James W. Janetka, Ph.D.

Associate Professor

Biochemistry and Molecular Biophysics

Lab Website
Publications (PubMed / NIH)

Office: 2614 Cancer Research
Phone: 314-362-0509
Email: janetkaj(at)wustl.edu


The Janetka research group is studying therapeutic targets and cellular mechanisms in cancer and infectious disease. The overall focus of the lab is to interfere with key biological processes outside the cell, by inhibiting one or more key proteins, which are important in bacterial pathogenesis or tumor progression. We employ rational structure-based drug design and synthetic medicinal chemistry to develop peptide-based and small molecule inhibitors as chemical tools to help decipher mechanisms of disease. In one project we are developing glycoside-based antagonists of adhesins, such as FimH, FmlD, and PapG, in E. coli., which are essential for host-bacteria interactions in UTI. In another project, we are developing peptide-based and small molecule inhibitors of serine proteases, including HGFA, matriptase and hepsin, which post-translationally process the growth factor ligands of c-MET and RON receptor tyrosine kinases, both important in tumor progression and metastatic cancer. The long-term goal of our research is to identify preclinical candidate drugs as new and innovative medicines for treating patients with resistant infections and cancer.

jim janetka lab pic


  • Yang B., Vasbinder M., Hird A.W., Su Q., Wang H., Yu Y., Toader D., Lyne P.D., Read J.A., Breed J., Ioannidis S., Deng C., Grondine M., DeGrace N., Whitston D., Brassil P., and Janetka J.W.
    Adventures in Scaffold Morphing: Discovery of Fused Ring Heterocyclic Checkpoint Kinase 1 (CHK1) Inhibitors.
    J Med Chem. doi: 10.1021/acs.jmedchem.7b01490. (2018) (Abstract)

  • Rutaganira F.U., Barks J., Dhason M.S., Wang Q., Lopez M.S., Long S., Radke J.B., Jones N.G., Maddirala A.R., Janetka J.W., El Bakkouri M., Hui R., Shokat K.M., and Sibley L.D.
    Inhibition of calcium dependent protein kinase 1 (CDPK1) by pyrazolopyrimidine analogs decreases establishment and reoccurrence of central nervous system disease by Toxoplasma gondii.
    J Med Chem. doi: 10.1021/acs.jmedchem.7b01192. (2017) (Abstract)

  • Spaulding C.N., Klein R.D., Ruer S., Kau A.L., Schreiber H.L., Cusumano Z.T., Dodson K.W., Pinkner J.S., Fremont D.H., Janetka J.W., Remaut H., Gordon J.I., and Hultgren S.J.
    Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist.
    Nature. 546(7659):528-532. doi: 10.1038/nature22972. (2017) (Abstract, Article)

  • Owusu B.Y., Thomas S., Venukadasula P., Han Z., Janetka J.W., Galemmo R.A. Jr., and Klampfer L.
    Targeting the tumor-promoting microenvironment in MET-amplified NSCLC cells with a novel inhibitor of pro-HGF activation
    Oncotarget. 8(38):63014-63025. doi: 10.18632/oncotarget.18260. (2017) (Abstract)

  • Mydock-McGrane L.K., Hannan T.J., and Janetka J.W.
    Rational Design Strategies for FimH Antagonists: New Drugs on the Horizon for Urinary Tract Infection and Crohn’s Disease.
    Expert Opin Drug Discov. (2017) (Abstract)

  • Benjamin Yaw Owusu, Robert Galemmo, James Janetka, and Lidija Klampfer
    Hepatocyte Growth Factor, a Key Tumor-Promoting Factor in the Tumor Microenvironment
    Cancers 2017, 9(4), 35 (2017) (Abstract)

  • Melissa M Budelier, Wayland WL Cheng, Lucie Bergdoll, Zi-Wei Chen, James W Janetka, Jeff Abramson, Kathiresan Krishnan, Laurel Mydock-McGrane, Douglas F Covey, Julian P Whitelegge, and Alex S Evers
    Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1
    Journal of Biological Chemistry (2017) (Abstract)

  • Vasilios Kalas, Jerome S. Pinkner, Thomas J. Hannan, Michael E. Hibbing, Karen W. Dodson, Alex S. Holehouse, Hao Zhang, Niraj H. Tolia, Michael L. Gross, Rohit V. Pappu, James Janetka and Scott J. Hultgren
    Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions
    Science Advances Vol. 3, no. 2 (2017) (Abstract)

  • Melissa M. Budelier, Wayland W. L. Cheng, Lucie Bergdoll, Zi-Wei Chen, Jeff Abramson, Kathiresan Krishnan, Mingxing Qian, Douglas F. Covey, James W. Janetka, and Alex S. Evers
    Click Chemistry Reagent for Identification of Sites of Covalent Ligand Incorporation in Integral Membrane Proteins
    Analytical Chem. (2017) (Abstract)

  • Mydock-McGrane L., Cusumano Z., Han Z., Binkley J., Kostakioti M., Hannan T., Pinkner J.S., Klein R., Kalas V., Crowley J., Rath N.P., Hultgren S.J., and Janetka J.W.
    Antivirulence C-Mannosides as Antibiotic-Sparing, Oral Therapeutics for Urinary Tract Infections
    J Med Chem. (2016) (Abstract)

  • Han, Z., Harris, P.K.W., Karmakar, P., Kim, T., Owusu, B.Y., Wildman, S.A., Klampfer, L. and Janetka, J.W. alpha-Ketobenzothiazole serine protease inhibitors of aberrant HGF/c-MET and MSP/RON kinase pathway signaling in cancer. ChemMedChem 11:585-599 (2016). (Cover Story) [Abstract]
  • Wang, Q., Heizer, E., Rosa, B.A., Wildman, S.A., Janetka, J.W. and Mitreva, M. Characterizaton of parasite-specific indels and their proposed relevance for selective anthelminithic drug targeting. Infection, Genetics and Evolution 39:201-211 (2016). [Abstract]
  • Jarvis, C., Han, Z., Kalas, V., Klein, R., Pinkner, J.S., Ford, B., Binkley, J., Cusumano, C.K., Cusumano, Z., Mydock-McGrane, L., Hultren, S.J. and Janetka, J.W. Antivirulence isoquinolone mannosides: Optimization of the biaryl aglycone for FimH lectin binding affinity and efficacy in the treatment of chronic UTI. Chem Med Chem 11:367-373 (2016). (Cover Story) [Abstract]
  • Mydock-McGrane, L.K., Cusumano, Z.T. and Janetka, J.W. Mannose-derived FimH antagonists: Promising anti-virulence therapeutic strategy for urinary tract infections and Crohn’s disease. Expert Opin Ther Pat 26:175-197 (2016). [Abstract]
  • Simpson, C., Jones, N.G., Hull-Ryde, E.A., Kireev, D.B., Stashko, M., Tang, K., Janetka, J., Wildman, S.A., Zuercher, W.J., Schapira, M., Hui, R., Janzen, W.P. and Sibley, L.D. Identification of small molecule inhibitors that block the Toxoplasma gondii rhoptry kinase ROP18. ACS Infect. Dis. 2:194-206 (2015). [Abstract]
  • Greene, S.E., Hibbing, M.E., Janetka, J.W., Chen, S.L. and Hultgren, S.J. Human urine decreases function and expression of type 1 pili in uropathogenic Escherichia coli. mBio 6:e00820-15 (2015). [Abstract]
  • Franco, F.M., Jones, D.E., Harris, P.K.W., Han, Z., Wildman, S.A., Jarvis, C. and Janetka, J.W. Structure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets. Biooranic & Medicinal Chemistry SO968-0896:00268-0 (2015). [Abstract]
  • Han, Z., Harris, P.K.W., Jones, D.E., Chugani, R., Kim, T., Agarwal, M., Shen, W., Wildman, S.A. and Janetka, J.W. Inhibitors of HGFA, matriptase and hepsin serine proteases: A non-kinase strategy to block cell signaling in cancer. ACS Med. Chem. Lett. 5:1219-1224 (2014). [Abstract]
  • Totsika, M., Kostakioti, M., Hannan, T.J., Upton, M., Beaton, S.A., Janetka, J.W., Hultgren, S.J. and Schembri, M.A. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug resistant uropathogenic Escherichia coli ST131. J Infec Dis 208:921-928 (2013). [Abstract]

  • Guiton, P.S., Cusumano, C.K., Kline, K.A., Dodson, D.W., Han, Z., Janetka, J.W., Henderson, J.P., Caparon, M.G. and Hultgren, S.J. Combination small molecular therapy prevents uropathogenic Escherichia coli cather-associated urinary tract infections in mice. Antimicrob Agents Chemother. 56:4738-4745 (2012). [Abstract]

  • Kostakioti, M., Hadjifrangiskou, M., Cusumano, C.K., Hannan, T.J., Janetka, J.W. and Hultgren, S.J. Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection. Infect Immun 80:2826-2834 (2012). [Abstract]
  • Oza, V.B., Ashwell, S., Almeida, L., Brassil, P., Bree, J., Deng, C., Gero, T., Grondine, M., Horn, C., Ioannidis, S., Liu, D., Lyne, P.D., Newcombe, N., Pass, M., Read, J., Ready, S., Rowsell, S., Su, M., Toader, D., Vasbinder, M., Yu, D., Yu, Y., Xue, Y., Zabludoff, S. and Janetka, J.W. Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure based design and optimization of thiophene carboxamide ureas. Journal of Medicinal Chemistry 55:5130-5142 (2012). [Abstract]
  • Yang, B., Hird, A.W., Russell, D.J., Fauber, B.P., Dakin, L.A., Zheng, X., Su, Q., Godin, R., Brassil, P., Devereaux, E. and Janetka, J.W. Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO. Bioorganic & Medicinal Chemistry Letters 22:4907-4911 (2012). [Abstract]
  • Han, Z., Pinkner, J.S., Ford, B., Chorell, E., Crowley, J.M., Cusumano, C.K., Campbell, S., Henderson, J.P., Hultgren, S.J. and Janetka, J.W. Lead optimization studies on FimH antagonists: Discovery of potent and orally bioavailable ortho-substituted biphenyl mannosides. Journal of Medicinal Chemistry 55:3945-3959 (2012). [Abstract]
  • Cusumano, C.K., Pinkner, J.S., Han, Z., Greene, S.E., Ford, B.A., Crowley, J.R., Henderson, J.P., Janetka, J.W. and Hultgren, S.J. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Science Translational Medicine 3:1-10 (2011). [Abstract]
  • Ma, C.X., Janetka, J.W. and Piwnica-Worms, H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends in Molecular Medicine 17:88-96 (2011). [Abstract]
  • Oza, V., Ashwell, S., Brassil, P., Breed, J., Deng, C., Ezhuthachan, J., Haye, H., Horn, C., Janetka, J., Lyne, P., Newcombe, N., Otterbien, L., Pass, M., Read, J., Roswell, S., Su, M. Toader, D., u, D., Yu, Y., Valentine, A., Webborn, P., White, A., Zabludoff, S. and Zheng, X. Discovery of a novel class of triazolones as checkpoint kinase inhibitors – Hit to lead exploration. Bioorganic & Medicinal Chemistry Letters 20:5133-5138 (2010). [Abstract]
  • Han, Z., Pinkner, J.S., Ford, B., Obermann, R., Nolan, W., Wildman, S.A., Hobbs, D., Ellenberger, T., Cusumano, C.K., Hultgren, S.J. and Janetka, J.W. Structure-based drug design and optimization of mannoside bacterial FimH antagonists. J Med Chem 53:4779-4792 (2010). [Abstract]