Defining a novel subset of metastasis-associated monocytes

定义转移相关单核细胞的新子集

• 批准号: 10751562
• 负责人: Daphne A Superville
• 金额: $ 4.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-03 至 2025-08-02
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751562
• 关键词: Academia; Anoikis; Biology; Body part; Breast cancer metastasis; Cell Separation; Cell Survival; Cells; Cessation of life; Communication; Communities; Coupled; Data; Data Analyses; Dendritic Cells; Disease; Disseminated Malignant Neoplasm; Distant; Education; Educational process of instructing; Extracellular Matrix; Fibronectins; Future; Gene Expression Profile; Gene Expression Profiling; Gene set enrichment analysis; Genes; Heterogeneity; Human; Immune; Immune response; Institution; Knowledge; Lung; Macrophage; Malignant Neoplasms; Measures; Mediator; Medical center; Mentors; Mentorship; Metabolic; Metabolism; Modeling; Mus; Myelogenous; Myeloid Cells; Neoplasm Metastasis; Oncologist; Organ; Oxidative Phosphorylation; Patient-derived xenograft models of breast cancer; Patients; Pattern; Phenotype; Play; Population; Population Heterogeneity; Process; Publishing; Research; Research Personnel; Research Training; Resistance; Role; Science; Shapes; Site; Structure of parenchyma of lung; Students; Testing; Therapeutic; Tissue-Specific Gene Expression; Tissues; Training; Transcript; Up-Regulation; Work; Workplace; advanced disease; career; cell type; cytokine; design; experience; immune cell infiltrate; lung metastatic; monocyte; neoplastic cell; neutrophil; new therapeutic target; novel; novel therapeutics; overexpression; patient derived xenograft model; preservation; programs; protein complex; protein expression; recruit; single-cell RNA sequencing; skills; targeted treatment; transcriptomics; tumor; tumor immunology; tumor progression; tumor-immune system interactions

Project Summary/Abstract Metastasis is a feature of advanced disease whereby tumor cells spread to distant parts of the body, and is responsible for the vast majority of cancer-related deaths. Unfortunately, targeted therapies often aren’t effective in controlling metastatic disease, as tumors cells have been observed to employ a variety of mechanisms to metastasize. Therefore, many have begun to look to the surrounding microenvironment as a potential therapeutic avenue. Previous studies investigating the tumor immune microenvironment have identified monocytes as important mediators of metastatic progression. However, recent single cell transcriptomic studies have demonstrated that monocytes are a heterogeneous population of cells, and the role of specific subsets of monocytes in metastasis remains poorly understood. Preliminary work from the Goga lab has identified a novel subset of metastasis-associated monocytes with a discrete metabolic and phenotypic transcriptional profile. This proposal seeks to investigate the impact of metabolism on metastasis- associated monocytes and interrogate their role in the lung metastatic niche. We believe that a better understanding of the vulnerabilities of different subsets of immune cells will lead to new therapeutic targets for metastatic cancer. The proposed research training will take place at UCSF, a top-tier research institution and medical center at the cutting edge of cancer immunology research. The Biomedical Sciences program at UCSF provides a rigorous education in translational biology and science communication which prepares students to become future leaders in their fields. Under the mentorship of Dr. Andrei Goga, a practicing oncologist and expert in breast cancer metastasis, I am well poised to carry out the proposed research which will leave me with a broad experimental and computational skillset. Additionally, the training plan we have developed for the remainder of my thesis work places a strong emphasis on developing my teaching and mentoring skills, as well as my communication skills through various opportunities to present my work to the scientific community. This training, coupled with the experience I will gain in carrying out the proposed research, will leave me equipped for a future career in academia studying cancer metastasis as an independent investigator.

项目摘要/摘要 转移是晚期疾病的一个特征，肿瘤细胞扩散到人体的遥远部分， 并负责绝大多数与癌症有关的死亡。不幸的是，有针对性的疗法通常不是 有效控制转移性疾病，因为已经观察到肿瘤细胞采用多种 转移的机制。因此，许多人开始将周围的微环境视为 潜在的治疗大道。先前研究肿瘤免疫微环境的研究已经 确定单核细胞是转移性进展的重要介质。但是，最近的单细胞 转录组学研究表明，单核细胞是细胞的异质群，并且是 单核细胞在转移中的特定子集的作用仍然很少了解。初步工作 Goga Lab已确定了与转移相关的单核细胞的新型子集，具有离散的代谢和 表型转录轮廓。该提案旨在调查代谢对转移的影响 相关的单核细胞并询问其在肺转移性小众中的作用。我们相信更好 了解不同子集的免疫细胞的脆弱性将导致新的治疗靶点 转移性癌。 拟议的研究培训将在UCSF（一家顶级研究机构和医疗机构）举行 中心位于癌症免疫学研究的最前沿。 UCSF的生物医学科学计划 在翻译生物学和科学传播方面提供了严格的教育，这使学生准备 成为他们领域的未来领导者。在肿瘤学家安德烈·戈加（Andrei Goga）博士的指导下， 乳腺癌转移的专家，我很毒，可以进行拟议的研究，这会让我 具有广泛的实验和计算技能。此外，我们为 我的论文工作的其余部分也非常重视发展我的教学和心理技能 作为我通过各种机会的沟通技巧，将我的作品展示给科学界。这 培训，再加上我将获得拟议研究的经验，这将使我等同于 对于学术界的未来职业，研究癌症转移作为独立研究者。