Exquisite regulation of gene expression in time and space underlies essentially all biological processes. However, understanding gene regulation in mammals is challenging because mammalian genomes are enormous and largely non-coding. Specifically, mammalian genes are controlled by enhancers that can be hundreds of kilobases away from the genes they control. How the cell ensures that the right enhancer contacts and activates the right gene in 3D is not well understood. We are broadly interested in understanding the interplay between 3D genome organization and the regulation of gene expression, with a particular focus on development and disease.

We take a unique approach to these problems. Most biological processes are inherently dynamic, yet most current methods generate static snapshots and cannot report on dynamics. To overcome these limitations, we develop new experimental, optical and computational methods for following processes at the single-molecule level with millisecond and nanometer precision in time and space inside living cells. We integrate these approaches with traditional methods from genomics, biochemistry, genome-editing, stem cell differentiation and organoid modeling. Current areas of interest include:

• The molecular mechanisms that regulate 3D genome organization
• Regulation of 3D genome organization and transcription during development and their dysregulation in cancer
• Developing new tools for following single-molecules inside of living cells
• Developing predictive computational models of 3D genome organization
• Applying and testing our understanding through synthetic biology approaches