Xenobiotic Disruption of the Perinatal Testosterone Surge and Neurobehavioral Development
Endocrine active chemicals (EACs) have been increasingly implicated in neurobehavioral and reproductive disorders, particularly those with sex-biased prevalence rates. Over 900 endocrine active chemicals have been identified. As such, humans are consistently exposed to mixtures of EACs. Importantly, there is increasing evidence that mixtures of low-dose EACs can act synergistically, even via different mechanisms, to converge on downstream targets and result in a spectrum of reproductive deficits known as the male reproductive syndrome. Whether such cumulative influence extends to the central nervous system (CNS) and behavior is unknown.
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Epigenetic Mechanisms Underlying Behavioral Toxicity
We have long known that altered developmental exposure to steroid hormones can alter behavior into adulthood; however, the mechanisms of cellular transmission were unknown. Increasingly, epigenetic mechanisms of cellular memory across the lifespan have been identified. In collaboration with Dr. Deborah Cory-Slechta, we study how developmental endocrine disruption through exposure to lead (Pb), prenatal stress (PS), and their combination alter epigenetic profiles in mice, including DNA methyltransferase concentrations, post translational histone modifications, and DNA methylation, in the frontal cortex and hippocampus across the lifespan. Importantly, the epigenetic alterations produced by Pb exposure are significantly modified by the type of behavioral experiences that mice are subsequently exposed to.
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Developing Translational Methods in Neurotoxicology
An interdisciplinary perspective is required to navigate translation from simplistic animal models to the complex etiology of neurobehavioral disorders in humans. We use techniques and theory from neurotoxicology, behavioral endocrinology, evolution and development, and epigenetics to improve the translational relevance of our experiments. We strive to use translational and real world relevant multi-factor toxicant exposures. We aim to remove experimental manipulations that confound interpretation.
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