Ceramide, AMPK, and YAP/TAZ Signaling in Hepatic Fibrogenesis
肝纤维形成中的神经酰胺、AMPK 和 YAP/TAZ 信号转导
基本信息
- 批准号:10544748
- 负责人:
- 金额:$ 12.11万
- 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:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:5&apos-AMP-activated protein kinaseAdvisory CommitteesAwardBasic ScienceBiochemicalCaliforniaCarbon TetrachlorideCeramidesClinicalClinical TreatmentCo-ImmunoprecipitationsDataDevelopmentDiseaseDisease ProgressionEnsureEnvironmentEnzyme InhibitionFibrosisFundingGastroenterologyGoalsHepatic FibrogenesisHepatic Stellate CellHumanHydrolysisIn VitroKnockout MiceKnowledgeLATS1 geneLifeLiverLiver FailureLiver FibrosisMediatingMentorshipMissionModelingModificationMolecularMolecular BiologyMusOutcomePathway interactionsPatientsPharmacologyPhosphorylationPhosphotransferasesPhysiciansPublic HealthPublicationsRegulationResearchRoleSan FranciscoScientistSignal PathwaySignal TransductionSphingolipidsSupervisionTechniquesTherapeuticTimeUnited States National Institutes of HealthUniversitiesWorkantifibrotic treatmentcandidate identificationcareercell typechronic liver diseasecollaborative environmentconditional knockoutdruggable targetexperimental studyfibrogenesisgain of functiongalactosylgalactosylglucosylceramidaseimprovedin vivoloss of functionmouse modelnon-alcoholic fatty liver diseasenovelnovel therapeuticspreclinical developmentprogramssuccesssupportive environment
项目摘要
ABSTRACT
This is an application for an R03 Award by Dr. Jennifer Y. Chen, a hepatologist at the University of California,
San Francisco (UCSF). Dr. Chen's long-term career goal is to become an independently funded physician
scientist, devoting more than 75% of her time to establish and maintain a basic science research program in
hepatic fibrosis. Fibrosis is driven by activation of hepatic stellate cells (HSCs) and therapies to inactivate HSCs
have clinical potential as antifibrotic agents. The overall goal of Dr. Chen's research program is to develop novel
antifibrotic therapies for the clinical treatment of hepatic fibrosis. She has demonstrated that the sphingolipid
ceramide inactivates HSCs by inhibiting the YAP/TAZ signaling pathway. In this proposal, the candidate seeks
to elucidate how ceramide regulates upstream effectors of the YAP/TAZ pathway to inactivate HSCs and reduce
hepatic fibrogenesis. The applicant will utilize gain of function and loss of function approaches for the in vitro
studies. She will also perform co-immunoprecipitation experiments to determine the extent by which ceramide
modulates interactions with key regulators. For the in vivo studies, she will analyze conditional knockout mice
in a mouse model of fibrosis. A formal mentorship committee and advisory team will provide supervision,
guidance, and assistance for the candidate to achieve her goals. The research environment, which includes the
Division of Gastroenterology and the UCSF Liver Center, will provide a rich, collaborative, and supportive
atmosphere to ensure the candidate's success. The mechanistic understanding to be gained from the successful
completion of the proposed studies promises to reveal new nodes and targets for rational disease modification
in hepatic fibrosis, a disease with limited treatment options available. Completion of the studies will produce the
data and publication record necessary for a successful R01 application and significantly facilitate the transition
of the candidate to an independent physician-scientist.
抽象的
这是加州大学肝病学家 Jennifer Y. Chen 博士提交的 R03 奖申请,
旧金山(加州大学旧金山分校)。陈医生的长期职业目标是成为一名独立资助的医师
科学家,投入超过 75% 的时间来建立和维护基础科学研究项目
肝纤维化。纤维化是由肝星状细胞 (HSC) 的激活和 HSC 失活疗法驱动的
具有作为抗纤维化药物的临床潜力。陈博士研究计划的总体目标是开发新颖的
抗纤维化疗法用于临床治疗肝纤维化。她证明了鞘脂
神经酰胺通过抑制 YAP/TAZ 信号通路来灭活 HSC。在此提案中,候选人寻求
阐明神经酰胺如何调节 YAP/TAZ 通路的上游效应器以灭活 HSC 并减少
肝纤维化。申请人将利用功能获得和功能丧失方法进行体外
研究。她还将进行免疫共沉淀实验,以确定神经酰胺的程度
调节与主要监管机构的互动。对于体内研究,她将分析条件基因敲除小鼠
在纤维化小鼠模型中。正式的导师委员会和顾问团队将提供监督,
为候选人实现其目标提供指导和帮助。研究环境,包括
胃肠病学部门和 UCSF 肝脏中心将提供丰富的、协作的和支持性的
确保候选人成功的氛围。从成功的案例中获得的机械理解
拟议研究的完成有望揭示合理疾病调整的新节点和目标
肝纤维化是一种治疗选择有限的疾病。完成研究将产生
成功 R01 申请所需的数据和发布记录,并显着促进过渡
独立医师科学家候选人的资格。
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)
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Jennifer Y. Chen其他文献
Use of sublimation for template removal from menthol templated mesoporous organosilica prepared via sol–gel process
使用升华从溶胶-凝胶工艺制备的薄荷醇模板化介孔有机二氧化硅中去除模板
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
I. Mukherjee;Jennifer Y. Chen;H. Yin;Yen Wei - 通讯作者:
Yen Wei
Reproductive care and rates of pregnancy in teenagers with negative pregnancy test results.
妊娠试验结果呈阴性的青少年的生殖保健和怀孕率。
- DOI:
10.1016/j.jadohealth.2004.10.007 - 发表时间:
2006 - 期刊:
- 影响因子:0
- 作者:
L. Sadler;Jennifer Y. Chen;A. Daley;J. Leventhal;H. Reynolds - 通讯作者:
H. Reynolds
Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis
细胞应激在非酒精性脂肪性肝炎和肝纤维化发病机制中的作用
- DOI:
10.1038/s41575-023-00832-w - 发表时间:
2023-09-07 - 期刊:
- 影响因子:51.000
- 作者:
Sachin Sharma;Dounia Le Guillou;Jennifer Y. Chen - 通讯作者:
Jennifer Y. Chen
Dynamic Mechanical Response of Epithelial Cells to Epidermal Growth Factor
上皮细胞对表皮生长因子的动态机械反应
- DOI:
10.5772/49977 - 发表时间:
2012 - 期刊:
- 影响因子:11.5
- 作者:
Jun Xi;L. Penn;N. Xi;Jennifer Y. Chen;Ruiguo Yang - 通讯作者:
Ruiguo Yang
Use of the Quartz Crystal Microbalance with Dissipation Monitoring for Pharmacological Evaluation of Cell Signaling Pathways Mediated by Epidermal Growth Factor Receptors
使用石英晶体微天平和耗散监测对表皮生长因子受体介导的细胞信号通路进行药理学评价
- DOI:
10.1007/978-1-4939-2617-6_14 - 发表时间:
2015 - 期刊:
- 影响因子:2.1
- 作者:
Jennifer Y. Chen;Marcela P. Garcia;L. Penn;Jun Xi - 通讯作者:
Jun Xi
Jennifer Y. Chen的其他文献
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{{ truncateString('Jennifer Y. Chen', 18)}}的其他基金
Dissecting the Acid Ceramidase Pathway in Hepatic Fibrogenesis
剖析肝纤维形成中的酸性神经酰胺酶途径
- 批准号:
10736680 - 财政年份:2023
- 资助金额:
$ 12.11万 - 项目类别:
Ceramide, AMPK, and YAP/TAZ Signaling in Hepatic Fibrogenesis
肝纤维形成中的神经酰胺、AMPK 和 YAP/TAZ 信号转导
- 批准号:
10352024 - 财政年份:2022
- 资助金额:
$ 12.11万 - 项目类别:
Role of Ceramide in Hepatic Stellate Cell Activation and Liver Fibrosis
神经酰胺在肝星状细胞活化和肝纤维化中的作用
- 批准号:
9751847 - 财政年份:2017
- 资助金额:
$ 12.11万 - 项目类别:
Role of Ceramide in Hepatic Stellate Cell Activation and Liver Fibrosis
神经酰胺在肝星状细胞活化和肝纤维化中的作用
- 批准号:
10475911 - 财政年份:2017
- 资助金额:
$ 12.11万 - 项目类别:
Role of Ceramide in Hepatic Stellate Cell Activation and Liver Fibrosis
神经酰胺在肝星状细胞活化和肝纤维化中的作用
- 批准号:
10222658 - 财政年份:2017
- 资助金额:
$ 12.11万 - 项目类别:
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