It is a good rule not to put too much confidence in the observational results that are put forward until they are confirmed by theory.
-attributed to Sir Arthur Eddington in Horace Freeland Judson's The Eighth Day of Creation
We have two broad interests in transcription: transcription insulation and transcription elongation.
Transcription InsulationWe study nuclear processes and mechanisms that segregate, fold and unfold chromosome fibers and disease causing changes that disrupt normal location, arrangement and interpretation of the human genome. Recently, we have determined the locations of a large number of insulators in the genome of primary fibroblasts. Insulators are an important class of transcriptional regulatory elements that affect gene expression by preventing the spread of heterochromatin and restricting how enhancers select their target promoters. We currently investigate the mechanisms involved in establishment and segregation of euchromatin and heterochromatin, and in folding of chromatin into higher order structures and how these insulation mechanisms are perturbed in cancer cells. We employ ChIP-seq (chromatin immunoprecipitation), 3C (chromosome conformation capture), GRO-seq (nascent RNA maping) and other functional genomics tools to define and analyze how the human genome is regulated. We utilize human cell lines and tissues (embryonic stem cells, primary fibroblasts, cancer/immortalized cells and primary cancer tissues). We couple these genome-wide experimental strategies with computational methods to systematically determine patterns, modes and mechanisms of genome expression.
Emerging functional genomic data suggest that transcription elongation is a critical step of oncogene expression in cancers. We are interested in defining pathways and networks that are critical for elongation step of oncogene transcription. We integrate global run-on sequencing (GRO-seq), copy number analysis, functional genomics and small molecule screening to achieve a comprehensive, systems level understanding of the transcription elongation control network at oncogenes and to develop strategies for selective inhibition of the network for cancer therapy.