Research Projects

Problem statement- Glioblastoma (GBM) is grade IV gliomas. Despite extensive research and advancements in therapy, 90% GBM patients experience tumor-recurrence and treatment resistance, with survival rate of 1 year in most-cases, & 5% patient survive upto 5-years. Presence of blood-brain-barrier, vast heterogeneity, & immunosuppressive tumor microenvironment (TME) allowing tumor cells to escape immune evasion & survive by acquiring resistance to standard treatment. Moreover, conventional 2D/preclinical models are restricted by lack of TME, low throughput & absence of immune microenvironment to interrogate treatment responses/therapy resistance in GBM. Besides, they inadequately replicate the invasion journey because of lack of brain-matrix environments, variable immune response & genetic-drift significantly impacting development of precision-therapy. Rationale of the proposed study: This study stems from the critical need to better understand & target the intricate-mechanisms driving GBM progression & resistance to the treatment. Additionally the tumor's interaction with extracellular matrix (ECM) & immune-cells further complicates treatment responses & promotes invasion into surrounding healthy brain. ECM-remodeling & its replacement with de-novo matrix is ultimately linked to cell infiltration/invasiveness, therefore it is crucial to understand them carefully. Thus, there is an unmet need to study the role of heterotypic crosstalk among different cells & their effect on ECM-remodeling that could be potential markers to overcome therapy-resistance for early clinical intervention. Hypothesis-We hypothesized to develop an advanced 3D-organoid model build-upon patient-derived tumor and a brain-mimetic ECM established by our research team to capture the complexity of GBM including heterotypic, bidirectional-interactions between tumor-immune cells, and matrix components. Furthermore to understand the role of ECM remodeling & cell-ECM interaction we will perform multi-omics analysis for identification of key biomarkers driving GBM progression & devising effective therapeutic strategies. Our aim is to overcome therapy-resistance for early therapeutic intervention. Our approach leverages DNA-nanotechnology utilizing DNA-nanotubes with multi-omics matched delivery system that can intelligently target specific pathways involved in treatment resistance & overcoming BBB, and immunosuppressive TME in GBM. 3D-organoid model combined with multi-omics guided targeted-nanotechnology we can recapitulate patient-specific TME to monitor/study nanotherapy progress in a contextually accurate manner enhancing predictability of patient responses.Significance of the proposed study:Innovation of novel DNA-nanoformulation based-on multi-omics integrated 3D-organoid platform to overcome tumor progression/therapy resistance 3D-organoid integrated multi-omics nanoplatform for being informative in tailoring/prioritizing therapeutic options in the era of precision-medicine