Robert J Kerns

Robert J Kerns

, PhD
  • Department Chair, Pharmaceutical Sciences & Experimental Therapeutics
  • Professor, Department of Pharmaceutical Sciences and Experimental Therapeutics / Division of Medicinal and Natural Products Chemistry

Research Narrative

Dr. Kerns’ research is focused in three programmatic areas. One research program is focused on antibiotic resistance and anti-infective drug discovery. This program employs synthetic chemistry as the foundation of an interdisciplinary strategy utilizing the design, synthesis and evaluation of novel antibiotics, analogs and molecular probes to study bacterial resistance mechanisms and to explore the development of new agents that are active against drug-resistant pathogens.

A second area of study in the Kern laboratory focuses on biologically important glycoconjugates. An emphasis within this program is the evaluation of new approaches to inhibit cellular interactions and biological processes mediated by cell surface glycosaminoglycans. The Kerns group is developing new strategies to design and synthesize non-polyanionic molecules that block or modulate physiological processes mediated by glycosaminoglycan-protein interactions.

The Kerns group also provides Medicinal Chemistry expertise and support for follow-up to high throughput screening and for a number of interdisciplinary, translational research projects focused on the design, synthesis and evaluation of novel bioactive small molecules and molecular probes. Ongoing studies include optimizing lead structures for use as chemical probes to validate new drug targets and characterizing structure-function relationships for lead structures toward the discovery of new therapeutics for a number of diseases including infectious diseases, inflammatory lung disease, diabetes, obesity and cancer.

Curriculum vitae

Education
BS, Chemistry, Iowa State University, Department of Chemistry, 1987-1991
PhD, Medicinal and Natural Products Chemistry (NIH Predoctoral Fellow, Traineeship in Biotechnology) The University of Iowa, College of Pharmacy, 1992-1996

Professional Experience
1995, Predoctoral Traineeship in Biotechnology, Research Externship, AMGEN, Thousand Oaks, CA, Supervisor: Dr. Andre Venot
1996-1998, NIH Postdoctoral Fellow, (NRSA Through the NIAID) , Princeton University, Department of Chemistry, Sponsor: Professor Daniel Kahne
1998-2002, Assistant Professor of Medicinal Chemistry, Wayne State University, Eugene Applebaum College of Pharmacy and Health Sciences, (Associate Appointment, Department of Immunology and Microbiology, Wayne State University School of Medicine)
2002-2006, Assistant Professor of Medicinal & Natural Products Chemistry, University of Iowa, College of Pharmacy
2006-2012, Associate Professor of Medicinal & Natural Products Chemistry, University of Iowa, College of Pharmacy
2010-present, Division Head of Medicinal & Natural Products Chemistry, University of Iowa, College of Pharmacy
2012-present, Professor of Medicinal & Natural Products Chemistry, University of Iowa, College of Pharmacy

Awards
2008 Class of 2011 Teacher of the Year, University of Iowa College of Pharmacy
2004 Collegiate Teacher of the Year, University of Iowa College of Pharmacy
2004 Class of 2007 Teacher of the Year, University of Iowa College of Pharmacy
2000 - 2001 American Association of Colleges of Pharmacy, New Investigators in Pharmacy Award
2000 - 2003 American Heart Association, Midwest Affiliate, Scientist Development Grant
1997 - 1998 National Institutes of Health Postdoctoral Fellowship - National Research Service Award, distributed through the National Institute of Allergy and Infectious Disease
1994 - 1996 National Institutes of Health Predoctoral Fellowship - A competitive traineeship in Biotechnology awarded through The University of Iowa Biocatalysis and Bioprocessing program

Representative Publications
Aldred, K.J., Kerns, R.J., Osheroff, N. Mechanism of quinolone action and resistance. Biochem. 2014, 53(10): 1565-74. PMCID: PMC3985860.

Mustaev, A., Malik, M., Zhao, X., Kurepina, N., Luan, G., Oppegard, L.M., Hiasa, H., Marks, K.R., Kerns, R.J., Berger, J.M., Drlica, K. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding. J. Biol. Chem. 2014, 289(18): 12300-12. PMCID:PMC4007428.

Aldred, K.J., Schwanz, H.A., Li, G., McPherson, S.A., Turnbough, C.L. Jr., Kerns, R.J., Osheroff, N. Overcoming target-mediated quinolone resistance in topoisomerase IV by introducing metal-ion-independent drug-enzyme interactions. ACS Chem. Biol. 2013, 8(12): 2660-8. PMCID: PMC3870039.

Fenner, A.M., Oppegard, L., Hiasa, H., Kerns, R.J. Selective inhibition of bacterial and human topoisomerases by N-arylacyl O-sulfonated aminoglycoside derivatives. ACS. Med. Chem. Lett. 2013, 4(5): 470-474. PMCID: PMC3694624

Towle, T., Change, I., Kerns, R.J., Bhanot, P. Chemical probes of a trisubstituted pyrrole to identify its protein target in Plasmodium sporozoites. Bioorg. Med. Chem. Lett. 2013, 23: 1874-1877. PMID: 23395653

Aldred, K.J., McPherson, S.A., Turnbough, C.L., Kerns, R.J., Osheroff, N. Topoisomerase IV-Quinolone Interactions Are Mediated Through a Water-Metal Ion Bridge: Mechanistic Basis of Quinolone Resistance. Nucleic Acids Research, 2013, 41(8): 4628-4639. PMCID: PMC3632122

Fink, B. D., Herlein, J. A., Yorek, M. A., Fenner, A. M., Kerns, R. J., Sivitz, W. I. Bioenergetic Effects of Mitochondrial-Targeted Coenzyme Q Analogs in Endothelial Cells. J. Pharmacol. Exper. Ther. 2012, 342(3): 709-719. PMCID: PMC3422527

Malik, M.; Chavda, K.; Zhao, X.; Shah, N.; Hussain, S.; Kurepina, N.; Kreiswirth, B. N.; Kerns, R. J.; Drlica, K. Induction of mycobacterial resistance to quinolone-class antimicrobials. Antimicrob. Agents Chemother. 2012, 56(7): 3879-3887. PMCID: PMC3393424

Aldred, K. J., McPherson, S. A., Wang, P., Kerns, R. J., Graves, D. E., Turnbough, C. L., Osheroff, N. Drug Interactions with Bacillus anthracis Topoisomerase IV: Biochemical Basis for Quinolone Action and Resistance. Biochemistry, 2012, 51: 370-381. PMCID: PMC3261753

Fenner, A.M., Kerns, R.J. Synthesis, separation, and characterization of amphiphilic sulfated oligosaccharides enabled by reversed-phase ion pairing LC and LC-MS methods. Carbohydr Res. 2011, 346(17):2792-800.

Marks, K.R., Malik, M., Mustaev, A., Hiasa, H., Drlica, K., Kerns, R.J. Synthesis and evaluation of 1-cyclopropyl-2-thioalkyl-8-methoxy fluoroquinolones. Bioorg Med Chem Lett. 2011, 21(15):4585-8.

Malik, M., Marks, K.R., Schwanz, H.A., German, N., Drlica, K., Kerns, R.J. Effect of N-1/C-8 ring fusion and C7 ring structure on fluoroquinolone lethality. Antimicrob. Agents Chemother. 2010, 54(12): 5214-21.

Oppegard, L.M., Streck, K.R., Rosen, J.D., Schwanz, H.A., Drlica, K., Kerns, R.J., Hiasa, H. Comparison of in vitro activities of fluoroquinolone-like 2,4- and 1,3-diones. Antimicrob. Agents Chemother. 2010, 54(7) 3011-3014.

Malik, M., Hoatam, G., Chavda, K., Kerns, R.J., Drlica, K. Novel approach for comparing the ability of quinolones to restrict the emergence of resistant mutants during quinolone exposure, Antimicrob. Agents Chemother. 2010, 54(1): 149–156. PMCID: PMC2798492

Rosen, J., German, N., Kerns, R.J. Efficient Synthesis of the 2-amino-6-chloro-4-cyclopropyl-7-fluoro-5-methoxy-pyrido[1,2-c]pyrimidine-1,3-dione core ring system, Tet. Lett. 2009, 50: 785-789. PMCID: PMC2631556.

German, N., Malik, M., Rosen, J.D., Drlica, K., Kerns, R.J. Use of gyrase resistance mutants to guide selection of 8-methoxy-quinazoline-2,4-diones, Antimicrob. Agents Chemother. 2008, 52(11): 3915–3921. PMCID: PMC2573108

German, N., Kaatz, G.W., Kerns, R.J. Synthesis and evaluation of PSSRI-based inhibitors of Staphylococcus aureus multidrug efflux pumps, Bioorg. Med. Chem. Lett. 2008, 18: 1368-1373.

German, N., Wei, P., Kaatz, G.W., Kerns, R.J. Synthesis and evaluation of fluoroquinolone derivatives as substrate-based inhibitors of bacterial efflux pumps, Eur. J. Med. Chem. 2008, 43(11): 2453-2463.

Huang, L., Fernández, C., Kerns, R.J. Different protein-binding selectivities for N-acyl heparin derivatives having N-phenylacetyl and heterocycle analogs of N-phenylacetyl substituted in place of N-sulfo groups, Bioorg. Med. Chem. Lett. 2007, 17: 419-423.

Zhao, X., Quinn, B., Kerns, R.J., Drlica, K. Bactericidal activity and target preference of a piperazinyl-crosslinked ciprofloxacin dimer with Staphylococcus aureus and Escherichia coli. J. Antimicrob. Chemother. 2006,58: 1283-1286.

Fernández, C., Hattan, C.M., Kerns, R.J. Semi-synthetic heparin derivatives: chemical modifications of heparin beyond chain length, sulfate substitution pattern and N-sulfo/N-acetyl groups. Carbohydr. Res. 2006, 341: 1253-1265.

Huang, L., Kerns, R.J. Diversity-Oriented Chemical Modification of Heparin: Identification of Charge-Reduced N-Acyl Heparin Derivatives Having Increased Selectivity for Heparin-Binding Proteins. Bioorg. Med. Chem. 2006, 14: 2300-2313.

Kerns, R.J., Rybak, M.J., Cheung, C.M. Susceptibility studies of piperazinyl-cross-linked fluoroquinolone dimers against test strains of Gram-positive and Gram-negative bacteria. Diagn. Microbiol. Infect. Dis. 2006, 54: 305-310.

Wei, P., Kerns, R.J. Chemoselective deprotection and functional group interconversion of ring-fused 2N,3O-oxazolidinones of N-acetyl-D-glucosamine. Tetrahedron Lett. 2005, 46: 6901-6905.

Wei, P., Kerns, R.J. Factors Affecting Stereocontrol during Glycosidation of 2,3-Oxazolidinone Protected 1-Tolylthio-N-acetyl-D-glucosamine. J. Org. Chem. 2005, 70: 4195-4198.

Wei, P., Kaatz, G.W., Kerns, R.J. Structural Differences Between Paroxetine and Femoxetine Responsible for Differential Inhibition of Staphylococcus aureus Efflux Pumps. Bioorg. Med. Chem. Lett. 2004, 14: 3093-3097.

Kerns, R.J., Zha, C., Benakli. K., Liang YZ. Extended Applications and Potential Limitations of Ring-Fused 2,3-Oxazolidinone Thioglycosides in Glycoconjugate Synthesis. Tetrahedron. Lett. 2003, 44: 8069-8072.

Kerns, R.J., Rybak, M.J., Kaatz, G.W., Vaka, F., Cha, R., Grucz, R.G., Diwadkar, V.U. Structural Requirements of Piperazinyl-Linked Fluoroquinolone Dimers for Activity Against Drug-Resistant Strains of Staphylococcus aureus. Bioorg. Med. Chem. Lett. 2003, 13(13): 2109-2112.

Kerns, R.J., Rybak, M.J., Kaatz, G.W., Vaka, F., Cha, R., Grucz, R.G., Diwadkar, V.U., Ward, T.D. Piperazinyl-Linked Fluoroquinolone Dimers Possessing Potent Antibacterial Activity Against Drug-Resistant Strains of Staphylococcus aureus. Bioorg. Med. Chem. Lett. 2003, 13(10): 1745-1749.

Benakli, K., Zha, C., Kerns R.J. Oxazolidinone Protected 2-Amino-2-Deoxy-D-Glucose Derivatives as Intermediates in Stereoselective Oligosaccharide Synthesis and the Formation of Alpha-Linked Glycosides. J. Am. Chem. Soc. 2001, 123: 9461-9462.