3D Epigenome Reconfiguration in Healthy and Diseased Neural Lineage Commitment

The Cremins Lab focuses on higher-order folding of the genome and how epigenetic marks work through long-range regulatory mechanisms to govern neural connections in the mammalian brain. We aim to investigate the higher-order folding of the chromatin fiber and the spatial connections between epigenetic marks on the linear genome and how they impact development and disease onset in the mammalian brain. Much is already known regarding how transcription factors and epigenetic marks work in the context of the linear genome to regulate neuronal development and function. Yet, severe limitations still exist in our ability to apply this knowledge to engineer neuron fate at will or correct brain diseases in vivo. The overarching goal of my laboratory is to obtain detailed mechanistic understanding of how the genome is folded and reconfigured during neural lineage commitment and synaptogenesis and how these folding patterns influence the specificity, maturation and pruning of neuronal connections in healthy and diseased mammalian brain development. Addressing this knowledge gap will provide an essential foundation for our long-term goal to engineer the 3-D genome to control neural cell fate in debilitating neurodevelopmental and neurodegenerative diseases.