Core C – Immunophenotyping Core

核心 C → 免疫表型核心

• 批准号: 10634592
• 负责人: Martin John Romeo
• 金额: $ 19.81万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634592
• 关键词: Adipose tissue; Advanced Malignant Neoplasm; Affect; Animal Model; Architecture; Biological Assay; Body Weight decreased; Cachexia; Cancer Patient; Catabolism; Cell Survival; Cells; Data; Data Analyses; Diagnosis; Disease; Fatigue; Fatty acid glycerol esters; Gene Expression; Genomics; Goals; Histology; Image; Imaging Techniques; Immune; Immunofluorescence Immunologic; Immunophenotyping; Incidence; Indiana; Inflammatory; Interleukin-6; Libraries; Malignant neoplasm of pancreas; Medical; Molecular; Morbidity - disease rate; Mus; Muscle; Muscular Atrophy; Nature; Pancreatic Ductal Adenocarcinoma; Pathway Analysis; Pathway interactions; Patients; Population; Prognosis; Program Research Project Grants; Quality of life; Research; Research Project Grants; Role; STAT3 gene; Sampling; Signal Transduction; Skeletal Muscle; South Carolina; Syndrome; Techniques; Technology; Time; Tissues; Tumor Tissue; Universities; Wasting Syndrome; Weight; cancer cachexia; cell type; cytokine; deep learning; fat wasting; genetic manipulation; histological studies; immune imaging; improved; learning strategy; machine learning algorithm; mortality; mouse model; multiplexed imaging; next generation; novel therapeutics; pancreas development; pancreatic ductal adenocarcinoma model; programs; recruit; single cell sequencing; single-cell RNA sequencing; skeletal tissue; spectrograph; transcription factor; transcriptome sequencing; tumor; tumor microenvironment; tumor progression; user-friendly; wasting

SUMMARY: CORE C Cachexia is a wasting syndrome that significantly contributes to the morbidity and mortality of cancer patients, especially those diagnosed with pancreatic ductal adenocarcinoma (PDAC). The overarching hypothesis of this P01 project is that the NF-κB/IL-6/STAT3 signaling axis acts as a central regulator of the macroenvironment in PDAC-induced cachexia, encompassing tumor, skeletal muscle and adipose tissues. Three projects in this P01 focus on specific components of this signaling axis integrating on the use of mouse models and patient samples. The role of the Immunophenotyping Core will be to support molecular and histological studies in the projects requiring next generation single cell sequencing (scRNA-seq) and multispectral imaging. In addition, the Immunophenotyping Core will use deep learning methods to perform the quantitation of multiplex images of immune cells to assess the function of the NF-κB/IL-6/STAT3 signaling axis in the progression of PDAC and wasting of muscle and adipose tissues in cachexia. The two specific aims of the Immunophenotyping core is to 1) Utilize multiplex immunofluorescence panels and multispectral imaging to evaluate how the NF-κB/STAT3/IL- 6 signaling axis regulates the immune architecture contributing to PDAC tumor progression and muscle and adipose wasting; and 2) Perform single-cell RNA-sequencing (scRNA-seq) to reveal functional pathways regulated by the NF-κB/STAT3/IL-6 signaling axis in the macroenvironment of murine models of PDAC-induced cachexia.

摘要：核心 C 恶病质是一种消耗综合征，显着增加癌症患者的发病率和死亡率， 尤其是那些被诊断患有胰腺导管腺癌（PDAC）的人。 P01项目认为NF-κB/IL-6/STAT3信号轴作为宏观环境的中央调节器 PDAC 引起的恶病质，包括肿瘤、骨骼肌和脂肪组织。P01 中的三个项目。 重点关注该信号轴的特定组成部分，整合小鼠模型和患者样本的使用。 免疫表型核心的作用将是支持项目中的分子和组织学研究 需要下一代单细胞测序 (scRNA-seq) 和多光谱成像。 免疫表型核心将使用深度学习方法对多重图像进行定量 免疫细胞评估 NF-κB/IL-6/STAT3 信号轴在 PDAC 进展中的功能 恶病质中肌肉和脂肪组织的消耗 免疫表型分析核心的两个具体目标是 1) 利用多重免疫荧光板和多光谱成像来评估 NF-κB/STAT3/IL- 6 信号轴调节免疫结构，促进 PDAC 肿瘤进展和肌肉和 脂肪消耗；2) 进行单细胞 RNA 测序 (scRNA-seq) 以揭示功能途径 PDAC诱导的小鼠模型大环境中NF-κB/STAT3/IL-6信号轴的调节 恶病质。