Overview
RNA alternative splicing (AS) is a finely tuned process through which pre-messenger RNA (pre-mRNA) is processed into two or more mature RNA (mRNA) isoforms in the nucleus, contributing to proteome diversity and gene-expression regulation. Cancer cells often exhibit aberrant splicing profiles, leading to the production of isoforms that increase cell proliferation, migration, or resistance to apoptosis.
Our laboratory seeks to understand the mechanisms by which RNA splicing is dysregulated to promote tumorigenesis and progression. We utilize transgenic mouse models and organoid culture to investigate the regulation of RNA splicing in physiological conditions and its dysregulation in inflammation and pancreatic cancer. Our expertise in small molecules and antisense technology enables us to modulate aberrant splicing in order to develop promising drugs for cancer therapy
1) Elucidating the role of AS in the maintenance of cellular homeostasis in response to oncogenic mutations.
2) Investigating how aberrant AS can accelerate cancer progression.
3) Evaluating the therapeutic efficacy of splice-switching antisense oligonucleotides (ASO) and small molecules based on the PDAC organoid platform.