Our research is focused on characterizing the structure and conformational dynamics of biological macromolecules using a range of biophysical methods, including heteronuclear NMR spectroscopy, fluorescence spectroscopy, transmission electron microscopy, small angle X-ray scattering, and mass spectrometry. In particular, we are interested in the development and implementation of new solution NMR methods to explore protein folding and misfolding, posttranslational modifications, and human diseases including HIV, Alzheimer’s, and diabetes.

Solution NMR spectroscopy.

Solution NMR spectroscopy enables researchers to elucidate three-dimensional structures of macromolecules in their native environment, providing quantifiable and calculable links between structure, function, and activity. It is also unique in its ability to elucidate a vast range of motions that are exhibited by biomolecules, which provides vital information regarding ligand recognition, protein assembly, conformational dynamics, protein folding, and many other essential cellular processes. This knowledge is critical for understanding disease processes at the molecular level, and for the development of new pharmaceuticals.

Protein folding, misfolding, and amyloids.

Amyloids are commonly viewed as irreversible end-products of uncontrolled aggregation events associated with proteinopathies, including Alzheimer’s and Parkinson’s diseases. Recent discoveries of functional amyloids have challenged this perception by elucidating the physiological roles of amyloids and their ubiquitous distribution in lower and higher-order organisms. We seek to understand the mechanistic underpinnings of amyloid formation and how eukaryotic cells generate functional amyloids without succumbing to pathology and exploit their useful properties.

Posttranslational modifications (PTMs).

PTMs are used to extend and diversify the signals encoded by a given protein. PTMs result in covalent modifications of the translated polypeptide chain, altering its structural and functional properties. These modifications involve conjugation of chemical groups/peptides/nucleic acids to the given polypeptide chain or its enzymatic cleavage or removal of the attached chemical groups. Some of the common PTMs include introduction of a functional group (e.g., phosphorylation), covalent conjugation of peptides/proteins (e.g., ubiquitination), alteration of the physicochemical properties (e.g., oxidation), and proteolytic cleavage of the target protein. PTMs are vital for normal cellular processes and their defects are linked to pathology. We are especially interested in quantitative analyses of proteolysis, tyrosine phosphorylation, and ubiquitination