A. JOSHUA WAND, Ph.D.

Benjamin Rush Professor of Biochemistry and Biophysics

215-573-7288 (office)
215-573-7289 (main lab)
215-573-5969 (NMR lab)
215-573-7290 (fax)
wand@mail.med.upenn.edu

Ph.D. University of Pennsylvania (1984)

Wand Lab

RESEARCH INTERESTS:

Dr. Wand's research focuses on exploring the relationships between static structure, structural dynamics and function in a range of protein systems. Current efforts are centered on calmodulin, a main player in calcium-mediated signal transduction, GP130, an somewhat promiscuous interleukin and antigen-antibody complexes. A key concept is the balance between changes in structure (enthalpy) and dynamics (entropy) in the setting of the free energy of association between proteins. They are also interested in similar issues in the context of interactions with small ligands such as drugs. Through these studies a remarkably rich manifold of fast dynamical modes have been revealed and a surprising functional role for them discovered.

The Wand lab is also committed to continuing improvement and development of novel NMR techniques.  They have recently focused on high pressure NMR to probe the protein ensemble, sparse sampling methods for rapid and sensitivity-optimized data collection, NMR relaxation methods to measure conformational dynamics throughout the protein and a novel method to approach large soluble, unstable and membrane proteins by solution NMR methods. The latter approach involves the use of reverse micelle encapsulation to provide a protective environment for proteins to allow them to be dissolved in low viscosity fluids such as liquid ethane. The initial idea was to use the low viscosity of ethane to overcome the slow tumbling problem for solution NMR spectroscopy presented by large protein in water. Applications have since been expanded to studies of proteins of marginal stability by employing the confined space of the reverse micelle, suppression of protein aggregation to allow study of intermediates of aggregation such as occur in amyloid formation, and studies of both integral and peripherally anchored membrane proteins.

RECENT REPRESENTATIVE PUBLICATIONS

  1. Nucci, N.V., M.S. Pometun, and A.J. Wand (2011) Site-resolved measurement of water-protein interactions by solution NMR. Nat. Struct. Mol. Biol. 18:245-249.
  2. Metcalf, D.G., D.T. Moore, Y. Wu, J.M. Kielec, K. Molnar, J.S. Bennett, K.G. Valentine, A.J. Wand, J.S. Bennett, and W.F. DeGrado (2011) Proc. Nat. Acad. Sci. USA 107:22481-22486.
  3. Marlow, M.S., J. Dogan, K.K. Frederick, K.G. Valentine, and A.J. Wand (2010) The role of conformational entropy in molecular recognition by calmodulin.  Nature Chem. Biol. 6:353-358.
  4. Valentine, K.G., R.W. Peterson, J.S. Saad, M.F. Summers, X. Xu, J.B. Ames, and A.J. Wand (2010) Reverse micelle encapsulation of membrane anchored proteins for solution NMR studies. Structure 18:9–16.
  5. Gledhill, J.M., B. Walters, and A.J. Wand (2009) Multidimensional optimization of radially enhanced NMR-based collection of hydrogen exchange data in proteins. J. Biomol. NMR 45:233-239.
  6. Kielec, J.M., K.G. Valentine, C.R. Babu, and A.J. Wand (2009) Reverse micelles in integral membrane protein structural biology by solution NMR spectroscopy. Structure 17:345-351.
  7. Liu, W., J.N. Rumbley, S.W. Englander, and A.J. Wand (2009) Fast structural dynamics in reduced and oxidized cytochrome c. Protein Sci., 18:670-674.
  8. Gledhill, J.M. and A.J. Wand (2008) Optimized angle selection for radial sampled NMR experiments. J. Magn. Reson. 195:169-178.
  9. Frederick, K.K., K.A. Sharp, N. Warischalk, and A.J. Wand (2008) Re-evaluation of the model-free analysis of fast internal motion in proteins using NMR. J. Phys. Chem. B. 112:12095-12103.
  10. Frederick, K.K., M.S. Marlow, K.G. Valentine, and A.J. Wand (2007) Conformational entropy in molecular recognition by proteins. Nature 448:325-329.
  11. Song, X.- J., P.F. Flynn, K.A. Sharp, and A.J. Wand (2007) Temperature dependence of fast dynamics in proteins. Biophys. J. 92:L43-45.

USEFUL HISTORICAL PUBLICATIONS:

  1. Igumenova, T.I. , K.K. Frederick, and A.J. Wand (2006) Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution. Chem. Rev. 106:1672-1699.
  2. Peterson, R.W., B.G. Lefebvre, and A.J. Wand (2005) High resolution NMR studies of encapsulated proteins in liquid ethane. J. Am. Chem. Soc. 127:10176-10177.
  3. Peterson, R.W. and A.J. Wand (2005) Self contained high pressure cell, apparatus and procedure for the preparation of encapsulated proteins dissolved in low viscosity fluids for NMR spectroscopy. Rev. Sci. Instr. 76, Art. No. 094101.
  4. Babu, C.R., V.J. Hilser, and A.J. Wand (2004) Direct access to the cooperative substructure of proteins and the protein ensemble via cold denaturation. Nature Struct. Mol. Biol. 11:353-357.
  5. Peterson, R.W., K. Anabalagan, C. Tommos, and A.J. Wand (2004) Forced folding and structural analysis of metastable proteins. J. Am. Chem. Soc. 126:9498-9499.
  6. Kranz, J.K., P.F. Flynn, E.J. Fuentes, and A.J. Wand (2002) Dissection of the pathway of molecular recognition by calmodulin. Biochemistry 41:2599-2608.
  7. Wand, A.J. (2001) Dynamic activation of protein function: A view emerging from NMR spectroscopy Nature Struct. Biol. 8:926-931.
  8. Lee, A.L. and A.J. Wand (2001) Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411:501-504.
  9. Lee, A.L, S.A. Kinnear, and A.J. Wand (2000) Redistribution and loss of side-chain entropy upon formation of a calmodulin-peptide complex. Nature Struct. Biol. 7:72-77.
  10. Wand, A.J., M.R. Ehrhardt, and P.F. Flynn (1998) High resolution NMR of encapsulated proteins dissolved in low viscosity fluids. Proc. Nat. Acad. Sci. USA 95:15299-15302.
  11. Li, Z., S. Raychaudhuri, and A.J. Wand (1996) Insights into the local residual entropy of proteins provided by NMR relaxation. Protein Science 5:2647-2650.
  12. Wand, A.J., J.L. Urbauer, R.P. McEvoy, and R.J. Bieber (1996) Internal dynamics of human ubiquitin revealed by 13C-relaxation of randomly, fractionally enriched protein. Biochemistry 35:6116-6125.
  13. Ehrhardt, M.R., J.L. Urbauer, and A.J. Wand (1995) The energetics and dynamics of molecular recognition by calmodulin. Biochemistry 34:2731-2738.
  14. Feng, Y., S.G. Sligar, and A.J. Wand (1994) Solution structure of apocytochrome b562. Nature Struct. Biol. 1:30-34.
  15. Schneider, D.M., M.J. Dellwo, and A.J. Wand (1992) Fast internal main chain dynamics of human ubiquitin. Biochemistry 31:3645-3652.
  16. Dellwo, M.J., and A. J. Wand (1989) Model-independent and model-dependent analysis of the global and internal dynamics of cyclosporin A. J. Amer. Chem. Soc. 111:4571-4578.