Haribabu Arthanari, Ph.D.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Department of Cancer Biology, Dana-Farber Cancer Institute
Therapeutic Targeting of Protein-Protein Interactions. Protein-Protein Interactions (PPIs) are the Holy Grail of therapeutic intervention, offering a plethora of distinct structural landscapes that can be targeted with high specificity. Arthanari lab uses structure-guided approaches to characterize and validate these interactions in the context of disease models. We utilize a combination of techniques including NMR spectroscopy, 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. Our work on novel NMR methods let us push the boundaries of NMR as a technique, allowing us to tackle larger and complex systems by NMR. We also develop NMR methods to dissect and uncover the secrets of the disordered part of the human proteome referred to as the “Dark Proteome".
Nishikawa JL, Boeszoermenyi A, Vale‑Silva LA, Torelli R, Posteraro B, Sohn YJ, Gelev V, Sanglard D, Sanguinetti M, Buhrlage SJ, Gray NS, Wagner G*, Näär AM* and Arthanari H.* “Inhibiting Fungal Multidrug Resistance by Disrupting an Activator‑Mediator Interaction.” (*co-corresponding authors) Nature. 2016 Feb 25; 530(7591): 485‑9.
Takeuchi K, Arthanari H, Imai M, Wagner G, and Shimada I. “Nitrogen‑detected TROSY yields comparable sensitivity to proton‑detected TROSY for non‑deuterated, large proteins under physiological salt conditions.” J Biomol NMR. 2016 Feb;64(2):143‑51.
Takeuchi K*, Arthanari H*, Shimada I, and Wagner G. “Nitrogen detected TROSY at high field yields high resolution and sensitivity for protein NMR.” (*co‑first authors) J Biomol NMR. 2015 Dec; 63(4):323‑31.
Leigh K, Sharma M, Mansueto MS, Boeszoermenyi A, Filman DJ, Hogle JM, Wagner G*, Coen DM, Arthanari H*. “The Conserved Core of a Herpesvirus Nuclear Egress Complex Subunit Exhibits a Novel Fold and a Subunit Interaction Groove with Residues Essential for Viral Replication.” PNAS. 2015 Jul 6 [epub] (*co‑corresponding author)
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