Simon-Pierre Gravel and his team are studying the metabolic and immunological remodeling mechanisms associated with tumor progression, aging, and resistance to targeted therapies and immunotherapy. Their work aims to identify new therapeutic targets in order to develop strategies that exploit the metabolic and immune vulnerabilities of tumor cells.

Research themes

One of the laboratory’s main areas of focus is the nuclear coactivator PGC-1β, a major transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. The work of Simon-Pierre Gravel’s team has highlighted non-canonical functions of PGC-1β in regulating the metabolic and immune identity of melanoma cells and aging keratinocytes, including its involvement in transcriptional programs associated with tumor progression, terminal differentiation, and therapeutic resistance. These studies have revealed that PGC-1β contributes to establishing distinct metabolic and transcriptional signatures associated with specific cellular states. In parallel, the team is exploring the role of mitochondrial proteins and the functional organization of mitochondria in tumor adaptation, skin aging, and resistance to therapies. Recent work has identified mitochondrial signatures associated with tolerance to oncogenic pathway inhibitors, tumor persistence, and age-related alterations. These findings suggest that the mitochondrial state of cancer and skin cells is a major determinant of their phenotypic plasticity and ability to evade therapy.

Research objectives

The overall objective of the research program is to determine how cellular metabolism, particularly mitochondrial function and organelle bioenergetics, controls signaling, transcriptional plasticity, ribosome biogenesis and translation, as well as intrinsic immune programs in melanoma cells and skin cells, including aging keratinocytes and their terminal differentiation. The laboratory seeks to define how specific metabolic perturbations reprogram processes such as interferon response, antigen presentation, inflammation, immunosuppression, and cell death, and how these states contribute to tumor progression, therapeutic resistance, and skin aging-related alterations. To achieve these objectives, the team combines complementary models (melanoma cell lines, primary skin cells, acquired or induced resistance systems) and integrated approaches involving metabolomics, transcriptomics, signaling, and screening. This work aims to define metabolic and mitochondrial signatures predictive of therapeutic response and cellular aging, and to identify new targets for modulating the intrinsic immune state of tumor and skin cells. This strategy paves the way for approaches combining metabolic modulation and immunotherapy to improve response and prevent resistance in melanoma and skin cancers.