Research Publications (Food Safety)

The environmental toxicant cadmium (Cd) impairs the growth of rodents and humans in utero which in turn heightens susceptibility to diseases later in life. We previously demonstrated that the maternal-facing efflux transporter, breast cancer resistance protein (human BCRP/ABCG2, mouse Bcrp/Abcg2) confers resistance against Cd toxicity in human trophoblasts.

Carvedilol is a widely used beta-adrenoreceptor antagonist for multiple cardiovascular indications; however, it may induce cholestasis in patients, but the mechanism for this effect is unclear. Carvedilol also prevents the development of various forms of experimental liver injury, but its effect on nonalcoholic steatohepatitis (NASH) is largely unknown.

The role of long noncoding RNAs (lncRNAs) regulators of toxicological responses to environmental chemicals is gaining prominence. Previously, our laboratory discovered an lncRNA, sox9b long intergenic noncoding RNA (slincR), that is activated by multiple ligands of aryl hydrocarbon receptor (AHR).

Epidemiological studies report associations between early-life exposure to persistent organic pollutants (POPs) and impaired metabolic homeostasis in adulthood. We investigated the impact of early-life exposure to low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or ‘dioxin’) on the establishment of β-cell area during the perinatal period, as well as β-cell health and glucose homeostasis later in life.

Exposure to environmental toxicants during preconception has been shown to affect offspring health and epigenetic mechanisms such as DNA methylation are hypothesized to be involved in adverse outcomes. However, studies addressing the effects of exposure to environmental toxicants during preconception on epigenetic changes in gametes are limited.

Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models.

In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in uptake and changes in essential metal concentrations contribute to metabolic outcomes, placental and liver Cd and essential metal concentrations were quantified in male and female offspring perinatally exposed to 500 ppb CdCl2.

Lead is a nonessential metal and may be a coexposure in welding fumes. Preclinical data indicate lead may affect iron regulation. The current study investigated blood lead concentrations and their association with brain iron accumulation in workers with chronic welding fume exposure, with a focus on iron-rich subcortical regions of the cerebellum and basal ganglia. Occupational exposure, whole blood metal, and brain MRI data were obtained from 29 controls and 42 welders.

The aryl hydrocarbon receptor (AHR) is required for vertebrate development and is also activated by exogenous chemicals, including polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR activation is well-understood, but roles of downstream molecular signaling events are largely unknown.

Frog metamorphosis, the development of an air-breathing froglet from an aquatic tadpole, is controlled by thyroid hormone (TH) and glucocorticoids (GC). Metamorphosis is susceptible to disruption by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AHR) agonist. Krüppel-like factor 9 (klf9), an immediate early gene in the endocrine-controlled cascade of expression changes governing metamorphosis, can be synergistically induced by both hormones.

Cadmium (Cd) is a highly toxic heavy metal in our environment. The influence of Cd on the development of platelets, or megakaryocytopoiesis, remains to be defined. The aim of this study was to investigate the impact of Cd on megakaryocytopoiesis. C57BL/6 (B6) mice aged 6–8 weeks were treated with 10 ppm Cd via drinking water or control for 3 months, and megakaryocytopoiesis was evaluated thereafter.

Development of in vitro new approach methodologies has been driven by the need for developmental neurotoxicity (DNT) hazard data on thousands of chemicals. The network formation assay characterizes DNT hazard based on changes in network formation but provides no mechanistic information. This study investigated nervous system signaling pathways and upstream physiological regulators underlying chemically induced neural network dysfunction.

Cutaneous squamous cell carcinoma (cSCC) is a major deleterious health effect of chronic arsenic (iAs) exposure. The molecular mechanism of arsenic-induced cSCC remains poorly understood. We recently demonstrated that chronic iAs exposure leads to temporally regulated genome-wide changes in profiles of differentially expressed mRNAs and miRNAs at each stage of carcinogenesis (7, 19, and 28 weeks) employing a well-established passage-matched HaCaT cell line model of arsenic-induced cSCC.

Studies have shown that some peptides and small molecules can induce non IgE-mediated anaphylactoid reactions through mast cell activation. Upon activation, mast cells degranulate and release vasoactive and proinflammatory mediators, from cytoplasmic granules into the extracellular environment which can induce a cascade of severe adverse reactions.

Occupational exposures to volatile organic compounds (VOCs) have been associated with numerous health complications including steatohepatitis and liver cancer. However, the potential impact of environmental/residential VOC exposures on liver health and function is largely unknown. To address this knowledge gap, the objective of this cross-sectional study is to investigate associations between VOCs and liver injury biomarkers in community residents.

Humans are exposed to a broad range of organic chemicals. Although targeted gas chromatography mass spectrometry techniques are used to quantify a limited number of persistent organic pollutants and trace organic contaminants in biological samples, nontargeted, high-resolution mass spectrometry (HRMS) methods assess the human exposome more extensively.

Occupational exposures to volatile organic compounds (VOCs) have been associated with numerous health complications including steatohepatitis and liver cancer. However, the potential impact of environmental/residential VOC exposures on liver health and function is largely unknown. To address this knowledge gap, the objective of this cross-sectional study is to investigate associations between VOCs and liver injury biomarkers in community residents.

Neurotoxicity is a principal concern in nonclinical drug development. However, standardized and universally accepted fluid biomarkers for evaluating neurotoxicity are lacking.

Methylmercury (MeHg) is a developmental toxicant capable of eliciting neurocognitive and neuromuscular deficits in children with in utero exposure. Previous research in Drosophila melanogaster uncovered that developmental MeHg exposure simultaneously targets the developing musculature and innervating motor neuron in the embryo, along with identifying Drosophila neuroligin 1 (nlg1) as a gene associated with developmental MeHg sensitivity.

Screening for drug discovery targeting the central nervous system requires the establishment of efficient and highly accurate toxicity test methods that can reduce costs and time while maintaining high throughput using the function of an in vitro neural network. In particular, an evaluation system using a human-derived neural network is desirable in terms of species difference.

Molecular signatures are being increasingly integrated into predictive biology applications. However, there are limited studies comparing the overall predictivity of transcriptomic versus epigenomic signatures in relation to perinatal outcomes.

Aflatoxin B1 (AFB1) induced intestinal epithelial damage in rodent models, which indicates that long-term exposure to AFB1 may cause chronic gut disorders. In this study, we tested the hypothesis that AFB1-induced adverse effects on gut is mediated by gut-microbiota, which is partially reflected by the changes of fecal microbiome and metabolome. F344 rats were orally exposed to AFB1 of 0, 5, 25, and 75 µg kg−1 body weight for 4 weeks and fecal samples were collected.

Oxytetracycline (OTC) is a widely used antibiotic in food-producing animals. Extralabel use of OTC is common and may lead to violative residues in edible tissues. It is important to have a quantitative tool to predict scientifically based withdrawal intervals (WDIs) after extralabel use in food animals to ensure human food safety. This study focuses on developing a physiologically based pharmacokinetic (PBPK) model for OTC in sheep and goats.

The global burden of male infertility is rising at an alarming rate affecting the lives of millions in terms of physical, emotional, and societal perspectives. Among several existing endocrine-disrupting chemicals, bisphenol A (BPA) has been reported by many to inflict male reproductive toxicity in different experimental models, especially in mice.

Organochlorine pesticides (OCPs) are persistent pollutants linked to diverse adverse health outcomes. Environmental exposure to OCPs has been suggested to negatively impact the immune system but their effects on cellular antiviral responses remain unknown.