Research

The lab studies how dynamic, spatially organized molecular events control gene expression and cell fate. We develop single-molecule imaging, modeling, and perturbation tools that make these processes directly measurable in living cells, allowing us to address longstanding questions inaccessible to genomics alone: how transcription factors find and act on their targets, how 3D genome organization shapes transcription, and how dynamic cell states drive cancer adaptation.

Current Directions

How Do Transcription Factors Find and Control Their Target Genes?

The lab connects single-molecule Transcription Factor (TF) behavior and genomics to fundamental questions of regulatory specificity. A central question is how the disordered domains of TFs shape their regulatory function, for instance by guiding genomic target search, and/or by directing distinct transcriptional dynamics once TFs are bound.

How Does 3D Genome Organization Control Gene Expression?

Nuclear organization and chromatin architecture shape transcription regulation, but understanding the underlying mechanisms requires techniques able to interrogate these processes at the appropriate spatiotemporal scales. Using the histone locus as a model, and combining imaging with genomics, we found that the compartmentalization of RNA Polymerase II into clusters regulates the timing of transcriptional activation. These clusters contain a substantial fraction of factors not bound to chromatin, revealing regulatory features invisible to genomics alone. The lab also build tools to visualize genome organization in fixed and live cells.

How Do Dynamic Gene Expression States Drive Drug Resistance in Cancer?

We study how dynamic transcriptional states allow cancer cells to survive therapy. Increasing evidence indicates that drug resistance is often preceded by reversible, epigenetic adaptations. We study these processes using live imaging, single-cell approaches, and spatially resolved RNA measurements.