Biological Chemistry & Molecular Pharmacology
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.
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.
Haribabu Arthanari received his Bachelors in Chemistry from the Madras Christian College and his Masters in Chemistry from the Indian Institute of Technology (IIT)-Madras. He did his graduate studies at Wesleyan University with Philip Bolton and earned his PhD in 2004. He then joined the laboratory of Gerhard Wagner for his post-doctoral training. He was promoted to a lecturer in 2010 and moved to his independent position in 2016.
1. Mixed pyruvate labeling enables backbone resonance assignment of large proteins using a single experiment.
Robson SA, Takeuchi K, Boeszoermenyi A, Coote PW, Dubey A, Hyberts S, Wagner G, Arthanari H. Nat Commun. 2018 Jan 24;9(1):356.
2. Rapid convergence of optimal control in NMR using numerically-constructed toggling frames.
Coote P, Anklin C, Massefski W, Wagner G, Arthanari H. J Magn Reson. 2017 Aug;281:94-10
3. Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction.
Nishikawa JL, Boeszoermenyi A, Vale-Silva LA, Torelli R, Posteraro B, Sohn YJ, Ji F, Gelev V, Sanglard D, Sanguinetti M, Sadreyev RI, Mukherjee G,
Bhyravabhotla J, Buhrlage SJ, Gray NS, Wagner G, Näär AM, Arthanari H. Nature. 2016 Feb 25;530(7591):485-9 4. Structure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication.
Leigh KE, Sharma M, Mansueto MS, Boeszoermenyi A, Filman DJ, Hogle JM, Wagner G, Coen DM, Arthanari H. Proc Natl Acad Sci U S A. 2015 Jul
5. Analytical optimization of active bandwidth and quality factor for TOCSY experiments in NMR spectroscopy.
Coote P, Bermel W, Wagner G, Arthanari H. J Biomol NMR. 2016 Sep;66(1):9-20.
6. A nuclear receptor-like pathway regulating multidrug resistance in fungi.
Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Näär AM. Nature. 2008 Apr 3;452(7187):604-9.
Click HERE for a list of all the publications on PubMed.