Defining a novel subset of metastasis-associated monocytes

定义转移相关单核细胞的新子集

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/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部位，不幸的是，靶向治疗往往不是造成绝大多数癌症相关死亡的原因。有效控制转移性疾病，因为已观察到肿瘤细胞采用多种因此，许多人开始将周围的微环境视为一种转移机制。先前研究肿瘤免疫微环境的研究已经发现了潜在的治疗途径。确定单核细胞是转移进展的重要介质，然而，最近的单细胞研究。转录组学研究表明，单核细胞是异质细胞群，并且单核细胞特定亚群在转移中的作用仍知之甚少。 Goga 实验室发现了一种与转移相关的单核细胞的新子集，具有离散的代谢和该提案旨在研究代谢对转移的影响。我们认为，相关的单核细胞并探讨它们在肺转移生态位中的作用更好。了解不同免疫细胞亚群的脆弱性将带来新的治疗靶点转移性癌症。拟议的研究培训将在加州大学旧金山分校（UCSF）进行，加州大学旧金山分校是一家顶级研究机构和医疗机构加州大学旧金山分校生物医学科学项目的前沿癌症免疫学研究中心。提供严格的转化生物学和科学传播教育，帮助学生做好准备在执业肿瘤学家 Andrei Goga 博士的指导下成为各自领域的未来领导者作为乳腺癌转移方面的专家，我已做好准备进行拟议的研究，这将使我具有广泛的实验和计算技能。我的论文工作的其余部分也非常重视发展我的教学和指导技能作为我通过各种机会向科学界展示我的工作的沟通技巧。培训，加上我在开展拟议研究中获得的经验，将使我做好准备未来在学术界作为独立研究者研究癌症转移。