A. Joshua Wand, Ph.D
Department of Biochemistry & Biophysics
University of Pennsylvania
Philadelphia, PA 19104
Lab: (215) 573-7289
B.Sc. (Biochemistry (Hons))
Carleton University, 1979.
Carleton University, 1981.
University of Pennsylvania, 1984.
Description of Research ExpertiseDr. Wand's research focuses on exploring the relationships between static structure, structural dynamics and function in a range of protein systems. A key concept is the balance between changes in structure (enthalpy) and dynamics (entropy) is the binding of ligands. A range of systems involving protein-protein interactions as well as interactions with small ligands are being pursued. Through these studies a remarkably rich manifold of fast dynamical modes have been revealed and a surprising functional role for them discovered. These observations are being exploited to generate access to new avenues for drug design and engineering in a number of validated drug targets in cancer biology.
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, 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 membrane proteins. Most recently, this approach is being utilized to screen fragement libraries for low affinity but high quality “hits” to elaborate to lead molecules for subsequent development of pharmaceuticals.
Selected PublicationsO'Brien, Evan S., Nucci, Nathaniel V., Fuglestad, Brian, Tommos, Cecilia, Wand, A. Joshua: Defining the Apoptotic Trigger THE INTERACTION OF CYTOCHROME c AND CARDIOLIPIN. journal of biological chemistry 290(52): 30879-30887, DEC 25 2015 2015.
Wand, AJ: BIOPHYSICS Enzymes surf the heat wave. nature 517(7533): 149-150, JAN 8 2015.
Fu, Y. N., Kasinath, V., Moorman, V. R., Nucci, N. V., Hilser, V. J., Wand, A. J.: Coupled Motion in Proteins Revealed by Pressure Perturbation. Journal of the American Chemical Society 134(20): 8543-8550, 2012.
Marlow, MS, Dogan, J, Frederick, KK, Valentine, KG, Wand, AJ: The role of conformational entropy in molecular recognition by calmodulin. Nature Chemical Biology 6(5): 352-358, MAY 2010.
Nucci, N. V., Pometun, M. S., Wand, A. J.: Site-resolved measurement of water-protein interactions by solution NMR. Nature Structural & Molecular Biology 18(2): 245-U315, 2011.
Frederick, KK, Marlow, MS, Valentine, KG, Wand, AJ: Conformational entropy in molecular recognition by proteins. Nature 448(7151): 325-U3, JUL 19 2007.
Igumenova, T.I. , K.K. Frederick, and A.J. Wand : Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution. Chem. Rev 106(5): 1672-1699, 2006.
Babu, CR, Hilser, VJ, Wand, AJ: Direct access to the cooperative substructure of proteins and the protein ensemble via cold denaturation. Nature Structural & Molecular Biology 11(4): 352-357, APR 2004.
Lee, A. L. and Wand, A. J: Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411: 501-504, 2001.
Lee, A. L, Kinnear, S. A. and Wand, A. J: Redistribution and loss of side-chain entropy upon formation of a calmodulinopeptide complex. Nature Struct. Biol 7: 72-77, 2000.
Kasinath, V, Sharp, KA, Wand, AJ: Microscopic Insights into the NMR Relaxation-Based Protein Conformational Entropy Meter. Journal of the American Chemical Society 135(40): 15092-15100, OCT 9 2013.