- Animal testing and alternatives
- Computational Drug Discovery Methods
- Effects and risks of endocrine disrupting chemicals
- Carcinogens and Genotoxicity Assessment
- Metabolomics and Mass Spectrometry Studies
- Health, Environment, Cognitive Aging
- Statistical Methods in Clinical Trials
- Genetic Syndromes and Imprinting
- Microbial Metabolic Engineering and Bioproduction
- Pharmacogenetics and Drug Metabolism
- Biomedical Text Mining and Ontologies
- Gene expression and cancer classification
- Analytical Chemistry and Chromatography
- Bioinformatics and Genomic Networks
- Health Systems, Economic Evaluations, Quality of Life
- Genomics and Rare Diseases
- Process Optimization and Integration
- Pesticide Residue Analysis and Safety
- Chemistry and Chemical Engineering
- Biochemical Analysis and Sensing Techniques
- Research Data Management Practices
- Genomics and Chromatin Dynamics
- Oral and gingival health research
- RNA regulation and disease
- Lipid metabolism and biosynthesis
RTI International
2023
Integrated Laboratory Systems, Inc.
2017-2022
Greenwood Genetic Center
2021-2022
Triangle
2014-2022
Research Triangle Park Foundation
2015-2022
Oak Ridge Associated Universities
2016-2019
Oak Ridge Institute for Science and Education
2014-2019
Environmental Protection Agency
2014-2019
National Institute of Environmental Health Sciences
2017-2018
Michigan State University
2009-2012
la diffusion de documents scientifiques niveau recherche, publiés ou non, émanant des établissements d'enseignement et recherche français étrangers, laboratoires publics privés.
Abstract Traditionally, phenotype-driven forward genetic plant mutant studies have been among the most successful approaches to revealing roles of genes and their products elucidating biochemical, developmental, signaling pathways. A limitation is that it time consuming, sometimes technically challenging, discover gene responsible for a phenotype by map-based cloning or discovery insertion element. Reverse genetics also an excellent way associate with phenotypes, although absence detectable...
New in vitro testing strategies make it possible to design batteries for large numbers of environmental chemicals. Full utilization the results requires knowledge underlying biological networks and adverse outcome pathways (AOPs) that describe route from early molecular perturbations an outcome. Curation a formal AOP is time-intensive process rate-limiting step designing these test batteries. Here, we method integrating publicly available data order generate computationally predicted (cpAOP)...
New approach methodologies (NAMs) for toxicological applications such as in vitro assays and silico models generate data that can be useful assessing potential health impacts of chemicals. The National Toxicology Program's (NTP's) Integrated Chemical Environment (ICE; https://ice.ntp.niehs.nih.gov/) provides user-friendly access to NAM tools explore contextualize chemical bioactivity molecular properties. ICE contains curated vivo toxicity testing experimental physicochemical property...
Abstract The replacement of animal use in testing for regulatory classification skin sensitizers is a priority US federal agencies that data from such testing. Machine learning models classify substances as or non‐sensitizers without using have been developed and evaluated. Because some require be further classified into potency categories, we statistical to predict sensitization murine local lymph node assay (LLNA) human outcomes. Input variables our included six physicochemical properties...
Summary: Access to high-quality reference data is essential for the development, validation, and implementation of in vitro silico approaches that reduce replace use animals toxicity testing. Currently, these must often be pooled from a variety disparate sources efficiently link set assay responses model predictions an outcome or hazard classification. To provide central access point purposes, National Toxicology Program Interagency Center Evaluation Alternative Toxicological Methods...
Humans are exposed to large numbers of chemicals during their daily activities. To assess and understand potential health impacts chemical exposure, investigators regulators need access reliable toxicity data. In particular, data for a wide range chemistries needed support development new approach methodologies (NAMs) such as computational models, which offer increased throughput relative traditional approaches reduce or replace animal use. NAMs evaluation require chemically diverse sets...
Oculocutaneous albinism (OCA) is caused by a group of genetically heterogeneous inherited defects that result in the loss pigmentation eyes, skin and hair. Mutations TYR, OCA2, TYRP1 SLC45A2 genes have been shown to cause isolated OCA. No comprehensive analysis has conducted study spectrum OCA alleles prevailing Pakistani albino populations.We enrolled 40 large families screened them for candidate gene, SLC24A5. Protein function effects were evaluated using silico prediction algorithms ex...
There are > 80,000 chemicals in commerce with few data available describing their impacts on human health. Biomonitoring surveys, such as the NHANES (National Health and Nutrition Examination Survey), offer one route to identifying possible relationships between environmental health impacts, but sparse complexity of traditional models make it difficult leverage effectively.We describe a workflow efficiently comprehensively evaluate prioritize chemical-health impact from biomonitoring survey...
Regulatory toxicology testing has traditionally relied on in vivo methods to inform decision-making. However, scientific, practical, and ethical considerations have led an increased interest the use of vitro silico fill data gaps. While experiments advantage rapid application across large chemical sets, interpretation coming from these non-animal can be challenging due mechanistic nature many assays. In extrapolation (IVIVE) emerged as a computational tool help facilitate this task....
Abstract Background The developmental toxicity potential (dTP) concentration from the devTOX quick Predict (devTOX qP ) assay, a metabolomics‐based human induced pluripotent stem cell predicts chemical's potency. Here, in vitro to vivo extrapolation (IVIVE) approaches were applied address whether assay could quantitatively predict lowest effect levels (LELs) for prototypical teratogen valproic acid (VPA) and group of structural analogues. Methods VPA series analogues tested with determine...
High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function drug candidate identification. These large-scale experiments typically carried out over the course of months years, often without controls needed compare directly across dataset. Few methods available comparisons high metabolic data generated in batches where explicit in-group for normalization lacking.Here we describe...
Environmental health risk assessors are challenged to understand and incorporate new data streams as the field of toxicology continues adopt molecular systems biology technologies. Systematic screening reviews can help assessment teams determine which studies consider for inclusion in a human assessment. A tool systematic should be standardized transparent order consistently meet minimum quality criteria prior performing in-depth analyses data. The Omics Analysis Review (SOAR) is focused on...
Previous chapter Next Full AccessProceedings Proceedings of the 2014 SIAM International Conference on Data Mining (SDM)Building associations between markers environmental stressors and adverse human health impacts using frequent itemset miningShannon M. Bell Stephen W. EdwardsShannon Edwardspp.551 - 559Chapter DOI:https://doi.org/10.1137/1.9781611973440.64PDFBibTexSections ToolsAdd to favoritesExport CitationTrack CitationsEmail SectionsAboutAbstract Health effects are unknown for vast...
In vitro to in vivo extrapolation (IVIVE) leverages biological activities predict corresponding exposures, therefore potentially reducing the need for animal safety testing that are traditionally performed support hazard and risk assessment. Interpretation of IVIVE predictions affected by various factors including model type, exposure route kinetic assumptions test article, choice assay(s) relevant clinical outcomes. Exposure scenarios further complicated mixtures where activity may stem...
In vitro methods offer opportunities to provide mechanistic insight into bioactivity as well human-relevant toxicological assessments compared animal testing. One of the challenges for this task is putting in data an vivo exposure context, which extrapolation (IVIVE) translates clinically relevant metrics using reverse dosimetry. This study applies IVIVE approach toxicity assessment ingredients and their mixtures e-cigarette (EC) aerosols a case study. Reported cytotoxicity EC aerosols,...
Harmonized language is essential to finding, sharing, and reusing large-scale, complex data. Gaps barriers prevent the adoption of harmonized approaches in environmental health sciences (EHS). To address this, National Institute Environmental Health Sciences partners created Language Collaborative (EHLC). The purpose EHLC facilitate a community-driven effort advance development EHS. forum pinpoint harmonization gaps, of, raise awareness encourage use tools, develop new standards...
Physiologically Based Pharmacokinetic (PBPK) models are often developed using animal data and applied to predict chemical movement concentration in humans. However, differences physiology exposure routes between experiments human exposures may impact the predictions interpretation of PBPK model results. Data needed parameterize models, potentially requiring chemical-specific adjustment inputs. Since be limited for a or interest, silico approaches such as structure-based modeling can help...