John O. Trent, Ph. D.

Wendell Cherry Endowed Chair in Cancer Translational Research

Phone Number: (502) 852 2194 (Office)
Fax Number: (502) 852 4311

Suite 323, J.G. Brown Cancer Center
527 South Jackson St. Louisville, KY 40202




Additional Appointments:

  • Professor of Medicine, of Chemistry and of Biochemistry & Molecular Genetics
  • Professor, Division of Hematology/Oncology, Dept. of Medicine
  • Professor, Division of Internal Medicine, Department of Medicine
  • Director, Kosair Pediatric Oncology Research Program
  • Director, Molecular Modeling Facility, James Graham Brown Cancer Center


  • Ph. D. 1992, University of Canterbury, New Zealand

Laboratory Team Members:

Indira Chaudhuri, Ph. D. - Postdoctoral Fellow
Rafael Del Villar Guerra, Ph. D. - Postdoctoral Fellow
Huy Le - MD/Ph. D. student


Research Focus:

Structure-based drug design, macromolecular molecular dynamics modeling of proteins, DNA and RNA drug discovery.

My group uses numerous computational techniques to complement experimental approaches aimed at understanding macromolecular interactions. The methods include molecular dynamics, free energy perturbation calculations, and Monte-Carlo methods as applied to real world problems. The combination of modeling techniques with different experimental modalities such as NMR, X-ray diffraction and thermodynamic methods is synergistic, and is the key to understanding structure and function. We have successfully modeled the structure of the nucleolin binding quadruplex, as verified by biophysical studies such as CD (with P. Bates), analytical ultracentrifugation and NMR (with A. Lane). We also have produced detailed rhodopsin-based homology models of the CCR5 and CXCR4 chemokine receptors, embedded in a complete, solvated lipid bilayer, that successfully account for the saturation mutation data obtained by Dr. S. C. Peiper at the Brown Cancer Center (now at Georgia Medical College, Augusta). We have a strong interest in quadruplex structure and as a drug target and collaborate with Dr. J. B. Chaires on the biophysical aspect of this work.

We also have enhanced our drug discovery program by establishing a distributing computing Grid for virtual screening. The Grid development is in collaboration with Dataseam and uses thousands of computer processors in schools across the Commonwealth of Kentucky. It is now routine in my laboratory to screen millions of potential compounds against a cancer target in days. We have successfully screened over 60 cancer targets that are moving into the laboratories for anticancer activity testing.


Selected Publications:

  • van der Watt PJ, Chi A, Stelma T, Stowell C, Strydom E, Carden S, Angus L, Hadley K, Lang D, Wei W, Birrer MJ, Trent JO, Leaner VD. Targeting the Nuclear Import Receptor Kpnβ1 as an Anticancer Therapeutic. Mol Cancer Ther. 2016 Apr;15(4):560-73. doi: 10.1158/1535-7163.MCT-15-0052. Epub 2016 Feb 1. PubMed PMID: 26832790.
  • Sabo TM, Trent JO, Lee D. Population shuffling between ground and high energy excited states. Protein Sci. 2015 Nov;24(11):1714-9. doi: 10.1002/pro.2797. Epub 2015 Oct 15. PubMed PMID: 26316263; PubMed Central PMCID: PMC4622205.
  • Chesney J, Clark J, Lanceta L, Trent JO, Telang S. Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor. Oncotarget. 2015 Jul 20;6(20):18001-11. PubMed PMID: 26221874; PubMed Central PMCID: PMC4627231.
  • Miller MC, Ohrenberg CJ, Kuttan A, Trent JO. Separation of Quadruplex Polymorphism in DNA Sequences by Reversed-Phase Chromatography. Curr Protoc Nucleic Acid Chem. 2015 Jun 1;61:17.7.1-18. doi: 10.1002/0471142700.nc1707s61. PubMed PMID: 26344226; PubMed Central PMCID: PMC4561857.
  • England CG, Miller MC, Kuttan A, Trent JO, Frieboes HB. Release kinetics of paclitaxel and cisplatin from two and three layered gold nanoparticles. Eur J Pharm Biopharm. 2015 May;92:120-9. doi: 10.1016/j.ejpb.2015.02.017. Epub 2015 Mar 7. PubMed PMID: 25753197; PubMed Central PMCID: PMC4430429.
  • Snyder RD, Holt PA, Maguire JM, Trent JO. Evidence for the contribution of non-covalent steroid interactions between DNA and topoisomerase in the genotoxicity of steroids. Drug Chem Toxicol. 2015 Apr;38(2):212-9. doi: 10.3109/01480545.2014.928725. Epub 2014 Jun 30. PubMed PMID: 24975547.
  • Gaddipati S, Lu Q, Kasetti RB, Miller MC, Lu Q, Trent JO, Kaplan HJ, Li Q. IKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced choroidal neovascularization and macrophage recruitment. PLoS One. 2015 Mar 24;10(3):e0121185. doi: 10.1371/journal.pone.0121185. eCollection 2015. PubMed PMID: 25803615; PubMed Central PMCID: PMC4372421.
  • Chaires JB, Dean WL, Le HT, Trent JO. Hydrodynamic Models of G-Quadruplex Structures. Methods Enzymol. 2015;562:287-304. doi: 10.1016/bs.mie.2015.04.011. Epub 2015 Jun 19. PubMed PMID: 26412657.
  • Le HT, Dean WL, Buscaglia R, Chaires JB, Trent JO. An investigation of G-quadruplex structural polymorphism in the human telomere using a combined approach of hydrodynamic bead modeling and molecular dynamics simulation. J Phys Chem B. 2014 May 22;118(20):5390-405. doi: 10.1021/jp502213y. Epub 2014 May 8. PubMed PMID: 24779348; PubMed Central PMCID: PMC4032189.
  • Zhao G, Zhu Y, Eno CO, Liu Y, Deleeuw L, Burlison JA, Chaires JB, Trent JO, Li C. Activation of the proapoptotic Bcl-2 protein Bax by a small molecule induces tumor cell apoptosis. Mol Cell Biol. 2014 Apr;34(7):1198-207. doi: 10.1128/MCB.00996-13. Epub 2014 Jan 13. PubMed PMID: 24421393; PubMed Central PMCID: PMC3993561.
  • Li J, Zheng H, Bates PJ, Malik T, Li XF, Trent JO, Ng CK. Aptamer imaging with Cu-64 labeled AS1411: preliminary assessment in lung cancer. Nucl Med Biol. 2014 Feb;41(2):179-85. doi: 10.1016/j.nucmedbio.2013.10.008. Epub 2013 Oct 29. PubMed PMID: 24373858.
  • Chaires JB, Trent JO, Gray RD, Dean WL, Buscaglia R, Thomas SD, Miller DM. An improved model for the hTERT promoter quadruplex. PLoS One. 2014 Dec 19;9(12):e115580. doi: 10.1371/journal.pone.0115580. eCollection 2014. PubMed PMID: 25526084; PubMed Central PMCID: PMC4272262.


Patents & Licenses:

  • 12-Feb-10 Treatment of Age-Related Macular Degeneration Using a Molecular Antagonist of MIF, 61/396,009 (prov. appln), Robert Mitchell, John Trent, Tongalp Tezel, Henry Kaplan
  • 28-May-10 ANAPC11 as a Target for Chemotherapy, J. Christopher States, Ben Frazier, John Trent
  • 13-Jun-11 A New Method for the Diagnosis and Prognosis of Malignant Diseases "7,541,150 (US -issued) PCT/US03/10745  (PCT) 2003-583205 (Japan) 2003234694 (Australia-issued)  2,490,724 (Canada-Issued) 3728350.4 (EU) Validation-France Validation-Germany  Validation-Italy Validation-Spain Validation-United Kingdom CIP FAMILY 7,357,928  (US-CIP issued) 12/041,969 (USA-CIP) PCT/US04/033174 (PCT-CIP) 2,546,730 (Canada-CIP)  2004279837 (Australia-CIP) 4785392.4 (EU-CIP)  2006-534360 (Japan-CIP) 7101518.4 (Hong Kong-CIP) The CIP family (treatment claims) are licensed to CharlestonPharma (March 2011).     A license to the original, parental family (diagnostic claims) is currently under negotiation with CharlestonPharma.
  • 24-Aug-10 Mammory Carcinogen-Protein Binding Potentials: Novel and Biologically Relevant Structure-Activity Relationship Model Descriptors  61/380,048 (prov. appln), PCT/US11/50350, 13/224,915 (U.S. nonprov) Albert R. Cunningham, John O. Trent To be optioned by Gnarus
  • 12-Oct-10 Identification of a Novel Small Molecule Antagonist of the MIF Homolog, D-Dopachrome Tautomerase. Robert A. Mitchel, John O. Trent, research disclosure with OTT
  • 20-Nov-11 Use of a Novel Lactate Dehydrogenase A Inhibitor 5-[(3R)-3-(2-Chloro-6-Methoxyquinolin-3-YL)-5-(4-Chlorophenyl)-3,4-Dihydropyrazol-2-YL]-5-Oxopentanoate (termed CCDO-1; Zinc09043798), for the Treatment of Cancer   Jason Chesney, John Trent, Sucheta Telang, Brian Clem, research disclosure with OTT
  • 5-Dec-11  Identification and Validation of Novel Arylamine N-Acetyltransferase Small Molecule Inhibitors   Mark A. Doll, David W. Hein, Carmine Leggett, John O. Trent, Jason Walraven research disclosure with OTT; prior art search underway (2012)
  • 21-Dec-11 Promoting Tumor Cell Apoptosis by Directly Activating the Pro-Apoptotic Bel-2 Protein Bax   Chi Li, John O. Trent, research disclosure with OTT
  • 10-May-12 Targeted Inhibition of Karyopherin B-Mediated Nuclear Transport (KpnB1) Using Small Molecule Inhibitors Virna Leaner, John Trent joint research disclosure with University of Capetown, S.A.