Life Sciences & Biotechnology
Title : | Influence of uneven vascularization on intratumoral heterogeneity and cell plasticity in glioblastoma |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Saran Kumar, Indian Institute Of Technology (IIT) Delhi |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | ksaran@iitd.ac.in |
Equipments : | "Deep Freezer (-20 C)
Ultra Low Temperature Freezer (-80C)
Electrophoresis Apparatus (DNA and Protein)
Fluorescent Microscope
Gradient PCR" |
Details
Executive Summary : | This project aims to determine the key epigenetic regulators that govern non-genetic intra-tumoral heterogeneity (ITH) in human glioblastoma multiforme (GBM) due to uneven tumor blood vessels (TBVs). The research aims to explore the regulatory factors critical for cancer stem cells (CSCs) and how inhibiting these factors/pathways will affect their response to therapy. The hypotheses are that tumor metabolic zonation due to unequal distribution of TBVs is a critical driver of non-genetic ITH, impacting tumor aggressiveness and therapy response. The specific objectives of the project include identifying epigenetic dysregulation in GBM sub-compartments that shapes ITH resulting from imbalanced vasculature, gaining insights into how position-dependent spatial zonation affects tumor-stromal crosstalk, and isolating and characterizing CSCs in different metabolic niches based on their functional properties. The experimental plan will use a newly developed methodology (Perfusion-based Fluorescent Dye Labeling of Cells) for retrospective sorting of fully functional tumor cells from intracranially-inoculated human GBM tumors based on their distance from BVs. The candidate gene approach will be employed to validate specific genes and genetic loci important for ITH. Spatial distribution patterns of key components will be validated through in situ analyses of both xenografts and human tumor tissue samples. The results of this project will yield exciting and unexplored insights on how TBVs shape ITH in GBM, paving the way for the design of effective combinatorial therapies to overcome ITH. |
Total Budget (INR): | 30,36,000 |
Organizations involved