The ultimate goal of the Nijhawan lab aims is to discover first in class drugs for the treatment of cancer. We believe that the underlying challenge of cancer drug discovery is to identify “druggable” targets. Druggable targets are proteins whose activity can be influenced by small molecules. Our research is based in the belief that there are new strategies with which to target proteins with small molecules that have yet to be discovered.
To accomplish this goal, we use both biochemistry and forward genetics to discover the protein targets for small molecules with anti-cancer activity. Historically, small molecule target identification has been challenging. However, with the advent of new technologies including whole exome sequencing and click chemistry, it is now possible to efficiently and unambiguously discover chemical targets.
We use two approaches for chemical target identification:
- Use photochemistry and click chemistry to identify proteins that directly interact with the small molecule
- Use a mammalian cancer cell line as a forward genetic tool to discover compound-resistant alleles
Using these techniques, we have identified numerous small molecule targets that influence proteins involved in different biological pathways including fatty acid metabolism, cholesterol biosynthesis, DNA replication, and pre-mRNA splicing.