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James C. Barrow

James C. Barrow
Department Affiliation: Primary: Pharmacology and Molecular Sciences;
Lieber Institute for Brain Development 
Degree: Ph.D., Harvard University
Rank: Associate Professor
Telephone Number : 410-955-0894
Fax Number: 410-955-3023
E-mail address:
School of Medicine Address: Room 374, John G. Rangos, Sr., Building, 855 N. Wolfe Street, Baltimore, MD  21205

Drug discovery for disorders of neurodevelopment.

The research group is a laboratory focused on medicinal chemistry and drug discovery, primarily addressing diseases of neurodevelopment such as schizophrenia. Biological activity and structure-based drug design are used to drive chemistry target selection, and we are developing synthetic methods to efficiently prepare those targets. These efforts are tightly coupled with in vitro and in vivo testing and analysis, in collaboration with other research groups and core facilities at Johns Hopkins University or externally. At the core, the lab is engaged in the design and synthesis of molecules for a given biological target, analysis of in vitro and in vivo results, as well as further refinement through multiple cycles of synthesis and testing. Advances in reaction methodology, reagent availability, parallel synthesis, and purification technology now allow preparation of compounds in an efficient manner so that we can quickly drive structure-activity relationship studies and identify advanced leads. These advanced leads will have good potency and selectivity for the target of interest, and will be used to test biological hypotheses both in vitro and in vivo to determine if modulating the target is indeed a viable therapeutic strategy. By executing on medicinal chemistry programs, we will drive translational science from target and pathway discovery to novel medicines for patients.

Representative Publications:  

  • Calcaterra, N.E., Hoeppner, D.J., Wei, H., Jaffe, A.E., Maher, B.J., Barrow, J.C.  Schizophrenia-Associated hERG channel Kv11.1-3.1 Exhibits a Unique Trafficking Deficit that is Rescued through Proteasome Inhibition for High Throughput Screening. Scientific Reports 6: 19976, 2016. Pub Med Reference
  • Carr, G.V., Chen, J., Yang, F., Ren, M., Yuan, P., Tian, Q., Bebensee, A., Zhang, G.Y., Du, J., Glineburg, P., Xun, R., Akhile, O., Akuma, D., Pickel, J., Barrow, J.C., Papaleo, F., Weinberger, D.R. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. Molecular Psychiatry  2016 [Epub ahead of print].  Pub Med Reference
  • Harrison, S.T., Poslusney, M.S., Mulhearn, J.J., Zhao, Z., Kett, N.R., Schubert, J.W., Melamed, J.Y., Allison, T.J., Patel, S., Sanders, J.M., Sharma, S., Smith, R.F., Hall, D.L., Robinson, R.G., Sachs, N.A., Hutson, P.H., Wolkenberg, S.E., Barrow, J.C. Synthesis and Evaluation of Heterocyclic Catechol Mimics as Inhibitors of Catechol-O-methyltransferase (COMT). ACS Med. Chem. Lett. 6: 318-323, 2015.  Pub Med Reference
  • Egbertson, M., McGaughey, G.B., Pitzenberger, S.M., Stauffer, S.R., Coburn, C.A., Stachel, S.J., Yang, W., Barrow, J.C., Neilson, L.A., McWherter, M., Perlow, D., Fahr, B., Munshi, S., Allison, T.J., Holloway, K., Selnick, H.G., Yang, Z., Swestock, J., Simon, A.J., Sankaranarayanan, S., Colussi, D., Tugusheva, K., Lai, M.T., Pietrak, B., Haugabook, S., Jin, L., Chen, I.W., Holahan, M., Stranieri-Michener, M., Cook, J.J., Vacca, J., Graham, S.L. Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency. Bioorg. Med. Chem. Lett.  25: 4812-4819, 2015. Pub Med Reference
  • Shipe, W.D., Sharik, S.S., Barrow, J.C., McGaughey, G.B., Theberge, C.R., Uslaner, J.M., Yan, Y., Renger, J.J., Smith, S.M., Coleman, P.J., Cox, C.D. Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis. J Med Chem.  58: 7888-7894, 2015.  Pub Med Reference
  • Rao, F., Xu, J., Fu, C., Cha, J.Y., Gadalla, M.M., Xu, R., Barrow, J.C., Snyder, S.H. Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1. Proc Natl Acad Sci  112: 1773-1778, 2015. Pub Med Reference
  • Colis, L., Ernst, G., Sanders, S., Liu, H., Sirajuddin, P., Peltonen, K., DePasquale, M., Barrow, J.C., Laiho, M. Design, synthesis, and structure-activity relationships of pyridoquinazolinecarboxamides as RNA polymerase I inhibitors. J Med Chem.  57: 4950-4961, 2014.  Pub Med Reference
  • Barrow, J.C. Inhibitors of Catechol-O-Methyltransferase. CNS Neurol Disord Drug Targets. 11: 324-332 , 2012.  Pub Med Reference

  • Coleman, P.J., Barrow, J.C. Challenges and opportunities in neuroscience research. ChemMedChem.  7: 339-341, 2012. Pub Med Reference

  • Uslaner, J.M., Smith, S.M., Huszar, S.L., Pachmerhiwala, R., Hinchliffe, R.M., Vardigan, J.D., Nguyen, S.J., Surles, N.O., Yao, L., Barrow, J.C., Uebele, V.N., Renger, J.J., Clark, J., Hutson, P.H.  T-type calcium channel antagonism produces antipsychotic-like effects and reduces stimulant-induced glutamate release in the nucleus accumbens of rats.  Neuropharmacology.  62: 1413-1421, 2012.  Pub Med Reference
  • Harrison, S.T., Mulhearn, J., Wolkenberg, S.E., Miller, P.J., O'Malley, S.S., Zeng, Z., Williams, D.L., Hostetler, E.D., Sanabria-Bohrquez, S., Gammage, L., Fan, H., Sur, C., Culberson, J.C., Hargreaves, R.J., Cook, J.J., Hartman, G.D., Barrow, J.C.  Synthesis and evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as ß-Amyloid PET ligands and identification of MK-3328.  ACS Med. Chem. Lett. 2(7):498-502, 2011.  Link to ACS Med. Chem. Lett.

    Other graduate programs in which Dr. Barrow participates:  None