Year: 2025
Type: dissertation
Abstract: Lung adenocarcinomas (LUAD) transdifferentiate into the lethal neuroendocrine (NE) small-cell lung cancer (SCLC) lineage in up to 3-14% of clinical cases. Here I sought to develop a platform to dissect factors that drive this switch. By ectopically overexpressing the bHLH proneural transcription factor ASCL1 in LUAD lines, I detected concurrent upregulation of the NE marker SYP in 3-8% of cells. We further designed and synthesized a custom self-selecting SAM-CRISPRa cassette for multiplexed activation of candidate neuroendocrine lineage drivers to eventually screen for hits that drive lineage conversion. I validated this CRISPRa system by inducing NE lineage drivers ASCL1, INSM1 and the NE marker NCAM1 in LUAD cell lines, whose expression was detected via the PrimeFlowTM RNA assay. Altogether, my experiments provide a platform to uncover the molecular drivers of LUAD-SCLC transdifferentiation.
Source: TSpace (University of Toronto)
Author: Yim, Andrew Junyoung
Institution: University of Toronto
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7132941008