Giuseppe Testa, MD., Ph.D - "Disease avatars: cell reprogramming and the functional annotation of human genomes"
Feb 21, 2017
from 12:00 PM to 01:30 PM
|Where||Tigem Auditorium "Vesuvius"|
|Contact Name||Andrea Ballabio|
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The in vitro recapitulation of human development, largely propelled by cell reprogramming, is transforming medicine by making genetic variation and disease predisposition experimentally tractable. This is especially true for disorders of the nervous system, for which cell reprogramming is particularly relevant due to the inaccessibility of relevant tissues, and whose main disease-associated genes are strongly enriched for transcription factors and chromatin regulators. Chromatin function has emerged as a central domain of dysregulation in the pathogenesis of intellectual disability (ID) and autism spectrum disorder (ASD), with a steadily increasing number of genes encoding for key chromatin modulators causally associated to these conditions. Transcriptional and chromatin dysregulation is thus a privileged entry point into the mechanistic underpinnings of neurodevelopmental conditions, yielding relatively rapid molecular insight for bridging genetic or environmental lesions to in vivo phenotypes. In our lab we focus on a selected group of ID and/or ASD conditions caused by point mutations or dosage imbalances affecting chromatin pathways with a critical function in neural development. I will discuss a summary of our latest inroads into these disorders, including novel insights from an integrated platform of 2D and 3D stem cell-based models of neural development through which we investigate convergent chromatin dysfunction brought about by genetic and environmental causes of intellectual disability.