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 恶病质是一种浪费综合征，显着有助于癌症患者的发病率和死亡率， 特别是那些被诊断为胰腺导管腺癌（PDAC）的人。总体假设 p01项目是NF-κB/IL-6/STAT3信号轴充当大型环境中的中心调节器 PDAC诱导的缓存，包括肿瘤，骨骼肌和脂肪组织。该P01中的三个项目 专注于该信号轴的特定组件，该组件集成在小鼠模型和患者样品的使用上。 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。另外， 免疫表型核心将使用深度学习方法来执行多重图像的定量 免疫细胞评估NF-κB/IL-6/STAT3信号轴在PDAC和 浪费恶病质中的肌肉和脂肪组织。免疫表型核心的两个具体目标是 1）利用多重免疫荧光面板和多光谱成像来评估NF-κB/STAT3/IL-如何 6信号轴调节有助于PDAC肿瘤进展和肌肉的免疫结构， 脂肪浪费；和2）执行单细胞RNA-sequest（SCRNA-SEQ）以揭示功能途径 由NF-κB/STAT3/IL-6信号轴调节，在PDAC诱导的鼠模型的宏观环境中 卡希克西亚。