Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and Disease
Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and Disease
批准号:
10337288
负责人:
Rebekah L. Gundry
金额:
$76.11万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-02-01 至 2028-01-31
关键词:
BiologyCardiacCardiac MyocytesCardiotoxicityCell Surface ProteinsCell surfaceCellsDataDevelopmentDiseaseDisease modelFutureGeneticHeartHeart failureHumanLigandsMass Spectrum AnalysisMembraneMembrane GlycoproteinsMethodologyMethodsMonitorOutcome StudyPathologyPatient CarePatientsPharmaceutical PreparationsPluripotent Stem CellsPolysaccharidesProteomeReagentReproducibilityResearchSignal TransductionSpecificitySpeedSystemTechnologyTherapeuticTissuesbasebioinformatics toolbiomarker panelcell typeclinical applicationdrug testingexperienceglycoproteomicsimprovedinnovationmolecular phenotypenext generationnovel markerprogramsreceptorremote sensingstem cell biologystem cellstechnology developmenttranslational study
中文摘要
摘要
英文摘要
ABSTRACT
Our research program develops and applies innovative mass spectrometry technologies, bioinformatics tools,
and methodologies to transform our understanding of cell surface proteins and glycans and answer outstanding
questions in stem cell biology and cardiac pathology. Our analytical platforms promote the development of new
reagents and strategies to improve the quality and homogeneity of stem cell-derived cardiomyocytes for research
and clinical applications and the discovery of strategies to monitor and treat patients with advanced heart failure.
Specifically, our approaches enable the identification, characterization, and quantification of cell surface
glycoproteins and glycans from small numbers of human cells. To date, we have developed new markers for
identifying cardiomyocytes with high specificity and selecting maturation stage-specific stem cell derived
cardiomyocytes to enable reproducible assessment and isolation of functionally-defined cells. Applying our
technologies to primary human heart tissue, we have begun to develop cell-type specific views of the cell surface
proteome and glycome within normal and failing hearts. We have also developed innovative bioinformatics tools
to inform our next level of technology development to enhance our capabilities and improve the speed and
accuracy with which we analyze our mass spectrometry data. The proposed studies build on these experiences
to: 1) develop the next generation technology that will provide unparalleled specificity regarding the molecular
phenotypes presented at the cell surface, information that is not possible to obtain by any current method, 2)
develop marker panels that enable the assessment and selection of chamber- and maturation-stage specific
stem cell derived cardiomyocytes without genetic editing, 3) define the cell-type specific receptors, membrane-
bound ligands and secreted factors present in the normal human heart and how they change in disease to
provide new understanding of intercellular signaling and inform the development of remote sensing markers to
benefit the care of patients with advanced heart failure. The impact from the proposed studies lies within future
applications and mechanistic studies that will be possible based on the approaches and data that we generate.
As our program evolves to pursue mechanistic and translational studies of the molecules revealed by our
discovery efforts, we expect the outcomes of these studies will broadly impact the development of strategies to
improve the quality of stem cell derivatives to promote their utility for drug testing, disease modeling, and
therapeutic applications, inform the development of cell-type directed payload delivery systems and drugs that
avoid cardiotoxic effects, and yield new strategies to assess and treat advanced heart failure.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and Disease
-
批准号:10555323
-
项目类别:
-
资助金额:$76.48万
-
财政年份:2021
-
负责人:Rebekah L. Gundry
-
依托单位:
Development of a next-generation glycomics platform to enable glycan structure analyses for precision medicine
-
批准号:10054508
-
项目类别:
-
资助金额:$45.86万
-
财政年份:2020
-
负责人:Rebekah L. Gundry
-
依托单位:
Development of a next-generation glycomics platform to enable glycan structure analyses for precision medicine
-
批准号:10239250
-
项目类别:
-
资助金额:$45.1万
-
财政年份:2020
-
负责人:Rebekah L. Gundry
-
依托单位:
Cell Surface Phenotyping Human Primary Cells
-
批准号:10034909
-
项目类别:
-
资助金额:$38.13万
-
财政年份:2019
-
负责人:Rebekah L. Gundry
-
依托单位:
Cell Surface Proteins in Human Cardiomyocytes
-
批准号:10037355
-
项目类别:
-
资助金额:$32.52万
-
财政年份:2019
-
负责人:Rebekah L. Gundry
-
依托单位:
Cell Surface Proteins in Human Cardiomyocytes
-
批准号:9027643
-
项目类别:
-
资助金额:$34.94万
-
财政年份:2016
-
负责人:Rebekah L. Gundry
-
依托单位:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
-
批准号:8249072
-
项目类别:
-
资助金额:$24.27万
-
财政年份:2011
-
负责人:Rebekah L. Gundry
-
依托单位:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
-
批准号:8449291
-
项目类别:
-
资助金额:$22.53万
-
财政年份:2011
-
负责人:Rebekah L. Gundry
-
依托单位:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
-
批准号:8166085
-
项目类别:
-
资助金额:$23.4万
-
财政年份:2011
-
负责人:Rebekah L. Gundry
-
依托单位:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
-
批准号:7572060
-
项目类别:
-
资助金额:$9.74万
-
财政年份:2009
-
负责人:Rebekah L. Gundry
-
依托单位:
海外基金