Hai Jiang

Research Directions

Cancer is a malignant disease caused by complex gene mutations. Large-scale cancer genome studies have advanced our understanding of cancer, yet some key questions remain to be resolved. Tumors with certain genotypes lack therapeutic targets, whereas many established oncodrivers belong to the “undruggable” category. We conduct research in the following directions to expand precision cancer medicine.

• 1. Discovery of new cancer targets. Using genome-wide CRISPR screening, we conducted in-depth search on classic cancer signaling pathways such as Wnt, TGF, VHL-HIF, etc., and to find new regulatory genes indispensable for these pathways, some of which may provide new therapeutic targets for cancer. We conducted a comprehensive analysis of nearly 40 anticancer drugs using genome-wide CRISPR screen and discovered genes that most crucially determine the efficacy of each drug. Results from such studies can provide synthetic lethal targets for these drugs, pointing to new directions for improving treatment outcome.
• 2. Many well-established disease drivers belong to the “undruggable” category and represent huge unmet medical needs. Finding molecular glue degraders for such targets is a major focus of current pharmaceutical research. We designed a target-centric high throughput degrader screen system that enables fast discovery of chemical degraders of POIs. Using this platform, we are conducting large scale degrader screen for “undruggable” disease drivers. Such efforts may provide new drug candidates for targeted therapy.