Multidimensional chemical proteomics for transforming tumor vulnerabilities into novel therapeutics in colon cancer

This project aims to combine frontline technologies in mass spectrometry-based proteomics and systems biology to study the cell-cell interactions within the colon tumor and its complex microenvironment.

Our hypothesis is that mammalian tumor associated cells such as macrophages and the naturally occurring microbial entities in the colon microenvironment can modulate colon cancer cell growth.

We will employ co-culture and complex microbiota systems to profile and identify cell-cell interactions that modulate the growth of colon cancer cells.

Subsequently, for the first time, we will apply multidimensional chemical proteomics to understand the effect of such co-cultured cells on the colon cancer proteome. This approach will identify druggable targets and pathways in the human host for therapeutic intervention.

Furthermore, through connectivity mapping, we will identify the co-cultured cell-derived molecules that modulate colon cancer cell growth and validate their effects. The targets of such molecules will be identified by chemical proteomics and validated in vivo.

The above target and pathway information will be used to repurpose FDA-approved drugs against colon cancer, design strategies to remodel the gut microbiome, or develop novel therapeutics targeting colon cancer cells or the microbial entities. Given that colon cancer constitutes 9.2% of all cancer mortality, this research is of high priority.

This project will commence in 2024 and we will recruit one Ph.D. student.