Translational Environmental Epigenetics
Environmental factors strongly contribute to the development of psychiatric disorders. Evidence suggest that environmental cues as early as in antecedent generations and throughout the lifespan can substantially influence developmental trajectories towards health and disease. We are specifically interested in the effects of early life stress and how these adverse factors influence the risk for stress-related disorders including major depression and post-traumatic stress disorder. However, how the environment affects long-term brain function remains unclear. We focus on epigenetic changes, broadly defined as functionally relevant changes to our genome without alterations of its sequence. In particular, we investigate DNA methylation profiles in humans and animal models to detect epigenetic signatures that are predictive of disease trajectories or provide insight into disease mechanism.
Non-Coding RNAs in the Mammalian Brain
Only about 2% of our genome is actively translated into proteins, however, up to 80% of the entire genome is transcribed into RNA. Despite good evidence for a good portion of our DNA being indeed “junk-DNA”, more recent evidence suggest that the non-coding part of our genome has relevant function in genome stability, regulation and function. Among the broad variety of non-coding RNAs expressed from the mammalian genome, we focus on circular RNAs, which form a unique closed-loop structure. Circular RNAs are expressed from many neuron-specific loci and show an enrichment in the brain. However, their function is largely unknown. We investigate circular RNAs in post-mortem brain tissue and in animal models to better understand their role in the healthy brain as well as in disease.
Effects of Type and Timing of childhood maltreatment on disease trajectories
Childhood maltreatment is one of the most important environmental contributors to the development of a wide range of psychiatric disorders. However, not everyone exposed to traumatic events during childhood progresses to develop mental health problems. In addition, disease trajectories in individuals exposed to maltreatment show a broad variation in symptom type and severity later in life. This indicates a specific impact of type and timing of maltreatment on later symptom development with discernable sensitive periods mediating the effects of maltreatment on outcomes. Using clinical data and animal models, we seek to understand how type and timing of environmental factors influence outcomes and how genetic and other molecular mechanisms interact with exposure to maltreatment.