The Lisi laboratory studies the chemistry and biology of enzymes in order to understand how these complex biomolecules function in disease. The lab uses biophysical and biochemical tools to generate molecular level fingerprints of enzyme structures and characterize picosecond-to-second dynamics that propagate mechanistically important biological signals.
George is a native of New England, receiving his undergraduate education at Fairfield University (2009) and Ph.D. at Dartmouth (2014) under the direction of Dean E. Wilcox and Ekaterina Pletneva. George was a postdoctoral fellow in biochemistry and biophysics at Yale University (2014 - 2018) under the mentorship of Pat Loria. He joined the Brown faculty in late 2018. Check out the lab at lisilabnmr.com
|Belato HB, D'Ordine AM, Nierzwicki L, Arantes PR, Jogl G, Palermo G, Lisi GP. "Structural and dynamic insights into the HNH nuclease of divergent Cas9 species." Journal of Structural Biology, vol. 214, no. 1, 2022, pp. 107814.|
|Wang J, Skeens E, Arantes PR, Maschietto F, Allen B, Kyro GW, Lisi GP, Palermo G, Batista VS. "Structural Basis for Reduced Dynamics of Three Engineered HNH Endonuclease Lys-to-Ala Mutants for the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Associated 9 (CRISPR/Cas9) Enzyme." Biochemistry, vol. 61, no. 9, 2022, pp. 785-794.|
|Skeens E, East KW, Lisi GP. "1H, 13C, 15 N backbone resonance assignment of the recognition lobe subdomain 3 (Rec3) from Streptococcus pyogenes CRISPR-Cas9." Biomolecular NMR assignments, vol. 15, no. 1, 2021, pp. 25-28.|
|Nierzwicki L, East KW, Morzan UN, Arantes PR, Batista VS, Lisi GP, Palermo G. "Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9." eLife, vol. 10, 2021.|
|Wang J, Reiss K, Shi Y, Lolis E, Lisi GP, Batista VS. "Mechanism of Inhibition of the Reproduction of SARS-CoV-2 and Ebola Viruses by Remdesivir." Biochemistry, vol. 60, no. 24, 2021, pp. 1869-1875.|
|Cui JY, Lisi GP. "Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function." Frontiers in molecular biosciences, vol. 8, 2021, pp. 773252.|
|Parkins A, Skeens E, McCallum CM, Lisi GP, Pantouris G. "The N-terminus of MIF regulates the dynamic profile of residues involved in CD74 activation." Biophysical Journal, vol. 120, no. 18, 2021, pp. 3893-3900.|
|East KW, Newton JC, Morzan UN, Narkhede YB, Acharya A, Skeens E, Jogl G, Batista VS, Palermo G, Lisi GP. "Allosteric Motions of the CRISPR-Cas9 HNH Nuclease Probed by NMR and Molecular Dynamics." J. Am. Chem. Soc., vol. 142, no. 3, 2020, pp. 1348-1358.|
East, K. W., Newton, J. C., Morzan, U. N., Narkhede, Y. B., Acharya, A., Skeens, E., Jogl, G., Batista, V. S., Palermo, G., Lisi, G. P.
"Allosteric Motions of the CRISPR–Cas9 HNH Nuclease Probed by NMR and Molecular Dynamics." Journal of the American Chemical Society, vol. 142, no. 3, 2020, pp. 1348-1358.
|Murphy JW, Rajasekaran D, Merkel J, Skeens E, Keeler C, Hodsdon ME, Lisi GP, Lolis E. "High-Throughput Screening of a Functional Human CXCL12-CXCR4 Signaling Axis in a Genetically Modified S. cerevisiae: Discovery of a Novel Up-Regulator of CXCR4 Activity." Frontiers in molecular biosciences, vol. 7, 2020, pp. 164.|
|Cui JY, Zhang F, Nierzwicki L, Palermo G, Linhardt RJ, Lisi GP. "Mapping the Structural and Dynamic Determinants of pH-Sensitive Heparin Binding to Granulocyte Macrophage Colony Stimulating Factor." Biochemistry, vol. 59, no. 38, 2020, pp. 3541-3553.|
East, K. W., Skeens, E., Cui, J. Y., Belato, H. B., Mitchell, B., Hsu, R., Batista, V. S., Palermo, G., Lisi, G. P.
"NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes." Biophysical Reviews, vol. 12, no. 1, 2020, pp. 155-174.
|East KW, Skeens E, Cui JY, Belato HB, Mitchell B, Hsu R, Batista VS, Palermo G, Lisi GP. "NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes." Biophysical Reviews, vol. 12, no. 1, 2020, pp. 155-174.|
|Belato H.B., East K.W., Lisi G.P. "1H, 13C, 15N Backbone and Side Chain Resonance Assignment of the HNH Nuclease from Streptococcus pyogenes CRISPR-Cas9." Biomolecular NMR assignments, vol. 13, no. 2, 2019, pp. 367-370.|
|Negre C.F.A., Morzan U.N., Hendrickson H.P., Pal R., Lisi G.P., Loria J.P., Rivalta I., Ho J., Batista V.S. "Eigenvector Centrality for Characterization of Protein Allosteric Pathways." Proceedings of the National Academy of Sciences, vol. 115, no. 52, 2018, pp. E12201-E12208.|
|Lisi GP, Currier AA, Loria JP. "Glutamine Hydrolysis by Imidazole Glycerol Phosphate Synthase Displays Temperature Dependent Allosteric Activation." Frontiers in molecular biosciences, vol. 5, 2018, pp. 4.|
|Lisi, G.P.,* Loria, J.P.* (*Corresponding Authors, Thematic Issue on Catalysis and Regulation). "Allostery in Enzyme Catalysis." Current Opinion in Structural Biology, vol. 47, 2017, pp. 123-130.|
|Lisi, G.P., East, K.W., Batista, V.S., Loria, J.P. "Altering the Allosteric Pathway in IGPS Suppresses Millisecond Motions and Catalytic Activity." Proceedings of the National Academy of Sciences, vol. 114, no. 17, 2017, pp. E3414-E3423.|
|Rivalta I, Lisi GP, Snoeberger NS, Manley G, Loria JP, Batista VS. "Allosteric Communication Disrupted by a Small Molecule Binding to the Imidazole Glycerol Phosphate Synthase Protein-Protein Interface." Biochemistry, vol. 55, no. 47, 2016, pp. 6484-6494.|
|Lisi GP, Hughes RP, Wilcox DE. "Coordination contributions to protein stability in metal-substituted carbonic anhydrase." Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, vol. 21, no. 5-6, 2016, pp. 659-67.|
|Lisi, G.P.,* Loria, J.P.* (*Corresponding Authors, Thematic Issue on Protein Ensembles and Allostery). "Solution NMR Spectroscopy for the Study of Enzyme Allostery." Chemical Reviews, vol. 116, 2016, pp. 6323-6369.|
|Lisi G.P., Loria J.P. "Using NMR spectroscopy to elucidate the role of molecular motions in enzyme function." Progress in nuclear magnetic resonance spectroscopy, vol. 92-93, 2016, pp. 1-17.|
|Amacher JF, Zhong F, Lisi GP, Zhu MQ, Alden SL, Hoke KR, Madden DR, Pletneva EV. "A Compact Structure of Cytochrome c Trapped in a Lysine-Ligated State: Loop Refolding and Functional Implications of a Conformational Switch." J. Am. Chem. Soc., vol. 137, no. 26, 2015, pp. 8435-49.|
|Zhong F, Lisi GP, Collins DP, Dawson JH, Pletneva EV. "Redox-dependent stability, protonation, and reactivity of cysteine-bound heme proteins." Proceedings of the National Academy of Sciences, vol. 111, no. 3, 2014, pp. E306-15.|
|Lisi GP, Png CY, Wilcox DE. "Thermodynamic contributions to the stability of the insulin hexamer." Biochemistry, vol. 53, no. 22, 2014, pp. 3576-84.|
|Harper-Leatherman AS, Iftikhar M, Ndoi A, Scappaticci SJ, Lisi GP, Buzard KL, Garvey EM. "Simplified procedure for encapsulating cytochrome c in silica aerogel nanoarchitectures while retaining gas-phase bioactivity." Langmuir, vol. 28, no. 41, 2012, pp. 14756-65.|
The Lisi laboratory utilizes solution NMR methods along with techniques in biochemistry, biophysics, and molecular biology to interrogate changes in protein structure and conformational motions that underlie function. We are especially focused on enzyme complexes, aiming to understand how biological events such as protein-protein interaction or the binding of allosteric effectors and drug-like molecules modulate functionally relevant protein motions, intra- and intermolecular signaling, and/or catalytic reactivity. There are several projects underway in the laboratory, including:
1) Regulation of protein structure, dynamics, and interactions by local changes to cellular environments
2) "Dynamic allostery" - Elucidating long-range signaling pathways in large enzyme complexes and machines
3) "Latent allostery" - Uncovering new or dormant functional sites in protein complexes
Trainer, Program in Molecular Biology, Cell Biology, & Biochemistry
Trainer, Program in Molecular Pharmacology & Physiology
Trainer, Program in Pathobiology
|BIOL 0280 - Biochemistry|
|BIOL 1270 - Advanced Biochemistry|
|BIOL 2270 - Advanced Biochemistry|