Babis Kalodimos Lab

Involved in important processes both inside and outside of the cell, protein kinases are the most frequently mutated domains in cancer and are therefore often targeted for therapeutic intervention. In our protein kinase research, we explore – on an atomic level – the rare conformational states that kinases transiently adopt as it functions. These states have historically been difficult, if not impossible, to capture and visualize but our laboratory recently employed state-of-the-art NMR spectroscopy techniques to show the different active and inactive conformations of the Abl kinase. We are now extending this novel approach to other kinases involved in disease.

The ultimate goal of this area of research is to better understand how the activity of protein kinases is regulated, since out-of-control kinase activity often leads to tumorigenesis, cancer, inflammation, and neurological diseases. In addition, our laboratory aims to understand the mechanisms of disease, leveraging the data we generate to identify selective inhibitors for therapeutic intervention and gain insight into drug resistance.

In our molecular chaperone research, we are exploring large and dynamic complexes and the proteins that are upregulated when there are many unfolded or misfolded proteins in the cell. Molecular chaperones represent the first line of defense by working to prevent misfolding or aggregation but the interaction of chaperones with these unfolded or misfolded substrates is transient in nature. 

Our laboratory has spearheaded novel approaches that use NMR spectroscopy and other techniques to observe the molecular chaperones with their unfolded proteins. The technique we pioneered allows us to develop high-resolution structures and to observe how chaperones recognize and connect with proteins. Armed with a more in-depth understanding of what is happening within the cell between molecular chaperones and proteins, we aim to apply this line of investigation to other systems and develop new therapeutic interventions.