Assistant Professor

Molecular Biology

Princeton University (Princeton, NJ)

My research is focused on understanding how cells use metabolic energy to modify protein structure and control the assembly and disassembly of large macromolecular complexes.

We have examined protein assembly and disassembly using two model systems: intracellular protein folding and vesicle trafficking. In both cases, protein assembly and/or disassembly depends upon ATP-utilizing molecular chaperones and we have used biophysical and structural tools to develop a detailed mechanistic picture of how these systems function. As part of our work, we have developed a set of high-sensitivity fluorescence assays for studying molecular chaperones like GroEL. Using these assays, we have shown that GroEL employs active protein unfolding to stimulate the productive folding of misfolded proteins. We have also demonstrated how this physical mechanism is linked to the complex molecular allostery of the GroEL reaction cycle. Most recently we have developed a novel single-particle fluorescence method capable of examining the real-time distribution of complex protein assemblies in free solution. We have applied this technique to a study of the Hsc70-dependent disassembly of clathrin coats and to the recognition and disassembly of protein aggregates by various molecular chaperones.

2001 Beckman Young Investigator Award

1992 Outstanding Teaching Award, UC Berkeley

1989 Phi Beta Kappa, Rice University