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  3. Colloquium on the Brain and Cognition with Michelle Monje, MD, PhD, Stanford University
Colloquium on the Brain and Cognition with Michelle Monje, MD, PhD, Stanford University
The Picower Institute for Learning and Memory

Colloquium on the Brain and Cognition with Michelle Monje, MD, PhD, Stanford University

Add to CalendarAmerica/New_YorkColloquium on the Brain and Cognition with Michelle Monje, MD, PhD, Stanford University09/23/2021 4:00 pm09/23/2021 5:00 pm
September 23, 2021
4:00 pm - 5:00 pm
Contact
bgreeno@mit.edu
    Description

              This seminar is being held virtually. Please click here to attend. 

     

    Neuron-glial interactions in health and disease: from cognition to cancer

    Michelle Monje, MD PhD

    Stanford University

    The nervous system regulates stem and precursor cell behavior across a range of tissues. 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 tunes neural circuit function and contributes to healthy cognition. 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 proliferation and growth of both high-grade and low-grade glioma subtypes in preclinical models. Crucial mechanisms mediating activity-regulated glioma growth include secretion of BDNF and the synaptic protein neuroligin-3 (NLGN3). NLGN3 induces multiple oncogenic signaling pathways in the cancer cell, and also promotes glutamatergic synapse formation between neurons and glioma cells. This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. NLGN3 is necessary for the growth of gliomas in a range of preclinical models, and therapeutic targeting of NLGN3 is presently under clinical investigation. Thus, neuron-glial interactions not only modulate neural circuit structure and function in the healthy brain, but paracrine and synaptic 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 an associate professor of Neurology and Neurological Sciences at Stanford University. She received her M.D. and Ph.D. in Neuroscience from Stanford and completed her residency training in neurology at the Massachusetts General Hospital/Brigham and Women's Hospital/Harvard Medical School Partners program, and then returned to Stanford for a clinical fellowship in pediatric neuro-oncology and postdoctoral fellowship in developmental and cancer biology. Dr. Monje is recognized as an international leader in the pathophysiology of glioma, especially diffuse intrinsic pontine glioma (DIPG)/H3K27M-mutated diffuse midline gliomas and a pioneer in the emerging field of Cancer Neuroscience. Her clinical focus is on childhood glial malignancies and cognitive impairment after childhood cancer therapy. Her laboratory studies neuron-glial interactions in health and disease, with a particular focus on mechanisms and consequences of neuron-glial interactions in health, glial dysfunction in cancer therapy-related cognitive impairment and neuron-glial interactions in malignant glioma. Together with these basic studies, her research program has advanced preclinical studies of novel therapeutics for pediatric high-grade gliomas and cancer therapy-related cognitive impairment in order to translate new therapies to the clinic. She has led several of her discoveries from basic molecular work to clinical trials for children and young adults with brain tumors.

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