Picture of Gerhard Wagner
Gerhard Wagner, Ph.D.
Elkan Blout Professor of Biological Chemistry and Molecular Pharmacology

Our research is concerned with structures of proteins and protein complexes and their functional roles. We use NMR spectroscopy, other biophysical techniques, computational tools and small molecule inhibitors to reveal mechanisms and cellular significance of protein interactions.

Research:

Our research is concerned with structures of proteins and protein complexes and their functional roles. We use NMR spectroscopy, other biophysical techniques, computational tools and small molecule inhibitors to reveal mechanisms and cellular significance of protein interactions.

The primary structural focus is on how eukaryotic translation initiation regulates the fate of cells. In particular, we are interested in the interaction of the cap-binding proteins eIF4E with the mRNA cap, the scaffold protein eIF4G, and the regulatory 4E-BPs, and how these interactions are related to cell transformation and apoptosis. To address this, we have identified small-molecule inhibitors of the eIF4E/eIF4G interaction and found that these may have anti-tumor activity. We are also working on other factors involved in eukaryotic translation initiation, such as eIF2, eIF2B, eIF5, eiF4H, eIF4A, and small-molecule inhibitors.

We also seek to understand mechanisms of T-cell function from structural studies. This includes the abTCR and the associated CD3 complexes. In addition, we try to understand mechanisms of downstream signaling at the level of nuclear translocation of nuclear factor of activated T cells (NFAT) through de-phosphorylation by calcineurin.

How transcriptional activators interact with co-activators from the Mediator family is another theme pursued in collaboration with the group of Anders Näär (MGH). We are determining structures of complexes, search for inhibitors of such interactions and validate the compounds as anti-cancer or anti-fungal agents.

We are interested in protein-protein interactions in apoptosis. These include molecules from the Bcl-2 family and the mitochondrial membrane protein VDAC. Recently we have developed procedures for incorporating membrane proteins in covalently circularized phospholipid nanodiscs creating stable membrane protein preparations usable for numerous membrane protein studies.

Furthermore, we work on non-ribosomal peptide synthetases and try to understand mechanisms by which building blocks of natural products are selected, processed and cyclized.

Address: 

Room C1-112

240 Longwood Avenue

Boston, MA 02115

Publications View
Topological analysis of the gp41 MPER on lipid bilayers relevant to the metastable HIV-1 envelope prefusion state.
Authors: Authors: Wang Y, Kaur P, Sun ZJ, Elbahnasawy MA, Hayati Z, Qiao ZS, Bui NN, Chile C, Nasr ML, Wagner G, Wang JH, Song L, Reinherz EL, Kim M.
Proc Natl Acad Sci U S A
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Emerging solution NMR methods to illuminate the structural and dynamic properties of proteins.
Authors: Authors: Arthanari H, Takeuchi K, Dubey A, Wagner G.
Curr Opin Struct Biol
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A nanobody that recognizes a 14-residue peptide epitope in the E2 ubiquitin-conjugating enzyme UBC6e modulates its activity.
Authors: Authors: Ling J, Cheloha RW, McCaul N, Sun ZJ, Wagner G, Ploegh HL.
Mol Immunol
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Structural characterization of the human membrane protein VDAC2 in lipid bilayers by MAS NMR.
Authors: Authors: Eddy MT, Yu TY, Wagner G, Griffin RG.
J Biomol NMR
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Integrative methods in structural biology.
Authors: Authors: Kaptein R, Wagner G.
J Biomol NMR
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NMR: an essential structural tool for integrative studies of T cell development, pMHC ligand recognition and TCR mechanobiology.
Authors: Authors: Mallis RJ, Brazin KN, Duke-Cohan JS, Hwang W, Wang JH, Wagner G, Arthanari H, Lang MJ, Reinherz EL.
J Biomol NMR
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Aromatic 19F-13C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics.
Authors: Authors: Boeszoermenyi A, Chhabra S, Dubey A, Radeva DL, Burdzhiev NT, Chanev CD, Petrov OI, Gelev VM, Zhang M, Anklin C, Kovacs H, Wagner G, Kuprov I, Takeuchi K, Arthanari H.
Nat Methods
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Editorial.
Authors: Authors: Wagner G.
J Biomol NMR
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Nonuniform Sampling for NMR Spectroscopy.
Authors: Authors: Robson S, Arthanari H, Hyberts SG, Wagner G.
Methods Enzymol
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High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3.
Authors: Authors: Gandhi AK, Kim WM, Sun ZJ, Huang YH, Bonsor DA, Sundberg EJ, Kondo Y, Wagner G, Kuchroo VK, Petsko G, Blumberg RS.
Sci Rep
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