Our lab is interested in how microenvironmental factors drive metastasis. The pre-metastatic niche was identified based on the observation that tumor-secreted factors create a metastasis-conducive microenvironment at distant sites that promotes the growth and survival of disseminated tumor cells. Our work is focused on understanding the immunological changes that occur in the pre-metastatic niche and identify targets for therapeutic intervention. Our group identified that there is an expansion of hematopoietic stem and progenitor cells in the bone marrow that home to pre-metastatic sites, such as the lung, prior to evidence of metastatic lesions. These bone marrow-derived cells differentiate into suppressive myeloid cells and limit T cell responses. We comprehensively characterized the immune population dynamics in the pre-metastatic niche and identified a core program of myeloid-mediated immune suppression. To take advantage of the large infiltration of myeloid cells into tumor and metastatic sites, we developed the genetically engineered myeloid (GEMy) cell technology to deliver therapeutic factors to reprogram the microenvironment and restore antitumor immunity. Further, we are leading multi-institutional collaborative efforts to investigate the role of myeloid-mediated immune suppression in limiting CAR T cell therapy in solid tumor patients and investigating key functional genes in human monocytes to identify therapeutic interventions. The ultimate goal of our lab is to translate our pre-clinical work from the bench to the bedside to prevent and treat metastasis in advanced solid tumor patients.