Defining a novel subset of metastasis-associated monocytes

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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.