journal = {Environ. Sci. Technol. Lett}, year = {2023}, author = {Schwartz-Narbonne, Heather and Xia, CJ and Shalin, A and Whitehead, HD and Yang, DW and Peaslee, Graham F and Wang, ZY and Wu, Y and Peng, H and Blum, A and Venier, M and Diamond, ML} } @article {178, title = {Quantitative Chemical Proteomics Reveals Interspecies Variations on Binding Schemes of L-FABP with Perfluorooctanesulfonate}, journal = {Environ. Sci. Technol.}, volume = {55}, year = {2021}, abstract = {

Evaluating interspecies toxicity variation is a long-standing challenge for chemical hazard assessment. This study developed a Quantitative Interspecies Thermal Shift Assay (QITSA) for in-situ, quantitative, and modest-throughput investigation of chemical-protein interactions in cell and tissue samples across species. By using liver fatty acid binding protein (L-FABP) as a case study, the QITSA method was benchmarked with six per- and polyfluoroalkyl substances (PFAS) and thermal shifts (∆Tm) were inversely related to their dissociation constants (R2=0.98). QITSA can also distinguish binding modes of chemicals exemplified by palmitic acid. The QITSA was applied to determine the interactions between perfluorooctanesulfonate(PFOS) and L-FABP in liver cells or tissues from human, mouse, rat, and zebrafish. The largest thermal stability enhancement by PFOS was observed for human L-FABP, followed by mouse, rat and zebrafish. While endogenous ligands were revealed to partially contribute to the large interspecies variation, recombinant proteins were employed to confirm the high binding affinity of PFOS to human L-FABP, compared to rat and mouse. This study implemented an experimental strategy to characterize chemical-protein interactions across species and future application of QITSA to other chemical contaminants is of great interest.

}, author = {Han, JJ and Fu, J and Sun, JX and Hall, DR and Yang, DW and Blatz, D and Houck, KA and Ng, CA and Doering, JA and LaLone, CA and Peng, H} } @article {175, title = {A Roadmap to the Structure-Related Metabolism Pathways of Per- and Polyfluoroalkyl Substances in the Early Life Stages of Zebrafish (Danio rerio)}, journal = {Environ. Health. Perspect.}, volume = {129}, year = {2021}, abstract = {

BACKGROUND: Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear.

OBJECTIVES: To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U.S. EPA{\textquoteright}s PFAS screening library.

METHODS: Using the early life stages of zebrafish (Danio rerio) as a model, we determined the bioconcentration factors and phenotypic toxicities of 74 PFAS. Then, we applied High-Resolution Mass Spectrometry based non-targeted analysis to identify metabolites of PFAS in zebrafish larvae after five days of exposure, by incorporating retention time and mass spectra. In vitro enzymatic activity experiments with human recombinant liver carboxylesterase (hCES1) were employed to validate the structure-related hydrolysis of 11 selected PFASs.

RESULTS: Our findings identified five structural categories of PFAS prone to metabolism. The metabolism pathways of PFAS are highly related to their structures as exemplified by fluorotelomer alcohols that the predominance of β-oxidation or taurine conjugation pathways were primarily determined by the number of hydrocarbons. Hydrolysis is a major metabolism pathway for diverse PFAS and perfluoroalkyl carboxamides showed the highest in vivo hydrolysis rates, followed by carboxyesters and sulfonamides. The hydrolysis of PFAS was verified with recombinant hCES1, with strong substrate preferences towards perfluoroalkyl carboxamides.

CONCLUSIONS:We suggest that the roadmap of the structure-related metabolism pathways of PFAS established in this study would provide a starting point to inform the potential health risks of other PFAS.

}, author = {Han, JJ and Gu, W and Barrett, H and Yang, DW and Tang, S and Sun, JX and Liu, JB and Krause, HM and Houck, KA and Peng, H} } @article {138, title = {Nontarget Screening of Per- and Polyfluoroalkyl Substances Binding to Human Liver Fatty Acid Binding Protein}, journal = {Environ. Sci. Technol.}, volume = {54}, year = {2020}, chapter = {5676-5686}, author = {Yang, DW and Han, JJ and Hall, DR and Sun, JX and Fu, J and Kutarna, S and Houck, KA and LaLone, CA and Doering, JA and Ng, CA and Peng, H} }