Exploring the Life of mRNA in Disease

mRNA decay is a critical post-transcriptional mechanism that regulates mRNA stability and affects translation, thereby fine-tuning protein abundance. Among the most important sequence elements affecting post-transcriptional regulation are AU-rich elements (AREs), which are located in the 3'UTR on mRNAs. Aberrations in ARE-dependent regulation contribute to a variety of diseases and disorders, including cancer and chronic inflammatory diseases. The goal is to investigate mechanisms of disease affected by abnormal mRNA decay using our innovative experimental approaches with potential translational outcomes in therapy and medical biotechnology. Most of our Group projects focused on this theme. Specifically, the following disease/research areas are being explored:

(I) Breast cancer: Specifically, we study the post-transcriptional control (mRNA decay) for the following processes in cancer: mitosis, DNA replication, apoptosis, and the immune checkpoint. Here, as a translational outcome, we discovered potential biomarkers and validated (in vitro) drug targets.

(II) KRAS-mutant colon and lung cancer: Mutations in the KRASa gene promote tumorigenesis and resistance to therapy. We investigate the impact of mutant KRAS and its inhibitors on post-transcriptional control (mRNA decay).

(III) Aging: This project studies mRNA stabilization in aging models (both in vitro and in vivo) and demonstrates the consequences on age-related cellular decline. This knowledge is important to advance our understanding in developing novel interventions against degenerative diseases.

(IV) Viral infections. This work explores the role of mRNA stabilization in coronaviral infections and the consequential acute inflammatory response. Understanding this link can provide further understanding of how acute coronaviral infections trigger the “cytokine storm,” a major morbidity and mortality factor. This should provide new avenues for diagnostics and therapeutic interventions.