Arthanari
Hari Arthanari
Associate Professor of BCMP

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.

Longwood Center, LC3311
360 Longwood Ave.
Boston, MA 02215

Tel:617-632-6422

Email: hari_arthanari@hms.harvard.edu

Website: https://artlab.dana-farber.org/

Lab Size: Between 5-10

Summary: 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.

Publications:

Identification of small molecule antivirals against HTLV-1 by targeting the hDLG1-Tax-1 protein-protein interaction.

Authors: Authors: Maseko SB, Brammerloo Y, Van Molle I, Sogues A, Martin C, Gorgulla C, Plant E, Olivet J, Blavier J, Ntombela T, Delvigne F, Arthanari H, El Hajj H, Bazarbachi A, Van Lint C, Salehi-Ashtiani K, Remaut H, Ballet S, Volkov AN, Twizere JC.  
Antiviral Res 2023-07-21 
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SALL4B, not targeted by IMiD, is important for SALL4-mediated tumorigenesis.

Authors: Authors: L Vu KA, Kumari K, Liu BH, Gao C, Li F, Tang JP, Maddalo D, Auld DS, Casalena DE, Tian X, Liu M, Bassal MA, Moein S, Iakovleva V, Tan JL, Stein AJ, Zhou Q, Fischer PD, Sigua LH, Qi J, Arthanari H, Tenen DG, Chai L.  
bioRxiv 2023-07-07 
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Minimum information guidelines for experiments structurally characterizing intrinsically disordered protein regions.

Authors: Authors: Mészáros B, Hatos A, Palopoli N, Quaglia F, Salladini E, Van Roey K, Arthanari H, Dosztányi Z, Felli IC, Fischer PD, Hoch JC, Jeffries CM, Longhi S, Maiani E, Orchard S, Pancsa R, Papaleo E, Pierattelli R, Piovesan D, Pritisanac I, Tenorio L, Viennet T, Tompa P, Vranken W, Tosatto SCE, Davey NE.  
Nat Methods 2023-07-03 
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Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90a.

Authors: Authors: A M, Wales TE, Zhou H, Draga-Coleta SV, Gorgulla C, Blackmore KA, Mittenbühler MJ, Kim CR, Bogoslavski D, Zhang Q, Wang ZF, Jedrychowski MP, Seo HS, Song K, Xu AZ, Sebastian L, Gygi SP, Arthanari H, Dhe-Paganon S, Griffin PR, Engen JR, Spiegelman BM.  
Mol Cell 2023-06-01 
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Complete non-proline backbone resonance assignments of the S. aureus neutrophil serine protease inhibitor, EapH1.

Authors: Authors: Mishra N, Pal I, Herrera AI, Dubey A, Arthanari H, Geisbrecht BV, Prakash O.  
Biomol NMR Assign 2023-06-01 
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