Zhang Laboratory

Specific Research Directions:

1. Early Oncogenesis and Immunoprevention: We investigate the genomic and immunological events that drive the initiation and progression of lung precancers. By characterizing interactions between evolving precancerous cells and the host immune response, we aim to identify mechanisms of cancer progression, biomarkers for risk stratification and actionable vulnerabilities for cancer interception. Our research has led to clinical trials evaluating immune- and inflammation-targeted approaches, including IMPRINT-Lung, Can-Prevent-Lung and the planned Isu-Prevent-Lung trial.
2. Intratumor Heterogeneity (ITH) and Therapeutic Resistance: We investigate intratumor heterogeneity at the genomic, epigenetic, transcriptomic and immunological levels and its impact on tumor evolution, treatment response and clinical outcomes. Using bulk and single-cell sequencing, spatial profiling and integrative computational approaches, we study how heterogeneous tumor ecosystems evolve and contribute to therapeutic resistance, with the goal of identifying mechanisms and predictive biomarkers that can guide more effective treatment strategies.
3. Immune Evasion and Immunotherapy Response: We investigate how tumor cells evade immune surveillance and suppress anti-tumor immunity. By integrating genomic, transcriptomic, single-cell, spatial and immune profiling with clinical data, we characterize interactions between tumor cells and the immune microenvironment and identify mechanisms and biomarkers associated with response and resistance to immunotherapy. We also apply computational approaches, including machine learning, to uncover clinically relevant patterns that may inform therapeutic strategies.