Our lab has established a protocol to study neuronal regeneration using in vitro primary culture of cortical and hippocampal neurons. In addition, organotypic 3D brain slice culture has been established in the lab to examine the neuronal regeneration at tissue level. We have identified several regeneration-associated genes (RAGs) using genome-wide chromatin immunoprecipitation-sequencing of histone H3K4m3 and H3K27ac modifications, and RNA-sequencing analysis.
Neurons are highly energy demanding and require sufficient mitochondria to support cellular activities. In response to stimuli, mitochondria undergo fusion/fission cycles to adapt to environment. We have shown that injury induces mitochondrial fission and supplement of freshly isolated mitochondria promotes neuronal regeneration. Our findings support the importance of mitochondrial dynamics during regeneration of injured hippocampal neurons and highlight the therapeutic prospect of mitochondria to the injured central nervous system.
Epigenetic Regulation of ROS1 Oncogene
Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy.