I have a broad background in cancer biology and neuroscience with specific training and expertise in i) characterization of the cellular kinome and cytoskeleton involved in GABA and Glutamate receptor regulation in normal and pathological conditions; ii) identification of cell-signaling pathways involved in centrosome abnormalities and genomic instabilities in the early stages of glioma development; iii) establishment of the drug discovery axis of post-translational modifications of the mRNA binding protein HuR, whose up-regulation and multimerization are essential for brain tumor progression, iv) delineation of mechanisms of HuR protein multimerization and oncogenic function in glioma; v) establishment of the drug discovery axis of post-translational modifications of the PDL1 ligand. In the past 10 years, I have been deeply engaged in the drug-discovery effort (to include the development of high throughput alpha screen assay, high throughput cell-based bioluminescence reporter assays, target-structure based drug design, high throughput compound screening, identification of lead compounds and lead compound scaffolds, and SAR optimization). As a result of our drug-discovery effort in collaboration with the SRI, a new class of inhibitors of HuR dimerization in cancer cells was developed (the U.S. Provisional Patent Application No. 63/013,451). Identification of the key signaling pathways involved in genomic instabilities, glioma heterogeneity, and immune escape is the goal of my current research. The main outcome of my research is the development of a new chemotherapeutic scheme engaged with the adaptive arm of the immune response for glioma treatment and elimination of cell-signaling pathways leading to glioma heterogeneity. I propose to investigate one of the main causes of glioma heterogeneity and treatment resistance, intercellular gene transfer between glioma and normal host cells in glioma microenvironment, and the potential chemotherapeutic pathways of the intervention of this process.
