Epigenetic mechanisms of toxicity

Dr Mathew Van de Pette

We study Developmental and Reproductive Toxicity (DART), identifying short-term and lasting changes that occur from drug exposures, to the mother and the developing offspring.

Drug exposures and pregnancy are a particularly troubling, and yet poorly understood area of toxicology. The vast majority of drugs have at most anecdotal information regarding their impact on development, and often we have little knowledge of whether they can be safely taken during pregnancy. "Epidrugs" represent a rapidly increasing array of medicines that have the potential to change epigenetic marks, including DNA methylation and histone modifications. These epigenetic marks represent layers of control to how our genetic code can be read and the correct pattern of these marks is essential to all aspects of cellular function, with changes to them known to cause a wide-range of diseases. This is especially true during embryonic development, where the epigenetic marks may differ from those in the mother, and currently we have almost no information on how epidrugs may affect the developing embryo.
To this end, the lab is interested in Developmental and Reproductive Toxicology (DART). We use both in vivo and in vitro approaches to explore the impact of human relevant doses of Epidrugs. Using reporter models of epigenetic state, we aim to distinguish short term epigenetic changes following drug exposure, and lasting changes that will be present throughout life, and potentially into the next generation(s). We collaborate with industrial and academic partners, applying an array of molecular biology techniques to answer key mechanistic questions.