ZIA BC 011695 (ZIA) | |||
---|---|---|---|
Title | Understand metabolic reprogramming in IDH1 mutant glioma | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Yang, Chun Zhang | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $293,947 | Project Dates | 00/00/0000 - 00/00/0000 |
Fiscal Year | 2016 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) |
Brain (100.0%) Nervous System (100.0%) |
||
Research Type | |||
Cancer Initiation: Oncogenes & Tumor Suppressor Genes Endogenous Factors in the Origin and Cause of Cancer |
|||
Abstract | |||
1. Bioinformatics finding for metabolic detour in Kreb cycle in IDH1 mutant gliomas. We performed survival analysis on the RNA sequencing data in TCGA database. Based on the investigation on the overall survival in 530 patients, we identified glutamine metabolic pathway is critically important for the survival of patients with IDH1 mutant glioma. The expression level of key enzymes in glutamine utilization pathway determines the outcome of patient. Patients with stronger glutamine-associated enzymes exhibit longer survival, suggesting a key role in glutamine metabolic pathway in IDH mutant glioma. 2. Establishment of metabolic defect cell lines. To better understand the metabolic changes in IDH mutant cells, we took advantage of our existed IDH1 mutant cell lines, and established knock out cell lines based on IDH1 mutation genetic background. We established and validated CRISPR/Cas9 targeting glutamine metabolic pathway, produced lentivirus particles, and achieved isogenic cell lines with genetic defects in glutamine metabolism. Cell lines are under validation through sequencing and protein expression analysis. 3. 13C-coupled metabolic flux study in metabolic defect cells. To investigate the metabolic detour in IDH1 mutant cells, we performed stable isotope conjugated metabolite labeling in metabolic defect cells, which involved 13C-coupled glucose, glutamine, glutamate, palmitate, or alanine. Cells were labeled and metabolites were sent to mass spectrum analysis on whole metabolomic analysis. |