Vision

My research focuses on unraveling the cellular and molecular mechanisms underlying tissue-specific cancer risk, with a particular emphasis on colorectal cancer (CRC) and the developmental origins of the gut epithelium. By integrating lineage tracing, single-cell genomics, and multi-omics approaches, I aim to uncover fundamental principles of tumor evolution, tissue regeneration, and immune interactions that drive disease progression.

1. Clonal Dynamics & Tumor Progression: I have developed a molecular clock approach using CRISPR-based lineage tracing to record the timing of cellular events in vivo. This approach revealed clonal selection as a hallmark of precancer-to-cancer transition, showing how early-stage polyclonal tumors evolve into monoclonal malignancies. By dissecting these evolutionary dynamics, my research sheds light on how clonal selection shapes tumor progression and therapeutic resistance.

2. Regeneration & Developmental Origins of Cancer Susceptibility: My work uncovered a unique regenerative cell population in the mouse intestinal epithelium, providing critical insights into injury-induced regeneration and tissue homeostasis. Looking ahead, I aim to explore how developmental origins contribute to cancer susceptibility by comparing the functional and molecular differences between the colon and small intestine.

3. Bridging Tumor Genomics & Immune Microenvironment: To understand how tumor-immune interactions shape cancer evolution, my research will integrate immune profiling with tumor cell lineage trees at single-cell resolution. By identifying clonal bottlenecks in CRC progression, I aim to uncover new therapeutic vulnerabilities and mechanisms of immune evasion.

4. Future Directions & Impact:

(i) Develop a mouse model for in vivo inflammation recording to study how chronic inflammation influences tumor initiation and tissue regeneration.

(ii) Bridge the gap between genomic variations and phenotypic consequences by mapping genotype-phenotype relationships in CRC.

(iii) Leverage multi-omics technologies to develop early intervention strategies and precision medicine approaches for cancer and epithelial regenerative disorders like IBD.

By combining developmental biology, cancer genomics, and single-cell technologies, my research aims to uncover fundamental principles of tumor evolution and translate these insights into targeted therapeutic strategies that can improve patient outcomes.