Dr. Grelet's research program is dedicated to understanding how the tumor microenvironment shapes cancer progression, with a particular emphasis on the interplay between cancer cells, the nervous system, and cellular metabolism.
In his earlier work, Dr. Grelet investigated the functional roles of long non-coding RNAs (lncRNAs) in cancer. This research uncovered novel mechanisms by which these transcripts regulate gene expression through the alternative splicing of protein-coding genes (Grelet et al. Nature Cell Biology, 2017). He demonstrated that this regulation leads to the generation of functionally active lncRNAs that promote cancer cell plasticity and aggressiveness. Through integrative transcriptomic analyses and functional assays, he contributed to identifying a set of lncRNAs reactivated during breast cancer plasticity and showed how they modulate the expression of axon guidance molecules (Grelet et al. Life Science Alliance, 2022). These findings revealed a mechanistic link between tumor innervation and cancer cell plasticity, establishing a foundation for the study of neuro-cancer interactions.
Building on this molecular insight, Dr. Grelet's current research focuses on cancer innervation, the infiltration of tumors by nerves, and its impact on cancer cell behavior. He is particularly interested in how neural inputs influence cancer cell metabolism, survival under stress, and the acquisition of metastatic traits. By developing novel in vitro and in vivo models, his group is uncovering key mechanisms that drive nerve-mediated tumor progression, with the goal of identifying therapeutic targets. They developed a CRISPR/Cas9-based reporter system to monitor cancer-induced axonogenesis in live cells (Galappaththi et al. Cancers, 2022). They confirmed the association between cancer cell plasticity and tumour innervation in this high-throughput setup.
Currently, a central focus of the laboratory is the phenomenon of intercellular mitochondrial transfer. They have shown that neurons can donate mitochondria to cancer cells, a process that enhances the bioenergetic capacity and stress resilience of the recipient cells (Hoover et al. Nature, 2025). Ongoing work aims to define the molecular mediators of this exchange, assess its contribution to metastatic dissemination in vivo, and explore strategies to disrupt this metabolic symbiosis for therapeutic gain.
Hoover G, Gilbert S, Curley O, Obellianne C, Lin MT, Hixson W, Pierce TW, Andrews JF, Alexeyev MF, Ding Y, Bu P, Behbod F, Medina D, Chang JT, Ayala G, and Grelet S. “Nerve-to-Cancer Transfer of Mitochondria during Cancer Metastasis” Nature (2025).
Galappaththi SL, Katz B, Howze PH, Hoover G, and Grelet S. “A CRISPR/Cas9-Based Assay for High-Throughput Studies of Cancer-Induced Innervation” Cancers (2023)
Grelet S, Fréreux C, Obellianne C, Noguchi K, Howley BV, Dalton AC, and Howe PH. “TGFβ-Induced Expression of Long Noncoding lincRNA Platr18 Controls Breast Cancer Axonogenesis” Life Science Alliance (2022)
Grelet S, Link LA, Howley B, Obellianne C, Palanisamy V, Gangaraju VK, Diehl JA, and Howe PH. “A Regulated PNUTS mRNA to lncRNA Splice Switch Mediates EMT and Tumour Progression” Nature Cell Biology (2017).
USA Health has a comprehensive biomedical research program that spans a wide range of clinical, basic and translational research. At the Mitchell Cancer Institute, our physicians and scientific investigators are searching for breakthrough discoveries to improve the lives of cancer patients.
Earlier in 2023, Simon Grelet, Ph.D., and his colleagues developed a provisional patent for the technology, which involves labeling cells that have received mitochondria from donor cells.
The highly competitive grants provide each investigator $100,000 in funding over a two-year period.
