Ross Gillette, PhD
Environmental Contaminants and Their Role on Heritable Disease and Traumatic Stress
Summary
Man-made environmental toxicants have permanently and irreversibly contaminated the environment. Certain chemicals created for the industrial and agricultural industries are classified as endocrine disrupting chemicals (EDCs) and cause a broad range of hormone-sensitive diseases like cancer, reproductive abnormalities, and behavioral disorders. Two ubiquitous EDCs, polychlorinated biphenyls (PCBs – industrial) and Vinclozolin (agricultural), cause heritable disease that is not due to DNA mutation. The mechanisms that allow EDCs to cause heritable disease are not fully understood and it is unclear why such a mechanism exists. Traumatic stress is the only other life event known to be heritable and is suspected to act through a conserved evolutionary mechanism meant to provide future generations with information essential for survival. The novel hypothesis proposed here is that EDCs hijack or interact with the same mechanisms by which traumatic stress informs future generations. To test this hypothesis, male rats will be exposed to either PCBs or Vinclozolin from fetal development to adulthood and then exposed to traumatic stress paired with a strong odor. If heritable, their sons, who never experienced EDCs or traumatic stress, are predicted to display a fear response when presented with the same odor, an effect that is predicted to diminish due to EDC exposure. The brain, blood, and sperm of rat fathers and sons will be used to isolate extracellular vesicles (EVs), which are cellular components that contain material believed to be involved in the transfer of information across generation. The EV contents are used for gene sequencing, and advanced bioinformatics will be used to identify the components that are necessary for the heritability of experience. The goal of this work is to determine the mechanisms that allow heritable disease to be passed between generations and to identify potential targets for future therapeutic intervention and mitigation.
The PhRMA Foundation Postdoctoral Fellowship has allowed me to ask, test, and answer novel questions that are fundamental to how man-made environmental toxicants cause heritable diseases. This work would not have been possible without the support of the PhRMA Foundation and I am honored to have been selected for this fellowship.
