NOV 14, 2018 04:00 PM PST
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Modeling Inflammation And Fibrosis In Humans with PSC-derived Steatohepatitis Liver Organoids

Speakers
  • Associate Director, CuSTOM, Professor and Assistant Professor, Cincinnati Children's Hospital Tokyo Medical and Dental University Yokohama City University, Principal Investigator, Takeda-CiRA
    Biography
      Dr. Takebe is an Associate Director of Center for Stem Cell and Organoid Medicine (CuSTOM) at the Cincinnati Children's Hospital Medical Center and Professor at Yokohama City University, and Tokyo Medical and Dental University, Japan. He serves as Board of Directors at International Society of Stem Cell Research (ISSCR). His lab investigates the mechanisms of human organogenesis, and develops mini-organ technologies from human stem cells - namely organ bud based approaches. He is applying iPSC-liver buds into drug discovery study as well as transplant application - for patients with a rare congenital metabolic disorder, ultimately expanding the clinical indications to diseases like liver cirrhosis.

    Abstract:

    Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Using human genetics approaches, we recently identified bi-allelic truncating mutations in CTNNA2, encoding N-catenin, in patients with a phenotypically distinct recessive form of pachygyria. Interestingly, two mouse lines harboring nonsense mutations of the ortholog to human CTNNA2 (Catna2) have been characterized, but failed to recapitulate the human cortical lamination phenotype observed in our patients. Therefore, to investigate neuronal phenotypes in a human model, we developed stem cell-derived neuronal assays to assess neuron morphology as well as define the molecular disease mechanism. I will highlight the need for human cell-based models for neocortical gyration disorders as well as discuss the advantages of using stem cell based systems to discover pathogenic mechanisms and novel insight into human brain development, with this case as an example.


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