We are interested in decoding the genomic regulatory code and understanding how genomic regulatory programs drive dynamic changes in cellular states, both in normal and disease processes. Transcriptional states emerge from complex gene regulatory networks. The nodes in these networks are cis-regulatory regions such as enhancers and promoters, where usually multiple transcription factors bind to regulate the expression of their target genes.
Our lab is a “humid” lab, half wet and half dry. In the wet-lab we apply high-throughput technologies to decipher enhancer logic and map gene regulatory networks, such as RNA-seq for transcriptomics and ATAC-seq and ChIP-seq for epigenomic profiling. To test the activities of promoters and enhancers we use massively parallel enhancer-reporter assays. Finally, to map high-resolution landscapes of possible cellular states we use single-cell transcriptomics and single-cell epigenomics.
We are interested in a variety of biological problems, and use as main model system the fruit fly Drosophila melanogaster, with a focus on the retina and the brain. Our fly lab houses multiple Drosophila species, natural inbred strains, and mutant lines, allowing to incorporate evolutionary models, natural variation (Quantitative Trait Loci), and disease mutations in our studies of the genomic regulatory code.
We are also interested in deciphering regulatory programs of cellular state switches in mammalian systems, including human and mouse. To study the cis-regulatory code in mammalian genomes we mainly use cancer as model system. During cancer progression, gene expression profiles of cancer cells can change, causing regulatory heterogeneity in tumors. This heterogeneity has an important impact on therapy response, since some cell states may be more or less vulnerable to a particular drug therapy.
In our dry lab we use bioinformatics methods for network inference and computational modeling of enhancers, such as Random Forest machine learning and Deep neural networks. Some of the bioinformatics methods we have developed and made available to the community include TOUCAN, ENDEAVOUR, iRegulon and i-cisTarget.