Characterising Intra-tumor heterogeneity & its role in treatment resistance in colorectal cancer metastasis | Melodie Grandin

MELODIE GRANDIN
Postdoctoral Fellow,  Tumour Heterogeneity in Metastatic Cancer
UMCCR & Department of Clinical Pathology

By using 3D organoids derived from patients, we aim to unravel the intra-tumor heterogeneity and its dynamics during drug treatment. To do so, we develop several approaches including barcoding, multiome single-cell RNA sequencing, optical-based longitudinal following of cell vitality upon drug treatment. This work will provide new insights on the dynamic process of tumor resistance to therapy, and will hopefully provide new therapeutic options for the treatment of patients with metastatic colorectal cancer.

Melodie Grandin obtained a Master degree in functional genetics and cellular pathology at the University of Lyon, in France. She then undertook a PhD in molecular biology, oncology and cellular pathology at the Cancer Centre of Lyon in Patrick Mehlen’s laboratory. Melodie described the epigenetic alterations of the Netrin-1 dependence receptor pathway and developed a combined therapy based on the transcriptional reexpression of key genes involved in apoptosis. This work has led to the publication of a few papers as a first author, including one in EMBO Molecular Medicine and one in Cancer Cell as well as a patent.

In October 2019, Melodie started working at the UMCCR in Frederic Hollande’s lab thanks to a generous donation from John Landerer, and aim to unravel the cellular mechanisms driving intra-tumoral heterogeneity. To do so, the group is aiming to use cutting-edge technologies such as single-cell RNA sequencing, genetic and optical barcoding, drug screens. The group use patient-derived organoids to improve our understanding of the subcellular processes driving drug resistance in advanced bowel tumours.