When Simon Grelet, PhD, joined the University of South Alabama, Department of  Biochemistry and Molecular Biology in 2021, he launched the Cancer Innervation and Neurobiology Laboratory at the Mitchell Cancer Institute to investigate a fundamental question: how do nerves influence tumor development and spread? This work has now earned national recognition through an NCI and NIH R37 MERIT Award (1R37CA292711), which provides long-term support for his research on nerve to cancer mitochondria transfer and its influence on metastasis.

Simon Grelet, PhD, Assistant Professor of Biochemistry and Molecular Biology, University of South Alabama

Grelet’s research focuses on cancer innervation, meaning the presence of nerves within a tumor and the biological communication that takes place between neuronal and cancer cells. He first observed this process during his postdoctoral training, then completed, published, and independently revalidated and extended this body of work after establishing his laboratory at the University of South Alabama (see PMID: 37046688). These findings, together with clinical evidence linking nerve density to aggressive disease, shaped the direction of his laboratory and informed the project supported by the Center for Clinical and Translational Science (CCTS) Pilot Program.

Building a translational model with CCTS Pilot support

The CCTS Pilot Award (UL1TR003096-05) provided an essential early investment that allowed the Grelet Lab to develop three-dimensional models that better recapitulate the architecture of innervated tumors. With pilot support, the team created mixed-cell spheroids and organoids containing breast cancer cells and neurons in proportions similar to what clinicians observe in patient samples. This 3D system enabled the team to study how neurons and cancer cells interact in a more structurally relevant environment than is possible with traditional two-dimensional cultures.

The CCTS Pilot Program is designed to support the development of generalizable innovations that address common challenges in translating research findings into improvements for human health and healthcare delivery. Pilot projects emphasize feasibility and method development, allowing investigators to refine tools and approaches that can support larger studies. By supporting the creation of Grelet’s 3D tumor models, the CCTS Pilot Program helped establish a platform that continues to inform fundamental questions about nerve to cancer communication and its impact on disease progression.

Tracing mitochondria transfer from nerves to cancer cells

3D spheroids of SVZ-NSCsMitoTRACER mixed with 4T1 recipient cancer cells confirmed mitochondria transfer, evidenced by red-to-green fluorescence conversion in 4T1 cells (white arrows). Image credit: Grelet S, et al., Nature (2025), Figure 5a.

Using the 3D tumor models developed with CCTS Pilot support, the Grelet Lab identified a significant biological event. Rather than only activating cancer cells through surface signaling, neurons were physically transferring mitochondria to cancer cells. Mitochondria play a central role in cellular energy production, and cancer cells that acquired neuronal mitochondria showed a notable survival advantage during the metastatic cascade, particularly while traveling through challenging environments such as the bloodstream.

To investigate this process, the team developed MitoTRACER, a genetic system that permanently labels cells that have received mitochondria from another cell. When combined with the 3D organoids and in vivo mouse studies, MitoTRACER allowed the team to track these labeled cancer cells from the primary tumor to distant metastatic sites. The results showed that the small group of cancer cells marked by neuronal mitochondria at the primary tumor site were the same cells that successfully formed metastatic lesions.

This work was published in the scientific journal Nature and has since received significant international recognition, including the World Mitochondria Society’s Best Scientific Contribution Award 2025 for what the society described as “groundbreaking” advances in understanding how mitochondria transfer from nerves to cancer cells.

A strong foundation for the R37 MERIT Award

The NCI R37 Method to Extend Research in Time (MERIT) Award recognizes exceptional early stage investigators whose R01 applications score within the top percentile range. The award provides up to seven years of support in two segments. The initial period functions as a standard R01, followed by a possible two-year extension based on progress.

For Grelet, the CCTS Pilot Award strengthened his R01 application by providing high quality preliminary data and demonstrating the feasibility and relevance of the 3D model system. These elements helped position the proposal for a highly competitive score and subsequent MERIT designation.

Translating nerve to cancer biology into new possibilities

The Grelet Lab is continuing to explore how nerve to cancer mitochondria exchange shapes tumor behavior and how this knowledge may support the development of new intervention strategies. The team is collaborating with clinicians such as Gustavo Ayala, MD, at UT Health. His clinical work involving botulinum toxin treatment in prostate cancer has provided human tissue samples that help validate the relationship between nerve activity and mitochondrial abundance in tumor cells. These human samples complement the laboratory’s mouse studies and have strengthened the clinical relevance of the findings.

Grelet also recognizes the contributions of his team members, including Gregory Hoover, Shila Gilbert, Olivia Curley, and Clémence Obellianne, whose work among the team supported the development of the models, tools, and data that have advanced this research.

This project reflects the mission of the Center for Clinical and Translational Science to accelerate the translation of research discoveries into improved human health. The CCTS Pilot Program played a central role in establishing the models and early findings that now drive the lab’s long-term direction.

Learn more about the Grelet Lab at cancersgetnervous.com.
Learn more about the CCTS at uab.edu/ccts.
Learn more about the CCTS Pilot Program at uab.edu/ccts/funding-opportunities/pilots.

References and Sources

• Grelet S, et al. Nerve-to-cancer mitochondria transfer drives metastatic fitness. Nature. 2025.
• National Institutes of Health (NIH). RePORTER Project Information for Simon Grelet, PhD: R37 MERIT Award (Project ID 11226396).
• National Cancer Institute. R37 Method to Extend Research in Time (MERIT) Award.
• World Mitochondria Society.
• Center for Clinical and Translational Science (CCTS). Pilot Program.
• Grelet Lab. Cancer Innervation and Neurobiology Laboratory.