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，肿瘤细胞扩散到身体的远处， 并对绝大多数与癌症相关的死亡负有责任。不幸的是，靶向治疗通常不会 有效地控制转移疾病，因为已经观察到肿瘤细胞利用各种不同的 转移的机制。因此，许多人开始将周围的微环境视为 潜在的治疗途径。先前关于肿瘤免疫微环境的研究已经 发现单核细胞是转移进展的重要介质。然而，最近的单细胞 转录学研究表明，单核细胞是一种异质性的细胞群体，而 单核细胞的特定亚群在肿瘤转移中的作用尚不清楚。前期工作来自 GOGA实验室发现了一种新的与转移相关的单核细胞亚群，具有离散的代谢和 表型转录图谱。这项建议旨在研究代谢对转移的影响- 相关的单核细胞，并询问它们在肺转移生态位中的作用。我们相信，一个更好的 了解不同免疫细胞亚群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加州大学旧金山分校进行，这是一家顶级的研究机构和医疗机构 中心处于癌症免疫学研究的前沿。加州大学旧金山分校的生物医学科学项目 提供翻译生物学和科学交流方面的严格教育，使学生做好准备 成为各自领域的未来领导者。在安德烈·戈加博士的指导下，他是一名执业肿瘤学家， 作为乳腺癌转移方面的专家，我已经做好准备进行这项拟议的研究，这将留给我 具有广泛的实验和计算技能。此外，我们为员工制定的培训计划 我的论文工作的其余部分也非常强调发展我的教学和指导技能 作为我的沟通技巧，通过各种机会向科学界展示我的工作。这 培训，再加上我将在进行拟议的研究中获得的经验，将使我有能力 在未来的学术生涯中，以独立调查员的身份研究癌症转移。