Myeloid cells belong to the innate immune system and include monocytes, macrophages, neutrophils and dendritic cells, among others. These cells can modulate key cancer-related activities and affect virtually all types of cancer treatment; however, we have a limited understanding of the complexity and functions of these cells and how they might best be exploited therapeutically to fight cancer. In this program, we are comprehensively mapping myeloid (and other) cells in tumors of patients and experimental models. Once the myeloid cell states are discovered, we exploit the information obtained to generate hypotheses about the functions of these states and to guide the design of functional studies to test these hypotheses. In doing so, we are able to distinguish between cells that do and do not promote tumor growth, and to discover molecular pathways and myeloid cell states that could be exploited for therapeutic purposes.

What happens after an anticancer drug is administered? Where does it go? How does it work? Why does it sometimes fail to control cancer? In this program, we seek to answer these questions by combining two complementary tools: i) single-cell "omics", which provide high-dimensional information about the cells under study and how they are perturbed by drugs, and ii) intravital imaging, which we exploit to discover drug actions in real time and in the geographic context of the tissue being analyzed. This allows us to define where the drug accumulates (drug biodistribution), on which cells it binds (drug pharmacokinetics, PK), and how these cells and their neighbors respond to treatment (drug pharmacodynamics, PD). Through this approach, we can discover how the body and its constituent cells functionally respond to drugs, what mechanisms define treatment success or failure, and how to modify a treatment to make it more effective.