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A list of all the posts and pages found on the site. For you robots out there is an XML version available for digesting as well.
Pages
Posts
Future Blog Post
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Blog Post number 4
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Blog Post number 3
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Blog Post number 2
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Blog Post number 1
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portfolio
Portfolio item number 1
Short description of portfolio item number 1
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publications
Disruption of β-Catenin–Dependent Wnt Signaling in Colon Cancer Cells Remodels the Microenvironment to Promote Tumor Invasion
Published in Molecular Cancer Research, 2022
We determine that Wnt-reduced cancer cells exhibit a more aggressive disease phenotype, including increased mobility in vitro and disruptive invasion into mucosa and smooth muscle in an orthotopic mouse model. RNA sequencing reveals that interference with Wnt signaling leads to an upregulation of gene programs that favor cell migration and invasion and a downregulation of inflammation signatures in the tumor microenvironment. We identify a set of upregulated genes common among the Wnt perturbations that are predictive of poor patient outcomes in early-invasive colon cancer.
Recommended citation: Chen GT, Tifrea DF, Murad R, Habowski AN, Lyou Y, Duong MR, et al. Disruption of β-Catenin–Dependent Wnt Signaling in Colon Cancer Cells Remodels the Microenvironment to Promote Tumor Invasion. Mol Cancer Res. 2022;20:468–84.
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Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD
Published in Nature, 2022
We performed RNA-sequencing analysis of 725 brain samples spanning 11 cortical areas from 112 post-mortem samples from individuals with ASD and neurotypical controls. We find widespread transcriptomic changes across the cortex in ASD, exhibiting an anterior-to-posterior gradient, with the greatest differences in primary visual cortex, coincident with an attenuation of the typical transcriptomic differences between cortical regions.
Recommended citation: Gandal MJ, Haney JR, Wamsley B, Yap CX, Parhami S, Emani PS, Chang N, Chen GT, et al. Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD. Nature. 2022;611:532–9
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Challenges and opportunities for precision medicine in neurodevelopmental disorders
Published in Advanced Drug Discovery Reviews, 2022
Neurodevelopmental Disorders (NDDs) encompass a broad spectrum of disorders, linked because of their origins in brain developmental processes, including diverse conditions across the age span, including autism spectrum disorders (ASD) and schizophrenia (SCZ). Clinical treatment of these disorders has traditionally focused on symptom management, as the severity of developmental disruption varies widely and the precise molecular mechanisms, timing, and progression of these disorders is usually not known.
Recommended citation: Chen GT, Geschwind DH. Challenges and opportunities for precision medicine in neurodevelopmental disorders. Adv Drug Deliv Rev. 2022;191:114564.
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Enhancer-Targeted CRISPR-Activation Rescues Haploinsufficient Autism Risk Genes
Published in BioRxiv, 2024
Autism Spectrum Disorder (ASD) is a highly heritable condition with diverse clinical presentations. Approximately 20% of ASD’s genetic susceptibility is imparted by de novo mutations of major effect, most of which cause haploinsufficiency. We mapped enhancers of two high confidence autism genes – CHD8 and SCN2A and used CRISPR-based gene activation (CRISPR-A) in hPSC-derived excitatory neurons and cerebral forebrain organoids to correct the effects of haploinsufficiency, taking advantage of the presence of a wildtype allele of each gene and endogenous gene regulation. We found that CRISPR-A induced a sustained increase in CHD8 and SCN2A expression in treated neurons and organoids, with rescue of gene expression levels and mutation-associated phenotypes, including gene expression and physiology. These data support gene activation via targeting enhancers of haploinsufficient genes, as a therapeutic intervention in ASD and other neurodevelopmental disorders.
Recommended citation: Chen GT, Nair G, Osorio A J, Holley SM, Ghazzemzadeh K, Gonzalez JG, Cepeda, C, Geschwind DH. “Enhancer-Targeted CRISPR-Activation Rescues Haploinsufficient Autism Risk Genes.” BioRxiv, 2024. https://doi.org/10.1101/2024.03.13.584921.
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talks
Talk 1 on Relevant Topic in Your Field
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Conference Proceeding talk 3 on Relevant Topic in Your Field
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This is a description of your conference proceedings talk, note the different field in type. You can put anything in this field.
teaching
Teaching experience 1
Undergraduate course, University 1, Department, 2014
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Teaching experience 2
Workshop, University 1, Department, 2015
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