Pou4f3 enhancers in hearing loss treatment
Pou4f3 增强剂在听力损失治疗中的应用
基本信息
- 批准号:10663166
- 负责人:
- 金额:$ 25.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-05 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAdultAffectAgonistAllelesAnimal ModelAromataseBindingBirthCRISPR-mediated transcriptional activationCell DeathCell Differentiation processCellsChimeric ProteinsClustered Regularly Interspaced Short Palindromic RepeatsCochleaCompensationConsumptionDNA Sequence AlterationDataDevelopmentDistalEnhancersEpigenetic ProcessGFI1 geneGene ExpressionGenerationsGenesGenetic TranscriptionGuide RNAHair CellsHearingHistonesHomeostasisHumanMethodsMusMutationNatural regenerationOrgan Culture TechniquesPatientsPersonsProcessRegulatory ElementResourcesSensorineural Hearing LossSensory HairSpecificityStimulusSupporting CellSystemTechniquesTestingTherapeuticTimeTransgenic AnimalsWorkautosomecell typecurative treatmentsdesignefficacy evaluationflexibilityhair cell regenerationhearing impairmenthearing loss treatmentimprovedin vivoin vivo Modelmutantoverexpressionpreventprogressive hearing losspromoterrecruittranscription factortransdifferentiation
项目摘要
Millions of people are affected by sensorineural hearing loss caused by genetic mutations or
environmental stimuli, and currently there is no curative treatment for sensorineural hearing loss. Transcription
factor POU4F3 is essential for sensory hair cell differentiation, homeostasis and regeneration. During
development, POU4F3 is required for ATOH1 to bind to enhancers of many hair cell genes to initiate their
expression; after hearing onset, reduced transcription activity of POU4F3 due to mutations of one allele leads
to hair cell death and hearing loss (DFNA15, autosomal dominant non-syndromic hearing loss 15, in human
patients); and overexpression of POU4F3 in supporting cells stimulates hair cell fate conversion. However, the
transcription of the Pou4f3 gene is poorly understood and there is no feasible method to regulate Pou4f3
expression from the endogenous allele to treat DFNA15 or to regenerate hair cells. In this project, we will
characterize putative Pou4f3 enhancers to investigate the transcription regulatory mechanisms controlling
Pou4f3 expression and utilize these putative enhancers to stimulate Pou4f3 expression in hair cells for a
potential DFNA15 treatment or in supporting cells for a new strategy to regenerate hair cells. This work will
further our understanding of the regulatory network governing hair cell specific gene expression, develop
therapeutic treatments of DFNA15 and other forms of hearing loss associated with haploinsufficiency, and
provide a new hair cell regeneration strategy with sufficient flexibility for a variety of factor combinations.
数以百万计的人受到由基因突变引起的感音神经性听力损失的影响,
感音神经性听力损失通常是由环境刺激引起的,并且目前没有针对感音神经性听力损失的治愈性治疗。转录
POU 4F 3因子是感觉毛细胞分化、稳态和再生所必需的。期间
POU 4F 3是ATOH 1与许多毛细胞基因的增强子结合所必需的,
表达;听力发作后,由于一个等位基因突变导致POU 4F 3转录活性降低,
毛细胞死亡和听力损失(DFNA 15,常染色体显性遗传性非综合征性听力损失15,在人类
患者);并且支持细胞中POU 4F 3的过表达刺激毛细胞命运转换。但
对Pou 4f 3基因的转录了解甚少,并且没有可行的方法来调节Pou 4f 3
在一些实施方案中,所述方法包括从内源等位基因表达来治疗DFNA 15或再生毛细胞。在这个项目中,我们将
表征推定的Pou 4f 3增强子,以研究控制转录的转录调节机制。
Pou 4f 3的表达,并利用这些推定的增强子刺激毛细胞中Pou 4f 3的表达,
潜在的DFNA 15治疗或支持细胞再生毛细胞的新策略。这项工作将
进一步了解毛细胞特异性基因表达的调控网络,
DFNA 15和与单倍不足相关的其他形式的听力损失的治疗性治疗,以及
提供了一种新的毛细胞再生策略,其对于多种因子组合具有足够的灵活性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Litao Tao其他文献
Litao Tao的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Litao Tao', 18)}}的其他基金
Pou4f3 enhancers in hearing loss treatment
Pou4f3 增强剂在听力损失治疗中的应用
- 批准号:
10662584 - 财政年份:2022
- 资助金额:
$ 25.58万 - 项目类别:
Dissecting the sensory hair cell nucleus: Development of a novel method for investigating chromatin interactions (Tn5-Capture) in small cell numbers
解剖感觉毛细胞核:开发一种研究小细胞中染色质相互作用(Tn5-Capture)的新方法
- 批准号:
10571130 - 财政年份:2022
- 资助金额:
$ 25.58万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 25.58万 - 项目类别:
Research Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 25.58万 - 项目类别:
Standard Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 25.58万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 25.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 25.58万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 25.58万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 25.58万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 25.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 25.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 25.58万 - 项目类别:
Grant-in-Aid for Scientific Research (C)