yale mbb

Research Interests
The Regan Lab is interested in the relationships between structure, function and stability. We employ a wide array of methods to study protein-protein, protein-RNA and protein-DNA interactions.

 

Molecular Recognition
We are interested in protein-protein interactions and the ways in which the affinity and specificity of such interactions can be manipulated. Our studies range from the atomic – the design and characterization of novel binding modules – to the re-wiring of cellular pathways by inhibiting specific protein-protein interactions.

We also take advantage of the modularity, specificity and tunability TPR-peptide interactions to create more extensive molecular assemblies:  Stimuli-responsive smartgels.

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 cancer. Many such growth-promoting proteins, including HER2, exhibit an increased dependence on the activity of the chaperone Hsp90 for correct folding and maturation. We have identified small molecules that inhibit Hsp90 by disrupting its interaction with an essential co-chaperone and kill cancer cells. We are currently investigating the molecular and cellular details of the mechanism of action of these compounds. More generally, we are investigating the balance between folding and ubiquitinylation for Hsp90 client protein, and the ways in which this balance can be perturbed.

Protein Folding
We study protein folding and stability in vitro, using variety of solution biophysical methods, including fluorescence (ensemble and single molecule), circular dichroism and NMR. We are particularly interested in tetratricopeptide repeat proteins (TPR) because the modular nature of repeat proteins allows us to understand, and predict, their thermodynamic properties in an unprecedented fashion.

Chromatin Structure and Remodeling
Within every eukaryotic cell, a total length of about one meter of DNA is packaged into the nucleus. But this packaging must be dynamic, so that at appropriate times specific segments of DNA become accessible, for example to allow transcription factors to bind. We seek to understand how this dynamic access is achieved. Specifically, we use single molecule optical tweezers measurements of reconstituted chromatin to measure the energetic consequences of specific histone modifications.

New fluorescent proteins
Fluorescent proteins have a myriad of uses, and many different ones have been discovered or created. New proteins with increased brightness, faster-maturation, more colors and different photo-stabilities are still greatly desired. We are characterizing new fluorescent proteins, from organisms collected by our collaborators on diving expeditions, to identify ones with sought-after characteristics. Such proteins are used in various aspects of our research.

The molecular basis of Fragile X Mental Retardation Syndrome
Fragile X mental retardation syndrome is the most common form of inherited mental retardation in humans. It is caused by the lack or malfunction of a single protein - Fragile X Mental Retardation Protein (FMRP). We seek to understand the normal function of FMRP and to elucidate the molecular basis of Fragile X mental retardation syndrome.

 
 

Questions or Comments? Email Nicholas Sawyer