1. Understanding oncogenic metabolic pathways in glioma stem cells (GSC) and their role in glioma progression and response to treatment. My laboratory has identified significant differences in protein processing and degradation in GSC, which led to impaired metabolic pathways and altered apoptotic mechanisms. Notable results include discovering decreased proteasome expression in GSC, the first description of increased expression of oncogenic ubiquitin ligases (TRIM11) in GSC, and increased GSC sensitivity to hsp90 mediated protein folding and degradation pathways. We have recently identified that the mitochondrial protein LONP1 plays an essential role in glioma resistance to hypoxia, nutrient deprivation, and commonly used chemotherapeutic treatments, and are developing therapeutic agents to modulate LonP1 activity.
2. Researching the neurobiological mechanisms underlying the profound problem of cognitive dysfunction in cancer survivors treated with chemotherapy. Research in cognition and cancer has shown that many patients are developing severe memory and attention problems after receiving chemotherapy. We first showed that chemotherapeutic drugs such as cisplatin severely damage neural stem cells. Our following articles demonstrated chemotherapy’s ability to induce synaptic damage in cultured hippocampal neurons and the rat hippocampus in adult rats, which can be prevented by treatment with the anti-oxidant N-Acetyl-Cysteine. The effects of cisplatin are age-dependent- with the pediatric-age animals being afflicted by global deficits. WE are currently working on further understanding the biological underpinning of neurological deficits induced by chemotherapeutic agents.