Deciphering non-genetic mechanisms of response or resistance to treatment
My research is focused on identifying critical oncogenic pathways and drug resistance mechanisms using cancer driver modeling, single cell RNA sequencing and CRISPR screening.
1. Organoids are in vitro 3D cell clusters that recapitulate specific organ structure and are capable of multi-lineage differentiation and self-renewal. We established an organoid model from murine gastric tissues using the air-liquid interphase (ALI). I am validating potential metastatic driver genes using this model.
2. Tumor is not only clones of cancer cells, but is composed of multiple cell types. Tumor microenvironment (TME) plays an important role in tumor progression, metastasis, and therapy response. I am interested in using single cell RNA sequencing to delineate cellular heterogeneity and intercellular signaling in microenvironment.
3. Tumors with FGFR2 amplification are highly sensitive to AZD4547, a small-molecule tyrosine kinase (TRK) inhibitor, but invariably develop resistance during the treatment. To systematically delineate the pathways that modulate response to FGFR2 inhibitors, I am applying a CRISPR-library-based screening to identify gene knockouts and alternative activated pathways resulting in resistance to AZD4547.