Program Faculty

Research in the Guo Lab focuses on cancer metabolism, utilizing advanced techniques such as isotope tracing, mass spectrometry, and genetically engineered mouse models (GEMMs). RAS-driven lung cancers are among the deadliest, and despite extensive efforts, direct targeting of RAS has remained a challenge. Since cancer cells exhibit distinct metabolic profiles compared to normal cells, targeting metabolism presents a promising therapeutic avenue. Dr. Guo’s research has shown that both cell-autonomous and host autophagy are essential for KRAS-driven lung tumor progression. The autophagy-mediated mechanism of tumor promotion involves recycling metabolites to maintain redox balance, energy homeostasis, and nucleotide pools, while also protecting tumors from T-cell-mediated destruction. Additionally, Dr. Guo’s work demonstrated that the autophagy inhibitor HCQ increases the sensitivity of LKB1-deficient KRAS-driven (KL) lung tumors to the MEK inhibitor Trametinib, indicating that autophagy inhibition could be a viable therapeutic strategy. Metastasis is a major cause of mortality in NSCLC patients, and Dr. Guo is also investigating the role of autophagy in NSCLC metastasis and its underlying mechanisms. Beyond autophagy, Dr. Guo is investigating other metabolic vulnerabilities in KRAS-driven NSCLC. Her research found that G6PD, the rate-limiting enzyme of the pentose phosphate pathway (PPP), promotes KL lung tumorigenesis but is not required for the growth of p53-deficient KRAS-driven (KP) lung tumors. This underscores the potential of targeting cytosolic NADPH production as a therapeutic strategy for lung cancers harboring KRAS and LKB1 co-mutations. Knowledge gained from Dr. Guo research program will increase our understanding of KRAS-driven lung cancer metabolism, which is critical for discovering new drug targets for lung cancer.

Publications

NCBI Bibliography