Scott Belcher

Cadmium is a toxic metal that is a major public health concern, due to its ubiquity in the human environment. If successful, our work will show that exposure to cadmium during development causes non-alcoholic fatty liver disease in later life through activating a specific set of genes, identifying these genes as potential markers of disease susceptibility and novel targets for treatment. Given that NAFLD affects 30-40 % of the US adult population, and has been linked to metabolic impairments and a shorter lifespan, findings from our work have the potential to improve disease prediction and management for a large number of people.

The mission of the Center for Human Health and the Environment (CHHE) is to advance understanding of environmental impacts on human health. Through a systems biology framework integrating all levels of biological organization, CHHE aims to elucidate the fundamental mechanisms through which environmental exposures/stressors interface with biomolecules, pathways, the genome, and epigenome to influence human disease. CHHE will develop three interdisciplinary research teams that represent NC State??????????????????s distinctive strengths. CHHE will implement specific mechanisms to promote intra- and inter-team interactions and build interdisciplinary bridges to advance basic science discovery and translational research in environmental health science along the continuum from genes to population. These teams are; - The Molecular/Cellular-Based Systems and Model Organisms Team will utilize cutting edge molecular/cellular-based systems and powerful vertebrate and invertebrate model organisms to define mechanisms, pathways, GxE interactions, and individual susceptibility to environmental agents. - The Human Population Science Team will integrate expertise on environmental exposures, epidemiology, genomics and epigenomics to identify key human pathways and link exposure and disease across populations. - Bioinformatics Team will develop novel analytics and computational tools to translate Big Data generated across high-throughput and multiscale experiments into systems-level discoveries To further increase the impact and translational capacity of these teams, CHHE will develop three new facility cores that will provide instrumentation, expertise, and training to facilitate basic mechanism- to population-based research. - The Integrative Health Sciences Facility Core will expand the ability of CHHE members to translate basic science discoveries across species and provide mechanistic insights into epidemiological studies by partnering with: a) NC State??????????????????s Comparative Toxicogenomics Database (CTD); b) East Carolina University Brody School of Medicine and c) NC Dept. of Health and Human Services. - The Comparative Pathobiology Core will be located at NC State??????????????????s top-ranked College of Veterinary Medicine and its nationally recognized veterinary pathology group to facilitate assessment of the effects of environmental stressors in the many model organisms utilized by CHHE members. - The Systems Technologies Core will introduce state-of-the-art proteomics capabilities and dedicated bioinformatics support to expand the ability of CHHE members to analyze the Next Generation Sequencing data involving the genome, transcriptome and epigenome. As a land-grant university, NC State has an extensive and active Cooperative Extension Service network throughout North Carolina. CHHE will utilize this unique network to develop a highly effective, multi-directional Community Outreach and Engagement Core to disseminate findings that will contribute to addressing disparity in exposures and health outcomes and to educate communities about environmental influences on health. A strong Career Development Core for early stage scientists that is coordinated with a robust Pilot Project Program will support cutting-edge, collaborative and multidisciplinary environmental health projects to enhance the research success and impact of our membership. Through these activities and the purposeful interfacing of different disciplines CHHE will build on NC State??????????????????s unique research and community outreach strengths to become a premier transformative and synergistic EHS Core Center.

Per- and polyfluoroalkyl substances (PFAS) are emerging as a major public health problem in North Carolina and across the United States. PFAS comprise a class of over 5,000 compounds. Their unique chemical properties have been harnessed to make consumer and industrial products more water, stain, and grease resistant; they are found in products as diverse as cosmetics and flame-retardants. PFAS are resistant to degradation, move easily through the environment, and accumulate in living organisms. Exposure to PFAS has been associated with health effects including cancer and toxicity to the liver, reproductive development, and thyroid and immune systems. Despite widespread detection in the environment and evidence of increasing human exposure, understanding about PFAS toxicity, its bioaccumulative potential in dietary sources such as aquatic organisms, and effective remediation remain notably understudied. The recent discovery by this proposed Center??????????????????s Deputy Director, Dr. Detlef Knappe, of widespread PFAS contamination in the Cape Fear River watershed in NC underscores that these compounds are in need of immediate investigation.. The goal of our Center is to advance understanding about the environmental and health impacts of PFAS. To meet this goal we are employing a highly trans-disciplinary approach that will integrate leaders in diverse fields (epidemiology, environmental science and engineering, biology, toxicology, immunology, data science, and advanced analytics); all levels of biological organization (biomolecule, pathway, cell, tissue, organ, model organism, human, and human population); state-of-the-art analytical technologies; cutting-edge data science approaches; a recognized track record in interdisciplinary, environmental health science (EHS) training; and well-established partnerships with government and community stakeholders.

The goal of the project is to serve as a pilot project to determine the variance and extent of contamination in species local commonly caught for consumption in North Carolina waters as they related to known aspects of species ecology or physiology. The objectives of the research are to: 1.Collect paired samples of female-embryo tissues of across several species of coastal sharks that span a variety of ecological niches 2.Analyze muscle tissue samples (i.e. edible portion) for mercury and a suite of man-made organic contaminated (i.e. DDT, PCBs and chlorinated pesticides) 3.Correlate levels across species?????????????????? known ecological niches 4.Assign each species a ????????????????consumption rating??????????????? to evaluate those that may be of higher risk and can inform consumer choice

The aim of the project is to evaluate contaminate transfer from pregnant female sharks to developing embryos. The Belcher lab will provide contaminate levels in tissues and blood for ~100 samples. Work product will include quantitative measures of Hg in each sample and perform initial quality assurance data analysis.

We will demonstrate the utility of a rapid, high-throughput fluorescent approach for determining protein binding properties and toxic properties of PFAS mediated by binding of the human blood transport protein albumin.

Poly and perfluorinated compounds (PFCs) are persistent water-soluble chemicals of concern that do not break down in the environment. Many of these chemicals are suspected toxins. Recent water sampling data suggests a large prevalence of GenX and other emerging PFC contaminants within the Cape Fear watershed [1]. Neither the toxic potential, nor the exposure profiles of these contaminants are well defined. Current studies investigating the impacts of Cape Fear River contamination has focused on possible adverse public health effects resulting from effected drinking water; impacts on the health of the Cape Fear River aquatic ecosystem are unknown. As an initial step toward understanding the potential for adverse impacts of these emerging contaminants on the health of the Cape Fear River aquatic ecosystem, detailed ecological exposure and health data will be collected from American alligator and fish from the Cape Fear River. Persistence, bioaccumulation and health impacts of these contaminants will be determined in these sentinel species. Those findings will be compared in aggregate with findings from ongoing studies evaluating exposure and potent human health impacts of GenX on residents of New Hanover County. Highly sensitive liquid chromatography and mass spectrometry (LC MS/MS) approaches will be used to identify legacy and novel PFCs contaminate levels to estimate the scope of PFC exposures. There is also much concern within the coastal community of Wilmington that consuming fish from the Cape Fear River can increase PFC exposures and cause adverse health effects. There is no information on PFC levels in Cape Fear River fish. To address this knowledge gap, levels of PFCs of 2 fish species (striped bass and catfish) will also be determined, results of analysis will be compared with human data, and current understand of risks to human and ecosystem health resulting from these exposures will be shared with the community.

Cadmium (Cd) is a toxic non-essential metal common in natural and built landscapes. Chronic low dose exposure to this metal has been implicated in the etiology of cardiovascular disease, obesity and type 2 diabetes in adults. Mounting evidence demonstrates that early life exposure to Cd may program later life, and adult disease. There is no experimental data directly linking early-life Cd and risk factors for these diseases in children and adults. The long-term goal of the proposed experiments is to determine whether and how chronic exposures to low, Cd in early life contribute to metabolic dysfunction and obesity. The hypothesis for this pilot proposal is maternal ingestion and gestational exposures to low levels of Cd, modifies epigenetic status of genes encoding Slc39 and Slc30 transporters in the liver of offspring. The resulting epigenetic changes in transporter expression alters essential metal homeostasis that in turn modifies metabolic-related gene expression networks and dysregulated metabolic functions of the liver. The specific experimental Aims addressed are: 1) determine the functional metabolic gene networks modified in liver by gestational Cd exposure; and 2) characterize the epigenetic differences in Slc30a10, Slc39a14, and MT1 CpG methylation associated low-dose Cd exposure during gestation. Targeted analysis of promoter CpG methylation will be used to identify alterations for each gene. Comparative RNAseq analysis of transcripts expressed in control and Cd-exposed livers will be used to identify exposure-related alterations in the liver transcriptome and define the impacts of Cd exposure on metabolic gene expression networks.

Obesity rates in the US are rapidly climbing and it has been hypothesized that early life exposure to chemicals which act as obesogens may be contributing. The goal of this research is to test the hypothesis that early life exposure to a newly discovered flame retardant mixture, Firemaster 550, induces sex-specific metabolic reprogramming which then results in a higher risk of obesity and cardiovascular disease later in life. We will also explore the mechanisms by which this might occur, and the individual contributions of each component of the mixture. This work will contribute new data regarding the potential health impacts of this fire retardant mixture and the mechanisms by which obesogenic chemicals induce metabolic disease.