Toxicogenomic, Epigenetic and Carcinogenesis

Current projects are focused on (1) the identification of early epigenetic changes that would likely contributed to the cancer risk in our DMBA-induced rat mammary gland cancer model; (2) global RNA expression fingerprint profiling during the early stage of breast cancer development and compare them to the parallel epigenetic study results; (3) the elucidation of the mechanistic role of both Phase I & II detoxification enzymes in the rat mammary gland cancer model.

For the epigenetic studies, Dr. Cheng is using one of the global methylation profiling techniques, Methylation Sensitive Restriction Fingerprinting (MSRF) Differential Display Polymerase Chain Reaction (DD-PCR) approach to identify both hypermethylated and hypomethylated genes. Candidates bands are sub-cloned, sequenced and then identified by gene database search. Potential gene targets will be further characterized by bisulfite genomic sequencing and quantitative real time PCR. Dr. Cheng is using the microarray approach for the high throughput gene expression profiling. All microarray data will be explored with various non-supervised clustering algorithms. Data obtained from consistently clustered dendrograms will be exported for downstream pathway and gene ontology analysis. Quantitative real time PCR and various enzyme activity assays will be used to elucidate how the Phase I & 2 genes/enzymes reacted to xenobiotics. EROD assay will also be used to measure the activity of Cytochrome P450.