Our research is centered on understanding neuroepigenetic mechanisms responsible for transcriptional and synaptic plasticity in the central nervous system. Our work represents a unique blend of chromatin biochemistry, chemical biology and functional neurobiology to address fundamental questions related to the molecular underpinnings of neurodevelopmental disorders and adult psychiatric illness. Examples of current projects in the lab include:
1) Functional dissection of regulatory roles for histone turnover versus nucleosomal remodeling in the mediation of activity-dependent gene transcription in neurons.
2) The role of nucleosomal turnover in corticostriatal limbic circuitry in the regulation of depressive-like behaviors in both rodents and humans.
3) Combinatorial histone posttranslational modification profiling and genome-wide chromatin analyses to investigate developmental trajectories of human psychiatric illness (e.g., schizophrenia – in collaboration with Dr. Kristen Brennand).
4) Biochemical and functional characterization of novel neuronally enriched histone modification states in the central nervous system (relationships to major depressive disorder, drug addiction, etc.).
5) Identification and characterization of neuronal specific histone “reader” proteins, and their respective roles in neurodevelopmental plasticity and disease (e.g., Down syndrome associated intellectual disability).
6) Development of novel epigenomic editing tools to disrupt or potentiate histone modification states in brain.