Deciphering the Neural Basis of Metastatic Colonization

Dr. Ribeiro’s research focuses on sensory nerves and how they can be used to manipulate immunity and tissue programs. Sensory nerves are part of the body’s early-warning system; when tissue is injured, these nerves help coordinate a local repair response that protects cells and supports regeneration. His preliminary data suggest that metastatic cancer cells can physically attach to sensory nerve fibers in the lung through a surface protein called NINJ1 (Nerve Injury–Induced Protein 1) and use them to help cancer spread. When NINJ1 on a cancer cell binds to NINJ1 on a nerve, it creates an abnormal contact that mimics an injury signal, switching on a repair-like program inside the cancer cell. As a result, the cancer cell becomes more adaptable, more able to survive stress and respond strongly to normal growth cues in lung tissue that would otherwise help healthy cells promote healing. Importantly, when he disrupts sensory-nerve input or blocks the NINJ1 interaction in his models, metastatic growth is markedly reduced.

Dr. Ribero is particularly interested in the vagus nerve and its interaction with metastatic cancer cells. He posits that NINJ1-dependent interactions between metastatic cancer cells and vagal sensory neurons enable cancer cells to amplify their sensitivity to growth factors, promoting metastatic survival and proliferation in new organ sites. Using advanced neural depletion strategies targeting vagal sensory neurons. Dr. Ribero will be able to parse separate sensory neuron fibers and confirm the role of vagal sensory nerves in supporting metastatic growth. He will further try to map out how NINJ1 mediates the crosstalk between cancer cells and neurons and whether it represents a signaling hub that could be a therapeutic target. Dr. Ribero’s work here will be primarily in melanoma and lung cancer, his hypothesis that sensory nerves are a critical tool for metastasizing cells could have long ranging implications for cancer treatment.