James Barrow, Ph.D.

About

Dr. James Barrow is a Professor of Pharmacology at Johns Hopkins University and Senior Investigator and Director of the Drug Discovery Division at the Lieber Institute. Dr. Barrow has 14 years of industrial experience in drug discovery research at Merck Research Laboratories and held many leadership roles before coming to the Lieber Institute in 2010. He has published over 70 peer-reviewed articles, reviews, and book chapters dealing with organic synthesis and drug discovery, most for central nervous system disorders, as well as 36 issued patents. He was part of development teams at Merck that brought new chemical entities through toxicology studies and into Phase 1 and 2 clinical trials. At the Lieber Institute, he has continued to lead drug discovery teams looking for treatments of psychiatric disorders, resulting in several programs out-licensed to biopharmaceutical companies. Dr. Barrow received a B.S. in chemistry from the University of North Carolina, Chapel Hill, graduating with highest honors and highest distinction. He received his Ph.D. from Harvard University, working in the laboratory of Professor David A. Evans.

Selected Publications

Carr GV, Chen J, Yang F, Ren M, Yuan P, Tian Q, Bebensee A, Zhang GY, Du J, Glineburg P, Xun, R, Akhile, O, Pickel, J, Barrow, JC, Papaleo, F, Weinberger, DR. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. Mol Psychiat. 2016; 21: 1517.

Calcaterra NE, Hoeppner DJ, Wei H, Jaffe AE, Maher BJ, Barrow JC. Schizophrenia-Associated hERG channel Kv11.1-3.1 Exhibits a Unique Trafficking Deficit that is Rescued through Proteasome Inhibition for High Throughput Screening. Sci Rep. 2016;6:19976.

Kimos M, Burton M, Urbain D, Caudron D, Martini M, Famelart M, Gillard M, Barrow J, Wood M. Development of an HTRF Assay for the Detection and Characterization of Inhibitors of Catechol-O-Methyltransferase. J Biomol Screen. 2016,21: 490.

Zhu Q, Ghoshal S, Rodrigues A, Gao S, Asterian A, Kamenecka TM, Barrow JC, Chakraborty A. Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis. J Clin Invest. 2016;126:4273-4288.

Ghoshal S, Zhu Q, Asteian A, Lin H, Xu H, Ernst G, Barrow JC, Xu B, Cameron MD, Kamenecka TM, Chakraborty A. TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway. Mol Metab. 2016;5:903-17.

Wormald M, Liao G, Kimos M, Barrow J, Wei H. Development of a homogenous high throughput assay for inositol hexakisphosphate kinase 1 activity. PLoS ONE. 2017; 12(11): e0188852.

Bürli RW, Wei H, Ernst G, Mariga A, Hardern IM, Herlihy K, Cross AJ, Wesolowski SS, Chen H, McKay RDG, Weinberger DR, Brandon NJ, Barrow JC. Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening. Bioorg Med Chem Lett. 2018;28: 3231.

Buchler I, Akuma D, Au V, Carr G, de León P, DePasquale M, Ernst G, Huang Y, Kimos M, Kolobova A, Poslusney M, Wei H, Swinnen D, Montel F, Moureau F, Jigorel E, Schulze MED, Wood M, Barrow JC Optimization of 8-Hydroxyquinolines as Inhibitors of Catechol O-Methyltransferase. J Med Chem. 2018;61: 9647

Wormald MM, Ernst G, Wei H, Barrow JC. Synthesis and characterization of novel isoform-selective IP6K1 inhibitors. Bioorg Med Chem Lett. 2019;29:126628.

Zhang G, Buchler IP, DePasquale M, Wormald M, Liao G, Wei H, Barrow JC, Carr GV. Development of a PC12 Cell Based Assay for Screening Catechol-O-methyltransferase Inhibitors. ACS Chem Neurosci. 2019; 10:4221-4226

Ernst G, Akuma D, Au V, Buchler IP, Byers S, Carr GV, Defays S, de León P, Demaude T, DePasquale M, Durieu V, Huang Y, Jigorel E, Kimos M, Kolobova A, Montel F, Moureau F, Poslusney M, Swinnen D, Vandergeten MC, Van Houtvin N, Wei H, White N, Wood M, Barrow JC. Synthesis and Evaluation of Bicyclic Hydroxypyridones as Inhibitors of Catechol O-Methyltransferase. ACS Med Chem Lett. 2019;10: 1573-1578.

DeBrosse AC, Wheeler AM, Barrow JC, Carr GV Inhibition of catechol-O-methyltransferase does not alter effort- related choice behavior in a fixed ratio/concurrent chow task in male mice. Front Behav Neurosci. 2020, 14, 73.

Burke EE, Chenoweth JG, Shin JH, Collado-Torres L, Kim SK, Micali N, Wang Y, Colantuoni C, Straub RE, Hoeppner DJ, Chen HY, Sellers A, Shibbani K, Hamersky GR, Diaz Bustamante M, Phan BN, Ulrich WS, Valencia C, Jaishankar A, Price AJ, Rajpurohit A, Semick SA, Bürli RW, Barrow JC, Hiler DJ, Page SC, Martinowich K, Hyde TM, Kleinman JE, Berman KF, Apud JA, Cross AJ, Brandon NJ, Weinberger DR, Maher BJ, McKay RDG, Jaffe AE Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs. Nature Commun. 2020;11:462.

Byers S, Buchler IP, DePasquale M, Rowley HL, Kulkarni RS, Pinder L, Kolobova A, Li C, Au V, Akuma D, Zhang G, Wei H, Cheetham SC, Barrow JC, Carr GV. Novel, non-nitrocatechol catechol-O-methyltransferase inhibitors modulate dopamine neurotransmission in the frontal cortex and improve cognitive flexibility. Psychopharm. 2020, 237, 2695.

Su, Y., DePasquale, M., Liao, G., Buchler, I., Zhang, G., Byers, S., Carr, G.V., Barrow, J. and Wei, H., Membrane bound catechol-O-methytransferase is the dominant isoform for dopamine metabolism in PC12 cells and rat brain. European Journal of Pharmacology, 2021, 896, 173909

Liao G, Ye W, Heitmann T, Ernst G, DePasquale M, Xu L, Wormald M, Hu X, Ferrer M, Harmel RK, Fiedler D, Barrow J, and Wei H Identification of Small-Molecule Inhibitors of Human Inositol Hexakisphosphate Kinases by High-Throughput Screening ACS Pharmacol. Transl. Sci. 2021. doi.org/10.1021/acsptsci.0c00218

Team Members