Team RSC

Our team sought to identify key molecular mechanisms that generate mRNA splicing abnormalities in cancer. Splicing of mRNA is a crucial process in eukaryotic gene expression regulation. In addition to canonical splicing, which leads to the inclusion of constitutive exons into the mature mRNA, the transcriptome is subject to alternative splicing.

More than 90% of eukaryotic mRNAs undergo alternative splicing, giving rise to multiple protein-coding isoforms from a single precursor mRNA. Alternative splicing is therefore a major determinant of proteome diversity and organism complexity.

Emerging data indicate that aberrant alternative splicing plays a critical role in the pathogenesis of several molecular subtypes of cancer. Such splicing abnormalities can lead to constitutive activity of oncogenes, reduced expression of tumor suppressors, or drug resistance.

By employing transcriptomic and gene-editing technologies combined with mechanistic cellular biology, we explored the interplay of cis- and trans-regulatory splicing elements in cancer. Our goal was to understand how these elements shape the complex pathophysiology of tumor cells and to identify tumor-specific vulnerabilities for targeted cancer therapy. Although the full results remain confidential, selected findings are reflected in the publications below.

Publications

1. Gallego-Paez LM and Mauer J (2022): DJ Express: An Integrated Application for Differential Splicing Analysis and Visualization
   Frontiers in Bioinformatics 2:786898
2. Gallego-Paez LM, Edwards WJS, Chanduri M, Guo Y, Koorman T, Lee CY, Grexa N, Derksen P, Yan J, Schwartz MA, Mauer J, Goult BT (2023): TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity
   Journal of Cell Biology 222(5), e202209010