Our laboratory’s major goals are to understand the tumor-microenvironment interactions that control cancer cell migration, dormancy, and therapy resistance. This includes identifying and dissecting key molecular cross-talk between tumors cells and the vasculature, stroma, and immune microenvironment. A unique aspect to our research program is the use of cutting-edge intravital confocal and multiphoton microscopy in mouse models of acute leukemia and metastatic breast cancer. This powerful approach allows us to track tumor cell movement, co-localization with specific cells and molecules, and response to therapies in real time, at video rate. Our research is highly clinically relevant. Findings from our laboratory have been translated from the bench to the clinic through investigator-initiated clinical trials in breast cancer and acute leukemia studying agents that modulate the tumor immune response and bone marrow and CNS metastasis.
Prior research by our group has led to many novel discoveries. Our work was the first to identify specialized E-selectin+/SDF-1+ blood vessels in the bone marrow that regulate stem, leukemia, and breast cancer (BC) cell trafficking from the bloodstream and contribute to tumor cell dormancy (Nature 2005, Science Translational Medicine 2016). Our work has also demonstrated how changes in the microenvironment caused by cancer allow malignant cells to evade chemotherapy and out-compete normal stem cells for survival (Science 2008). Recent work from our laboratory has described a new and unexpected mechanism of cell trafficking and cancer cell metastasis to the CNS (Nature 2018). We found that acute lymphoblastic leukemia (ALL) cells in circulation are unable to breach the blood brain barrier, but instead migrate into the CNS along vessels that passage directly between vertebral or calvarial BM and the meninges. Further, we showed that pharmacologic (PI3K) inhibition of a6 integrin receptor – laminin basement membrane matrix interactions prevented CNS metastasis in ALL mouse models. Members of our lab team have developed an investigator-initiated trial of the PI3K inhibitor copanlisib in relapsed/refractory B cell ALL that is translating this finding into the clinic.
Ongoing research is seeking to extend our understanding of the critical tumor-stromal and immune microenvironment interactions that control the fate of cancer metastases. Undergraduates, graduate student, medical students, residents, postdoctoral and clinical fellows who are excited about the biologic and clinical questions investigated by our laboratory are invited to join our group!
