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Metabolic Liabilities in Lung Cancer 

The oncogene KRAS  and  tumor  suppressor STK11, encoding  the  kinase  LKB1, are frequently co-mutated (6-11%) in  non-small  cell lung  cancer (NSCLC), the leading cause of cancer death worldwide. Concomitant mutations of KRAS and LKB1 promote tumor progression and metastasis.
In a study published in Nature, we (from DeBerardinis lab at UTSW) disclosed an alteration of nitrogen metabolism in KRAS/LKB1 co-mutant cancer cells and human tumors. In these co-mutants, the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) enables an unconventional pathway in which nitrogen is trafficked from ammonia in the mitochondria to pyrimidines in the cytosol.  We will further investigate underlying mechanism of CPS1 dependence and nitrogen trafficking/transport.

Research Projects: Welcome

Discovery of New Metabolic Pathways Altered in KRAS/LKB1 co-mutant NSCLC.

We are seeking to uncover additional vulnerabilities related to nitrogen metabolism by a comprehensive analysis of metabolite levels in tumor/or cancer cells with mutations in one or both genes.  Additionally, with a combination of unbiased CRISPR screening, metabolomics methods and in vivo nutrient infusion, we plan to identify and understand key genes/metabolic pathways involved in tumor aggressiveness in KRAS/LKB1 co-mutant NSCLC.

Research Projects: Welcome

Discovering and Understanding Metabolic Vulnerabilities in Bladder Cancer.

The long-term goal of our lab is to broaden our research to examine and identify altered metabolic pathways, specifically nitrogen metabolism, in various types of cancer where mutation profiling, biomarker discovery, or targeted therapy has not been thoroughly explored, including bladder cancer. By integrating metabolomics analysis of human bladder tumors with gene expression data, we will reveal what metabolic pathway(s) are perturbed in different disease stages and investigate whether these changes impose liabilities that could be exploited therapeutically.

Research Projects: Welcome
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