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Chemical Biology of Protein Misfolding

We combine experimental and computational approaches from chemistry and biology to probe the errors in complex molecules that drive important diseases like Parkinson's and Alzheimer's.

The cells of all organisms are powered by complex molecular machines called proteins. Unlike machines made by humans, which are rigidly constructed to ensure proper function, proteins are highly flexible and dynamic. As a result, they often change structure into nonfunctional species in a process called protein misfolding. Not only are these aberrant species incapable of performing their evolved functions, but they can actively interfere with the other activities a cell needs to perform to live. Unsurprisingly, protein misfolding is implicated in many prevalent diseases, including Alzheimer's, Parkinson's, and diabetes, among others. Unfortunately, we do not understand the nature of misfolded proteins or why they form, preventing effective disease interventions.

To solve these problems, our lab is dissecting the chemical features of proteins and their cellular environments that govern misfolding.  We develop new technologies to study proteins in their native cellular environments, and we discover new chemical and biological phenomena that result in pathological phenotypes.  Our work integrates perspectives from chemical biology, biophysics, and molecular genetics, and we use approaches and techniques from synthetic, analytical, and computational chemistry, as well as cellular, molecular, structural, and computational biology.

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