cell biology and immunology with an emphasis on extracellular vesicles/exosomes, immunotherapy, and biomarkers.
Colorado Anschutz Medical Campus, Department of Neurosurgery
One year of college with an emphasis in the biological sciences
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.
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.
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.
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.