Developmental and multigenerational toxicity of THC and CBD

Project Description: The goal of this project is to compare the relative morphological, behavioral, reproductive and multigenerational phenotypes that result after developmental exposures to cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Due to relaxed prohibitions on marijuana use and therapeutic potential of cannabis constituents in the treatment of early-onset pharmaco-resistant epilepsy, exposure of children to these chemicals is increasing.In this study we will leverage the advantages of the zebrafish model including high fecundity, low culture costs, transparent and conserved developmental biology and genomics. We will comprehensively assess phenotypic alterations caused by two developmental exposures (either during organogenesis or sexual differentiation) and mechanistically link the adverse outcomes with targeted and global transcriptomic analyses. This research will address the significant knowledge gap that exists related to adult and multigenerational behavioral and reproductive consequences of early life cannabinoid exposure.

Desired Student Qualifications: Background coursework in biology and/or pharmacy.

Project Timeline: ongoing

Duties of Student Researcher: Laboratory research, data presentation and thesis writing.

Last Updated on 2017-01-23 13:31:46

Mechanisms of brain/CNS toxicity following exposure to Benzo[a]pyrene

Project Description: The goal of this project is to probe in-depth the mechanisms of benzo[a]pyrene (BaP) action in the brain. Our objective is to establish how BaP exposure changes the transcriptome and methylome to result in persistent toxicological consequences. Our study design, using the zebrafish (Danio rerio) model, will allow us to determine if parental dietary BaP exposure produces changes in brain gene expression and methylation status that are persistent in future generations (F1- F3). We have on-hand a unique multigenerational tissue sample collection, corresponding reproductive and developmental outcomes, and histopathology already measured or ongoing. We expect to phenotypically anchor new gene pathways and critical biomarkers altered by BaP exposure. Polycyclic aromatic hydrocarbons (PAHs), like BaP, are implicated in IQ, learning and memory decrements, and endocrine disruption reported in offspring following parental exposure. A significant knowledge gap exists in the molecular mechanisms for these neurotoxic and potential multi/trans-generational effects associated with environmental exposures. This proposal will further establish the zebrafish as a model organism to test environmental contaminants for their ability to cause multigenerational effects through epigenetic mechanisms. Importantly, this proposed project addresses the NIH emphasis areas of environmental epigenetics and fetal basis of adult disease; areas currently lacking appropriate consideration in risk assessment.

Desired Student Qualifications: Background coursework in biology and/or pharmacy.

Project Timeline: ongoing

Duties of Student Researcher: Laboratory research, data presentation and thesis writing.

Last Updated on 2014-01-31 12:01:02

Reproductive toxicity due to benzo[a]pyrene exposure

Project Description: The overall goal of this project is to establish zebrafish as a faster and relevant model to study multigenerational and epigenetic consequences of developmental exposure to environmental toxicants. Because of their rapid development, fecundity and relatively lower culture cost, fish are a uniquely suited but underutilized model to study multi- and trans-generational, epigenetic effects of environmental contaminant exposure. Effects of benzo[a]pyrene an environmentally relevant carcinogenic and endocrine disrupting compound that causes multigenerational effects in mammals will be the focus of this study. Polycyclic aromatic hydrocarbons (PAHs), like BaP, are implicated in preterm deliveries, low birth weights, and childhood cancers in offspring of exposed mothers. However, a significant knowledge gap exists in the molecular mechanisms for reproductive, developmental and multi/trans-generational effects associated with these environmental exposures. We hypothesize that parental exposure to BaP will adversely affect reproduction, alter gene specific and global methylation status, and cause quantifiable pathologies. Importantly, we expect that these effects could be preserved in subsequent F1, F2 and F3 generations. With our experimental plan we expect to identify new pathways altered by BaP exposure and assess critical time periods, tissue specificities, and sex dependence for epigenetic changes. Most importantly we will validate the zebrafish model and identify critical biomarkers that will be able to be used to further screen other chemicals for the fetal basis of adult disease and multigenerational toxic effects.

Desired Student Qualifications: Background coursework in biology and/or pharmacy.

Project Timeline: ongoing

Duties of Student Researcher: Laboratory research, data presentation and thesis writing.

Last Updated on 2014-01-31 12:01:07