Our goal: to elucidate the molecular mechanisms of gene control by regulatory non-coding DNA

A fundamental question in developmental biology is how cell identity and cell fate are defined. During cell differentiation, the dynamics of gene activity is controlled by changing sets of transcription factors that bind the genome within cis-acting regulatory elements, such as transcriptional enhancers, which are scattered across the genome and can modulate gene transcription. Physical interactions through chromatin folding are key for these distal elements to convey regulatory information to target gene promoters, but the underlying molecular mechanisms are not understood. Many pathologies, ranging from congenital malformations to cancer, are caused by the disruption of trans-acting factors, cis-acting elements, or their ability to communicate.

The goal of our group is to understand the molecular mechanisms underlying long-range control of gene activity and, ultimately, to develop innovative therapies that target them. To do this, we will develop and apply novel technologies to the study of embryonic stem cell differentiation, allowing unprecedented control over transcription factors and chromatin regulators. We will combine high-throughput engineering of regulatory elements with read-outs of gene activity that integrate genome-wide -omics approaches with single-cell assays by flow-cytometry and live cell imaging.

Our broad aims are:

1. Uncovering the molecular mechanisms that connect different portions of the genome together

2. Understanding what confer regulatory DNA with the ability to modulate the activity of nearby genes

3. Creating molecular tools that will enable controlling chromosome organization and functions

List of publications here