Eachan Johnson

Understanding infection biology using systems chemical biology

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Eachan Johnson

Understanding infection biology using systems chemical biology



Working at the intersection, of biology, chemistry, and computation, I combine large-scale genomics with 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, 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.

tSNE of chemical genetic interaction profiles

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.

Systems chemical biology


Large-scale chemical-genetic strategy to design antimicrobial combination chemotherapy for Mycobacterium tuberculosis

Johnson EO, Office E, Kawate T, Orzechowski M, Hung DT

ACS Infectious Diseases, Jan 2020, 6(1), 56–63

PubMed ID: 31721551 | doi: 10.1021/acsinfecdis.9b00373

A point of inflection and reflection on systems chemical biology

Johnson EO, Hung DT

ACS Chemical Biology, Dec 2019, 14(12), 2497–2511

PubMed ID: 31613592 | doi: 10.1021/acschembio.9b00714

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

Johnson EO, LaVerriere E, Office E, Stanley M, Meyer E, Kawate T, Gomez J, Audette RE, Bandyopadhyay N, Betancourt N, Delano K, Da Silva I, Davis J, Gallo C, Gardner M, Golas A, Guinn KM, Kennedy S, Korn R, McConnell JA, Moss CE, Murphy KC, Nietupski R, Papavinasasundaram KG, Pinkham JT, Pino PA, Proulx MK, Ruecker N, Song N, Thompson M, Trujillo C, Wakabayashi S, Wallach JB, Watson C, Ioerger TR, Lander ES, Hubbard BK, Serrano-Wu MH, Ehrt S, Fitzgerald M, Rubin EJ, Sassetti CM, Schnappinger D, Hung DT

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, McCullagh JSO, Lovett JE, Bell SG, Zhou W, Timmel CR, Wong LL, Harmer JR

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 2016, 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, Khoudian C, Smith D, Noble ME, Gordon C, Endicott JA

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, Zhang A, Zhou W, Rao Z, Wong LL

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, Rao Z, Wong LL

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, Rao Z, Wong LL

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

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