Biophysics, Structure:Function, Technology Development
Protein-Protein Interactions (PPIs) is the Holy Grail of therapeutic intervention, offering a plethora of unique structural landscapes as potential targets. I use structure-guided approaches to characterize and validate these interactions in the context of disease models. We utilize a combination of techniques including NMR spectroscopy, NMR-based fragment and high throughput screening, and biophysical and cell-based assays to map hotspots in the interaction interface, to further understand the molecular mechanisms orchestrated by these interactions, and to identify disruptive inhibitors that may be developed into treatments for the related pathologies. Our current areas of focus are 1) the critical interactions between transcription factors and the general transcriptional machinery, including the Mediator complex, co-activators, and remodeling factors, and 2) translation initiation machinery demonstrated to be dysregulated in cancer disease states. We are working on making use of NMR-derived metabolomics data in the identification of novel metabolite disease markers that in combination with cellular pathway analysis can be used to identify new potential therapeutic targets. In order to facilitate our research goals, we also work on the development of new NMR methods for fragment screening, metabolite fingerprinting and protein-ligand interaction identification. Our work on novel pulse sequences, pulse designs, labeling strategies and sampling schemes let us push the boundaries of NMR as a technique, allowing us to tackle larger systems by NMR.