![]() ![]() Gliomas also exhibit high levels of heterogeneity, making them challenging to treat long-term. ![]() Wu’s research is focused on the clinical aspects of gliomas, which are rarely fully curable-whether or not they’re diagnosed as low- or high-grade tumors. As a consequence of this ATPĭisruption, the cells undergo apoptosis and necrosis.ĭr. Therefore, TG02 and TMZ downregulate the expression of HK2, PKM2, and LDHA proteins due to suppressed glycolysis and inhibited ATP generation (purple). TMZ induces DNA damage, effectively reducing the level of nicotinamide adenine dinucleotide (NAD+) through PARP activity, and thus suppresses glycolysis to reduce energy production in the cells (blue). On the other hand, TG02 also disrupts the mitochondrial respiration complexes and inhibits glycolysis, resulting in ATP depletion. Cytochrome c is released, inducing mitochondrial-mediated apoptosis in glioblastoma cells (red). TG02 decreases the phosphorylation of CDK9 and inhibits RNA Pol II-mediated transcriptional regulation of anti-apoptotic proteins, including Mcl-1 and Survivin (also known as BIRC5 gene). This schematic illustrates the synergism between the multi-kinase inhibitor TG02 and Temozolomide (TMZ). Her second goal is to test the efficacy of the multi-kinase inhibitor TG02 in clinical trials, in order to understand its effects on high-grade astrocytomas and IDH-mutant gliomas.Įxplore the NOB's Research Programs > Areas of Expertise First, she seeks to understand gliomas that exhibit an aggressive phenotype, in order to develop a diagnostic tool to monitor their transformation from low-grade to high-grade disease when they exhibit rapid growth. Her goal is to observe phenotypes and gaps in knowledge through her clinical practice, in order to address these questions in the laboratory and subsequently develop hypothesis-based clinical trials. Her clinical interests revolve around understanding challenges in neuro-oncology care, and developing laboratory and clinical research programs to understand glioma biology and investigate novel therapeutic approaches to improve patient clinical outcomes. Wu is a clinical neuro-oncologist who leads the Translational Research Program at the Neuro-Oncology Branch (NOB). Head, Translational Research Program RESEARCH SUMMARYĭr. ![]()
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