LabNarrative concept · prepared as an independent design proposal
Zhang LaboratoryTranscription · RNA regulation · Therapy resistance
All research

Research programme 01

Cofactor cooperativity and BET-inhibitor resistance

We define how BRD4, Mediator and elongation machinery sustain oncogenic transcription when bromodomain inhibition fails.
Central question

Which non-bromodomain interactions preserve estrogen-receptor and MYC transcription under BET inhibition?

BET inhibitors were developed to disrupt bromodomain recognition of acetylated chromatin, yet their clinical activity has been limited. The laboratory studies why essential transcription can remain intact when that interaction is blocked.

By mapping post-initiation transcription complexes and testing cofactor dependencies, the programme aims to distinguish dispensable chromatin contacts from essential protein–protein interfaces and identify next-generation therapeutic strategies.

Next programmeTherapy-induced senescence and adaptive transcription