Jian Feng

Epigenetic regulation of neuropsychiatric disorders. Brain function requires accurate control of gene transcription in response to environmental stimuli. Epigenetics plays a key role during this process by modulating gene expression without changing underlying DNA sequences. It has therefore been implicated in various neuropsychiatric disorders, in which environmental factors contribute significantly to the pathgenesis. With help of modern genomic tools and novel epigenetic concepts largely developed in proliferating cultured cells, our laboratory aims to decipher out the epigenetic underpinnings of neuropsychiatric diseases in vivo by using rodent models. We are currently persuing two major researches in drug addiction. 1) Three dimensional chromosome architecture in drug addiction. The compaction and organization of the linear DNA into the nucleus has been demonstrated to have a major influence on gene transcription by facilitating interactions between gene promoters and distal regulatory elements. To elucidate the uncharacterized three-dimensional chromatin architecture in drug addiction, we propose to study the long-range looping interactions between distal DNA elements and gene promoters within the specific neuronal subtypes differentially engaged in addiction. Our study will therefore provide novel insights into the transcriptional regulation underlying drug addiction. This research is currently supported by a NIDA Avenir Award. 2) Neuron subtype specific role of DNA methylcytosine dioxygenase TET1 in cocaine addiction. We propose to study the DNA epigenetic mechanism in drug addiction with a focus on TET1, a newly discovered methylated DNA dioxygenase that leads to DNA demethylation. We plan to elucidate the behavioral role of TET1 and its mediated DNA methylation turnover in the two major neuronal subtypes of the ventral striatum, the center of the brain reward pathway. Our study will not only elucidate a novel molecular mechanism of drug addiction within specific neuron types that are differentially engaged in drug addiction-like behavior, but may also provide a plausible path for therapeutic manipulation of addiction through DNA methylation perturbation. This research is currently supported by a NIDA R01 fund. Moreover, we are pursuing additional studies to expand our understanding of epigenetic underpinnings of neuropsychiatric disorders, some are through collaborations with other laboratories. With the integration of cutting-edge epigenetic/genomic tools and behavioral neuroscience, we aim to study biologically significant questions across a broader range of neuropsychiatric disorders.

Waddell NJ, Liu Y, Chitaman JM, Kaplan GJ, Wang Z#, Feng J#. (2023) Transcription and DNA methylation signatures of paternal care in hippocampal dentate gyrus of prairie voles. Scientific Reports (https://doi.org/10.1038/s41598-023-37521-2)