John Lab Research Overview

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Learn more about the research conducted within the John Lab:

We have a long-standing interest in understanding the fundamental biology and regulation of metabolism in Plasmodium falciparum: What does the parasite make, and why? By evolving resistance to metabolic inhibitors, our work has uncovered a novel function of haloacid dehalogenase (HAD)-like phosphatases in metabolic regulation in malaria parasites.

Related publications:

Guggisberg AM, Frasse PM, Jezewski AJ, Kafai NM, Gandhi AY, Erlinger SJ, Odom John AR. Suppression of Drug Resistance Reveals a Genetic Mechanism of Metabolic Plasticity in Malaria Parasites.mBio. 2018 Nov 13;9(6). PMID: 30425143.

Guggisberg AM, Sundararaman SA, Lanaspa M, Moraleda C, González R, Mayor A, Cisteró P, Hutchinson D, Kremsner PG, Hahn BH, Bassat Q, Odom AR. Whole-Genome Sequencing to Evaluate the Resistance Landscape Following Antimalarial Treatment Failure With Fosmidomycin-Clindamycin.J Infect Dis. 2016 Oct 1;214(7):1085-91. PMID: 27443612.

Frasse PM, Odom John AR. Haloacid Dehalogenase Proteins: Novel Mediators of Metabolic Plasticity in Plasmodium falciparum . Microbiol Insights. 2019;12:1178636119848435. PMID: 31205418.

Guggisberg AM, Park J, Edwards RL, Kelly ML, Hodge DM, Tolia NH, Odom AR. A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites. Nat Commun. 2014 Jul 24;5:4467. PMID: 25058848.

Due to spreading antimicrobial resistance, there is an urgent need to develop new treatments for infectious diseases such as malaria and staphylococcal infections. Our collaborative studies use target-based approaches to identify and advance new potential therapeutics that safely target microbe-specific metabolism.

Related publications:

Miller JJ, Shah IT, Hatten J, Barekatain Y, Mueller EA, Moustafa AM, Edwards RL, Dowd CS, Planet PJ, Muller FL, Jez JM, Odom John AR. Structure-guided microbial targeting of antistaphylococcal prodrugs. elife. 2021 Jul 19;10:e66657. doi: 10.7554/eLife.66657. PMID: 34279224; PMCID: PMC8318587.

Mikati MO, Miller JJ, Osbourn DM, Barekatain Y, Ghebremichael N, Shah IT, Burnham CD, Heidel KM, Yan VC, Muller FL, Dowd CS, Edwards RL, Odom John AR. Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB. ACS Infect Dis. 2020 Nov 13;6(11):3064-3075. PMID: 33118347.

Edwards RL, Heueck I, Lee SG, Shah IT, Miller JJ, Jezewski AJ, Mikati MO, Wang X, Brothers RC, Heidel KM, Osbourn DM, Burnham CD, Alvarez S, Fritz SA, Dowd CS, Jez JM, Odom John AR. Potent, specific MEPicides for treatment of zoonotic staphylococci. PLoS Pathog. 2020 Jun;16(6):e1007806. PMID: 32497104.

Wang X, Edwards RL, Ball H, Johnson C, Haymond A, Girma M, Manikkam M, Brothers RC, McKay KT, Arnett SD, Osbourn DM, Alvarez S, Boshoff HI, Meyers MJ, Couch RD, Odom John AR, Dowd CS. MEPicides: α,β-Unsaturated Fosmidomycin Analogues as DXR Inhibitors against Malaria .J Med Chem. 2018 Oct 11;61(19):8847-8858. PMID: 30192536.

Edwards RL, Brothers RC, Wang X, Maron MI, Ziniel PD, Tsang PS, Kraft TE, Hruz PW, Williamson KC, Dowd CS, John ARO. MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis.Sci Rep. 2017 Aug 21;7(1):8400. PMID: 28827774.

Imlay LS, Armstrong CM, Masters MC, Li T, Price KE, Edwards RL, Mann KM, Li LX, Stallings CL, Berry NG, O'Neill PM, Odom AR. Plasmodium IspD (2-C-Methyl-D-erythritol 4-Phosphate Cytidyltransferase), an Essential and Druggable Antimalarial Target.ACS Infect Dis. 2015 Apr 10;1(4):157-167. PMID: 26783558.

Kraft TE, Armstrong C, Heitmeier MR, Odom AR, Hruz PW. The Glucose Transporter PfHT1 Is an Antimalarial Target of the HIV Protease Inhibitor Lopinavir. Antimicrob Agents Chemother. 2015 Oct;59(10):6203-9. PMID: 26248369.

More recently, our longstanding studies of microbial metabolism have developed into an interest in volatile metabolites produced during health and disease in children. Our ongoing research projects aim to advance novel noninvasive “breathalyzer” tests for malaria, pediatric SARS-CoV-2, and other childhood diseases. Along with Hamid Bassiri, we are proud to lead the NIH RADx-rad PreVAIL kIds collaborative research program at CHOP, with a goal of developing new ways to diagnose MIS-C in children with fever.

Related publications:

Berna AZ, Akaho EH, Harris RM, Congdon M, Korn E, Neher S, M'Farrej M, Burns J, Odom John AR. Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection. ACS Infect Dis. 2021 Jul 28. doi: 10.1021/acsinfecdis.1c00248. Epub ahead of print. PMID: 34319698.

Schaber CL, Katta N, Bollinger LB, Mwale M, Mlotha-Mitole R, Trehan I, Raman B, Odom John AR. Breathprinting Reveals Malaria-Associated Biomarkers and Mosquito Attractants. J Infect Dis. 2018 Apr 23;217(10):1553-1560. PMID: 29415208.

Miller JJ, Odom John AR. The Malaria Metabolite HMBPP Does Not Trigger Erythrocyte Terpene Release. ACS Infect Dis. 2020 Oct 9;6(10):2567-2572. PMID: 32966041.

Berna AZ, DeBosch B, Stoll J, Odom John AR. Breath Collection from Children for Disease Biomarker Discovery. J Vis Exp. 2019 Feb 14;(144). PMID: 30829338.

Kelly M, Su CY, Schaber C, Crowley JR, Hsu FF, Carlson JR, Odom AR. Malaria parasites produce volatile mosquito attractants. mBio. 2015 Mar 24;6(2). PMID: 25805727.

Dr. John and colleagues have a number of ongoing studies on the diagnosis, management, and underlying biology of pediatric COVID-19 and the post-coronavirus multi-system inflammatory syndrome in children (MIS-C).

Related publications:

Lin EE, Akaho EH, Sobilo A, Young LR, Harris RM, Odom John AR. Concordance of Preprocedure Testing With Time-of-Surgery Testing for SARS-CoV-2 in Children. Pediatrics. 2021 Feb 2 [Epub ahead of print]. PMID: 33531335.

Blatz AM, Oboite M, Chiotos K, Castelo-Soccio L, Odom John AR. Children’s Hospital of Philadelphia MIS-C Research Collaborative. Cutaneous findings in SARS-CoV-2-associated Multisystem Inflammatory Disease in Children (MIS-C). Open Forum Infect Dis. 2021 Feb 16:ofab074. PMCID: PMC7928560.

Lin EE, Akaho EH, Sobilo A, Blatz AM, Otto WR, Odom John AR. Concordance of Upper and Lower Respiratory Tract Samples for SARS-CoV-2 in Pediatric Patients: Research Letter. Anesthesiology. 2021 Apr 5. [Epub ahead of print] PMID: 33819338.

Berna AZ, Akaho EH, Harris RM, Congdon M, Korn E, Neher S, M'Farrej M, Burns J, Odom John AR. Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection. ACS Infect Dis. 2021 Jul 28. doi: 10.1021/acsinfecdis.1c00248. Epub ahead of print. PMID: 34319698.

Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, Fitzgerald JC, Topjian A, John ARO. Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series. J Pediatric Infect Dis Soc. 2020 Jul 13;9(3):393-398. PMID: 32463092.