The research focuses on understanding how cancer spreads and how it develops its own blood supply. The work aims not only to understand these fundamental processes of cancer progression but also to develop novel therapies that target a tumor's ability to grow blood vessels and spread to distant sites. One of the research program's main aims is to detail the earliest microenvironmental events in the metastatic cascade and translate these findings into the clinical setting. This work led to the development of a novel paradigm demonstrating that even localized tumors have systemic effects to prepare distant tissue sites for metastases. This is based on our discoveries that bone marrow-derived cells are recruited to future sites of metastasis and establish a receptive microenvironment for incoming circulating tumor cells, termed the 'pre-metastatic niche'. We have determined that these specialized bone marrow-derived cells are present in the circulation as well as in metastatic tissue of patients with pediatric and adult cancers. These cells may serve not only as useful biomarkers for metastatic propensity, but also as fundamental mediators of the metastatic process and therefore a potential useful target for the prevention of metastatic spread. The role of these bone marrow-derived cells in tumor progression, neo-angiogenesis and promoting immune evasion, and the specific regulation of gene expression in the pre-metastatic niche are current areas of focus.

The laboratory is focused on translation of these preclinical findings into the development of clinical studies aimed at targeting the tumor microenvironment. Performing gene expression profiling of the cells in the tumor microenvironment in patient samples can support a personalized approach to treatment of how that tumor impacts its host. We are currently performing several correlational studies to determine the timing of mobilization of the bone marrow-derived cells, changes that occur with chemotherapy, radiation and surgery as well as differences in these cells in circulation and specific tissue sites. These studies will hopefully lay the ground work for design of targeted therapies to be administered at specific time points to thwart the critical interaction of a tumor and its microenvironment.