My research is focused on understanding the mechanisms of the pre-metastatic cascade in colorectal cancer and developing novel therapeutics.

My research is focused on understanding the mechanisms of the pre-metastatic cascade in colorectal cancer and developing novel therapeutics. During my graduate studies, I extensively worked on the genomic characterization of mutational signatures and neoantigen discovery using next-generation sequencing in cancer (Genome Medicine 2014;6(2):18, Nucleic Acids Res 2015;43(5), Ann Oncol 2018;29(4):1030-1036). I first identified the leukopenia susceptibility locus in the Asian population (Gut 2017;66(11):1926-1935) and a novel BRAF gene fusion in mucosal melanoma patients (Oncogene 2017;36(23):3334-3345). Beyond oncogenic activation from tumor-derived mutations, transformed cancer cells shape the tumor microenvironment and distant organs, preparing for future metastasis through pre-metastatic niches, mediated by extracellular vesicles and particles (EVPs) released by cancer and immune cells (Cancer Cell 2016;30(6):836-848). In my post-graduate studies, I investigated the role of EVPs in pre-metastatic niche formation and cancer metastasis. I characterized new protein biomarkers in EVPs that could be used to discriminate these particles from others isolated from tissue and blood samples, which could aid in the development of diagnostic panels for early malignancy detection (Cell 2020;182(4):1044-1061). EVPs associated with cancer also provide valuable drug development targets. Interestingly, tumor-secreted DNA can trigger an immune response that inhibits metastatic spread to the liver (Nature Cancer 2024 Dec;5(12):1815-1833). The next phase of my research focuses on pre-metastatic analysis in the clinical setting to prevent distant metastasis before micrometastasis. By analyzing the pre-metastatic liver at the time of primary treatment, when no distant metastasis is present, we can target key molecules and prevent future metastasis. As a medical oncologist, I participate in clinical trials developing novel anti-EGFR therapeutics, such as dacomitinib (Clinical Cancer Research 2015;21(3):544-52) and amivantamab (OrigAMI-1 study; Journal of Clinical Oncology Volume 42, Number 3_suppl, January 2024). Using genomic screening, we identified a novel KRAS mutation associated with resistance to the KRAS G12D inhibitor (Cancer Letters 2024; 591:216904).