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CCMT Seminar Series - May 11, 2023



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May 11, 2023 ‐ 11:00 am
End Date/Time-NEW
Location - People View
Room 5040

3501 Civic Center Blvd
Philadelphia, PA 19104
United States

This virtual meeting link has expired.

The Raymond G. Perelman Center for Cellular and Molecular Therapeutics presents a seminar series:

Modeling Late-Onset Neurodegenerative Disorders Through Direct Neuronal Reprogramming of Human Somatic Cells


Andrew Yoo, PhD
Professor of Developmental Biology
Washington University School of Medicine, St. Louis

About the Research:

Advancing age is the primary risk factor in most forms of neurodegenerative disorders. To model late-onset neurodegenerative disorders, we aim to generate human neurons that reflect the age of tissue donors by directly reprogramming patient-derived fibroblasts to neurons and providing a "snapshot" of the age-dependent degenerative state. By leveraging this approach, we investigate why human neurons become vulnerable to degeneration with aging. My lab advanced the use of brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124) as cell-reprogramming effectors that induce reshaping of chromatin and directly convert human fibroblasts to neurons, bypassing the pluripotent/multipotent stem cell state. The miRNA-induced neuronal state can synergize with subtype-defining transcription factors to generate disease-relevant neuronal subtypes. With relevance to aging of neurons, we found that miRNA-mediated direct reprogramming propagated the age signature stored in starting fibroblasts, thereby generating human neurons that reflect the chronological age of fibroblast donors. We implement directly reprogrammed striatal medium spiny neurons (MSNs) from Huntington’s disease (HD) patients to recapitulate adult-onset neuronal phenotypes of HD and model the age-dependent progression of HD. This approach allowed us to identify alterations of genetic pathways with disease progression and age-associated miRNAs, for example, miR-29b-3p driving the impairment of autophagy in patient-derived neurons. Extending these findings, our lab is actively pursuing the identification of other age-associated factors that contribute to the onset of neurodegeneration and their perturbation as a means to delay or reverse the disease-associated neuronal pathology.

Host: Naiara Aquizu, PhD

Please email if you would like to meet with the speaker.

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