Claudia Kutter

Deciphering new links between genotype and phenotype of healthy and diseased cells is an intense area of investigation. The genetic regulation by RNA, termed riboregulation, is essential to maintain cellular homeostasis, coordinating cell plasticity and preventing malignant cell transformation throughout the human lifespan. However, the impact of riboregulation in controlling these cellular processes remains largely unknow. We argue that RNA binding proteins (RBPs) govern these processes. Our proposed study aims to fill current knowledge gaps in riboregulation by (1) comprehensively characterizing RBP-RNA interactions at the physiological and pathological level in liver, (2) understanding cellular and molecular defects of RBP-mediated RNA processing in reversible and irreversible liver diseases and (3) deciphering underlying mechanisms of riboregulation to advance biomedical research. To successfully explore and expand this promising research area of riboregulation, we designed an integrative multiomics study based on our unique preliminary data. Altogether, our study will generate new insight into how riboregulation is altered in pathological cell stages. We envision that our findings provide targets for treatment and may open new possibilities in the development of innovative RNA-based therapeutics.

Liver cancer is common and only a few patients are still alive a year after diagnosis. Despite the growing number of patients and the high mortality, options for early diagnosis and treatment are still limited. This is because we still lack knowledge of how the cancer cell uses the genetic material to cause cells to grow abnormally. By analyzing data from many patients with liver cancer, my group has recently identified new regulators that affect the growth of cancer cells. These regulators have previously been overlooked because they assume new roles in cancer, which previous research did not consider. These new key regulators are called RNA-binding proteins (RBPs). These proteins control how the genetic material (RNA) is used. We have developed new experimental and specific bioinformatic methods to understand the mechanisms behind how RBP gives rise to different RNA molecules in liver cancer. We will map how the different RBP-RNA pairs contribute to liver cancer, change their amounts in the cancer cell and observe differences in cell growth and treatment response. Gaining more knowledge about the control of our genetic material is crucial to meeting an important challenge in cancer research. By exploring the mechanisms by which RBPs and RNAs interact in cancer

and how these interactions differ from those in normal cells, we can gain knowledge that can be applied not only to cancer diagnosis and prognosis but also to developing strategies for more targeted cancer cell therapy. This would be a powerful addition to existing methods.