Glioblastoma is the most common primary brain tumor and is fatal despite maximal therapy. Glioma stem cells (GSCs) are a subpopulation of cells that contribute to tumor progression. Glioma stem cells have a high capacity for self-renewal, survival under hypoxic conditions, resistance to radiation, and high invasive potential. Our lab is focused on understanding mechanisms underlying these key GSC tumorigenic properties with a long-term goal of uncovering potential therapeutic targets.
We have 3 major areas of focus:
GSC co-option of core developmental pathways
We have identified that GSCs preferentially re-activate the Semaphorin-Neuropilin-Plexin axonal guidance program. GSCs secrete Sema3C and engage PlexinA2/PlexinD1 receptors to regulate GSC survival and invasion. We are focused on understanding the mechanisms by which Sema3C contributes to tumor progression.
GSC survival under hypoxic conditions through HIF-mediated pathways
We aim to understand the repertoire of HIF1-target genes that contribute to GSC survival and expansion.
GSC resistance to radiation due to upregulation of pro-survival signaling and enhanced DNA damage repair capacity
We are interested in improving the radiosensitivity of GSCs with thermal therapy, modifications in radiation delivery and radiosensitizing drugs. Our goal is to expedite the translation of experimental therapeutics to clinical trials.