Ep. 288: “Cerebellar Organoids” Featuring Dr. Giorgia Quadrato
Feb 18, 2025
auto_awesome
Dr. Giorgia Quadrato, an Assistant Professor at USC, dives into her groundbreaking work on cerebellar organoids. She shares insights on generating these organoids with functional Purkinje cells and discusses the development of a transcriptomic atlas for neural organoids. The conversation sheds light on the advancements and challenges in California's stem cell research landscape. Additionally, Quadrato highlights the potential of organoids in personalized medicine and tumor modeling, emphasizing the crucial role of collaboration and mentorship in scientific progress.
Dr. Giorgia Quadrato discusses the creation of cerebellar organoids to enhance understanding of neurodevelopmental disorders like autism and intellectual disabilities.
The integration of single-cell omics technology is vital for identifying disease mechanisms and therapeutic targets within neural organoids.
Organoid models are advancing clinical applications by bridging developmental biology with potential treatments for brain disorders, emphasizing the promise of personalized medicine.
Deep dives
Cerebellar Organoids and Neurodevelopmental Disorders
Research on cerebellar organoids focuses on understanding neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disabilities. The goal is to enhance physiological relevance and develop models that replicate the complex cellular environment of the human brain. The integration of technologies such as single-cell omics is critical for identifying disease mechanisms and therapeutic targets. This work aims to bridge the gap between developmental biology and clinical applications, showcasing the potential of organoid models in advancing treatments for brain disorders.
Cell Plasticity and Hepatocyte Research
A study highlights the importance of the transcription factor PROX1 in maintaining hepatocyte identity and preventing liver tumors. Researchers demonstrated that PROX1 actively represses alternative liver cell fates and promotes effective regeneration following injury. This was validated through computational predictions and in vivo experiments in mice, indicating that liver cell plasticity plays a significant role in oncogenesis. The findings suggest that targeting transcriptional repressors like PROX1 could have therapeutic implications for liver cancer treatment.
Innovations in Liver Gene Targeting
A novel approach combines gene targeting with a selective survival advantage to enhance the targeting of liver cells for therapeutics. This technique involved knocking down essential genes while delivering a resistant variant alongside therapeutic transgenes, achieving a significant increase in targeted hepatocyte populations. The strategy resulted in a substantial expression boost of the therapeutic factor, potentially paving the way for treating liver diseases that require gene repair. The implications of this method extend beyond liver applications, opening avenues for regenerative therapies in other tissues.
Advancements in Parkinson's Disease Therapies
The development of autologous cell therapies using patient-derived induced pluripotent stem cells (iPSCs) presents a promising but challenging avenue for treating Parkinson's disease. While recent research focused on generating midbrain dopaminergic neurons from patient iPSCs, variability in response has raised questions about their efficacy. The intricacies of translating these therapies into clinical trials underscore the importance of understanding individual cellular responses and potential genetic factors. The ongoing pursuit highlights the hope for personalized medicine despite the obstacles faced in developing reliable treatments.
Individualized Patient Tumor Organoids
Innovative tumor organoid technology allows for the creation of individualized patient tumor models using cortical organoids as platforms. This method preserves the architectural integrity of the tumor while facilitating personalized drug response predictions. The integration of patient-specific tumor cells into organoid systems enhances the understanding of tumor biology and potential responses to therapies. This approach represents a significant advancement in personalized oncology, offering a dynamic model for assessing treatment efficacy and exploring drug resistance.
Dr. Giorgia Quadrato is Assistant Professor of Stem Cell and Regenerative Medicine at the University of Southern California. Her research focuses on brain developmental and neural organoids. She talks about protocols for generating cerebellar organoids, including those with functional Purkinje cells. She also discusses a transcriptomic atlas of neural organoids and the stem cell research landscape in California. (34:52)
Liver Cell Fate Plasticity – Researchers identified PROX1 as a safeguard to prevent liver tumorigenesis. (1:48)
Hepatocyte Gene Editing – Repair Drive is a platform technology for selectively expanding homology-directed repair-corrected hepatocytes in adult mice. (10:05)
