Development and Application of Organelle Chemotype Fingerprinting for the Functional Investigation of Organellar Chloride
细胞器化学型指纹图谱在氯化细胞器功能研究中的开发和应用
基本信息
- 批准号:10664018
- 负责人:
- 金额:$ 36.26万
- 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:2022-08-01 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AnionsAutophagocytosisCalciumCell membraneCellsChloride ChannelsChloridesClinical TrialsCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDevelopmentFDA approvedFingerprintFluorescenceHealthHealthcareHomeostasisHumanHuman bodyImageInvestigationIonsKidney CalculiMeasurementMethodsMinorMitochondriaMutationOrganellesOsteoporosisPathway interactionsPersonsPharmaceutical PreparationsPhysiologicalPlayPotassiumProteinsProteinuriaReporterReportingResearchRespirationRiskRoleSodiumTechniquesThree-dimensional analysisVariantcare burdeneffective therapyhuman diseasetargeted therapy trialstargeted treatmenttool
项目摘要
SUMMARY/ABSTRACT
As one of the most abundant anions in the human body, chloride plays a crucial role in human health. Chloride
homeostasis is maintained inside the cell while the chloride level is varied based on the function of organelles.
Dysregulation of chloride homeostasis caused by the mutation of chloride channels results in various human
diseases such as cystic fibrosis (CFTR, >70,000 people worldwide), proteinuria and kidney stones (ClC-5, 39
million people in US), Osteoporosis (ClC-7, 10 million people in US, 43 million people in the risk group). Although
five FDA-approved chloride channel modulators have been reported, they only target plasma membrane chloride
channels due to the technical barrier. There is no FDA-approved or clinical trial drug that targets organellar
chloride channel. The field of chloride channel-targeted therapy is still under-studied (5 FDA-approved drugs, 2
clinical trial) compared to other channels such as calcium, potassium, and sodium.
The lack of understanding of the physiological role of organellar chloride and the well-characterized
chloride channel are the biggest roadblocks for the development of chloride channel-targeted therapy.
Therefore, suitable research tools with a high resolving ability to examine the organelle chloride in live
cells is a highly urgent need, which is essential to elucidate the physiological role of organellar chloride
and characterize the chloride channel. However, the current chloride measurement with one-dimensional
analysis only shows the average ion level. It cannot observe the chloride level change in a minor subset of
organelles triggered by the cellular pathway such as STING and autophagy. Furthermore, the typical
fluorescence measurement can only tell the variation of the average chloride level (increase, decrease, and no
significant change) in certain conditions. The current methods significantly hinder the identification of deactivated
cell pathways or protein based on the chloride level measurement.
The proposed research integrate organelle selective dual reporters, single organelle measurement, sub-
cellular imaging, and the three-dimensional analysis, to fingerprint the chemotype of organelles along with STING
pathway, autophagy, and mitochondrial respiration. Completion of the proposed study will find out the
physiological role of organellar chloride which shed light on the chloride channel-targeted therapy. The
development of the organelle chemotype fingerprinting technique will also provide tools to characterize chloride
channels, evaluate chloride channel modulators and identify the deactivated cell pathways or proteins.
摘要/文摘
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)
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Ka Ho Leung其他文献
Ka Ho Leung的其他文献
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{{ truncateString('Ka Ho Leung', 18)}}的其他基金
Undergraduate Summer Research in Chemical Biology
化学生物学本科暑期研究
- 批准号:
10810210 - 财政年份:2022
- 资助金额:
$ 36.26万 - 项目类别:
Prospective Evaluation of Chloride Channel-Targeted Therapy for Alzheimer's disease
氯离子通道靶向治疗阿尔茨海默病的前瞻性评价
- 批准号:
10712797 - 财政年份:2022
- 资助金额:
$ 36.26万 - 项目类别:














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