Regulation of transcription condensate dynamics
  • We have uncovered cell cycle signaling pathways that control transcription condensate dynamics in proliferating cells
  • These pathways couple transcriptional activation of the replication-dependent histones to origin firing at the G1/S transition
  • Phosphorylation of intrinsically-disordered regions within transcription coactivators control condensate formation and dissolution
  • Dysregulation of condensate dynamics leads to nucleus-wide DNA damage

S/G2 cell cycle checkpoint​

  • We have uncovered an ATR-enforced S/G2 checkpoint that delays FOXM1-dependent transactivation of the mitotic gene network
  • The S/G2 checkpoint ensures the completion of DNA replication
  • Checkpoint failure causes shutdown of the replication program and severe mitotic defects
  • Checkpoint failure activates a p53-p21-RB1 axis that triggers an atypical G2-to-G0 cell cycle exit

Transcription - replication friendships at nuclear speckles​

  • We are exploring how origin firing near active genes targeted to nuclear speckles is regulated by CDK9-cyclin T
  • Using phospho-proteomics and quantitative imaging we have discovered transcription and replication "friendships", where these two processes work together to promote genome stability
  • We study how ATR-CHK1 signaling at nuclear speckles ensures cooperation between transcription and replication

Linker H1 histones and gene expression

  • We are interested in the unique functions of the different replication-dependent (RD) linker H1 histone genes
  • Human cells encode 5 RD linker H1 genes: H1.1, H1.2, H1.3, H1.4, and H1.5
  • Using mass spectrometry and high-throughput sequencing we have revealed linker H1-specific functions in gene regulation, RNA processing, and translation efficiency