Investigating the functional roles of CTSH and PGM1 in beta-cells during autoimmune diabetes development
研究 CTSH 和 PGM1 在自身免疫性糖尿病发展过程中在 β 细胞中的功能作用
基本信息
- 批准号:10351102
- 负责人:
- 金额:$ 15.49万
- 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:2022-02-01 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAmericanAntigen PresentationApoptosisAreaAutoimmuneAutoimmune DiabetesAutoimmune ResponsesAutomobile DrivingBeta CellCRISPR/Cas technologyCTSH geneCathepsinsCell physiologyCellsCellular StressChildClinicalDNAData AnalysesDevelopmentDiabetes MellitusDouble-Stranded RNAEnvironmentEnvironmental Risk FactorEnzymesEquipmentEtiologyFundingGenesGeneticGenetic RiskGenetic TranscriptionGoalsGrantHealthcareHumanHybridsIn VitroInbred NOD MiceInstitutionInsulin-Dependent Diabetes MellitusKnock-outKnowledgeLearningLoxP-flanked alleleLysosomesMediatingMedical EducationMedicineMentored Research Scientist Development AwardMentorsModelingMolecularMusPathogenicityPathway AnalysisPathway interactionsPeptide HydrolasesPlayPopulationPrevalenceResearchRoleRunningScientistStimulusStructure of beta Cell of isletSystemTalentsTechnologyTimeTrainingTransgenic MiceTranslational ResearchTranslationsViralVirus DiseasesWorkautoimmune pathogenesisbasebiological adaptation to stresscareercollegeearly onseteducation researcheffective therapyendoplasmic reticulum stressepidemiology studyexperimental studygene productgenetic epidemiologygenetic risk factorgenome wide association studyglycogenesisglycogenolysisglycosylationhuman embryonic stem cellimmunogenicityimprovedin vitro Modelinnovationinterestisletmouse modelnovelnovel therapeuticsoverexpressionpost-doctoral trainingpreservationpreventprotein degradationresponserisk variantstem cell differentiationstem cellssupportive environment
项目摘要
Project Summary / Abstract
This K01 award will allow Dr. Yi (Jody) Ye-Miller to advance her independent research career in the field of
type 1 diabetes (T1D). Dr. Ye’s overarching career goal is to understand the pathogenic mechanisms behind
the genetic and environmental influence of pancreatic beta-cells in T1D and to identify targeted pathways to
improve beta-cell function. The proposed project is carefully conceived, based on Dr.Ye’s previous work and
trains her to use novel models as well as cutting-edge technologies to study the mechanisms underlying T1D.
It is a timely opportunity and excellent training vehicle to enable an extremely talented young scientist to
achieve her career independence. The Albert Einstein College of Medicine is a national leader in medical
education, research, and health care. The institution and Dr. Ye’s mentors will provide a supportive
environment with all the necessary equipment and facilities, as well as many learning opportunities and
guidance for her professional development.
T1D affects 5% of the U.S. population with increasing prevalence in recent decades, especially among young
children. Current therapies are unable to provide long-lasting effects to improve beta cell function. The etiology
of T1D has both genetic and environmental components, but our understanding of the underlying mechanisms
is incomplete, hindering the development of novel therapies. In Dr. Ye’s previous postdoctoral trainings, she
identified two T1D loci, CTSH and PGM1, which showed evidence of genetic and environmental influence.
Both CTSH and PGM1 are expressed in pancreatic beta-cells. Her observations led to the hypothesis that
genetic and/or environment factors influence CTSH and PGM1 transcription and translation, which
alter the function and stress-response of beta-cells that consequently trigger T1D.
In this project, Dr. Ye will use CRISPR-Cas9 technology to modify the expression of CTSH and PGM1 in
human embryonic stem cells. Edited stem cells will subsequently be differentiated into pancreatic beta-cells in
vitro. Dr. Ye will investigate the effect of CTSH and PGM1 on beta-cell function with and without an
environmental stimulus such as viral infection. In addition, Dr. Ye will use a transgenic mouse model to
investigate whether CTSH or its related pathways can be targeted to prevent or slow autoimmune diabetes
development.
CTSH and PGM1 are T1D associated genes, but their beta-cells specific effects have not been thoroughly
studied. The proposed experiments are innovative and original. In a short term, funding will allow Dr. Ye to
establish her career independence in the field of T1D. In a long run, these studies will unravel the pathogenic
mechanisms associated with CTSH and PGM1 loci, allowing the development of new therapies to treat T1D in
humans.
项目摘要/摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Jody Ye其他文献
Jody Ye的其他文献
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{{ truncateString('Jody Ye', 18)}}的其他基金
Investigating the functional roles of CTSH and PGM1 in beta-cells during autoimmune diabetes development
研究 CTSH 和 PGM1 在自身免疫性糖尿病发展过程中在 β 细胞中的功能作用
- 批准号:
10559637 - 财政年份:2022
- 资助金额:
$ 15.49万 - 项目类别:
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