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Le Roch Lab
Schizont-stage Plasmodium parasite in the bloodstream

Research

Drug Discovery & Natural Products

The question

Finding a compound is the easy half.

Developing drug screening and systems biology pipelines to identify novel lead compounds and elucidate their modes of action, including marine natural-product extracts.

Malaria parasites have developed resistance to every antimalarial deployed at scale. Finding a molecule that kills them in culture is comparatively routine; establishing what it actually hits, and whether resistance can arise against it, is where most candidates fail.

We pair phenotypic screening — including marine natural-product extracts — with a systems-biology readout: transcriptomics, proteomics and metabolomics on treated parasites, so a compound's mode of action is characterised alongside its potency. That approach showed how a kalihinol analogue disrupts apicoplast function and vesicular trafficking, and it underpins the case for polypharmacology: single drugs designed to act on several mechanisms at once.

Circular schematic of a systems-biology drug discovery pipeline, from compound screening and dose-response curves through culture, omics and animal models
The systems-biology drug discovery pipeline: screening and dose–response, then culture, omics and animal models to establish how a compound works.

How we look

Techniques used in this area

Screening & phenotype

  • High-content confocal
  • Dose–response profiling

Mode of action

  • RNA-seq
  • Proteomics
  • MudPIT mass spectrometry
  • Metabolomics
  • CRISPR

Platforms

  • Illumina
eLife
eLife2025

A drug repurposing approach reveals targetable epigenetic pathways in Plasmodium vivax hypnozoites

Maher SP, Bakowski MA, Vantaux A, Flannery EL, Andolina C, Gupta M, Antonova-Koch Y, Argomaniz M, Cabrera-Mora M, Campo B, Chao AT, Chatterjee AK, Cheng WT, Chuenchob V, Cooper CA, Cottier K, Galinski MR, Harupa-Chung A, Ji H, Joseph SB, Lenz T, Lonardi S, Matheson J, Mikolajczak SA, Moeller T, Orban A, Padín-Irizarry V, Pan K, Péneau J, Prudhomme J, Roesch C, Ruberto A, Sabnis SS, Saney CL, Sattabongkot J, Sereshki S, Suriyakan S, Ubalee R, Wang Y, Wasisakun P, Yin J, Popovici J, McNamara CW, Joyner C, Nosten FH, Witkowski B, Le Roch KG, Kyle DE

Nature Microbiology
Nature Microbiology2023

Babesia duncani multi-omics identifies virulence factors and drug targets

Singh P, Lonardi S, Liang Q, Vydyam P, Khabirova E, Fang T, Gihaz S, Thekkiniath J, Munshi M, Abel S, Ciampossin L, Batugedara G, Gupta M, Lu XM, Lenz T, Chakravarty S, Cornillot E, Hu Y, Ma W, Gonzalez LM, Sánchez S, Estrada K, Sánchez-Flores A, Montero E, Harb OS, Le Roch KG, Ben Mamoun C

All 8 papers on drug discovery & natural products
All research areas