This project investigates RNA-binding proteins (RBPs) and their roles in diseases like cancer, neurodegeneration, and metabolic disorders, paving the way for new treatments.
Key discoveries include the identification of QKI and CELF2 as crucial for myelination, offering insights into Charcot-Marie-Tooth disease. CIRBP was found to regulate liver fibrosis progression, shedding light on its inflammatory role. In cancer research, better understanding of the MAPK pathway, implicated in 30-50% of cancers, may help develop targeted therapies. RBM10’s role in pancreatic cancer proliferation was also identified, suggesting potential intervention strategies.
Advancements in T-cell function mapping under stress and normal conditions were made using cutting-edge multiplexing technology, improving sensitivity and efficiency. A reconstituted cell-free translation system (ReCet) was developed, enabling efficient protein synthesis outside living cells for synthetic biology, drug discovery, and biotechnology.
In melanoma, CRISPR/Cas9 screening revealed RBPs regulating CD155 immune checkpoint expression. Initial tests of small-molecule inhibitors provided new immune-targeting insights. Small-molecule inhibitors for HuR and YTHDF2 were identified, offering new therapeutic possibilities, alongside PROTAC technology for targeted protein degradation.
Research on RNA-mediated metabolic enzyme regulation is ongoing, with potential breakthroughs in riboregulation. A long-term goal is to determine the structure of human ENO1 with an RNA inhibitor, offering novel insights into metabolic control.
These discoveries and innovations have significant implications for advancing diagnostics and treatments across multiple diseases.
The project also explores the role of the autophagy adaptor p62/SQSTM1 in viral infections, particularly SARS-CoV-2. Using engineered Huh-7 liver cancer cells expressing the ACE2 receptor, researchers examined the impact of p62 knockout on viral gene expression. The study extended to other RNA viruses, including Zika, Coxsackievirus, human coronavirus OC43, and Sindbis virus, to assess p62’s broader relevance in viral pathogenesis.
