Research Lecture at Nobel Forum
Date: March 7, 2025, 1 pm
Venue: Wallenbergsalen, Nobel Forum, Nobels Väg 1, Karolinska Institutet
Speaker: Michelle Monje
Title: Neuron-glial interactions in health and disease: from cognition to cancer
In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Activity-dependent proliferation of healthy glial progenitors, oligodendrocyte precursor cells (OPCs), and the consequent generation of new oligodendrocytes contributes to adaptive myelination. This plasticity of myelin is adaptive in the healthy brain and contributes to cognitive functions such as attention, learning and memory, while disruption of myelin plasticity contributes to cognitive disorders like cancer therapy-related cognitive impairment. Conversely, myelin plasticity can become maladaptive in disease states characterized by abnormal patterns of neural circuit activity, such as epilepsy and opiate addiction. The robust mitogenic effect of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, suggests that dysregulated or “hijacked” mechanisms of myelin plasticity might similarly promote malignant cell proliferation in this devastating group of brain cancers. Indeed, neuronal activity promotes the growth and progression of gliomas. Thus, neuron-glial interactions not only modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also play important roles in the pathogenesis of glial cancers. The mechanistic parallels between normal and malignant neuron-glial interactions underscores the extent to which mechanisms of neurodevelopment and plasticity are subverted by malignant gliomas, and the importance of understanding the neuroscience of cancer.
Michelle Monje, MD, PhD, is the Milan Gambhir Professor of Pediatric Neuro-Oncology in the Department of Neurology and Neurological Sciences at Stanford University and a Howard Hughes Medical Institute Investigator. She received her M.D. and Ph.D. in neuroscience from Stanford, completed her residency training in neurology at Massachusetts General Hospital/Harvard Medical School, and then returned to Stanford for a clinical fellowship in pediatric neuro-oncology and post-doctoral fellowship in developmental and cancer biology. Her research program focuses at the intersection of neuroscience, immunology and cancer biology with an emphasis on neuron-glial interactions in health and disease. Her laboratory studies how neuronal activity regulates glial precursor cell proliferation, new oligodendrocyte generation, and changes in myelination; she has shown that this plasticity of myelin contributes to both healthy brain functions and a diverse range of brain diseases. Dr. Monje discovered that neuronal activity similarly promotes the progression of malignant gliomas, driving glioma growth through both paracrine factors and through electrophysiologically functional neuron-to-glioma synapses, work that has proven foundational for the field of Cancer Neuroscience. Dr. Monje has led several of her discoveries from basic molecular discoveries to clinical trials. Her work has been recognized with numerous honors, including an NIH Director’s Pioneer Award, a MacArthur Fellowship, election to the U.S. National Academy of Medicine, the 2023 Paul Marks Prize, the 2023 Richard Lounsbery Award from the National Academy of Sciences, the 2024 Ross Prize in Molecular Medicine.
Host: Gonçalo Castelo-Branco, PhD, is a Professor of Glial Cell Biology, Karolinska Institutet.
Contact: Ann-Mari Dumanski, Nobel Office, 08-524 87 800, nobelforum@nobelprizemedicine.org