Defining a novel subset of metastasis-associated monocytes

项目总结/摘要 转移是晚期疾病的特征，其中肿瘤细胞扩散到身体的远处部分， 并导致绝大多数癌症相关死亡。不幸的是，靶向治疗往往不是 有效地控制转移性疾病，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 潜在的治疗途径以前研究肿瘤免疫微环境的研究 鉴定单核细胞为转移进展的重要介质。最近，单细胞 转录组学研究表明，单核细胞是一种异质性细胞群， 单核细胞的特定亚群在转移中的作用仍然知之甚少。前期工作， Goga实验室已经发现了一种新的转移相关单核细胞亚群， 表型转录谱。该提案旨在研究代谢对转移的影响- 相关的单核细胞，并询问其在肺转移小生境中的作用。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， 转移性癌症 拟议的研究培训将在UCSF进行，UCSF是一家顶级研究机构和医疗机构。 癌症免疫学研究的前沿中心。加州大学旧金山分校的生物医学项目 提供转化生物学和科学传播方面的严格教育，使学生能够 成为各自领域的未来领导者。在执业肿瘤学家Andrei Goga博士的指导下， 作为乳腺癌转移方面的专家，我准备好了进行这项拟议中的研究，这将使我 拥有广泛的实验和计算技能此外，我们还制定了针对 我的论文工作的其余部分重点放在发展我的教学和指导技能，以及 作为我的沟通技巧，通过各种机会向科学界介绍我的工作。这 训练，加上我将在进行拟议的研究中获得的经验，将使我有能力 作为一名独立的研究者，在学术界研究癌症转移。

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.