Researcher Directory

Academic Appointment

Associate Professor
Division of Medical Oncology
Department of Medicine
Robert Wood Johnson Medical School
Rutgers, The State University of New Jersey

Links

• Guo Laboratory Webpage
• Department of Molecular Biology and Biochemistry Profile
• Rutgers Ernest Mario School of Pharmacy

Research Interests

• Research in the Guo Lab focuses on cancer metabolism in KRAS-driven lung cancer. We employ genetically engineered mouse models (GEMMs), in vivo isotope tracing, state-of-the-art metabolomic and lipidomic analyses, and CRISPR screening to investigate metabolic alterations during KRAS-driven lung tumorigenesis. Our goal is to identify metabolic vulnerabilities that can be therapeutically targeted for the treatment of lung cancer.
• A major focus of our work is autophagy, a conserved cellular recycling pathway that captures and degrades intracellular proteins and organelles to sustain cellular metabolism under stress conditions such as nutrient deprivation. We previously demonstrated that both tumor-intrinsic and host autophagy are essential for supporting KRAS-driven non-small cell lung cancer (NSCLC) growth. Our current studies aim to further elucidate the mechanisms by which autophagy regulates tumor metabolism, tumor progression, and metastasis, and to translate these findings into novel therapeutic strategies for KRAS-driven NSCLC.
• We are also interested in understanding how tumor cells maintain nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis to support redox balance and anabolic metabolism. NADPH production and consumption are compartmentalized between the cytosol and mitochondria and are tightly regulated by multiple metabolic pathways and enzymes. However, the relative contributions and functional importance of cytosolic NADPH-generating pathways in cancer progression in vivo remain incompletely understood. Our research investigates how cytosolic NADPH metabolism supports KRAS-driven lung tumorigenesis and metastasis, with the goal of identifying novel metabolic vulnerabilities for therapeutic intervention.
• In addition, our laboratory studies one-carbon metabolism and methionine synthase (MTR), a key enzyme linking the folate and methionine cycles. Through CRISPR-based metabolic screening, we identified MTR as a critical metabolic dependency in KRAS-driven lung cancer. Our work demonstrates that MTR supports tumor growth by sustaining nucleotide biosynthesis and metabolic fitness, while MTR deficiency suppresses tumor progression and enhances anti-tumor immunity. Ongoing studies seek to define how MTR-mediated one-carbon metabolism regulates tumor metabolism, redox homeostasis, and immune responses within the tumor microenvironment, with the long-term goal of developing new therapeutic strategies targeting one-carbon metabolism in KRAS-driven NSCLC.