Eachan Johnson

Systems chemical biology for drug discovery

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Eachan Johnson

Systems chemical biology for drug disovery


Research interests

Working at the intersection, of biology, chemistry, and computation, I combine new techniques with the emerging large-scale genomics, chemical biology, and chemical genetics to systematically discover new therapeutics.

Currently, I'm focussed on finding new treatments for tuberculosis (TB), a disease that kills 1.5 million people per year. Drug resistance is rising steadily, partly fueled by the standard of care for drug-susceptible TB: a poorly-tolerated regimen of ethambutol, isoniazid, pyrazinamide, and rifampin.

The causative agent of TB, bacterium Mycobacterium tuberculosis, has co-evolved with the human immune system to be an expert pathogen. It tolerates treatment by conventional antibiotics like the beta-lactams (think penicillin).

My work aims to find drugs which kill M. tuberculosis in new ways. By inhibiting new intracellular targets, current resistance can be circumvented, but this is a difficult task. With my colleagues at the Broad Institute, University of Massachusetts Medical School, Weill Cornell Medical College, and Harvard T.H. Chan School of Public Health, I developed a method to quickly prioritize potential new TB drugs based on their targets.

In the future, I plan to use my systems chemical biology approach to discover new drug combinations that could subvert the antimicrobial resistance crisis by driving pathogens into an evolutionary dead-end, and find antimicrobials that focus on saving the patient rather than directly killing the bug.


Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes

Johnson EO, LaVerriere E, Office E, Stanley M, Meyer E, et al.

Nature, Jul 2019, 571, 72-78

PubMed ID: 31217586 | doi: 10.1038/s41586-019-1315-z

A structural model of a P450-ferredoxin complex from orientation-selective double electron-electron resonance spectroscopy

Bowen AM, Johnson EO, Mercuri F, Hoskins NJ, Qiao R, et al.

Journal of the American Chemical Society, Feb 2018, 140(7), 2514-2527

PubMed ID: 29266939 | doi: 10.1021/jacs.7b11056

Partial fusion of a cytochrome P450 system by carboxy-terminal attachment of putidaredoxin reductase to P450cam (CYP101A1)

Johnson EO, Wong LL

Catalysis Science and Technology, Sep 2018, 6(20), 7549-7560

PubMed ID: 28944003 | doi: 10.1039/C6CY01042C

Tailoring an alien ferredoxin to support native-like P450 monooxygenase activity

Bell SG, McMillan JH, Yorke JA, Kavanagh E, Johnson EO, Wong LL

Chemical Communications, Dec 2012, 48(95), 11692-11694

PubMed ID: 23104016 | doi: 10.1039/c2cc35968e

Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation

Boehringer J, Riedinger C, Paraskevopoulos K, Johnson EO, Lowe ED, et al.

Biochemical Journal, Nov 2012, 448(1), 55-65

PubMed ID: 22906049 | doi: 10.1042/BJ20120542

The crystal structures of 4-methoxybenzoate bound CYP199A2 and CYP199A4: structural changes on substrate binding and the identification of an anion binding site

Bell SG, Yang W, Tan AB, Zhou R, Johnson EO, et al.

Dalton Transactions, Jul 2012, 41(28), 8703-8714

PubMed ID: 22695988 | doi: 10.1039/c2dt30783a

Selective oxidative demethylation of veratric acid to vanillic acid by CYP199A4 from Rhodopseudomonas palustris HaA2

Bell SG, Tan AB, Johnson EO, Wong LL

Molecular BioSystems, Jan 2010, 6(1), 206-214

PubMed ID: 20024082 | doi: 10.1039/b913487e

Protein recognition in ferredoxin-P450 electron transfer in the class I CYP199A2 system from Rhodopseudomonas palustris

Bell SG, Xu F, Johnson EO, Forward IM, Bartlam M, et al.

Journal of Biological Inorganic Chemistry, Mar 2010, 15(3), 315-28

PubMed ID: 19904564 | doi: 10.1007/s00775-009-0604-7

Crystal structure of a ferredoxin reductase for the CYP199A2 system from Rhodopseudomonas palustris

Xu F, Bell SG, Peng Y, Johnson EO, Bartlam M, et al.

Proteins, Dec 2009, 77(4), 867-880

PubMed ID: 19626710 | doi: 10.1002/prot.22510