Microfabricated instrumentation to measure sphingolipid signaling in human acute myeloid leukemia
用于测量人类急性髓系白血病中鞘脂信号传导的微型仪器
基本信息
- 批准号:9809343
- 负责人:
- 金额:$ 58.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-07 至 2019-12-31
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsAcute Myelocytic LeukemiaAcute leukemiaAdultAgeAllogenicApoptosisApoptoticAutomationAutomobile DrivingBehaviorBiochemicalBiochemical PathwayBiochemical ProcessBiological AssayBiomedical EngineeringCell DeathCell LineCell modelCellsCellular AssayCeramidaseCeramidesChemicalsChemotherapy-Oncologic ProcedureClinicalCollaborationsComorbidityCytogeneticsDNA SequenceDataDevelopmentDiseaseDrug resistanceEngineeringEnzymesEpigenetic ProcessEquilibriumExhibitsFluorescent ProbesFutureGene ExpressionGenesGeneticGlucosylceramidesGoalsGrowthHeterogeneityHumanHypoxiaIn complete remissionIndividualKnowledgeLeadLeukemic CellLinkLipidsLyaseMalignant NeoplasmsMeasurementMeasuresMedicalMetabolismMicrofluidicsModelingMolecularMonitorMulti-Drug ResistanceMutationNeoadjuvant TherapyOncologistPathway interactionsPatientsPharmaceutical PreparationsPharmacotherapyPhosphoric Monoester HydrolasesPlayPopulationProceduresProductionProteinsRecording of previous eventsRecurrent diseaseRefractory DiseaseRegimenRelapseReporterResearchRisk AssessmentRoleSamplingScientistSignal PathwaySignal TransductionSpecimenSphingolipidsSphingomyelinaseSphingomyelinsSphingosineStem cell transplantSurvival RateSystemTechniquesTestingTherapeuticTherapeutic AgentsTreatment EfficacyUp-RegulationWorkacute myeloid leukemia cellarmbiological heterogeneitycancer cellceramide 1-phosphateceramide kinasechemotherapydesaturasedesigndihydroceramidedihydroceramide desaturasedrug efficacygenomic signatureglycosylationimprovedindividual patientinnovationinorganic phosphateinsightinstrumentationkinase inhibitorleukemiamicrodevicemolecular markermortalitymultidisciplinaryneoplastic cellnew technologynon-geneticnoveloutcome forecastoverexpressionprecision medicineprognosticresponsesphingosine 1-phosphatesphingosine kinasetargeted treatmenttechnology developmenttreatment optimizationtreatment responsetumor
项目摘要
An innovative platform to measure the activity of the sphingolipid pathway in single cells from
primary, human, acute myeloid leukemia (AML) will be developed. A multidisciplinary group
(chemist, bioengineer, oncologist and computational scientist) with a history of successful
collaborations will pursue the development of engineered microfluidic instrumentation and
supporting hardware using medically relevant probes to answer fundamental questions
regarding heterogeneity in single AML cells. Fluorescent probes to track simultaneously the
three major pathways comprising the ceramide-sphingosine axis in AML cells will be
developed so that a detailed understanding of sphingolipid signaling in the tumor cells is
achieved. Electrophoretic separations within a microfabricated device will be optimized for the
single-cell measurements as a component of the work flow. Automation and integration will
greatly increase throughput to yield a microdevice which is compatible with common clinical
workflows. A powerful attribute of the proposal is that these measurements will be performed
on single cells from primary samples and will avoid the confounding aspects of population-
averaged data yielded by bulk cell assays. Furthermore, by simultaneously tracking all arms of
the sphingolipid pathway, we will identify the strategies that AML cells use to dynamically
reprogram their growth-promoting pathways via sphingolipid signaling during drug treatment.
The proposed microfabricated devices will in the future provide key information concerning the
best treatment option(s) for patients as well yielding an assessment of treatment efficacy to
contribute fundamental data to the emerging field of precision medicine.
一个创新的平台来测量单细胞中鞘脂途径的活性,
将发展成原发性人急性髓性白血病(AML)。多学科小组
(化学家,生物工程师,肿瘤学家和计算科学家),具有成功的
合作将致力于开发工程微流体仪器,
支持硬件使用医学相关探头来回答基本问题
关于单个AML细胞的异质性。荧光探针同时追踪
AML细胞中包含神经酰胺-鞘氨醇轴的三个主要途径将是
开发,以便详细了解肿瘤细胞中的鞘脂信号传导,
办妥了一批微加工装置内的电泳分离将针对以下方面进行优化:
单细胞测量作为工作流程的一部分。自动化和集成将
大大增加了生产量,以产生与普通临床
工作流程。该提案的一个强有力的特点是,这些测量将在
对来自原代样品的单细胞,并将避免群体的混淆方面-
通过大量细胞测定得到的平均数据。此外,通过同时跟踪所有武器,
鞘脂途径,我们将确定AML细胞动态使用的策略
在药物治疗期间,通过鞘脂信号转导重新编程其生长促进途径。
所提出的微加工装置将在未来提供关于
为患者提供最佳治疗选择,并对治疗疗效进行评估,
为新兴的精准医疗领域贡献基础数据。
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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Nancy L. Allbritton其他文献
Choosing one from the many: selection and sorting strategies for single adherent cells
- DOI:
10.1007/s00216-006-0612-1 - 发表时间:
2006-07-18 - 期刊:
- 影响因子:3.800
- 作者:
Christopher E. Sims;Mark Bachman;G. P. Li;Nancy L. Allbritton - 通讯作者:
Nancy L. Allbritton
Erratum to: Trapping cells on a stretchable microwell array for single-cell analysis
- DOI:
10.1007/s00216-012-6266-2 - 发表时间:
2012-07-21 - 期刊:
- 影响因子:3.800
- 作者:
Yuli Wang;Pavak Shah;Colleen Phillips;Christopher E. Sims;Nancy L. Allbritton - 通讯作者:
Nancy L. Allbritton
Measuring the Enzymatic Activity of Clinically Important Proteins in Single Cells
- DOI:
10.1016/j.bpj.2010.12.1401 - 发表时间:
2011-02-02 - 期刊:
- 影响因子:
- 作者:
Christopher E. Sims;Nancy L. Allbritton;Dechen Jiang;Shan Yang;Angie Proctor;Ryan Phillips - 通讯作者:
Ryan Phillips
Imaging 3D cell cultures with optical microscopy
用光学显微镜对三维细胞培养进行成像
- DOI:
10.1038/s41592-025-02647-w - 发表时间:
2025-04-17 - 期刊:
- 影响因子:32.100
- 作者:
Huai-Ching Hsieh;Qinghua Han;David Brenes;Kevin W. Bishop;Rui Wang;Yuli Wang;Chetan Poudel;Adam K. Glaser;Benjamin S. Freedman;Joshua C. Vaughan;Nancy L. Allbritton;Jonathan T. C. Liu - 通讯作者:
Jonathan T. C. Liu
Construction of Peptidase-Resistant Substrates for Kinases
- DOI:
10.1016/j.bpj.2011.11.1503 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Angela Proctor;Qunzhao Wang;David S. Lawrence;Nancy L. Allbritton - 通讯作者:
Nancy L. Allbritton
Nancy L. Allbritton的其他文献
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{{ truncateString('Nancy L. Allbritton', 18)}}的其他基金
Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficile
开发微生理系统来测定人结肠上皮对艰难梭菌的相互作用
- 批准号:
10321276 - 财政年份:2020
- 资助金额:
$ 58.68万 - 项目类别:
Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficile
开发微生理系统来测定人结肠上皮对艰难梭菌的相互作用
- 批准号:
10539253 - 财政年份:2020
- 资助金额:
$ 58.68万 - 项目类别:
Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficile
开发微生理系统来测定人结肠上皮对艰难梭菌的相互作用
- 批准号:
9884925 - 财政年份:2020
- 资助金额:
$ 58.68万 - 项目类别:
MICROFABRICATED INSTRUMENTATION TO MEASURE SPHINGOLIPID SIGNALING IN HUMAN ACUTE MYELOID LEUKEMIA
用于测量人类急性髓系白血病中鞘脂信号传导的微型仪器
- 批准号:
10667508 - 财政年份:2019
- 资助金额:
$ 58.68万 - 项目类别:
MICROFABRICATED INSTRUMENTATION TO MEASURE SPHINGOLIPID SIGNALING IN HUMAN ACUTE MYELOID LEUKEMIA
用于测量人类急性髓系白血病中鞘脂信号传导的微型仪器
- 批准号:
9926834 - 财政年份:2019
- 资助金额:
$ 58.68万 - 项目类别:
PROFILING SIGNALING ACTIVITY AND GENE EXPRESSION IN SINGLE, PANCREATIC ADENOCARCINOMA CELLS USING CE-RNA-SEQ
使用 CE-RNA-SEQ 对单个胰腺腺癌细胞中的信号传导活性和基因表达进行分析
- 批准号:
10373116 - 财政年份:2018
- 资助金额:
$ 58.68万 - 项目类别:
PROFILING SIGNALING ACTIVITY AND GENE EXPRESSION IN SINGLE, PANCREATIC ADENOCARCINOMA CELLS USING CE-RNA-SEQ
使用 CE-RNA-SEQ 对单个胰腺腺癌细胞中的信号传导活性和基因表达进行分析
- 批准号:
10115487 - 财政年份:2018
- 资助金额:
$ 58.68万 - 项目类别:
PROFILING SIGNALING ACTIVITY AND GENE EXPRESSION IN SINGLE, PANCREATIC ADENOCARCINOMA CELLS USING CE-RNA-SEQ
使用 CE-RNA-SEQ 分析单个胰腺腺癌细胞中的信号传导活性和基因表达
- 批准号:
10200700 - 财政年份:2018
- 资助金额:
$ 58.68万 - 项目类别:
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