A5079081701- Effects and risks of endocrine disrupting chemicals
- Computational Drug Discovery Methods
- Animal testing and alternatives
- Carcinogens and Genotoxicity Assessment
- Pluripotent Stem Cells Research
- Gene expression and cancer classification
- Pharmacogenetics and Drug Metabolism
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Zebrafish Biomedical Research Applications
- Neuroscience and Neural Engineering
- Analytical Chemistry and Chromatography
- Metabolomics and Mass Spectrometry Studies
- Molecular Biology Techniques and Applications
- Drug-Induced Hepatotoxicity and Protection
- Toxic Organic Pollutants Impact
- 3D Printing in Biomedical Research
- Consumer Attitudes and Food Labeling
- Statistical Methods in Clinical Trials
- Heavy Metal Exposure and Toxicity
- Agriculture, Soil, Plant Science
- Thyroid Disorders and Treatments
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Retinoids in leukemia and cellular processes
National Institute of Environmental Health Sciences
2012-2025
Triangle
2012-2018
National Institutes of Health
2002-2009
Ontario Association of Optometrists
1998
Research Triangle Park Foundation
1996
Florida State University
1992
A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created. The software addresses increasing use transcriptomic data in toxicology, drug design, risk assessment and translational research. In this version, we have implemented additional statistical filtering options (e.g. Williams' trend test), curve fitting models, Linux Macintosh compatibility support for platforms with up-to-date gene annotations. Furthermore, extensive visualizations,...
Abstract Background The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about molecular pathways regulated by these transcription factors. Results Here we identify downstream effectors genes telencephalon using a genomic approach to analyze transcriptome mice that either lacking or overexpressing genes. Novel targets and/or were identified, such as members Notch Wnt pathways, involved adhesion...
Neurological disorders affect millions of people worldwide and appear to be on the rise. Whereas reason for this increase remains unknown, environmental factors are a suspected contributor. Hence, there is an urgent need develop more complex, biologically relevant, predictive in vitro assays screen larger sets compounds with potential neurotoxicity. Here, we employed human induced pluripotent stem cell (iPSC)-based 3D neural platform composed mature cortical neurons astrocytes as model...
Abstract A 5-day in vivo rat model was evaluated as an approach to estimate chemical exposures that may pose minimal risk by comparing benchmark dose (BMD) values for transcriptional changes the liver and kidney BMD toxicological endpoints from traditional toxicity studies. Eighteen chemicals, most having been tested National Toxicology Program 2-year bioassays, were evaluated. Some of these chemicals are potent hepatotoxicants (eg, DE71, PFOA, furan) rodents, some exhibit but have hepatic...
Abstract Motivation Estimating a toxic reference point using tools like the benchmark dose (BMD) is critical step in setting policy to regulate pollution and ensure safe environments. Toxicity can be measured for different endpoints, including changes gene expression histopathology various tissues, typically explored one or tissue at time univariate that ignores correlation. In this work, we develop multivariate estimation procedure estimate BMD specified sets. Our approach extends...
The National Toxicology Program (NTP) receives requests to evaluate chemicals with potential cause adverse health effects, including developmental neurotoxicity (DNT). Some recent have included classes of such as flame retardants, polycyclic aromatic compounds, perfluoroalkyl substances, and bisphenol A analogs approximately 20-50 compounds per class, many which include commercial mixtures. However, all the within a class cannot be tested using traditional DNT animal testing guideline...
Population-based estimates of environmental exposures using biomarkers can be difficult to obtain for a variety reasons, including problems with limits detection, undersampling key strata, time between exposure and sampling, variation across individuals, within the ability find interpret given biomarker. In this article, we apply statistical likelihoods, weighted regression methods censored data analysis biomarker data. Urinary metabolites seven phthalates, reported by Blount et al., are...
Abstract A method is proposed that finds enriched pathways relevant to a studied condition using the measured molecular data and also structural information of pathway viewed as network nodes edges. Tests are performed simulated genomic sets compared two existing approaches. The analysis provided demonstrates very competitive with current approaches provides biologically results.
Over the past decade, zebrafish is increasingly being used as a model to screen for chemical-mediated toxicities including developmental toxicity (DT) and neurotoxicity (NT). One of major challenges lack harmonization in data analysis approaches, thereby posing difficulty comparing findings across laboratories. To address this, we sought establish unified strategy both DT NT data, by adopting benchmark concentration (BMC) analysis. There are two critical aspects BMC analysis: having endpoint...
Abstract In this paper, we provide a proof of concept evaluating the utility U.S. Tox21 high-throughput screening approach to assess hazard chemical mixtures using two estrogen receptor assays. A subset chemicals identified in Phase I program as active (ER) agonist assay were used design for testing II. Individual and evaluated cell-based alpha (ERα) activation assays: One incorporating transfected ligand-binding domain an ERα β-lactamase reporter cell line (ER-bla) full-length endogenous...
The National Research Council's vision for toxicity testing in the 21st century anticipates that points of departure (PODs) establishing human exposure guidelines future risk assessments will increasingly be based on vitro high-throughput screening (HTS) data.The aim this study was to compare different PODs HTS data. Specifically, benchmark doses (BMDs) were compared signal-to-noise crossover dose (SNCD), which has been suggested as lowest applicable a POD.Hill models fit > 10,000...
In the real world, individuals are exposed to chemicals from sources that vary over space and time. However, traditional risk assessments based on in vivo animal studies typically use a chemical-by-chemical approach apical disease endpoints. New methodologies (NAMs) toxicology, such as vitro high-throughput (HTS) assays generated Tox21 ToxCast, can more readily provide mechanistic chemical hazard information for with no existing data than methods. this paper, we establish workflow assess...
The field of toxicology has witnessed substantial advancements in recent years, particularly with the adoption new approach methodologies (NAMs) to understand and predict chemical toxicity. Class-based methods such as clustering classification are key NAMs development application, aiding understanding hazard risk concerns associated groups chemicals without additional laboratory work. Advances computational chemistry, data generation availability, machine learning algorithms represent...
Gene expression arrays (gene chips) have enabled researchers to roughly quantify the level of mRNA for a large number genes in single sample. Several methods been developed analysis gene array data including clustering, outlier detection, and correlation studies. Most these analyses are aimed at qualitative identification what is different between two samples and/or relationship genes. We propose quantitative, statistically sound methodology regulatory networks using sets. The method based...
A 44-day dosed feed study was performed to compare the bioavailability of lead from contaminated soil versus two salts and effect on gastrointestinal absorption ingested lead. Male Fischer rats (approximately 4 weeks age) received lead, 17, 42, or 127 ppm, in form acetate, sulfide, lead-contaminated soil, combinations thereof diet for 7, 15, 44 days. Control added diets some animals determine how it might alter bioavailability. Blood Δ-aminolevulinic acid dehydratase (Δ-ALAD) blood, bone,...
Gene expression arrays (gene chips) have enabled researchers to roughly quantify the level of mRNA for a large number genes in single sample. Several methods been developed analysis gene array data including clustering, outlier detection, and correlation studies. Most these analyses are aimed at qualitative identification what is different between two samples and/or relationship genes. We propose quantitative, statistically sound methodology regulatory networks using sets. The method based...
The National Toxicology Program is developing a high-throughput screening (HTS) program to set testing priorities for compounds of interest, identify mechanisms action, and potentially develop predictive models human toxicity. This will generate extensive data on the activity large numbers chemicals in wide variety biochemical- cell-based assays. first step relating patterns response among batteries HTS assays vivo toxicity distinguish between positive negative individual Here, authors...
Due to the increasing number of drugs and untested environmental compounds introduced into commercial use, there is recognition for a need develop reliable efficient screening methods identify that may adversely impact nervous system. One process has been implicated in neurodevelopment neurite outgrowth; disruption which can result adverse outcomes persist later life. Here, we developed green fluorescent protein (GFP) labeled outgrowth assay high-content, high-throughput format using induced...