The epidermal layer of human skin is continuously replenished by resident stem cells while differentiated cells are shed from the surface. Disrupting this balance of stem cell renewal and differentiation contributes to diseases, such as psoriasis and cancer. Therefore, the mechanisms governing epidermal stem cell fate decisions must be robust, precise and tightly controlled.
The Mulder lab investigates the mechanisms underlying human epidermal stem cell renewal & differentiation focusing on the epigenetic and non-coding RNA machineries. We are particularly interested in understanding how the functional interplay between seemingly unconnected genes and cellular processes confers robustness and precision to biological systems.
The approaches we use to address these questions include: molecular biology, cell biology, primary human epidermal (organotypic) culture, genomics, proteomics, siRNA/CRISPR-based genetic screening technologies, as well as novel computational methods.
Moreover, our lab is actively developing new technologies to open avenues towards new biological questions and insights. We recently described the ‘Immuno-Detection by Sequencing’ (ID-seq) technology that allows us to quantify >80 (phospho-)proteins in hundreds of samples in a single experiment (van Buggenum, Nature Communications 2018).
We have recently extended the ID-seq approach to measure 70 (phospho-)proteins in single cells (van Eijl, iScience 2018), as well as combine RNA and intracellular protein measurements from the same individual cell (RAID: Gerlach, Scientific Reports 2019).
We are now applying these new technologies to understand the connections between signalling pathway activity and transcriptional output at the single cell level in healthy and disease contexts.