Nathalie Longakit wins the Roman M. Babicki Fellowship

Nathalie is a PhD candidate in the Medical Genetics graduate program who is researching in the area of uveal melanoma, the most common cancer of the eye under Dr. Catherine Van Raamsdonk, Associate Professor, Department of Medical Genetics.

Every year, ~130 Canadians are diagnosed UM; in half of these patients, the cancer spreads to other parts of the body through a process called metastasis, after which treatment is much more difficult. Most UMs are initiated by a mutation in either the GNAQ or GNA11 gene, and almost all metastatic cases have a mutation in the BAP1 gene. Loss of BAP1 is strongly associated with worse patient outcomes and reduced survival. But, the link between BAP1 and metastasis has not been discovered. Preliminary data suggests that Epithelial to Mesenchymal Transition (EMT) is a significant process in UM metastasis. EMT allows cancer cells to migrate and invade tissues by converting epithelial cells to mesenchymal cells. Variations in EMT can prevent tumor cells from completing the transition, instead, acquiring an intermediate state between the epithelial-mesenchymal (EM) spectrum. In this grey area, tumor cells are more versatile, allowing them to easily adapt to new environments, which is key to metastatic success.

The goal of Nathalie’s research is to identify subpopulations of tumor cells, which undergo EMT-like programs to understand how BAP1 mutations drive metastases to specific organ sites, by using a combination of CRISPR-Cas9 technology, single cell RNA sequencing, and epigenomic analysis. Through this work, she hopes to identify potential therapeutic targets to mitigate or prevent UM metastasis, thus improving patient outcomes.