Current Research

Posttranslational modifications on histones play an important role in modulating chromatin dynamics and the accessibility of the underlying DNA, thus regulating all chromatin-associated processes, such as transcription. Dysregulation of the homeostasis of histone modifications leads to developmental disorders and genetic diseases, including cancer. However, despite this biological and clinical importance, it remains largely unknown how posttranslational modifications that take place on the histone tails dictate gene expression profiles. 

The long-term goal of our research is to understand the molecular mechanisms by which histone modifications, particularly lysine methylation and acetylation, regulate chromatin and transcription, and how dysregulation of histone modification homeostasis leads to human cancer.

The current research focus of our laboratory is to identify and characterize novel epigenetic readers and to elucidate their roles in cancer. One of the principal functions of histone methylation and acetylation is believed to be to recruit or repel “reader” proteins that recognize the methyl or acetyl moiety on specific amino acid residues and transduce the epigenetic signals to distinct outcomes. Therefore, identification of reader proteins is critical for understanding the mechanistic and functional consequences of histone modifications. 

Previously, we identified the PHD finger as a novel reader module for histone lysine methylation (Shi et al Nature 2006). Recently, we developed a histone peptide array for high throughput screening and identified several novel readers for histone methylation and acetylation (Wen et al Nature 2014; Li et al Cell 2014). Global alterations of histone modifications occur frequently in many types of human cancers. The identification of potent inhibitors, including JQ1 that targets BRD4 and other BET family Bromodomain-containing proteins, suggests that epigenetic readers are attractive therapeutic targets for cancer treatment. 

Ongoing projects in the lab aim to elucidate the biological functions of the new epigenetic readers that we identified using diverse biological systems as well as to develop and characterize small molecules targeting these epigenetic readers for the treatment of diverse human cancers.

Related Department

Epigenetics and Molecular Carcinogenesis

Related Program

Genes and Development Ph.D. Program