Anne M. Spuches
Associate Professor, Bioinorganic Chemistry
- Postdoctoral research, Dartmouth College (2003-2007)
- Ph.D., Chemistry, Yale University (2003)
- BS, Chemistry, Syracuse University (1996)
Research in Dr. Spuches’s lab focuses on how metals (both toxic and essential) are “trafficked” within the cell. Metals play many important roles in biochemistry and all organisms require metal ions to carry out very specific functions. However, many of the essential metals such as copper and iron are redox active and unless tightly regulated are highly toxic. Our goal is to understand how metals are regulated within the intra-cellular milieu. To achieve this understanding, we use thermodynamic and spectroscopic techniques to characterize the thermodynamics and kinetics of metals binding to various biological molecules such as peptides, proteins, and enzymes. Once we have this information in hand, we can begin to build models that describe the distribution of metal ions in the cell.
An important technique used in the laboratory is isothermal titration calorimetry (ITC). ITC measures the heat released or absorbed during a reaction or binding event. In a single titration experiment, one obtains three key pieces of information regarding metal binding: binding constants (K), enthalpies (∆H), and stoichiometries (N). With this information one can calculate the Gibbs free energy of binding (∆G), and the entropy (∆S) of the system thus providing a full thermodynamic survey of metal binding to the molecule. This information is important for understanding how tightly metal ions are associated to biological molecules and provides insight into what factors contribute to this interaction.
D. P. Gogineni, A. M. Spuches, C. S. Burns. Calorimetric Investigation of Copper Binding in the N-Terminal Region ofthe Prion Protein at Low Copper Loading: Evidence for an Entropically Favorable First Binding Event. Inorganic Chemistry, in press, 2015.
R. A. Skowronsky, M. Schroeter, T. Baxley, Y. Li, J. M. Chalovich, A. M. Spuches. Thermodynamics of Calcium Binding to the Regulatory Site of Human Cardiac TnC: Evidence for Communication with the Structural Calcium Binding Sites. Journal of Biological Inorganic Chemistry. 18(1), 49-58, 2013.
C. Sacco, R. A. Skowronsky, S. Gade, J. M. Kenney, A. M. Spuches. Calorimetric Investigation of Copper (II) Binding to Aβ Peptides: Thermodynamics of Coordination Plasticity. Journal of Biological Inorganic Chemistry. 17 (4), 531-541, 2012.
A. L. Russell, A. M. Spuches, B.C. Williams, D. Venugopal, D. Klapper, A. H. Srouji, and R. P. Hicks. The Effect of the Placement and Total Charge of the Basic Amino Acid Clusters on Antibacterial Organism Selectivity and Potency. Bioorganic and Medicinal Chemistry. 19, 7008-7022, 2011.
A. L. Russell, A. M. Kennedy, A. M. Spuches, W. S. Gibson, D. Venugopal, D. Klapper, A. H. Srouji, J.B. Bhonsle and R. P. Hicks. Determining the Effect of the Incorporation of Unnatural Amino Acids into Antimicrobial Peptides on the Interactions with Zwitterionic and Anionic Membrane Model Systems. Chemistry and Physics of Lipids, 164, 740-758, 2011.
S. Siamakpour-Reihani, A. M Bradford, T. A. Peterson, H. J. Argiros, L. L. Haas, S.N. Lor, Z. M. Haulsee, A. M. Spuches, D. L. Johnson, L. R. Rohrschneider, C. B. Shuster and B. A. Lyons. Grb7 Binds to Hax-1 and Undergoes an Intramolecular Domain Association that Offers a Model for Grb7 Regulation. Journal of Molecular Recognition, 24 (2), 314-321, 2011
A. L. Russell, A. M. Kennedy, A. M. Spuches, D. Venugopal and R. P. Hicks. Spectroscopic and Thermodynamic Evidence for Antimicrobial Peptide Membrane Selectivity. Chemistry and Physics of Lipids. 163, 488-497, 2010.
N. E. Grossoehme, A. M. Spuches, D. E. Wilcox. Application of isothermal titration calorimetry in bioinorganic chemistry. Journal of Biological Inorganic Chemistry. 15 (8), 1183-1191, 2010.
J. V. Gavette, J. M. McGrath, A. M. Spuches, A. L. Sargent and W. E. Allen. Fluorous Effects in Amide-Based Receptors for Anions. Journal of Organic Chemistry. 74 (10), 3706-3710, 2009.