Chromosomal instability (CIN) typically triggers cell death or malignant transformation. How placental trophoblasts are paradoxically able to tolerate extensive aneuploidy without functional impairment in a non-cancerous context remains poorly understood. With the support of an ISCRM fellowship, Sasha will investigate how autophagy and lysosomal activity play a role in trophoblast resilience using CIN-reflective trophoblast stem cells (TSCs). She will define whether autophagic/lysosomal gene expression scales directly with aneuploid burden, and determine whether TSCs become functionally dependent on autophagosome-lysosome fusion for survival under CIN, revealing how a normal cell tolerates genomic chaos without malignancy.
