Evidence map›Paper›PMID 37172592›Full record

ArticleCell chemical biology2023

Human nuclear hormone receptor activity contributes to malaria parasite liver stage development.

Nimisha Mittal, Chadwick Davis, Peter McLean, Jaeson Calla, Karla P Godinez-Macias, Alison Gardner, David Healey, Pamela Orjuela-Sanchez, Sabine Ottilie, Yolanda Chong and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Nimisha MittalDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Chadwick DavisRecursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA.
Peter McLeanRecursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA.
Jaeson CallaDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Karla P Godinez-MaciasDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Graduate Program, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Alison GardnerRecursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA.
David HealeyRecursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA.
Pamela Orjuela-SanchezDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA; Recursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA.
Sabine OttilieDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Yolanda ChongRecursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA.
Christopher GibsonRecursion, 41 S Rio Grande Street, Salt Lake City, UT 84101, USA. Electronic address: chris.gibson@recursionpharma.com.
Elizabeth A WinzelerDepartment of Pediatrics, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: ewinzeler@health.ucsd.edu.
Recursion (United States) · USUniversity of California San Diego · US

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Discovery of long-acting, chemoprotective antimalarial compoundsR01AI152533 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2020 to 2024
$3.5M
Discovery of chemically validated malaria liver stage targetsR01AI090141 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2011 to 2019
$3.4M
NIAID NIH HHS R01 AI090141NIAID NIH HHS R01 AI152533NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Chemical genetic approaches have had a transformative impact on discovery of drug targets for malaria but have primarily been used for parasite targets. To identify human pathways required for intrahepatic development of parasite, we implemented multiplex cytological profiling of malaria infected hepatocytes treated with liver stage active compounds. Some compounds, including MMV1088447 and MMV1346624, exhibited profiles similar to cells treated with nuclear hormone receptor (NHR) agonist/antagonists. siRNAs targeting human NHRs, or their signaling partners identified eight genes that were critical for Plasmodium berghei infection. Knockdown of NR1D2, a host NHR, significantly impaired parasite growth by downregulation of host lipid metabolism. Importantly, treatment with MMV1088447 and MMV1346624 but not other antimalarials, phenocopied the lipid metabolism defect of NR1D2 knockdown. Our data underlines the use of high-content imaging for host-cellular pathway deconvolution, highlights host lipid metabolism as a drug-able human pathway and provides new chemical biology tools for studying host-parasite interactions.

Indexed as

MalariaParasitesAnimalsHepatocytesHumansLiverPlasmodium bergheiReceptors, Cytoplasmic and NuclearRepressor ProteinsNR1D2 protein, humanReceptors, Cytoplasmic and NuclearRepressor Proteinsdrug discoverymalarianuclear hormone receptorsphenotypic screeningPlasmodiumsiRNA

Identifiers

PMID37172592
PMCPMC10878326
OpenAlexW4376135582

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.