Research
Our research program deciphers the molecular mechanisms of RNA regulation and modifications, exploring their roles in cellular functions and diseases like neurodegeneration and cancer. Our approach is rooted in functional genomics, and we have developed several high-throughput approaches to achieve our goals, including iCLIP for protein-RNA interaction mapping, in vitro iCLIP to map binding of recombinant proteins to complex mixtures of RNAs, as well as miCLIP2 for detecting m6A RNA modifications. In addition, we use massively parallel reporter assays to decode regulatory elements in RNA sequences.
Over the years, we have achieved several significant milestones: Exploring the function of RNA modifications, we discovered that m6A RNA modifications mediate X-to-autosome dosage compensation in mammals (Rücklé et al 2023). We discovered a new RNA decay pathway that is triggered by m6A sites in the coding region (Zhou et al., 2024).
Exploring mechanisms of RNA splicing we revealed that FUBP1 is a core splicing factor that is required for the splicing of long introns (Ebersberger et al., 2023). We generated the first map of all RNA regulatory elements that control a specific splicing decision and identified splicing regulators that may contribute to CART-19 therapy resistance in B-ALL leukemia (Braun et al 2018, Cortes-Lopez et al 2021) and we found that RNA regulation is extensively modulated by the interactions between different RNA-binding proteins inside cells (Sutandy et al. 2018; Kang et al 2020). Furthermore, we discovered that the RNA binding protein Makorin acts as a sensor for faulty RNAs (Hildebrandt et al. 2019).
Currently, we focus on decoding the (1) mechanisms of splicing regulation in disease (2) we dissect the roles of m6A RNA modifications in gene expression and dosage compensation and (3) we investigate mechanisms of RNA quality control. By achieving these goals, we hope to contribute significantly to decoding the molecular principles that govern RNA regulation in human physiology and age-related diseases. Ultimately, we hope that our work will help guide the development of specific treatments.
