Sarah McLarnan

Purpose of Review Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences that extend beyond the cell. Mitochondria are already susceptible to damage, which may be exacerbated by environmental exposures. Therefore, the aim of this review is to summarize the recent literature (2012–2022) looking at the effects of six ubiquitous classes of compounds on mitochondrial dysfunction in human populations. Recent Findings The literature suggests that there are a number of biomarkers that are commonly used to identify mitochondrial dysfunction, each with certain advantages and limitations. Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measur...

De novo mutations contribute to a large proportion of sporadic psychiatric and developmental disorders, yet the potential role of environmental carcinogens as drivers of causal de novo mutations in neurodevelopmental disorders is poorly studied. We demonstrate that several mutagens, including polycyclic aromatic hydrocarbons (PAHs), disproportionately mutate genes related to neurodevelopmental disorders including autism spectrum disorders (ASD), schizophrenia, and attention deficit hyperactivity disorder (ADHD). Other disease genes including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, congenital heart disease, orofacial clefts, and coronary artery disease were generally not mutated more than expected. Our findings support a new paradigm of neurodevelopmental disease etiology driven by a contribution of environmentally induced rather than random mutations.

OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design...

Water quality indicator organisms such as E. coli are used in the monitoring of recreational waterbodies to indicate the presence of fecal contamination. In 2009, a 1.5-mile stretch of Plum Creek in Stearns County, MN was classified by the Minnesota Pollution Control Agency as impaired due to high levels of E. coli. Citizen science to investigate the source of this contamination began in 2014 and with the addition of student research from CSB/SJU in 2016. This thesis presents results of the 2016 study, supplemented by summary of Minnesota water quality policy and recent research on indicator organisms. The 2016 study confirmed presence of fecal coliform indicator bacteria, but to date no source of contamination has been identified. As a result, a key contention of this thesis is that further research is necessary regarding the influence of sediment E. coli on stream E. coli in order to establish or maintain policies that protect human health and are fiscally and environmentally effe...