NOV 15, 2018 12:00 PM PST
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Using human stem cells to model neocortical gyration phenotypes

  • Assistant Professor, Department of Genetics and Genome Sciences, Case Western Reserve University
      Ashleigh Schaffer graduated with a B.S. in Genetics from University of Wisconsin-Madison and went on to earn her Ph.D. from the University of California, Irvine under the mentorship of Dr. Maike Sander. She continued her training as a postdoctoral fellow at the University of California, San Diego, and Howard Hughes Medical Institute under the guidance of Dr. Joseph G. Gleeson, focused on elucidating the genetic cause, and molecular mechanisms, underlying recessive pediatric neurological disease. During her time with Dr. Gleeson, Ashleigh discovered over 20 novel genetic causes of disease, many for recessive, syndromic pediatric neurodegenerative disorders. She joined the Department of Genetics and Genomes Sciences at Case Western Reserve University as an Assistant Professor in February 2017.


    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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