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: 9809343
• 负责人: Nancy L. Allbritton
• 金额: $ 58.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/9809343
• 关键词: Abbreviations; Acute Myelocytic Leukemia; Acute leukemia; Adult; Age; Allogenic; Apoptosis; Apoptotic; Automation; Automobile Driving; Behavior; Biochemical; Biochemical Pathway; Biochemical Process; Biological Assay; Biomedical Engineering; Cell Death; Cell Line; Cell model; Cells; Cellular Assay; Ceramidase; Ceramides; Chemicals; Chemotherapy-Oncologic Procedure; Clinical; Collaborations; Comorbidity; Cytogenetics; DNA Sequence; Data; Development; Disease; Drug resistance; Engineering; Enzymes; Epigenetic Process; Equilibrium; Exhibits; Fluorescent Probes; Future; Gene Expression; Genes; Genetic; Glucosylceramides; Goals; Growth; Heterogeneity; Human; Hypoxia; In complete remission; Individual; Knowledge; Lead; Leukemic Cell; Link; Lipids; Lyase; Malignant Neoplasms; Measurement; Measures; Medical; Metabolism; Microfluidics; Modeling; Molecular; Monitor; Multi-Drug Resistance; Mutation; Neoadjuvant Therapy; Oncologist; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phosphoric Monoester Hydrolases; Play; Population; Procedures; Production; Proteins; Recording of previous events; Recurrent disease; Refractory Disease; Regimen; Relapse; Reporter; Research; Risk Assessment; Role; Sampling; Scientist; Signal Pathway; Signal Transduction; Specimen; Sphingolipids; Sphingomyelinase; Sphingomyelins; Sphingosine; Stem cell transplant; Survival Rate; System; Techniques; Testing; Therapeutic; Therapeutic Agents; Treatment Efficacy; Up-Regulation; Work; acute myeloid leukemia cell; arm; biological heterogeneity; cancer cell; ceramide 1-phosphate; ceramide kinase; chemotherapy; desaturase; design; dihydroceramide; dihydroceramide desaturase; drug efficacy; genomic signature; glycosylation; improved; individual patient; innovation; inorganic phosphate; insight; instrumentation; kinase inhibitor; leukemia; microdevice; molecular marker; mortality; multidisciplinary; neoplastic cell; new technology; non-genetic; novel; outcome forecast; overexpression; precision medicine; prognostic; response; sphingosine 1-phosphate; sphingosine kinase; targeted treatment; technology development; treatment optimization; treatment response; tumor

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鞘脂途径的活性在单细胞从