Osteosarcoma is the most common pediatric/adolescent bone tumor and remains an unmet medical need as the therapeutic landscape and survival rates for these patients have remained unchanged in over three decades. While the genomic alterations that drive osteosarcoma have been well documented, studies regarding the molecular and cellular composition of the osteosarcoma microenvironment and the immunosuppressive mechanisms therein are scarce.  This lack of knowledge underlies the clinical observations that patients with advanced/metastatic osteosarcoma have largely demonstrated poor responses to immune checkpoint inhibition. It stands to reason that an increased comprehension of the osteosarcoma microenvironment (both immune and non-immune) will elucidate the mechanisms associated with the observed immunotherapeutic inefficacy and identify rational actionable therapeutic targets for subsequent clinical translation.

The overall objective of my laboratory is to thoroughly investigate the dynamic relationships between tumor cells and their tissue-specific microenvironments to identify and functionally validate actionable molecular and/or cellular targets for clinical translation.  Our primary focus is to reveal the tumor cell autonomous and non-cell autonomous mechanisms that promote immune evasion in metastatic osteosarcoma by using syngeneic murine models and clinically annotated patient specimens.  

Given the highly translational nature of the Pediatric Oncology Branch, we aim to use the data from these investigations as the rationale for further clinical investigations.