Leukemic Cell Homing and Engraftment in the Bone Marrow

The goal of this project is to understand the mechanisms leukemic cells use to survive and proliferate in the bone marrow and other organs. Once leukemia cells enter metastatic tissue, whether they die, proliferate, or lay dormant is in large part determined by signals within the local microenvironment. A precise understanding of these molecular cues would provide new targets for leukemia eradication and/or allow manipulation of leukemia cells in a manner that sensitizes resistant disease to currently used chemotherapies. Our ultimate goal is to inhibit these interactions in a specific manner, so as to block leukemic cell growth and metastasis while preserving normal blood development. This work may yield new agents that synergize with current therapies yet have non-overlapping toxicity, allowing cure of previously untreatable patients.

Breast Cancer Metastases in the Bone Marrow

Distant metastases are the major cause of death from breast cancer. In many patients, metastatic relapse occurs in bone years after initial treatment, suggesting that disseminated breast cancer cells can have a prolonged dormant phase before becoming proliferate. Eradicating these dormant cells with conventional chemotherapy is challenging, as these agents are typically active only against dividing cells. Some evidence suggests that there are very specific microenvironments within the bone marrow that are capable of supporting these tumors cells. The goal of this project is to uncover novel interactions between disseminated tumor cells and the bone marrow microenvironment that regulate breast cancer metastasis dormancy. In particular, we seek to determine what specific cell types and cell signals in the bone marrow provide this environment. Our ultimate goal is to target these interactions to sensitize breast cancer cells to conventional chemotherapy and eradicate these cells from patient’s bone marrow before overt disease relapse can occur.