Research in my lab investigates how binding interactions modulate protein structure and energetics. Determining how binding energy propagates in protein is important for understanding biological signaling and communication mechanisms, as well as functional allostery.

In these pursuits, I have two model systems. The first is a ligand-induced protein misfolding model, which is related to the protein misfolding disorders such as Alzheimer's, Parkinson's, and prion diseases. Previously, I developed a class of peptide ligands that promote amyloid-misfolding in protein, which allows for these misfolding reactions to be investigated in detail using various assays and solution NMR techniques. Amyloid inhibitors have also been developed, which is providing therapeutic possibilities.

The second model system investigates how binding energy propagates in natively unfolded proteins, a condition observed in 70% of all signaling proteins. For these proteins, it's difficult to understand how they regulate signaling pathways when these proteins do not adopt well-defined structures. An example is p53, a large signaling protein that has seven domains, five of which are unstructured under normal physiological conditions. 50% of all cancers are associated with mutations that occur in p53. To investigate p53 signaling, and how mutations affect its signaling properties, my lab is performing a series of binding experiments and measuring by thermodynamic methods how binding energy propagates between the various domains of the p53 molecule.