The emergence of cell clones that are resistant to targeted therapies poses a significant issue in the treatment of metastatic melanoma. While founding clones are often extremely rare in a starting population, their isolation and characterization hold unique potential for understanding disease processes, uncovering novel biomarkers, and developing therapeutic concepts.
In this webinar, Christian Umkehrer of Vienna’s Research Institute of Molecular Pathology describes the development and application of CaTCH (CRISPRa Tracing of Clones in Heterogeneous Cell Populations), which combines precise mapping of the lineage history of millions of cells with the ability to isolate any given clone alive from a complex population based on genetic barcodes.
CaTCH enables the retrospective isolation and analysis of founding clones from heterogeneous cell populations prior to evolutionary selection. The approach uses QuantSeq 3’ mRNA-Seq to characterize the isolated clones by efficiently profiling gene expression.
In his presentation Christian Umkehrer will explain how CaTCH can:
- be used to trace and isolate therapy-resistant clones from complex cancer cell populations in vitro.
- be applied to in vivo studies by investigating the origins of resistance to clinically relevant RAF/MEK inhibition in an immunocompetent melanoma mouse model.
- address further fundamental questions in basic and translational research (e.g., how cell identity states and trajectories are determined in therapy resistance, metastasis formation, or somatic cell re-programming).