帝王会所

Education

Ph.D., University of Michigan

Research

• The Hines Research Lab
• Structural and Chemical Biology
• Molecular Biology
• RNA-targeted Medicinal Chemistry

The focus of our research group is RNA drug discovery. We employ an interdisciplinary approach to developing RNA-targeted medicinal agents that could potentially treat diseases such as COVID-19, multidrug resistant bacterial infections, and cancer. RNA plays a critical role in viral replication, bacterial regulation and cancer biogenesis. By targeting key RNA-mediated regulatory processes for these diseases we hope to ultimately develop novel medicinal agents. Through a combination of chemical, molecular, and structural biology studies we are determining the structure-function relationships of medicinally relevant RNA targets and the structure-activity relationships of small molecule ligands that bind the RNA. We utilize a variety of approaches ranging from biophysical (fluorescence, UV, NMR) to bioinformatics, computational and molecular biology techniques. Our goal is to gain an in-depth understanding of the factors that govern molecular recognition of RNA by small molecules and to use this knowledge in the development of novel medicinal agents.

Selected Publications

Aldhumani, A. H., Hossain, Md. I., Fairchild, E. A., Boesger, H., Marino, E. C., Myers, M., and Hines, J. V.,  RNA sequence and ligand binding alter conformational profile of SARS-CoV-2 stem loop II motif, Biochem. Biophys. Res. Commun. 2021, 545, 75-85.

Shriwas, P., Roberts, D., Li, Y., Wang, L., Qian, Y., Bergmeier, S., Hines, J., Adhicary, S., Nielsen, C., and Chen, X. A small-molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism Cancer & Metabolism 2021, 9, 1-14.

Ghazanfari, D., Noori, M. S., Bergmeier, S. C., Hines, J. V., McCall, K. D., Goetz, D. J.  A novel GSK-3 inhibitor binds to GSK-3尾 via a reversible, time and Cys-199-dependent mechanism Bioorg. Med. Chem. 2021, 40, 116179.

E.R. Murphy, J. Rossmanith, J. Sieg, M.E. Fris, H. Hussein, A.B. Kouse, K. Gross, C. Zeng, J.V. Hines, F. Narberhause, P.W. Coshigano Regulation of OmpA translation and Shigella dysenteriae virulence by an RNA thermometer. Infection & Immunity  2020 Feb 20;88(3):e00871-19 doi: 10.1128/IAI.00871-19

I. Armstrong, A.H. Aldhumani, J. L. Schopis, F. Fang, E.Parsons, C. Zeng, Md. I. Hossain, S. C. Bergmeier, J.V. RNA Drug discovery: Conformational restriction enhances specific modulation of the T-Box riboswitch function Hines Bioorg. Med. Chem. 2020, 28, 115696.

Liu, J.; Zeng, C.; Hogan, V.; Zhou, S.; Monwar, M. M.; Hines, J. V. Identification of spermidine binding site in T-box riboswitch antiterminator RNA. Chem. Biol. Drug Design 2016, 87, 182-189.

Zhou, S.; Anupam, R.; Hines, J. V. Fluorescence anisotropy: Analysis of tRNA binding to the T box riboswitch. Methods in Mol. Biol. 2015, 1240, 143-152.

Zeng, C.; Zhou, S.; Bergmeier, S. C.; Hines, J. V. Factors that influence T box riboswitch efficacy and tRNA affinity. Bioorg. Med. Chem. 2015, 23, 5702-5708.

Liu, J.; Zeng, C.; Zhou, S.; Means, J. A.; Hines, J. V. Fluorescence assays for monitoring RNA-ligand interactions and riboswitch-targeted drug discovery screening. Methods Enzymol. 2015, 550, 363-383.

Anupam, R.; Zhou, S.; Hines, J. V. Electrophoretic mobility shift assay of RNA-RNA complexes. Methods in Mol. Biol. 2015, 1240, 153-164.

Zhou, S.; Acquaah-Harrison, G.; Bergmeier, S. C.; Hines, J. V. Anisotropy studies of tRNA - T box antiterminator RNA complex in the presence of 1,4-disubstituted 1,2,3-triazoles. Bioorg. Med. Chem. Lett. 2011, 21, 7059-7063.

Zhou, S.; Acquaah-Harrison, G.; Jack, K. D.; Bergmeier, S. C.; Hines, J. V. Ligand-induced changes in T box antiterminator RNA stability. Chem. Biol. Drug Design 2011, 79, 202-208.

Zhou, S.; Means, J. A.; Acquaah-Harrison, G.; Bergmeier, S. C.; Hines, J. V. Characterization of a 1,4-disubstituted 1,2,3-triazole binding to T box antiterminator RNA Bioorg. Med. Chem. 2011, 20, 1298-1302.

Orac, C. M.; Zhou, S.; Means, J. A.; Boehme, D.; Bergmeier, S. C.; Hines, J. V. Synthesis and stereospecificity of 4,5-disubstituted oxazolidinone ligands binding to T-box riboswitch RNA. J. Med. Chem. 2011, 54, 6786-6795.

Maciagiewicz, I.; Zhou, S.; Bergmeier, S. C.; Hines, J. V. Structure activity studies of RNA-binding oxazolidinone derivatives. Bioorg. Med. Chem. Letters 2011, 21, 4524-4527.

Jentzsh, F.; Hines, J. V. Interfacing medicinal chemistry with structural bioinformatics: Implications for T box riboswitch RNA drug discovery BMC Bioinformatics (GLBIO 2011 Special Issue) 2011, 13, S5-S10.

Acquaah-Harrison, G.; Zhou, S.; Hines, J. V.; Bergmeier, S. C. Library of 1,4-disubstituted 1,2,3-triazole analogs of oxazolidinone RNA-binding agents. J. Comb. Chem. 2010, 12, 491-496.

Means, J. A.; Simson, C. M.; Zhou, S.; Rachford, A. A.; Rack, J.; Hines, J. V. Fluorescence probing of T box antiterminator RNA: Insights into riboswitch discernment of the tRNA discriminator base. Biochem. Biophys. Res. Commun. 2009, 389, 616-621.

Fauzi, H.; Agyeman, A.; Hines, J. V. T box transcription antitermination riboswitch: Influence of nucleotide sequence and orientation on tRNA binding by the antiterminator element. BBA-Gene Reg. Mech. 2009, 1789, 185-191.

Jack, K. D.; Means, J. A.; Hines, J. V. Characterizing riboswitch function: Identification of Mg²⁺ binding site in T box antiterminator RNA. Biochem. Biophys. Res. Commun. 2008, 370, 306-310.

Anupam, R.; Bergmeier, S. C.; Green, N. J.; Grundy, F. J.; Henkin, T. M.; Means, J. A.; Nayek, A.; Hines, J. V. 4,5-Disubstituted Oxazolidinones: High affinity molecular effectors of RNA function. Bioorg. Med. Chem. Lett. 2008, 18, 3541-3544.

Anupam, R.; Denapoli, L.; Muchenditsi, A. M.; Hines, J. V. Identification of neomycin B binding site in T box antiterminator model RNA. Bioorg. Med. Chem. 2008, 16, 4466-4470.

Means, J. A.; Wolf, S.; Agyeman, A.; Burton, J. S.; Simson, C. M.; Hines, J. V. T box riboswitch antiterminator affinity modulated by tRNA structural elements Chem. Biol. Drug Design 2007, 69, 139-145.

Means, J. A.; Katz, S. J.; Nayek, A.; Anupam, R.; Hines, J. V.; Bergmeier, S. C. Structure activity studies of oxazolidinone analogs as RNA-binding agents. Bioorg. Med. Chem. Lett. 2006, 16, 3600-3604.

Means, J. A.; Hines, J. V. Fluorescence resonance energy transfer studies of aminoglycoside binding to a T box antiterminator RNA. Bioorg. Med. Chem. Lett. 2005, 15, 2169-2172.

Fauzi, H.; Jack, K. D.; Hines, J. V. In vitro selection to identify determinants in tRNA for Bacillus subtilis tyrS T box antiterminator mRNA binding. Nucleic Acids Res. 2005, 8, 2595-2602.

Gerdeman, M. S.; Henkin, T. M.; Hines, J. V. Solution structure of the B. subtilis T box antiterminator RNA: Seven-nucleotide bulge characterized by stacking and flexibility. J. Mol. Biol. 2003, 326, 189-201.

Gerdeman, M. S.; Henkin, T. M.; Hines, J. V. In vitro structure-function studies of the Bacillus subtilis tyrS mRNA antiterminator: Evidence for factor independent tRNA acceptor stem binding specificity. Nucleic Acids Res. 2002, 30, 1065-1072.