A pinboard by
Ulf Schmitz

Research Officer, Centenary Institute


In this project, I analyze mechanisms underlying a largely overlooked form of alternative splicing, intron retention (IR), with impact on gene regulation, cell physiology, and disease. IR is a widespread phenomenon in which the splicing machinery fails to excise introns from primary transcripts. This can lead to diverse downstream effects, such as the synthesis of novel peptides, RNA decay, or the suppression of protein or non-coding RNA synthesis. Recently, IR was described as a widespread mechanism of tumor suppressor inactivation, which suggests a significant contribution to cancer emergence and progression. I employ machine-learning approaches and pattern recognition algorithms to unravel the molecular causes for IR events and to determine the extent to which IR is conserved in other species. The integration and mining of massive amounts of RNA-sequencing and epigenomics data, including leukemia patient data, helps me to generate deeper insights into IR, its origins, mechanisms of regulation, and its role in cancer. There is evidence that IR can be used to enhance disease outcome predictions. Therefore, one of my aims is to derive an IR-based biomarker for leukemia. Understanding how IR events are triggered and suppressed will open the way for exploring novel avenues for cancer treatment. For this purpose, I am designing and implementing a cancer transcriptomics analysis pipeline to uncover alternative splicing events, including IR, that may lead to cancer pathogenesis and progression. Moreover, I'm developing an algorithm for the prediction of IR occurrences and possible pathogenic consequences. In summary, I'm actively involved in the advancements of our understanding of gene regulation, and implications for cancer pathogenesis. My ultimate goal is to develop patient-tailored therapeutic regimens with a particular emphasis on leukemia.