Tarun Kapoor

Developing chemical approaches to dissect mechanisms required for genome stability

We study basic mechanisms underlying cell division with the goal to develop new and effective therapies. We meld synthetic chemistry, the discovery and use of chemical probes, biochemistry and quantitative cell biology to answer long-standing questions relating to cell division. Studying cell division also provides us an important and unparalleled opportunity to develop new approaches that can be broadly used to analyze other complex and dynamic cellular mechanisms.

Errors in cell division have been linked to diseases and developmental defects in human. Drugs targeting many of the proteins we study are in clinical trials as anti-cancer agents and our work sheds light on how these drugs work. The chemical inhibitors we identify to examine cell division mechanisms can also provide starting points for developing new chemotherapeutic agents.  

I will highlight our recent efforts to develop potent and selective chemical probes for proteins in the AAA+ (ATPases associated with diverse cellular activities) family. In particular, I will discuss the discovery and characterization of first-in-class chemical inhibitors of dynein (a microtubule-based motor protein) and Midasin (an essential ATPase required for ribosome biogenesis). I will also describe our efforts to develop DrugTargetSeqR, an approach that combines genomics with cell biology to identify physiological targets of chemical inhibitors. This new multi-disciplinary approach can help address a major challenge in chemical biology and drug development.