Research Interests
The Regan Lab is interested in the relationships between structure, function,
and stability in protein-protein and protein-DNA interactions.

 

Protein-Protein Interaction Design
We are interested in protein-protein interactions and the ways in which the affinity and specificity of such interactions can be manipulated. Our studies include computational and experimental approaches, ranging from the atomic design and characterization of novel binding modules to the re-wiring of cellular pathways.

Stimulus-Responsive Bionanomaterials
Stimulus-responsive hydrogels are promising vehicles for the controlled delivery of small molecules, cells, and other molecular cargo to specific sites in the body. We take advantage of the modularity, specificity, and tunability of non-covalent tetratricopeptide repeat (TPR) protein-peptide interactions to create such hydrogels. Small molecules and proteins are encapsulated upon mixing of TPR protein and peptide components and subsequently released in response to changes in pH and ionic strength. We are investigating how the atomic detail of the TPR protein-peptide interactions translate to the macroscopic properties of the hydrogels, namely viscoelasticity and stimuli-responsiveness.

Novel Hsp90 Inhibitors as Potential Anti-Cancer Agents
Unregulated cellular proliferation caused by mutation or dysregulation of growth-promoting proteins is an underlying cause of many cancers. Many growth-promoting proteins, including Her2, are clients of the chaperone Hsp90, whose activity promotes correct folding and maturation of the clients. We have identified small molecules that kill cancer cells and inhibit Hsp90 activity by disrupting its interaction with an essential co-chaperone. We are currently investigating the molecular and cellular mechanism of action of these compounds. More generally, we are investigating the balance between folding and ubiquitylation of Hsp90 client proteins and ways in which this balance can be perturbed.

Chromatin Structure and Remodeling
Approximately one meter of DNA is hierarchically packaged in the nucleus of every eukaryotic cell into a structure known as chromatin. The basic unit of chromatin is the nucleosome, a ~150 bp segment of DNA wrapped almost twice around an octamer of histone proteins. The protein-DNA interactions within nucleosomes must be dynamic to allow other cellular factors to access DNA in processes such as DNA replication, repair, and transcription. We seek to understand the stability and dynamics of these protein-DNA interactions. Specifically, we use single molecule optical tweezers measurements of reconstituted chromatin to measure the energetics of specific histone modifications.

 

Questions or Comments? Email Nicholas Sawyer