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Gao, Fen-Biao

One or more keywords matched the following properties of Gao, Fen-Biao

Property	Value
overview	Research Focus: Understanding ALS and Frontotemporal Dementia Fen-Biao Gao Lab Website Frontotemporal dementia (FTD) is an age-dependent neurodegenerative condition associated with focal atrophy of the frontal and/or temporal lobes and recognized now as the most common form of dementia before the age of 60. Unfortunately, the molecular pathogenesis of FTD remains largely unknown and effective treatments are not available. Recent exciting advances indicate that FTD is often associated with amyotrophic lateral sclerosis (ALS) and several genes are involved in thepathogenesis of both ALS and FTD, including CHMP2B, TDP-43, FUS, TBK1, and C9ORF72. How these mutant proteins cause or contribute to neuronal dysfunction and neurodegeneration in ALS and FTD remains poorly defined. A few years ago, we cloned anovel Drosophila gene called shrub, which encodes a key component of ESCRT-III and regulates dendritic morphogenesis. In cultured cortical neurons, we found that dysfunctional ESCRT-III, lacking essential components (such as mSnf7-2, one of the mouse homologs of Shrub) or containing ectopically expressed FTD3-associated mutant CHMP2B, causes dendritic retraction,autophagosome accumulation and eventual neurodegeneration. Through an unbiased genetic screen in a Drosophila modelof FTD3, we identified several genetic modifiers of CHMP2B toxicity in vivo that are currently being characterized. We have also been using Drosophila models to study other ALS/FTD genes, in paticular, C9ORF72. We have also established patient-specific induced pluripotent stem cells (iPSC) models of FTD and ALS with mutations in progranulin, TDP-43, C9ORF72 and other genes. Over the next a few years, we will use a combination of molecular, cellular, and genetic approaches in both Drosophila and iPSCs models to further dissect the pathogenic mechanisms involving these ALS/FTD disease genes. Our ultimate goal is to identify common underlying pathogenic pathways as potential targets for therapeutic interventions in both ALS and FTD.
Summary	Our lab uses a combination of molecular, cellular, genetic, and behavioral approaches to further dissect the pathogenic mechanisms of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis with a focus on mutant CHMP2B, progranulin and C9ORF72. We will identify common underlying pathways as potential targets for therapeutic interventions.

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overview

Research Focus: Understanding ALS and Frontotemporal Dementia

Fen-Biao Gao Lab Website

Frontotemporal dementia (FTD) is an age-dependent neurodegenerative condition associated with focal atrophy of the frontal and/or temporal lobes and recognized now as the most common form of dementia before the age of 60. Unfortunately, the molecular pathogenesis of FTD remains largely unknown and effective treatments are not available. Recent exciting advances indicate that FTD is often associated with amyotrophic lateral sclerosis (ALS) and several genes are involved in thepathogenesis of both ALS and FTD, including CHMP2B, TDP-43, FUS, TBK1, and C9ORF72. How these mutant proteins cause or contribute to neuronal dysfunction and neurodegeneration in ALS and FTD remains poorly defined.

A few years ago, we cloned anovel Drosophila gene called shrub, which encodes a key component of ESCRT-III and regulates dendritic morphogenesis. In cultured cortical neurons, we found that dysfunctional ESCRT-III, lacking essential components (such as mSnf7-2, one of the mouse homologs of Shrub) or containing ectopically expressed FTD3-associated mutant CHMP2B, causes dendritic retraction,autophagosome accumulation and eventual neurodegeneration. Through an unbiased genetic screen in a Drosophila modelof FTD3, we identified several genetic modifiers of CHMP2B toxicity in vivo that are currently being characterized. We have also been using Drosophila models to study other ALS/FTD genes, in paticular, C9ORF72.

We have also established patient-specific induced pluripotent stem cells (iPSC) models of FTD and ALS with mutations in progranulin, TDP-43, C9ORF72 and other genes. Over the next a few years, we will use a combination of molecular, cellular, and genetic approaches in both Drosophila and iPSCs models to further dissect the pathogenic mechanisms involving these ALS/FTD disease genes. Our ultimate goal is to identify common underlying pathogenic pathways as potential targets for therapeutic interventions in both ALS and FTD.

Summary

Our lab uses a combination of molecular, cellular, genetic, and behavioral approaches to further dissect the pathogenic mechanisms of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis with a focus on mutant CHMP2B, progranulin and C9ORF72. We will identify common underlying pathways as potential targets for therapeutic interventions.

One or more keywords matched the following items that are connected to Gao, Fen-Biao

Item Type	Name
Academic Article	Frontotemporal dementia and amyotrophic lateral sclerosis-associated disease protein TDP-43 promotes dendritic branching.
Academic Article	Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons.
Academic Article	Association of UBQLN1 mutation with Brown-Vialetto-Van Laere syndrome but not typical ALS.
Concept	Amyotrophic Lateral Sclerosis
Academic Article	Downregulation of microRNA-9 in iPSC-derived neurons of FTD/ALS patients with TDP-43 mutations.
Academic Article	The emerging roles of microRNAs in the pathogenesis of frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum disorders.
Academic Article	FTD/ALS-associated poly(GR) protein impairs the Notch pathway and is recruited by poly(GA) into cytoplasmic inclusions.
Academic Article	Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice.
Academic Article	GGGGCC microsatellite RNA is neuritically localized, induces branching defects, and perturbs transport granule function.
Academic Article	ALS-linked protein disulfide isomerase variants cause motor dysfunction.
Academic Article	Lost & found: C9ORF72 and the autophagy pathway in ALS/FTD.
Academic Article	Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts.
Academic Article	Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.
Academic Article	A Drosophila model of ALS reveals a partial loss of function of causative human PFN1 mutants.
Academic Article	Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients.
Academic Article	Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder.
Academic Article	Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models.
Academic Article	Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.
Academic Article	The epidemiology and genetics of Amyotrophic lateral sclerosis in China.
Academic Article	Partial inhibition of the overactivated Ku80-dependent DNA repair pathway rescues neurodegeneration in C9ORF72-ALS/FTD.
Academic Article	C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo.
Academic Article	Transcription elongation factor AFF2/FMR2 regulates expression of expanded GGGGCC repeat-containing C9ORF72 allele in ALS/FTD.
Academic Article	CRISPR deletion of the C9ORF72 promoter in ALS/FTD patient motor neurons abolishes production of dipeptide repeat proteins and rescues neurodegeneration.
Academic Article	CRISPR-Cas9 Screens Identify the RNA Helicase DDX3X as a Repressor of C9ORF72 (GGGGCC)n Repeat-Associated Non-AUG Translation.
Academic Article	Altered MICOS Morphology and Mitochondrial Ion Homeostasis Contribute to Poly(GR) Toxicity Associated with C9-ALS/FTD.
Academic Article	TBK1 haploinsufficiency in ALS and FTD compromises membrane trafficking.
Academic Article	Translation of the poly(GR) frame in C9ORF72-ALS/FTD is regulated by cis-elements involved in alternative splicing.
Academic Article	Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM.
Academic Article	Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD.
Academic Article	CRISPR/Cas9-mediated excision of ALS/FTD-causing hexanucleotide repeat expansion in C9ORF72 rescues major disease mechanisms in vivo and in vitro.
Academic Article	Downregulation of Hsp90 and the antimicrobial peptide Mtk suppresses poly(GR)-induced neurotoxicity in C9ORF72-ALS/FTD.

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Motor Neuron Disease