Research

Our projects

We are a highly collaborative research group of curious individuals all pursuing answers to the age old question of "how does a singular genome give rise to a complex multicellular organism?" While we are primarily focused on the relationship between epigenetic regulation and 3D genome organization, we welcome additional questions that require the development of new imaging-based technologies.  Our team fundamentally believes in the value of interdisciplinary research and the strength of crossing disciplines to enable biological discoveries. As such, in additional to biologists, we encourage those from physics and optics backgrounds with a desire to conduct biological research to apply to our group. 

3D genome regulation of epigenetic memory

We apply chromatin tracing technology to measure the biophysical properties of thousands of individual cells in organoid models or developing mouse embryos to assess cell-type specific regulation of features like compaction and phase separation of a loci. We then perturb the epigenetic systems that target these loci with either synthetic engineering of the protein subunits or targeted modulation of their concentration. By doing these measurements in dynamic systems undergoing cell state transitions we can ask how the long term memory of repression changes as a function of the feedback between the regulators and chromatin organization. We also artificially engineer epigenetic circuits to directly quantify the biophysical properties of loci from a "bottom up" approach.  Additionally, combining our experimental measurements with modeling of chromatin dynamics and epigenetic spreading allows us to go where experiments alone cannot and better understand the parameters underlying maintenance of epigenetic memory. 

Develop novel microscopy technologies to sample the central dogma 

We are interested in developing live-cell imaging approaches as well as novel fixed-cell approaches to combine epigenetic imaging and chromatin tracing. This will allow better quantitative models of the dynamics of epigenetic spreading in 3D.  

Epigenetic regulation of extrachromosomal DNA

Extrachromosomal DNA (ecDNA) are large, megabase-scale, circular amplifications that are prevalent across cancer types and associated with poor prognosis. We measure the 3D chromatin organization of ecDNA compared to normal endogenous chromosomes.  We are particularly interested in the role of transposable elements and their epigenetic derepression on ecDNAs and how they can regulate oncogene expression in cis- and in trans.