A5057738594- Gene expression and cancer classification
- Zebrafish Biomedical Research Applications
- Molecular Biology Techniques and Applications
- Per- and polyfluoroalkyl substances research
- Metabolomics and Mass Spectrometry Studies
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Animal testing and alternatives
- Computational Drug Discovery Methods
- Cancer, Hypoxia, and Metabolism
- Nanoparticles: synthesis and applications
- Membrane Separation and Gas Transport
- Toxic Organic Pollutants Impact
- Environmental Toxicology and Ecotoxicology
- Genetic Associations and Epidemiology
- Health, Environment, Cognitive Aging
- Cancer Cells and Metastasis
- RNA and protein synthesis mechanisms
- Aquaculture disease management and microbiota
- Heavy Metal Exposure and Toxicity
- Microbial Metabolic Engineering and Bioproduction
- Genetics and Physical Performance
- 3D Printing in Biomedical Research
- Mathematical Biology Tumor Growth
- Bioinformatics and Genomic Networks
Research Triangle Park Foundation
2019-2025
North Carolina State University
2018-2020
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...
Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of chemicals used in industrial processes, consumer products, fire-fighting foams which have become environmental pollutants concern due to their persistence, ubiquity, associations with adverse human health outcomes, including pregnant persons offspring. Multiple PFAS are associated liver outcomes adult humans toxicological models, but effects on the developing not fully described. Here we performed transcriptomic analyses...
Toxicological and pharmacological researchers have seized upon the many benefits of zebrafish, including short generation time, well-characterized development, early maturation as clear embryos. A major difference from model organisms is that standard husbandry practices in zebrafish are designed to maintain population diversity. While this diversity attractive for translational applications human ecological health, it raises critical questions on how interindividual genetic variation might...
Abstract Because the liver plays a vital role in clearance of exogenous chemical compounds, it is susceptible to chemical-induced toxicity. Animal-based testing routinely used assess hepatotoxic potential chemicals. While large-scale high-throughput sequencing data can indicate genes affected by exposures, we need system-level approaches interpret these changes. To this end, developed an updated rat genome-scale metabolic model integrate transcriptomics and utilized structure...
Aqueous film-forming foams (AFFFs) are complex product mixtures that often contain per- and polyfluorinated alkyl substances (PFAS) to enhance fire suppression protect firefighters. However, PFAS have been associated with a range of adverse health effects (e.g., liver thyroid disease cancer), innovative approach methods better understand their toxicity potential identify safer alternatives needed. In this study, we investigated set 30 AFFF, PFAS, clinical drugs) using differentiated cultures...
Toxicants with the potential to bioaccumulate in humans and animals have long been a cause for concern, particularly due their association multiple diseases organ injuries. Per- polyfluoro alkyl substances (PFAS) polycyclic aromatic hydrocarbons (PAH) are two such classes of chemicals that associated steatosis liver. Although PFAS PAH classified as molecular mechanisms toxicity remain be explored detail. In this study, we aimed identify by which an acute exposure can induce lipid...
Background: Modern societies are exposed to vast numbers of potentially hazardous chemicals. Despite demonstrated linkages between chemical exposure and severe health effects, there limited, often conflicting, data on how adverse effects differ across individuals. Objectives: We tested the hypothesis that population variability in response certain chemicals could elucidate a role for gene–environment interactions (GxE) differential susceptibility. Methods: High-throughput screening (HTS)...
Predictive models for the impact of nanomaterials on biological systems remain elusive. Although there is agreement that physicochemical properties (particle diameter, shape, surface chemistry, and core material) influence toxicity, are limited often contradictory, data relating structure to even diameter. Given importance size in determining nanoscale properties, we aimed address this gap by examining effects a defined series gold nanoparticles (AuNPs) zebrafish embryos. Five AuNPs samples...
Animal models have historically been poor preclinical predictors of gastrointestinal (GI) directed therapeutic efficacy and drug-induced GI toxicity. Human stem primary cell-derived culture systems are a major focus efforts to create biologically relevant that enhance predictive value intestinal The inherent variability in cell-based cultures makes development useful challenge; the stochastic nature cell differentiation interferes with ability build validate reproducible assays query drug...
Currently, assessment of the potential immunotoxicity a given agent involves tiered approach for hazard identification and mechanistic studies, including observational evaluation immune function, measurement susceptibility to infectious neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due their rapid development, ease maintenance, homology system function development. Larval zebrafish also are...
Sentinel gene sets have been developed with the purpose of maximizing information from targeted transcriptomic platforms. We recently described development an S1500+ sentinel set, which was built for human transcriptome, utilizing a data- and knowledge-driven hybrid approach to select small subset genes that optimally capture transcriptional diversity, correlation other based on large-scale expression profiling, known pathway annotation within genome. While this detailed bioinformatics...
High-throughput transcriptomics has advanced through the introduction of TempO-seq, a targeted alternative to traditional RNA-seq. TempO-seq platforms use 50 nucleotide probes, each specifically designed target known transcript, thus allowing for reduced sequencing depth per sample compared with RNA-seq without compromising accuracy results. Thus far, studies using method have relied on existing tools processing resulting short read data. However, these were originally other data types....
Animal models have historically been poor preclinical predictors of gastrointestinal (GI) directed therapeutic efficacy and drug-induced GI toxicity. Human stem primary cell-derived culture systems are a major focus efforts to create biologically relevant that enhance predictive value intestinal The inherent variability in stem-cell-based complex cultures makes development useful challenge; the stochastic nature stem-cell differentiation interferes with ability build validate robust,...
To address the challenge of limited throughput with traditional toxicity testing, a newly developed high-throughput transcriptomics (HTT) platform, together 5-day in vivo rat model, offers an alternative approach to estimate chemical exposures and provide reasonable estimates toxicological endpoints. This study contains HTT analysis 18 environmental chemicals known liver toxicity. They were evaluated using male Sprague Dawley rats exposed various concentrations daily for five consecutive...
The TempO-Seq S1500+ platform(s), now available for human, mouse, rat, and zebrafish, measures a discrete number of genes that are representative biological pathway co-regulation across the entire genome in given species. While measurement these alone provides direct assessment gene expression activity, extrapolating values to whole transcriptome (~26 000 humans) can estimate measurements non-measured interest increases power analysis algorithms by using larger background space. Here, we use...