The broad focus of the Chen lab is to investigate epigenetic and genetic regulations of genes in human cancers related to environmental or occupational exposure to mineral dust, carcinogenic metals and chemical carcinogens. More specifically, the lab employs biochemical, gene editing and multi-omics approaches to elucidate molecular mechanisms by which the expression and function of genes contributing to epigenetics and cancer cell stemness are altered. One of the key signaling events in carcinogenesis is metabolic reprogramming from mitochondrial TCA cycle to glycolysis in response to oncogenic drivers. A principal question to be addressed is how such metabolic shift perturbs the intracellular regulatory circuits that control DNA and histone methylation and other posttranslational modifications of the histone proteins that determine chromatin configuration, the accessibility of the key oncogenic genes by transcription factors, the self-renewal of the cancer stem cells, and genomic instability.