Brain tumor cell biology and immunology with an emphasis on extracellular vesicles/exosomes, immunotherapy, and biomarkers.
University of Colorado Anschutz Medical Campus, Department of Neurosurgery
To determine the causes and effects of brain tumor extracellular vesicle release in response to cell stress (the Unfolded Protein Response); to potentially use that information to identify biomarkers in patient body fluids.
Brain tumors such as high grade gliomas are among the worst tumor types to treat, and patient prognosis is abysmal (survival is generally 14 months from diagnosis). Brain tumors prove very resistant to our current treatments, and the abilities of individual cells to migrate into other regions of the brain are major reasons for recurrence and eventual death. We were one of the first groups to identify and study extracellularly released vesicles (exosomes, “fat balls”) in brain tumors. We also have a long-standing interest in the effects of cellular stress on brain tumors.
Brain tumor cells employ a stress response (the Unfolded Protein Response, UPR) that leads to the release of exosomes from the cells. These exosomes can passage the stress response to neighboring unstressed cells, which results in increased protection from other insults such as chemotherapy. Cells receiving exosomes also experience changes in metabolism that correlate with therapeutic resistance, and exosomes are potent attractants for migrating tumor cells. Thus, exosomes are involved in the very processes that make brain tumors so dangerous. We are biochemically and genetically characterizing these exosomes and determining their broad effects on cells. We are now examining the cellular signaling pathways in recipient cells induced by exosomes, and are also looking at the mechanisms of immune suppression driven by tumor-derived exosomes.
The students will take part in experiments that flesh out the roles played by exosomes in tumor progression and resistance to therapies. They may also be involved in the search for biomarkers present in these extracellular vesicles as found in patient serum, cerebrospinal fluid, and urine. From this we hope to improve our understanding of how exosomes make tumors more difficult to treat, and we hope that the students learn both basic and novel concepts in tumor biology, cell biology, and biochemistry.