Dr. Sobolewski's lab focuses on sex-differentiated mechanisms of neurotoxicity. The perinatal endocrine environment of a developing mammal differs depending on sex. These sex-specific hormone profiles may result in unique sensitivity to endocrine active chemicals (EACs). We test the hypothesis that environmental disruption of perinatal hormone profiles results in lasting sex-specific changes to brain development and behavior. The goal is to advance our understanding of differential toxicity risk based on sex. Ultimately, our lab seeks to translate our mechanistic research into a deep understanding of the role the environment plays in the etiology of neurobehavioral disorders with sex-biased prevalence rates, such as Attention Deficit / Hyperactivity Disorder and Autism Spectrum Disorders.
Our first research aim examines EAC disruption of early sex steroids, specifically disruption of the male-specific testosterone surge before and after birth known as the perinatal testosterone surge (PTS). Steroid hormones are key regulators of reproductive tract and central nervous system development. Using EACs, our lab disrupts PTS signaling to elucidate its role in sex-specific nervous system development in rodents. Furthermore, given the vast number of compounds with endocrine disrupting properties, it is critical to characterize combinations of compounds that alter such key developmental pathways. Mixtures studies are significant for public health protection as current methods of risk assessment, based only on effect thresholds of single chemicals, may overestimate the actual no-adverse effect risk levels of EACs.
Our second research aim focuses on mechanisms connecting early hormone disruption with adult behavioral variability. Consistent with fetal origins of adult disease theory, environmental information gathered during development is carried forward into adulthood, influencing behavior. Increasingly, research is identifying that epigenetic modifications may provide the cellular memory for transmission. Our lab uses environmental stressors and endocrine active chemicals to elucidate mechanisms of cellular transmission from development into adulthood through epigenetic reprogramming.