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Defining new mechanisms of regulation of coding and non-coding RNA localization in healthy states and disease
Fine-tuning and the dynamic regulation of subcellular RNA localization are important for cellular functions, and they are frequently regulated by the non-coding regions of the transcript. Intron retention has emerged as a key factor in spatio-temporal regulation of many coding and non-coding RNAs. Fascinatingly, a large fraction of mRNAs and lncRNAs have high retention of at least one intron in human and mouse stem cells. We work to understand the biological relevance, functionality and the mechanism of subcellular RNA localization regulation through regulatory elements such as intron retention. We use single-molecule RNA imaging, RNA-protein interaction analyses, CRISPR-Cas9 in culture and in vivo and computational analyses to understand these processes on a functional and molecular level in health and in disease.
LncRNA biology and mechanisms of function​
The vast majority of the genome is non-coding and a large fraction of these non-coding genomic regions are transcribed, generating tens of thousands of long non-coding RNAs (lncRNAs). LncRNAs emerged as key regulators of gene expression and genome organization. The human genome has thousands of identified lncRNA loci, yet the mechanism by which they function remains largely unknown. The extent to which lncRNAs contribute to health and disease development, how they affect gene expression and genome organization and the mechanism of their function remain poorly characterized. We work towards understanding how lncRNAs and non-coding regulatory elements affect genome organization, stability and function and we pursue clinical applications of our findings. We use biochemical, computational and molecular tools to disentangle the molecular mechanism by which lncRNA loci function and identify crucial lncRNAs involved in cancer and cardiomyopathies.
Defining functions of repeat-containing lncRNAs in genome regulation
Repetitive sequences account for at least half of the human genome and many of these non-coding regions are transcriptionally activated in diseases such as cancer. We are interested to understand how expression of DNA repeats in the form of long non-coding RNAs contributes to genome architecture, transcriptome regulation, genome regulation and disease development. In our interdisciplinary approach we use computational and experimental approaches such as single-molecule RNA imaging, single-cell multiplexed RNA imaging, biochemical and functional assays to get a mechanistic insight into their molecular and biological function, and their impact on human health and disease.
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