Research

Research

My lab has a long-time interest in understanding the mechanisms of transcription and gene regulation in mammalian cells using initially cell-free systems reconstituted with purified gene-specific transcription factors, general cofactors, and components of the general transcription machinery to recapitulate transcriptional events in vitro. 

Mechanistic studies based on cell-free transcription systems with DNA and chromatin templates are further evaluated in vivo by chromatin immunoprecipitation (ChIP), RT-PCR, reporter gene assay, co-immunoprecipitation (co-IP), nucleosome mapping, siRNA/shRNA knockdown, and CRISPR-Cas9 knockout using different types of cultured cells. 

Recently, we have also adapted conditional knockout and transgenic knock-in mice to investigate the functional role of bromodomain-containing protein 4 (BRD4) using both xenograft and syngenic cancer models.  In addition, patient-derived xenografts (PDXs) and organoids are used to evaluate BRD4 protein isoforms in cancer initiation and progression.

Our goals are to elucidate the general principles underlying gene activation and repression in mammalian cells and their associated viruses, in particular, DNA tumor viruses such as human papillomaviruses (HPVs). 

The application of reconstituted chromatin transcription systems and HPV and cancer models has significantly advanced our mechanistic understanding of eukaryotic gene transcription and chromatin dynamics. 

Our research is broadly categorized in the following six areas:

  1. Role of Human General Transcription Factors and Cofactors in Eukaryotic Transcription

  2. Transcriptional Regulation and DNA Replication in Human Papillomaviruses (HPVs)

  3. Post-translational Modification

  4. Bromodomain-containing protein 4 (BRD4)

  5. BRD4-Regulated Transcription Programs and Cancer Pathways

  6. Therapeutics targeting Phospho-BRD4