A5085071991- Heavy Metal Exposure and Toxicity
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Birth, Development, and Health
- Genetic Mapping and Diversity in Plants and Animals
- Bioinformatics and Genomic Networks
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Effects and risks of endocrine disrupting chemicals
- Zebrafish Biomedical Research Applications
- Animal testing and alternatives
- Genomics and Chromatin Dynamics
- Mercury impact and mitigation studies
- Genetics and Neurodevelopmental Disorders
- Computational Drug Discovery Methods
- Environmental Toxicology and Ecotoxicology
- Plant Virus Research Studies
- Marine animal studies overview
- Protein Kinase Regulation and GTPase Signaling
- Trace Elements in Health
- Gene Regulatory Network Analysis
- NF-κB Signaling Pathways
- Plant and Fungal Interactions Research
- FOXO transcription factor regulation
- Cell Adhesion Molecules Research
- Reproductive biology and impacts on aquatic species
North Carolina State University
2014-2025
Mount Desert Island Biological Laboratory
2007-2011
Center for Environmental Health
2011
College of the Atlantic
2007
Bates College
2005-2006
Jackson Laboratory
2000-2005
Vanderbilt University
1993-1998
Abstract The molecular mechanisms connecting environmental exposures to adverse endpoints are often unknown, reflecting knowledge gaps. At the Comparative Toxicogenomics Database (CTD), we developed a bioinformatics approach that integrates manually curated, literature-based interactions from CTD generate “CGPD-tetramer”: 4-unit block of information organized as step-wise mechanism linking an initiating Chemical, interacting Gene, Phenotype, and Disease outcome. Here, describe novel,...
Imprinted genes – critical for growth, metabolism, and neuronal function are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs established before tissue specification, these marks similar across cell types. Thus, they attractive investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate in humans by performing...
Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We others have shown to at doses below the no-observed-adverse-effect level can expression estrogen-responsive genes neonatal rat including estrogen receptors (ERs). The present studies, conducted...
Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of biomedical reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models 21st Century Toxicology was held at North Carolina State University May 5-6, 2014, in Raleigh, Carolina, USA. Participants discussed the ways which small are being used as models screen toxicants...
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of emerging contaminants that have been in use industrially since the 1940s. Their long-term extensive commercial has led to their ubiquitous presence environment. The ability measure bioconcentration distribution PFAS tissue aquatic organisms helps elucidate persistence as well environmental impacts. Traditional analysis by LC-MS/MS can total concentrations within an organism but cannot provide comprehensive spatial...
Exposure to arsenic is a critical risk factor in the complex interplay among genetics, environment, and human disease. Despite potential for utero exposure, mechanism of action on vertebrate development disease unknown.The objective this study was identify genes gene networks perturbed by during order enhance understanding molecular mechanisms action.We exposed zebrafish embryos at 0.25-1.25 hr postfertilization 10 or 100 ppb 24 48 hr. We then used total RNA interrogate genome microarrays...
Per-and polyfluoroalkyl substances (PFAS) are ubiquitous contaminants in freshwater ecosystems. Many PFAS incorporated into food webs, with potential effects on ecological and human health. However, incorporation the base of aquatic webs remains poorly understood. The goal this study was to quantify uptake trophic transfer both legacy current use compounds using a simulated chain lab setting. Natural periphytic biofilms were placed trays containing equimolar binary aqueous mixtures at...
Vertebrate jaw development can be disrupted by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—a potent activator of the aryl hydrocarbon receptor (AHR) transcription factor required for transducing toxic effects TCDD. We used zebrafish (Danio rerio) embryos investigate transcriptional responses TCDD with goal discovering novel, jaw-specific genes affected exposure. Our results uncovered a novel target TCDD-activated Ahr belonging evolutionarily conserved family forkhead box factors....
Recent studies from mammalian, fish, and in vitro models have identified bone cartilage development as sensitive targets for dioxins other aryl hydrocarbon receptor ligands. In this study, we assess how embryonic 2,3,7,8-tetrachlorochlorodibenzo-p-dioxin (TCDD) exposure impacts axial osteogenesis Japanese medaka (Oryzias latipes), a vertebrate model of human development. Embryos inbred wild-type Orange-red Hd-dR 3 transgenic lines (twist:EGFP, osx/sp7:mCherry, col10a1:nlGFP) were exposed to...
BackgroundPoor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, attendant increased lipid peroxidation; however, empirical data linking stressors during pregnancy oxidative status limited.MethodsWe used established scales measure five stressors. Maternal adverse childhood experiences, financial stress, social support,...
Alzheimer's disease (AD) prevalence is twice as high in non-Hispanic Blacks (NHBs) Whites (NHWs). The objective of this study was to determine whether aberrant methylation at imprint control regions (ICRs) associated with AD. Differentially methylated (DMRs) were bioinformatically identified from whole-genome bisulfite sequenced DNA derived brain tissue 9 AD (5 NHBs and 4 NHWs) 8 controls (4 NHWs). We DMRs located within 120 defined candidate ICRs the human imprintome (...
Transmission ratio distortion (TRD) and sterility are male-specific quantitative trait phenomena associated with the mouse t haplotype. TRD occurs in haplotype-heterozygous males is caused by deleterious action of distorter products on sperm bearing a wild-type responder locus. It has been proposed that -mediated male severe manifestation homozygosity for loci; thus, loci would be identical. In this, study transgenic approach was used to identify proximal locus, tcs1 (S1), test its role TRD....
With growing abundance and awareness of endocrine disrupting compounds (EDCs) in the environment, there is a need for accurate reliable detection EDC exposure. Our objective present study was to observe differences within between global plasma proteomes sexually mature male female white perch ( Morone americana ) before (Initial Control, IC) after 17β‐estradiol (E 2 induction. Semiquantitative nanoLC‐MS/MS data were analyzed by machine learning support vector machines (SVMs) two‐way ANOVA....
Abstract The t complex spans 20 cM of the proximal region mouse chromosome 17. A variant form, haplotype (t), exists at significant frequencies in wild populations and is characterized by presence inversions that suppress recombination with wild-type (+) chromosomes. Transmission ratio distortion sterility are associated affect males only. It hypothesized these phenomena caused trans-acting distorter/sterility factors interact a responder locus (Tcrt) distorter same because homozygosity...
Addressing the complex relationship between public health and environmental exposure requires multiple types sources of data. An important source chemical data derives from high-throughput screening (HTS) efforts, such as Tox21/ToxCast program, which aim to identify hazard using primarily in vitro assays probe toxicity. While most these target specific genes, assessing disease-relevance remains challenging. Integration with additional sets may help resolve questions by providing broader...
Cadmium (Cd) is a ubiquitous environmental pollutant associated with wide range of health outcomes including cancer. However, obscure exposure sources often hinder prevention efforts. Further, although epigenetic mechanisms are suspected to link these associations, gene sequence regions targeted by Cd unclear. Aberrant methylation differentially methylated region (DMR) on the MEG3 that regulates expression cluster genes MEG3, DLK1, MEG8, MEG9 and DIO3 has been multiple cancers. In 287...
Abstract Background Differentially methylated imprint control regions (ICRs) regulate the monoallelic expression of imprinted genes. Their epigenetic dysregulation by environmental exposures throughout life results in formation common chronic diseases. Unfortunately, existing Infinium methylation arrays lack ability to profile these adequately. Whole genome bisulfite sequencing (WGBS) is unique method able ICRs. However, it very expensive and requires not only a high coverage, but also...