Cancer arises from breakdown in the normal cellular regulatory system. This malfunction can be a consequence of genetic mutation as well as epigenetic changes. Key epigenetic alterations, including histone modification and DNA methylation, often result in global as well as localized chromatin packaging that influences the transcription of genes important to cancer. While genetic changes are almost impossible to reverse, epigenetic alterations are potentially reversible. Drugs that modify the epigenetic state promise to be effective new cancer therapies. However, the mechanism(s) underlying the epigenetic regulation of cancer cells, as well as the way in which drugs manipulate the epigenetic state and transcription, remain largely unknown. Moreover, as epigenetic regulation is critical for maintaining normal cellular function, the characterization of cancer-specific epigenetic reprogramming is an essential step for increasing specificity of epigenetic therapy. Noncoding RNA, particularly long non-coding RNA (lncRNA), has recently become a new area of focus in cancer biology, with evidence suggesting that they are essential to epigenetic reprogramming during cancer development and progression.

The He laboratory applies a variety of genomic, epigenomic experimental and computational approaches to elucidate the functional role of epigenetic regulation in cancer development, progression and drug response, with a special focus on the interplay between epigenetic regulators and noncoding RNA. Using both experimental and computational expertise, we are in a unique position to make major contributions to both the general understanding of cancer biology and the improvement of epigenetic therapy. Our research focuses on three major directions:

  1. Role of noncoding RNA and epigenetic regulator in transcriptional regulation.
  2. Molecular mechanism(s) of epigenetic regulation in cancer development, progression, drug response and resistance.
  3. Development of experimental and computational approaches for genome-wide epigenetic and noncoding RNA analysis.