Regulation of Transcription

Within the Chemical Biology Program, several groups work collaboratively to discover small-molecule probes of transcriptional biology. We aim to develop direct probes of transcription factors or enzymes that modify chromatin and use these tools to understand the roles of these transcriptional regulators in disease and development. Our efforts fall into two categories:

Chromatin signaling and chromatin-targeting small-molecule probes of epigenetics:

  • Discovering structurally and mechanistically novel small-molecule modulators of chromatin-modifying enzymes
  • Determining the functions of individual histone deacetylase (HDAC) family members
  • Controlling the methylation of chromatin with small-molecule modulators of histone methyltransferases (HMTs) and histone demethylases (HDMs)
  • Building a look-up table for chromatin-targeting small molecules and their effects on the cellular levels of target RNAs
  • Developing new methods to analyze chromatin modifications

Direct modulation of transcription factors with small molecules:

  • Small-molecule profiling studies involving direct binding to transcription factors
  • Probe development and optimization for latent cytoplasmic transcription factors
  • Probe development and optimization for transcription factors involved in cancer dependencies
  • Discovering selective small-molecule modulators of aberrant transcriptional regulators arising from oncogenic translocations