FXTAS Key Molecular Pathways Converge with Other Neurodegenerative Disorders
FXTAS 关键分子通路与其他神经退行性疾病的融合
基本信息
- 批准号:10609928
- 负责人:
- 金额:$ 27.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-15 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:Academic achievementAgeAlzheimer&aposs DiseaseAreaAtaxiaAutomobile DrivingAutopsyBasic ScienceBiologicalBrainBrain regionC9ORF72CGG repeat expansionCell NucleusCell physiologyCellsChronicClinicalClinical ResearchClinical SciencesClinical ServicesCluster AnalysisCollaborationsComplexData ScienceData SetDegradation PathwayDementiaDepositionDiseaseEnvironmentEukaryotaFMR1FMRPFXTASFacultyFoundationsFragile X SyndromeGene ExpressionGene Expression ProfilingGeneticGenetic DiseasesGenetic Predisposition to DiseaseGenetic studyGoalsHybridsImmunohistochemistryImpaired cognitionIndividualInflammationInflammatoryInstructionLaboratoriesLateralLipidsMacrophageMalignant NeoplasmsMediatingMental DepressionMentorsMentorshipMessenger RNAMetabolicMethodsMicrogliaMolecularMolecular BiologyMotor CortexMusNerve DegenerationNeurodegenerative DisordersNeuronsNeurosciencesParkinson DiseaseParkinsonian DisordersPathogenesisPathologicPathologic ProcessesPathway AnalysisPathway interactionsPeptidesPharmaceutical PreparationsPhenotypePhysiciansPrefrontal CortexProcessProteinsProteomeRNAResearchResearch PersonnelResearch Project GrantsResolutionRoleSamplingScientistSclerosisSignal TransductionSomatic CellSystemTimeTissuesTrainingTranscriptTranscription AlterationTremorTremor/Ataxia SyndromeUbiquitinUbiquitinationWestern BlottingWorkbehavioral disinhibitionbiomarker discoverybrain tissuecareercareer developmentcell typecytokinedifferential expressioneffective therapyexcitatory neuronexcitotoxicitygenome scienceshuman tissueinsightinterdisciplinary approachmedical schoolsmetabotropic glutamate receptor 5mitochondrial dysfunctionneurotoxicnovelpolyglycinepolypeptideprogramsprotein aggregationprotein degradationproteostasisresponsesexsingle nucleus RNA-sequencingskillsstemtherapeutic targettranscriptometranscriptome sequencing
项目摘要
PROJECT SUMMARY/ABSTRACT
THE CANDIDATE. Dr. Lozano is an early career physician-scientist, who has drawn on his academic
achievement and diverse training in clinical and basic science to develop an independent research program.
Through his work, he has developed laboratory skills in genetics and molecular biology, as well as clinical
research which together form the foundations of this ongoing project.
CAREER DEVELOPMENT. Dr. Lozano's overall long-term career goal is to lead a meaningful and sustainable
research program that will allow him to remain a well-established and independent investigator in the area of
Fragile X-related disorders. These goals will be accomplished through intense mentorship (Drs. Alison Goate
(mentor), Bin Zhang (co-mentor), and George Diaz(co-mentor)), meaningful collaborations, and personalized
didactic mechanisms, which are outlined in this application.
INSTITUTIONAL ENVIRONMENT. The Department of Genetics & Genomic Sciences at the Icahn School of
Medicine at Mount Sinai is a hybrid world-class basic science and clinical program that offers a broad-based
program of instruction, research, and clinical services. The faculty are experts in the application of molecular
biology, data science, and somatic cell approaches for the study of genetic diseases. The environment
provided in the department is ideal for the execution of the studies outlined in this application.
RESEARCH PROJECT. There
In
understood.
the
hypothesis
the
in
RNA
transcriptome
mechanisms,
To
with
sclerosis/Frontotemporal
FXTAS
determine
are currently no effective treatments for neurodegenerative disorders (NDDs).
order to develop potential therapeutic targets the underlying biological mechanisms mus be more clearly
Fragile X-associated tremor/ataxia syndrome (FXTAS) ffers an opportunity to gain insights into
pathological mechanisms for an NDD disorder that stems from a defined genetic etiology. The overall
is that protein clearance deficits are exacerbated by polypeptides and mRNA-FMR1 produced from
CGG expansion. This results in neuronal response-driven increases in ubiquitin proteins that are deposited
inclusions, leading to cell dysfuction, reactive inflammatory microglial and eventually neurodegeneration
sequencing (bulk and single nuclei) will be used to qualitatively and quantitatively examine the
in postmortem human tissue. Since NDDs involve complex and intertwined biological
an unbiased and hypothesis-free approach for key molecular pathways discovery will be applied.
identify the converging pathologica l processes in NDDS, the novel FXTAS datasets will be cross-examined
available datasets of Alzheimer's Disease, Parkinson Disease and amyotrophic lateral
ementia . This tudy has the potential to not only identify critical mechanisms driving
pathogenesis that would acilitate the discovery of biomarkers and therapeutic targets but also
pathways most central to disease through a cross-examination approach with other NDDs.
, t
o
.
d s
f
项目总结/摘要
候选人。Lozano博士是一位早期的职业医生科学家,他利用自己的学术
在临床和基础科学的成就和多样化的培训,以发展独立的研究计划。
通过他的工作,他发展了遗传学和分子生物学以及临床实验室技能。
这些研究共同构成了这个正在进行的项目的基础。
职业发展。Lozano博士的总体长期职业目标是领导一个有意义的和可持续的
研究计划,这将使他仍然是一个完善的和独立的调查员在该地区的
脆性X相关疾病。这些目标将通过加强指导来实现(艾莉森·高特博士
(导师)、张斌(共同导师)和乔治迪亚兹(共同导师)),有意义的合作,以及个性化的
教学机制,这在本申请中概述。
体制环境。伊坎学院遗传学与基因组科学系
医学在西奈山是一个混合世界级的基础科学和临床计划,提供了一个广泛的基础
教学、研究和临床服务计划。教师是分子应用方面的专家
生物学、数据科学和用于遗传疾病研究的体细胞方法。环境
该部门提供的是执行本申请中概述的研究的理想选择。
研究项目。那里
在
明白
的
假设
的
在
RNA
转录组
机制,
到
与
硬化症/额颞叶
FXTAS
确定
目前还没有有效的治疗神经退行性疾病(NDD)的方法。
为了开发潜在的治疗靶点,
脆性X相关震颤/共济失调综合征(FXTAS)提供了一个机会,
NDD病症的病理机制,其源于确定的遗传病因学。整体
蛋白质清除缺陷会因多肽和mRNA-FMR 1而加剧,
CGG扩展。这导致神经元反应驱动的泛素蛋白的增加,
包涵体,导致细胞功能障碍,反应性炎症小胶质细胞,最终神经变性
将使用测序(批量和单个核)定性和定量检查
在死后的人体组织中由于NDD涉及复杂和相互交织的生物学
将采用无偏见和无假设的方法来发现关键的分子途径。
为了确定NDDS中的会聚病理过程,将交叉检查新的FXTAS数据集
阿尔茨海默病、帕金森病和肌萎缩侧索硬化症的可用数据集
痴呆症这项研究不仅有可能确定驱动
发病机制,这将有助于发现生物标志物和治疗靶点,但也
通过与其他NDD的交叉检查方法,研究疾病最核心的途径。
得双曲余切值.
O
.
D s
F
项目成果
期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Latent Class Analysis Identifies Distinctive Behavioral Subtypes in Children with Fragile X Syndrome.
潜在类别分析可识别脆性 X 综合征儿童的独特行为亚型。
- DOI:10.1007/s10803-022-05821-7
- 发表时间:2024
- 期刊:
- 影响因子:3.9
- 作者:Kaufmann,WalterE;Raspa,Melissa;Bann,CarlaM;Gable,JuliaM;Harris,HollyK;Budimirovic,DejanB;Lozano,Reymundo;FORWARDConsortium
- 通讯作者:FORWARDConsortium
Autosomal Recessive Limb-Girdle Muscular Dystrophy-3: A Case Report of a Patient with Autism Spectrum Disorder.
- DOI:10.3390/genes14081587
- 发表时间:2023-08-05
- 期刊:
- 影响因子:3.5
- 作者:Lewis, Sivan;Woroch, Amy;Hatch, Mary Kate;Lozano, Reymundo
- 通讯作者:Lozano, Reymundo
Exploring Parents' Concerns Regarding Long-Term Support and Living Arrangements for Their Children with Fragile X Syndrome.
- DOI:10.3390/genes13091654
- 发表时间:2022-09-15
- 期刊:
- 影响因子:3.5
- 作者:
- 通讯作者:
Observable Symptoms of Anxiety in Individuals with Fragile X Syndrome: Parent and Caregiver Perspectives.
- DOI:10.3390/genes13091660
- 发表时间:2022-09-16
- 期刊:
- 影响因子:3.5
- 作者:
- 通讯作者:
The Impact of the COVID-19 Pandemic on School-Aged Children with Fragile X Syndrome.
- DOI:10.3390/genes13091666
- 发表时间:2022-09-17
- 期刊:
- 影响因子:3.5
- 作者:
- 通讯作者:
{{
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 }}
Reymundo Lozano其他文献
Reymundo Lozano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('Reymundo Lozano', 18)}}的其他基金
FXTAS Key Molecular Pathways Converge with Other Neurodegenerative Disorders
FXTAS 关键分子通路与其他神经退行性疾病的融合
- 批准号:
10429040 - 财政年份:2022
- 资助金额:
$ 27.15万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政策的情绪动态
- 批准号:
10108433 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
- 批准号:
MR/X032809/1 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
- 批准号:
MR/X034690/1 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Fellowship
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341426 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341424 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Continuing Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
- 批准号:
2335955 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Standard Grant
The economics of (mis)information in the age of social media
社交媒体时代(错误)信息的经济学
- 批准号:
DP240103257 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Discovery Projects
How age & sex impact the transcriptional control of mammalian muscle growth
你多大
- 批准号:
DP240100408 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Discovery Projects
Supporting teachers and teaching in the age of Artificial Intelligence
支持人工智能时代的教师和教学
- 批准号:
DP240100111 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Discovery Projects
Enhancing Wahkohtowin (Kinship beyond the immediate family) Community-based models of care to reach and support Indigenous and racialized women of reproductive age and pregnant women in Canada for the prevention of congenital syphilis
加强 Wahkohtowin(直系亲属以外的亲属关系)以社区为基础的护理模式,以接触和支持加拿大的土著和种族育龄妇女以及孕妇,预防先天梅毒
- 批准号:
502786 - 财政年份:2024
- 资助金额:
$ 27.15万 - 项目类别:
Directed Grant














{{item.name}}会员




