Many disorders of mental health, including autism spectrum disorder (ASD) exhibit strong or, in some cases, exclusive, contributions from individual genomic variation. These types of genomic contribution are difficult, if not impossible, to accurately recapitulate in animal in vivo or cellular models. Human pluripotent stem cells (hPSCs) provide the opportunity to use state-of-the-art genetic tools to recreate individual genomic patterns of variation that contribute to, or cause, these disorders. In Project 1, we will develop optimized genome editing methods based on strategies previously developed in non-human models. We will engineer four fluorescent reporter and Cre driver lines (CTIP2-mCherry, GFAP-mCherry, CALB-mCherry-T2A-Cre, and GAD1-mCherry- T2A-Cre), a panel of four monogenic autism models: point mutations in MECP2, SHANK3, TSC2, and FMR1, and a panel of eight CNV autism models: reciprocal duplications and deletions at 7q11.23, 16p11.2, 17p11.2, and 15q11-13. We will also develop new strategies for haplotype exchange of hIPSC models.
| Mesci, Pinar; Macia, Angela; LaRock, Christopher N et al. (2018) Modeling neuro-immune interactions during Zika virus infection. Hum Mol Genet 27:41-52 |
| Chailangkarn, Thanathom; Noree, Chalongrat; Muotri, Alysson R (2018) The contribution of GTF2I haploinsufficiency to Williams syndrome. Mol Cell Probes 40:45-51 |
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| Fernandes, Isabella R; Cruz, Ana C P; Ferrasa, Adriano et al. (2018) Genetic variations on SETD5 underlying autistic conditions. Dev Neurobiol 78:500-518 |
| Mesci, Pinar; Macia, Angela; Moore, Spencer M et al. (2018) Blocking Zika virus vertical transmission. Sci Rep 8:1218 |
| Beltrão-Braga, Patricia C B; Muotri, Alysson R (2017) Modeling autism spectrum disorders with human neurons. Brain Res 1656:49-54 |
| Song, Yan; Botvinnik, Olga B; Lovci, Michael T et al. (2017) Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation. Mol Cell 67:148-161.e5 |
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| Shiryaev, Sergey A; Mesci, Pinar; Pinto, Antonella et al. (2017) Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis. Sci Rep 7:15771 |
| Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E et al. (2017) Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA sequencing. Nat Immunol 18:422-432 |
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