B.S. University of New Mexico, 1969
Ph.D. University of New Mexico, 1972
Currently, we are developing a better understanding of the structure, stability, and drug binding properties of G-quadruplex and i-Motif DNA's. Sequences capable of forming these unique intra-molecular-folded DNA structures are located in the regulatory regions of more than 40% of all human genes. The oncogenes c-MYC, Bcl-2, K-ras, and several others, are known to have P-1 promoter region sequences that can form single-stranded or looped-out G-quadruplex and i-Motif structures. Drugs that bind to and stabilize these structures may be able to turn off the expression of these oncogenes, providing a new approach to the treatment of cancer. By measuring the energetics of these specific DNA -binding interactions, we hope to provide the information needed to develop drugs that are more selective for cancer- target specific and therefore, more effective in the treatment of cancer.
Our lab is generally interested in the characterization of specific high affinity interactions that take place between small molecules and biopolymers, e.g. drug binding to nucleic acids and/or proteins. In these studies, we use a variety of microcalorimetry (ITC and DSC), light scattering (static and dynamic), and spectroscopic techniques (CD, Fluorescence, UV-vis, and NMR). We also use computational methods and molecular dynamics to model these interactions. The defining focus of our lab is the use of energetic or thermodynamic data in rational drug design.
We are always looking for quality graduate and undergraduate researchers to join our research team. Graduate students interested in joining the lab should have a strong background in biochemistry or biophysics and a basic understanding of nucleic acid and/or protein chemistry. Undergraduates with an interest in biochemistry and biophysics research are encouraged to apply.
1. Wang, C.; Carter-Cooper, B.; Du, Y.; Zhou, J.; Saeed, M. A.; Liu, J.; Guo, M.; Roembke, B.; Mikek, C.; Lewis, E. A.; Lapidus, R.G.; Sintim, H.O. (2016) “Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities.” European Journal of Medicinal Chemistry 2016. Aug 8. doi:10.1016/j.ejmech.2016.04.030 PDF (1360 KB)
2. Henderson, K. L.; Boyles D. K.; Le, V.H.; Lewis E. A.; and Emerson J. P. (2016) “ITC Methods for Assessing Buffer/Protein Interactions from the Perturbation of Steady-State Kinetics: A Reactivity Study of Homoprotocatechuate 2,3-Dioxygenase.” Methods in Enzymology (567), 257- 78. PDF (1875 KB)
3. DuPont, J. I.; Henderson, K. L.; Metz, A.; Le, V. H.; Emerson, J. P., and Lewis E. A. (2015) “Calorimetric and spectroscopic investigations of the binding of metallated porphyrins to G-quadruplex DNA.” Biochim Biophys Acta 2015 Sep 9. pii: S0304-4165(15)00235-4. PDF (1378 KB)
4. Henderson, K. L.; Francis, D. H.; Lewis E. A.; and Emerson J. P. (2015) “Thermodynamics of substrate binding to the metal site in homoprotocatechuate 2,3-dioxygenase: Using ITC under anaerobic conditions to study enzyme–substrate interactions.” Biochim Biophys Acta 2015. Aug 23. pii: S0304-4165(15)00210-X. PDF (871 KB)
5. Le, V. H.; McGuire, M.; Ahuja, P.; MacDonnell, F.; and Lewis E. A. (2015) “Thermodynamic investigation of [(phen)2Ru(tatpp)Ru(phen)2]4+ interactions with B-DNA.” Journal of Physical Chemistry, Part B, 119(1), 65-71. PDF (1017 KB)
6. Le, V. H.; Yanney, M.; McGuire, M.; Sygula, A.; and Lewis, E. A. (2014) “Thermodynamics of Host-Guest Interactions Between Fullerenes and a Buckycatcher”. Journal of Physical Chemistry, Part B, 118(41), 11956-11964. PDF (1708 KB)
7. Zhou, J.; Le, V. H.; Kalia, D.; Nakayamaa, S.; Mikek, C.; Lewis, E. A.; and Sintim, H. O. (2014), “Diminazene or berenil, a classic duplex minor groove binder, binds to G-quadruplexes with low nanomolar dissociation constants and the amidine groups are also critical for G- quadruplex binding.” Molecular BioSystems. 10,2724-2734. PDF (2649 KB)
8. Hudson, J. S.; Ding, L.; Le, V.; Lewis, E. A.; and Graves, D. E. (2014), “Recognition and Binding of Human Telomeric G-Quadruplex DNA by Unfolding Protein 1 (UP1)”. Biochemistry, 53(20), 3347-3356 PDF (1473 KB)
9. Lyons, D. F.; Le, V.; Kramer, W. H.; Bidwell, G.; Lewis, E. A.; Raucher, D.; and Correia, J. J. (2014), “The effect of basic cell penetrating peptides on the structural, thermodynamic and hydrodynamic properties of a novel drug delivery vector: ELP[V5G3A2-150]”. Biochemistry, 53(6), 1081-1091. PDF (2010 KB)
10. Machha, V.R, Jones, S.B., Waddle, J.R., Le, V.H., Wellman, S., and Lewis, E.A. (2014), “Exploring the Energetics of Histone H1.1 and H1.4 Duplex DNA Interactions”. Biophysical Chemistry, 185, 32-38. PDF (422 KB)
11. Song, H.; Weitz, A. C.; Hendrich, M. P.; Lewis, E. A.; and Emerson, J. P. (2013) “Building reactive copper centers in human carbonic anhydrase II.” Journal of Biological Inorganic Chemistry. 18(6): 595–598. PDF (255 KB)
12. Ramos, J. P.; Le, V. H.; and Lewis, E. A. (2013), “Role of Water in Netropsin Binding to an A2T2 Hairpin DNA Site: Osmotic Stress Experiments”. Journal of Physical Chemistry, Part B,117 (50), 15958-15965. PDF (432 KB)
13. Cui, J.; Waltman, P.; Le, V. H.; and Lewis, E. A. (2013), “The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence i-Motif at Neutral pH”. Molecules, 18, 12751-12767. PDF (422 KB)
14. Rowland, G. B.l Barnett, K.; DuPont, J. I.; Akurathi, G.; Le, V.H.; and Lewis, E. A. (2013), “The Effect of Pyridyl substitution on the Thermodynamics of Porphyrin Binding to G-quadruplex DNA”. Bioorganic & Medicinal Chemistry, 21, 7515-7522.PDF (1051 KB)
15. Machha, V. R.; Waddle, J.; Turner, A.; Wellman, S.; Le, V. H.; and Lewis, E. A. (2013) “Calorimetric Studies of the Interaction of Linker Histone H10 and its Carboxyl (H10-C) and Globular (H10-G) Domains with Calf-Thymus DNA”. Biophysical Chemistry, 184, 22-28. PDF (801 KB)
16. Le, V.H.; Nagesh, N.; and Lewis, E.A. (2013) “Bcl-2 Promoter Sequence G-Quadruplex Interactions with Three Planar and Non-Planar Cationic Porphyrins, TMPyP4, TMPyP3, and TMPyP2”. PLOSONE, 8(8): e72462. DOI:10.1371/journal.pone.0072462 PDF (716 KB)
17. Lyons, D.F.; Le, V.; Bidwell, G.L.; Kramer, W.H.; Lewis, E.A.; Raucher, D.; and Correia, J.J.(2013) “Structural and Hydrodynamic Analysis of a Novel Drug Delivery Vector: ELP[V5G3A2-150]”. Biophysical Journal, 104(9) 2009-2021. PDF (783 KB)
18. Le, V. H.; Buscaglia, R.; Chaires, J. B.; and Lewis, E. A. (2013), “Modeling Complex Equilibria in ITC Experiments: Thermodynamic Parameters Estimation for a Three Binding Site Model”, Analytical Biochemistry, 434(2) 233-241. PDF (1294 KB)