Each year, more than 1.6 million people in the U.S. are diagnosed with cancer. Globally, the number of people with the disease is expected to rise 50 percent in the coming years, jumping from 14 million in 2012 to an estimated 21 million by 2030.
This impending increase reinforces the importance of understanding the complex constellation of factors that contribute to cancer and leveraging this knowledge to find new, improved prevention and treatment methods. To this end, the Shi Laboratory seeks to discern how epigenetics — mechanisms that regulate how DNA is read and acted upon — impact cancer risk, development and progression.
Specifically, the Shi Laboratory investigates a number of posttranslational modifications on histones, which 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 histone modification homeostasis leads to pathogenesis of developmental disorders and genetic diseases, including cancer.
However, despite the clear biological and clinical importance, it remains largely unknown how modifications on the histone tails dictate gene expression profiles. 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 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.
The long-term goal of the Shi Laboratory’s research is to understand the molecular mechanisms by which histone modifications, particularly lysine methylation and acetylation, regulate chromatin and transcription and how dysregulation of the homeostasis of histone modifications leads to human cancer. Their current research focus is to identify and characterize novel epigenetic readers and to elucidate their roles in cancer.