our science
Our Research
A central mystery in cancer biology is how genomic instability—a hallmark driver of mutagenesis—arises and fuels tumor evolution. While genetic alterations have dominated this field, the non-genetic drivers of malignant transformation remain largely unexplored. We investigate how mitotic errors fundamentally reshape cellular function through non-genetic mechanisms, which may act independently or on top of genetic insults, opening new frontiers in understanding cancer origins and adaptation.
A Paradigm-Shifting Discovery
We recently unveiled a new form of transgenerational epigenetic instability [Papathanasiou S. et al, 2023]. When chromosomes mis-segregate during division, can form micronuclei that acquire catastrophic DNA damage. Remarkably, upon reincorporation into daughter cells, these damaged chromosomes persist as MN-bodies—abnormal nuclear structures carrying heritable chromatin lesions that propagate through cell lineages. This discovery reveals an unexpected mechanism linking single mitotic errors to long-term genome dysfunction and transcriptional heterogeneity.
Technological Innovation
Studying these dynamic, rare events demands unconventional thinking and new tool generation. We developed Look-Seq2 [patent]—a groundbreaking method that integrates live-cell imaging with single-cell sequencing, directly linking cellular phenotype to molecular function. We are advancing this concept to our integrated platform “SimaDi” (Same-cell Imaging and Direct Isolation for single-cell genomics) implementing multi-omics and increased throughput. Combined with engineered cellular systems for tracking mis-segregated chromosomes across generations, we can now capture and decode the immediate and long-term consequences of mitotic catastrophes.
Positioned for Breakthrough Discoveries
Approximately 90% of solid tumors are aneuploid, yet no therapies exploit this ubiquitous feature. The "aneuploidy paradox"—how cancer cells tolerate massive chromosomal imbalances—remains unsolved. We are uniquely positioned to answer fundamental questions: How do abnormal chromosomes rewire transcription and genome architecture? What transformations enable cells to survive and adapt to genomic chaos? What are the first molecular events that convert mitotic errors into malignant potential? By decoding the choreography of early tumor evolution, we aim to unveil vulnerabilities inherent to chromosomal instability and transform our understanding of cancer's origins.