Grantee Research Project Results
2014 Progress Report: Carolina Center for Computational Toxicology: Assays, models and tools for NextGen safety assessments
EPA Grant Number: R835166Title: Carolina Center for Computational Toxicology: Assays, models and tools for NextGen safety assessments
Investigators: Rusyn, Ivan , Wright, Fred A. , Yeatts, Karin B. , Tropsha, Alex
Current Investigators: Rusyn, Ivan , Wright, Fred A. , Tropsha, Alexander , Chiu, Weihsueh
Institution: University of North Carolina at Chapel Hill
Current Institution: University of North Carolina at Chapel Hill , North Carolina State University , Texas A & M University
EPA Project Officer: Aja, Hayley
Project Period: July 1, 2012 through June 30, 2016 (Extended to June 30, 2017)
Project Period Covered by this Report: July 1, 2013 through June 30,2014
Project Amount: $1,200,000
RFA: Developing High-Throughput Assays for Predictive Modeling of Reproductive and Developmental Toxicity Modulated Through the Endocrine System or Pertinent Pathways in Humans and Species Relevant to Ecological Risk Assessment (2011) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
Objective:
The objective of the Carolina Center for Computational Toxicology is to advance the science and practice of toxicology by (i) filling critical gaps in our knowledge of the toxicity mechanisms, (ii) incorporating the population-based screening methods into the practice of toxicity testing, (iii) developing reliable computational models and tools that address specific existing challenges in hazard identification, and (iv) engaging with the stakeholders to increase the impact of our work.
Progress Summary:
Future Activities:
In Specific Objective 1, we will finalize the analysis of the lymphoblast screening with pesticide mixtures and incorporate high-throughput genomics data into the analyses, and further explore the utility of iPSC models for population-based high-content/high-throughput screening by developing additional collaborations with Cellular Dynamics who are establishing iPSCs from hundreds of individuals with sequenced genomes. In Specific Objective 2, we will finish development of chemical structure- and biological data-based CTV, and continue development of HAWC in collaboration with end users. In Specific Objective 3, we will finalize our work with CERAPP collaborative.
References:
Abdo N, Marlot P, Pirmohamed M, Shea D, Wright FA, Rusyn I. 2014. Utilizing human population based in vitro model to investigate pesticide mixtures and drug/metabolite pairs. In: Society of Toxicology Annual Meeting. Phoenix, AZ.
Abdo N, Xia M, Brown CC, Kosyk O, Huang R, Sakamuru S, et al. 2015. Population-based in vitro hazard and concentration-response assessment of chemicals: The 1000 genomes high throughput screening study. Environ Health Perspect:(in press).
Grimm FA, Iwata Y, Sirenko O, Crittenden C, Roy T, Boogaard PJ, et al. 2015. Toxicological categorization of petroleum substances through high-content screening of induced pluripotent stem cell (ipsc) derived cardiomyocytes and hepatocytes In: Annual Meeting of the Society of Toxicology. San Diego, CA.
Politi R, Rusyn I, Tropsha A. 2014. Prediction of binding affinity and efficacy of thyroid hormone receptor ligands using qsar and structure-based modeling methods. Toxicol Appl Pharmacol 280:177-189.
Reif DM, Sypa M, Lock EF, Wright FA, Wilson A, Cathey T, et al. 2013. Toxpi gui: An interactive visualization tool for transparent integration of data from diverse sources of evidence. Bioinformatics 29:402-403.
Shapiro AJ, Cook N, Ross PK, Fox J, Cogliano V, Chiu WA, et al. 2013. Web-based benchmark dose modeling module as a prototype component of an informatics-based system for human health assessments of chemicals. In: Society of Toxicology Annual Meeting. San Antonio, TX.
Sirenko O, Crittenden C, Callamaras N, Hesley J, Chen YW, Funes C, et al. 2013a. Multiparameter in vitro assessment of compound effects on cardiomyocyte physiology using ipsc cells. J Biomol Screen 18:39-53.
Sirenko O, Cromwell EF, Crittenden C, Wignall JA, Wright FA, Rusyn I. 2013b. Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity. Toxicol Appl Pharmacol 273:500-507.
Sirenko O, Hesley J, Rusyn I, Cromwell EF. 2014. High-content assays for hepatotoxicity using induced pluripotent stem cell-derived cells. Assay Drug Dev Technol 12:43-54.
Sirenko O, Hesley J, Rusyn I, Cromwell EF. 2015. High-content high-throughput assays for characterizing the viability and morphology of human ipsc-derived neuronal cultures. Assay Drug Dev Technol:in press.
Wignall JA, Muratov E, Fourches D, Tropsha A, Woodruff T, Zeise L, et al. 2013. Conditional toxicity value (ctv) predictor for generating toxicity values for data-sparse chemicals. In: Society of Toxicology Annual Meeting. San Antonio, TX.
Wilson MR, Ball N, Carney EW, Rowlands JC, Rusyn I. 2015. Data integration and visualization for transparent communication of the category read across using toxpi (toxicological priority index) tool: P-series glycol ethers case study. In: Annual Meeting of the Society of Toxicology. San Diego, CA.
World Health Organization. 2014. Guidance document on evaluating and expressing uncertainty in hazard characterization. Harmonization document no. 11. Geneva, Switzerland.
Yeakley J, Abdo N, Chappell G, Shepard P, Rusyn I, Seligmann B. 2015. A cost effective targeted sequencing method for monitoring gene expression. In: Annual Meeting of the Society of Toxicology. San Diego, CA.
Journal Articles on this Report : 8 Displayed | Download in RIS Format
Other project views: | All 54 publications | 40 publications in selected types | All 40 journal articles |
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Abdo N, Xia M, Brown CC, Kosyk O, Huang R, Sakamuru S, Zhou YH, Jack JR, Gallins P, Xia K, Li Y, Chiu WA, Motsinger-Reif AA, Austin CP, Tice RR, Rusyn I, Wright FA. Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environmental Health Perspectives 2015;123(5):458-466. |
R835166 (2014) R835166 (2016) R835166 (Final) |
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Low YS, Sedykh AY, Rusyn I, Tropsha A. Integrative approaches for predicting in vivo effects of chemicals from their structural descriptors and the results of short-term biological assays. Current Topics in Medicinal Chemistry 2014;14(11):1356-1364. |
R835166 (2014) R835166 (2016) R835166 (Final) R832720 (2009) R833825 (Final) |
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Politi R, Rusyn I, Tropsha A. Prediction of binding affinity and efficacy of thyroid hormone receptor ligands using QSAR and structure-based modeling methods. Toxicology and Applied Pharmacology 2014;280(1):177-189. |
R835166 (2014) R835166 (2016) R835166 (Final) R833825 (Final) |
Exit Exit Exit |
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Rusyn I, Lemon SM. Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies? Cancer Letters 2014;345(2):210-215. |
R835166 (2014) R835166 (2016) |
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Sirenko O, Cromwell EF, Crittenden C, Wignall JA, Wright FA, Rusyn I. Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity. Toxicology and Applied Pharmacology 2013;273(3):500-507. |
R835166 (2013) R835166 (2014) R835166 (2016) R835166 (Final) |
Exit Exit Exit |
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Sirenko O, Hesley J, Rusyn I, Cromwell EF. High-content assays for hepatotoxicity using induced pluripotent stem cell-derived cells. Assay and Drug Development Technologies 2014;12(1):43-54. |
R835166 (2013) R835166 (2014) R835166 (2016) R835166 (Final) |
Exit |
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Sirenko O, Hesley J, Rusyn I, Cromwell E. High-content high-throughput assays for characterizing the viability and morphology of human iPSC-derived neuronal cultures. Assay and Drug Development Technologies 2014;12(9-10):536-547. |
R835166 (2014) R835166 (2016) R835166 (Final) |
Exit Exit Exit |
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Wignall JA, Shapiro AJ, Wright FA, Woodruff TJ, Chiu WA, Guyton KZ, Rusyn I. Standardizing benchmark dose calculations to improve science-based decisions in human health assessments. Environmental Health Perspectives 2014;122(5):499-505. |
R835166 (2013) R835166 (2014) R835166 (2016) R835166 (Final) |
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Supplemental Keywords:
Bioinformatics, biostatistics, computational toxicology, QSAR, ToxCast, high throughput screeningProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.