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  2. Safer Chemicals Research

Advanced Experimental Toxicological Models Research

On this page: 
  • Recent publications
  • Researchers

Recent Publications

  • Protection of cell therapeutics from antibody-mediated killing by CD64 overexpression.

Gravina A, Tediashvili G, Rajalingam R, Quandt Z, Deisenroth C, Schrepfer S, Deuse T.Nat Biotechnol. 2023 May;41(5):717-727. doi: 10.1038/s41587-022-01540-7. Epub 2023 Jan 2.PMID: 36593395 

  • Evaluation of a high-throughput H295R homogenous time resolved fluorescence assay for androgen and estrogen steroidogenesis screening.

Garnovskaya M, Feshuk M, Stewart W, Friedman KP, Thomas RS, Deisenroth C.Toxicol In Vitro. 2023 Oct;92:105659. doi: 10.1016/j.tiv.2023.105659. Epub 2023 Aug 7.PMID: 37557933 

  • Technical evaluation and standardization of the human thyroid microtissue assay.

Foley B, Hopperstad K, Gamble J, Lynn SG, Thomas RS, Deisenroth C.Toxicol Sci. 2024 Apr 29;199(1):89-107. doi: 10.1093/toxsci/kfae014.PMID: 38310358

  • Development of a bioprinter-based method for incorporating metabolic competence into high-throughput in vitro assays.

Hopperstad K, Deisenroth C.Front Toxicol. 2023 May 4;5:1196245. doi: 10.3389/ftox.2023.1196245. eCollection 2023.PMID: 37215384 

  • The DevTox Germ Layer Reporter Platform: An Assay Adaptation of the Human Pluripotent Stem Cell Test.

Gamble JT, Hopperstad K, Deisenroth C.Toxics. 2022 Jul 13;10(7):392. doi: 10.3390/toxics10070392.PMID: 35878297 

  • Chemical Screening in an Estrogen Receptor Transactivation Assay With Metabolic Competence.

Hopperstad K, DeGroot DE, Zurlinden T, Brinkman C, Thomas RS, Deisenroth C.Toxicol Sci. 2022 Apr 26;187(1):112-126. doi: 10.1093/toxsci/kfac019.PMID: 35172002

  • From vision toward best practices: Evaluating in vitro transcriptomic points of departure for application in risk assessment using a uniform workflow.

Reardon AJF, Farmahin R, Williams A, Meier MJ, Addicks GC, Yauk CL, Matteo G, Atlas E, Harrill J, Everett LJ, Shah I, Judson R, Ramaiahgari S, Ferguson SS, Barton-Maclaren TS.Front Toxicol. 2023 May 23;5:1194895. doi: 10.3389/ftox.2023.1194895. eCollection 2023.PMID: 3728800

  • Insights into Repeated Renal Injury Using RNA-Seq with Two New RPTEC Cell Lines.

Merrick BA, Martin NP, Brooks AM, Foley JF, Dunlap PE, Ramaiahgari S, Fannin RD, Gerrish KE.Int J Mol Sci. 2023 Sep 18;24(18):14228. doi: 10.3390/ijms241814228.PMID: 37762531 

  • Deep Learning Image Analysis of High-Throughput Toxicology Assay Images.

Tandon A, Howard B, Ramaiahgari S, Maharana A, Ferguson S, Shah R, Merrick BA.SLAS Discov. 2022 Jan;27(1):29-38. doi: 10.1016/j.slasd.2021.10.014. Epub 2021 Oct 27.PMID: 35058173

  • Benchmark Concentrations for Untargeted Metabolomics Versus Transcriptomics for Liver Injury Compounds in In Vitro Liver Models.

Crizer DM, Ramaiahgari SC, Ferguson SS, Rice JR, Dunlap PE, Sipes NS, Auerbach SS, Merrick BA, DeVito MJ.Toxicol Sci. 2021 May 27;181(2):175-186. doi: 10.1093/toxsci/kfab036.PMID: 33749773

  • A Unidirectional 96-Well Fluidic Culture Platform for Upstream Cell Dosing with Subsequent Downstream Nonlinear and Ascending Exposure Gradients for Real-Time and Cell-Based Toxicity Screening Environments.

John BA, Sloan DJ, Jensen TC, Ramaiahgari SC, End P, Resh GE, McClelland RE.Appl In Vitro Toxicol. 2021 Dec 1;7(4):175-191. doi: 10.1089/aivt.2021.0006. Epub 2021 Dec 16.PMID: 35028338

  • Episodic ozone exposure in Long-Evans rats has limited effects on cauda sperm motility and non-coding RNA populations.

Chorley BN, Klinefelter GR, Nelson GM, Strader LF, Nguyen HH, Schladweiler MC, Palmer G, Moore ML, Grindstaff RD, Padgett WT, Carswell GK, Fisher AA, Kodavanti UP, Dye JA, Miller CN.Reprod Toxicol. 2024 Jun 1;128:108631. doi: 10.1016/j.reprotox.2024.108631. Online ahead of print.PMID: 3883045

  • Persistent gene expression and DNA methylation alterations linked to carcinogenic effects of dichloroacetic acid.

Carswell G, Chamberlin J, Bennett BD, Bushel PR, Chorley BN.Front Oncol. 2024 May 3;14:1389634. doi: 10.3389/fonc.2024.1389634. eCollection 2024.PMID: 38764585 

  • Vinyl chloride enhances high-fat diet-induced proteome alterations in the mouse pancreas related to metabolic dysfunction.

Ge Y, Bruno M, Nash MS, Coates NH, Chorley BN, Cave MC, Beier JI.Toxicol Sci. 2023 May 12;193(1):103-114. doi: 10.1093/toxsci/kfad024.PMID: 36892438

  • Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.

Nelson GM, Carswell GK, Swartz CD, Recio L, Yauk CL, Chorley BN.Toxicol Lett. 2023 Aug 1;384:105-114. doi: 10.1016/j.toxlet.2023.07.015. Epub 2023 Jul 28.PMID: 37517673 

  • Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey.

Cave MC, Pinkston CM, Rai SN, Wahlang B, Pavuk M, Head KZ, Carswell GK, Nelson GM, Klinge CM, Bell DA, Birnbaum LS, Chorley BN.Environ Health Perspect. 2022 Jan;130(1):17003. doi: 10.1289/EHP9467. Epub 2022 Jan 6.PMID: 34989596 

  • Vinyl chloride enhances high-fat diet-induced proteome alterations in the mouse pancreas related to metabolic dysfunction.

Ge Y, Bruno M, Nash MS, Coates NH, Chorley BN, Cave MC, Beier JI.  Toxicol Sci. 2023 May 12;193(1):103-114. doi: 10.1093/toxsci/kfad024.PMID: 36892438

  • Editor's Highlight: Mechanistic Toxicity Tests Based on an Adverse Outcome Pathway Network for Hepatic Steatosis.

Angrish MM, McQueen CA, Cohen-Hubal E, Bruno M, Ge Y, Chorley BN.Toxicol Sci. 2017 Sep 1;159(1):159-169. doi: 10.1093/toxsci/kfx121.PMID: 28903485 

  • Chemical-agnostic hazard prediction: statistical inference of in vitro toxicity pathways from proteomics responses to chemical mixtures.

Ross JA, George BJ, Bruno M, Ge Y.Comput Toxicol. 2017 May;2:39-44. doi: 10.1016/j.comtox.2017.03.001.PMID: 30345409 

  • Proteomic Assessment of Biochemical Pathways That Are Critical to Nickel-Induced Toxicity Responses in Human Epithelial Cells.

Ge Y, Bruno M, Haykal-Coates N, Wallace K, Andrews D, Swank A, Winnik W, Ross JA.PLoS One. 2016 Sep 14;11(9):e0162522. doi: 10.1371/journal.pone.0162522. eCollection 2016.PMID: 27626938

  • Increased Cell Proliferation as a Key Event in Chemical Carcinogenesis: Application in an Integrated Approach for the Testing and Assessment of Non-Genotoxic Carcinogenesis.

Strupp C, Corvaro M, Cohen SM, Corton JC, Ogawa K, Richert L, Jacobs MN.Int J Mol Sci. 2023 Aug 26;24(17):13246. doi: 10.3390/ijms241713246.PMID: 37686053 

  • Hepatic Transcriptome Comparative In Silico Analysis Reveals Similar Pathways and Targets Altered by Legacy and Alternative Per- and Polyfluoroalkyl Substances in Mice.

Robarts DR, Dai J, Lau C, Apte U, Corton JC.Toxics. 2023 Nov 28;11(12):963. doi: 10.3390/toxics11120963.PMID: 3813336

  • A 50-gene biomarker identifies estrogen receptor-modulating chemicals in a microarray compendium.

Corton JC, Matteo G, Chorley B, Liu J, Vallanat B, Everett L, Atlas E, Meier MJ, Williams A, Yauk CL.Chem Biol Interact. 2024 May 1;394:110952. doi: 10.1016/j.cbi.2024.110952. Epub 2024 Apr 2.PMID: 38570061

  • Identifying Human Specific Adverse Outcome Pathways of Per- and Polyfluoroalkyl Substances Using Liver-Chimeric Humanized Mice.

Robarts DR, Paine-Cabrera D, Kotulkar M, Venneman KK, Gunewardena S, Corton JC, Lau C, Foquet L, Bial G, Apte U.bioRxiv [Preprint]. 2023 Feb 3:2023.02.01.526711. doi: 10.1101/2023.02.01.526711.PMID: 36778348 

  • Hepatic Transcriptome Comparative In Silico Analysis Reveals Similar Pathways and Targets Altered by Legacy and Alternative Per- and Polyfluoroalkyl Substances in Mice.

Robarts DR, Dai J, Lau C, Apte U, Corton JC.Toxics. 2023 Nov 28;11(12):963. doi: 10.3390/toxics11120963.PMID: 38133364 

  • Characterization of non-radiolabeled Thyroxine (T4) uptake in cryopreserved rat hepatocyte suspensions: Pharmacokinetic implications for PFOA and PFOS chemical exposure.

Selano J, Richardson V, Washington J, Mazur C.Toxicol In Vitro. 2019 Aug;58:230-238. doi: 10.1016/j.tiv.2019.03.022. Epub 2019 Mar 28.PMID: 30930230 

  • Effects of perinatal PBDE exposure on hepatic phase I, phase II, phase III, and deiodinase 1 gene expression involved in thyroid hormone metabolism in male rat pups.

Szabo DT, Richardson VM, Ross DG, Diliberto JJ, Kodavanti PR, Birnbaum LS.Toxicol Sci. 2009 Jan;107(1):27-39. doi: 10.1093/toxsci/kfn230. Epub 2008 Oct 31.PMID: 18978342

Researchers

John Cowden, Ph.D.

Dr. John Cowden is a supervisor in the Center for Computational Toxicology and Exposure.

Prior to serving as Branch Chief, John held a variety of research and management roles at the EPA, largely focused on developing and applying new approach methodologies for predictive toxicology. As the Acting Deputy Director for the Chemical Safety for Sustainability National Research Program he implemented interdisciplinary scientific research programs to evaluate chemical hazards. John also worked on toxicological reviews for hazardous chemicals and led the development of the IRIS assessment of inorganic arsenic. He has research experience using alternative species models to investigate chemical effects on the developing nervous system. John holds a Ph.D. in Molecular Biology and Genetics from the University of California at Berkeley and a Bachelor of Science in Biology, with a minor in Chemistry, from the College of William and Mary.

Cameron Alexander

Cameron Alexander is a post-baccalaureate researcher in the Center for Computational Toxicology and Exposure. Cameron holds a B.S. degree in molecular and structural biochemistry graduated from North Carolina State University. She is working in the Corton lab developing a biomarker for the glucocorticoid receptor (GR) which regulates genes that play roles in controlling development, metabolism, and immune responses. I am also looking at metabolomic and transcriptomic data of mice exposed to produced water. Produced Water is a byproduct of extracting oil and natural gas. Through these efforts, Cameron is developing methods to identify chemicals that may pose as a hazard to the environment.

Kristen Breaux, Ph.D.

Dr. Breaux is a biologist in the Center for Computational Toxicology and Exposure. Her work supports the development of novel in vitro assays to evaluate chemical effects on the endocrine system. Her current research focuses on the incorporation of xenobiotic metabolism to high-throughput chemical screening. In a recent study, she coupled a cell-based androgen receptor assay with the alginate immobilization of metabolic enzymes (AIME) method to evaluate the androgenic effect of chemicals in the presence and absence of metabolic enzymes. She has also developed a bioprinter-based method to incorporate metabolic competence into an in vitro estrogen receptor assay. Kristen received her Ph.D. in entomology from North Carolina State University and her Bachelor of Science in Biology from the University of Texas-Pan American.

Brian Chorley, Ph.D.

Dr. Brian Chorley has been working at US Environmental Protection Agency (US EPA) for 14 years and joined the Center for Computational Toxicology and Exposure in 2019. His research is focused on the identification of genomic and epigenomic biomarkers to inform chemical risk assessment and prioritization. He currently leads efforts on refining and developing high-throughput screening methods using molecular tools such as CRISPR, extracellular vesicle isolation, and single-cell transcriptomics. Brian holds a B.S. from North Carolina State University in Animal Science and a Ph.D. from North Carolina State University in Comparative Biomedical Sciences.

Chris Corton, Ph.D.

Chris Corton, Ph.D. is a principal investigator in the Center for Computational Toxicology and Exposure. He studies mechanisms of chemical carcinogenesis, focusing on nongenotoxic carcinogenesis. His research focuses on using gene expression profile data to correlate chemical exposure with human health effects. Currently, Chris’s lab is working to 1) reduce the need for animal testing by predicting carcinogenicity using gene expression profiles, 2) build tools to predict potential adverse effects, and 3) apply these tools to understand the potential toxicity of individual chemicals and complex mixtures released from oil and gas operations. Chris holds a Ph.D. degree from the University of Kansas Medical Center.

Chad Deisenroth, Ph.D.

Dr. Chad Deisenroth is a principal investigator in the Center for Computational Toxicology and Exposure at the U.S. EPA. Chad’s research focuses on the development and application of in vitro new approach methods for predictive toxicology. His areas of expertise include cell and molecular biology, in vitro toxicology, cell-based assay development and screening. Chad received his Ph.D. in Genetics and Molecular Biology from the University of North Carolina at Chapel Hill and completed postdoctoral training in chemical safety sciences at The Hamner Institutes for Health Sciences.

Briana Foley

Briana Foley is a research scientist in the Center for Computational Toxicology and Exposure. Briana supports efforts to develop and apply novel organotypic in vitro assays for evaluating effects of chemicals on the endocrine system.  She has robust technical experience in developing and executing in vitro assays to assess activities of pharmaceutical and environmental chemicals on mammalian cells.  Briana earned a BS in Plant Science from North Carolina State University and gardening endures as a favorite hobby.

Yue Ge, Ph.D.

Dr. Yue Ge is a principal investigator in the Center for Computational Toxicology and Exposure. Yue earned his Ph.D. in Molecular and Cellular Biology from the University of Michigan in 2002, with a focus on disease proteomics, particularly in the identification of protein biomarkers and the elucidation of molecular pathological pathways. His research focuses on the advancement of toxicoproteomics to address critical environmental health challenges and support the EPA’s core missions. His work includes the development and application of toxicoproteomics methodologies to characterize various chemicals, including metals, nanomaterials, pesticides, air pollutants, and developmental neurotoxicity (DNT) compounds. Additionally, Yue’s work addresses cumulative risks from aggregate exposure to toxicants, integrates diverse datasets to support human health risk assessment, innovates analytical methods for environmental exposure monitoring of PFAS, and identifies protein biomarkers for predicting the effects of climate change on endangered tree species.

Jessie Hanson, M.S.

Jessie Hanson is a research scientist in the Center for Computational Toxicology and Exposure. She leads a project if the impacts of chemical exposures on ecosystems can be informed by examining environmental DNA samples (e.g. sediment, water, and spider webs). Her research interests include aquatic ecology, fisheries, stable isotope analysis, food web dynamics, and environmental DNA. She has worked on various projects around the Great Lakes region dealing with raising endangered lake sturgeon at hatcheries, parasitic analyses on small stream fishes, She holds a B.S. from the University of Wisconsin – Green Bay and a M.S. from the University of Minnesota-Duluth.

Joan Hedge, M.S.

Joan Hedge is a research scientist in the Center for Computational Toxicology and Exposure. Joan holds a BS in Animal Science and a MS in Physiology from North Carolina State University.  Joan has contributed to research on rodent reproductive, thyroid, developmental and neurodevelopmental toxicology. She also uses experimental approaches to investigate aspects of zebrafish husbandry and colony maintenance to enhance data reproducibility and fish welfare of the zebrafish colony.

Carlton Jones

Carlton Jones is a research scientist in the Center for Computational Toxicology and Exposure.   Carlton research focus on developing biomarkers of human diseases. He is currently exploring extracelluar vesicles as markers of chemical exposures and potential markers of health impacts. Carlton research expertise includes molecular genetics, molecular biology, and laboratory animal science. 

Jie Liu, Ph.D.

Dr. Jie Liu is a research scientist in the Center for Computational Toxicology and Exposure. He has been studying gene expression for years.  Jie was the Research Professor at University of Kansas Medical Center from 2010-2013 and works in the Corton lab under the SEE program. Jie holds a Ph.D at the University of Kansas Medical Center. 

Suzanne Martos, Ph.D.

Dr. Suzanne Martos is a postdoctoral researcher in the Center for Computational Toxicology and Exposure. Her research in the Chorley lab applies CRISPR-based approaches and functional genomics to characterize poorly defined mechanisms-of-action. Suzanne works with functional genomics includes developing and applying laboratory methods and bioinformatic approaches to key questions for environmental chemicals. Her doctoral work at Johns Hopkins University focused on establishment and maintenance of DNA methylation to determine how epigenetics contribute to mechanisms of toxicity from prenatal exposures. She has also used single-cell approaches, T cell receptor repertoire analyses, and epigenetic aging models to characterized how environmental exposures and immunologic history contribute to late-life disease susceptibility.

Gail Nelson, M.S.

Gail Nelson is a research scientist in the Center for Computational Toxicology and Exposure.  She received a M.S. in biology from the University of Kansas, where her research focused on the effects of organophosphate insecticides on embryonic development.  Gail work to develop in vitro and in vivo assays to study chemical and microbial agent effects on the mammalian intestinal microbiota.  Her most recent work focuses on the identification of genomic and epigenomic biomarkers to inform chemical risk assessment and prioritization utilizing molecular tools such as quantitative real-time PCR, droplet digital PCR, RNA sequencing, and single-cell transcriptomics.

Jennifer O’Neill

Jennifer O’Neill is a post-baccalaureate research scientist in the Center for Computational Toxicology and Exposure. Jennifer is working in the Chorley lab, using CRISPR activation system to refine biomarker signatures in the Retinoic Acid pathway. She has a B.S. in Genetics from North Carolina State University. Jennifer’s experience includes research on development of whole brain cerebral organoids.  

Kenzie Pereira, Ph.D.

Dr. Kenzie Pereira is a postdoctoral researcher in the Center for Computational Toxicology and Exposure. Her research in the Deisenroth lab focuses on utilizing and validating in vitro human thyroid microtissue assays. These assays are used to evaluate chemicals for potential endocrine disrupting activity. Kenzie previous research experience included investigating associations among vertebrate immunity, stress physiology, disease, and the environment, and how these interactions shaped broad-scale disease patterns. She holds a Ph.D. from Duquesne University, a M.S. From Southeastern Louisiana University, and an B.S. from Louisiana State University.

Vicki Richardson, Ph.D.

Dr. Richardson’s is a principal investigator in the Center for Computational Toxicology and Exposure. Her research areas include the application of advanced cell culture models for toxicokinetic studies and toxicity testing. Vicki is utilizing these models to study the toxicological effect of cyanotoxins and evaluate the ability of chemicals to disrupt thyroid hormone homeostasis.  She earned her bachelor’s degree in biology in 2002 and her doctorate in toxicology in 2013 from the University of North Carolina at Chapel Hill.

Sreenivasa Ramaiahgari, Ph.D.

Dr. Sreenivasa Ramaiahgari is a principal investigator at the Center for Computational Toxicology and Exposure. His research focuses on integrating novel human cell based in vitro systems, such as organoids, microphysiological systems, and bioprinted tissues, with high-content screening approaches for chemical risk assessment strategies. These in vitro new approach methodologies (NAMs) support the EPA’s mission to reduce the use of vertebrate animal testing for environmental chemical testing. His current projects focus on developing and validating in vitro neurotoxicity testing methods that incorporates the blood-brain barrier. He applies both toxicokinetic and toxicodynamic approaches to study chemical exposure rates and the biological effects on brain tissue. Sreenivasa received his MS in Biotechnology from University of Abertay Dundee, Scotland, UK and Ph.D. degree from Leiden University, The Netherlands.

David Ross

David Ross is a research scientist in the Center for Computational Toxicology and Exposure. David explores the cytotoxic potency of microcystin congeners in spheroid certified cryopreserved primary human hepatocytes using cell culture technique.  He also performs ultra performance liquid chromatographic analysis of microcystin concentrations. These actions are in support of the Microcystin Project examining the effects of microcystin hydrophobicity and cytotoxicity. He is also developing methods in the emerging 3D organoid culture technology. Organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long‐term maintenance of the function and biological characteristics of the parental cells in vitro.  All these features of organoids open new opportunities for large‐scale toxicology screening.  David is working to create a method for measuring the cytotoxicity and uptake of microcystin congeners in human iPSC derived colon organoids. He received a B.S. in Biology from the University of North Carolina Chapel Hill.

Jennifer Walsh

Jennifer Walsh is a post-baccalaureate research scientist in the Center for Computational Toxicology and Exposure. Jennifer is working in the Ramaiahgari laboratory on in vitro models of the blood brain barrier for use in toxicological assessments of PFAS. Jennifer received her B.S. in Biology with a minor in neuroscience from UNC Chapel Hill. Her research experience includes investigating the impact of drugs of abuse on astrocyte structure.

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Last updated on October 7, 2024
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