Research

Gene regulatory programs in normal and disease states

Gene regulatory programs in normal and disease states

Transcriptional programs control key biological processes such as differentiation, development and cellular responses to environmental cues. Thus, their dysregulation promotes malignancy. In this process, normal cells can acquire one or many genetic alterations that dysregulate the gene expression program for cell survival thereby inducing a “cancer cell state”. As such, cancer cells are addicted to unique transcriptional programs that generate vulnerabilities that can be targeted therapeutically.

Our lab has recently identified a novel transcription elongation complex referred to as KEC, which controls the expression of thousands of genes (such as growth-driving genes) in cancer cells.

Our lab has recently identified a novel transcription elongation complex referred to as KEC, which controls the expression of thousands of genes (such as growth-driving genes) in cancer cells. Our lab is interested in defining how the KEC operates to regulate transcription to maintain the cancer cell state. At the molecular level, we have recently found that the KEC assembles at both promoters and enhancers in the human genome and that genetic deletion of KEC components dampens transcription of growth-driving genes thereby blocking cell growth. Our lab is currently defining the mechanisms by which the KEC assembles on chromatin through recognition of histone post-translational modifications and sequence-specific DNA elements. Defining the molecular basis of this process will lead us not only to a better understanding of gene regulation but to alternative strategies to target these transcriptional addictions in cancer.