Evidence map›Paper›PMID 28641113›Full record

ArticleNeuron2017

Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons.

Derek S Welsbie, Katherine L Mitchell, Vinod Jaskula-Ranga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit Patel, Scott E Martin, Ping-Wu Zhang and 11 more

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

Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

100 citing papers in PubMed, 164 citations in OpenAlex.

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  6. Restoring Iron Homeostasis via Smoothened Inhibition: A Novel Strategy Against Hearing Loss.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  19. Article
  20. A lead role for a "secondary" axonal injury response.Neural regeneration research · 2025
    Article

40 more citing papers are in PubMed but not listed here.

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

21 authors at 8 institutions in 1 country.

Derek S WelsbieDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: dwelsbie@ucsd.edu.
Katherine L MitchellDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Vinod Jaskula-RangaDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Valentin M SluchDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Zhiyong YangDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
Jessica KimDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Eugen BuehlerNational Center for Advancing Translational Sciences, NIH, Bethesda, MD 20892, USA.
Amit PatelDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Shiley Eye Institute, University of California, San Diego, La Jolla, CA 92093, USA.
Scott E MartinNational Center for Advancing Translational Sciences, NIH, Bethesda, MD 20892, USA.
Ping-Wu ZhangDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Yan GeDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Yukan DuanDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
John FullerDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Byung-Jin KimDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Eman HamedDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Xitiz ChamlingDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Lei LeiDepartment of Biology, University of New England, Biddeford, ME 04005, USA.
Iain D C FraserSignaling Systems Unit, Laboratory of Systems Biology, National Institute for Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Ze'ev A RonaiSignal Transduction Program, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Cynthia A BerlinickeDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Donald J ZackDepartment of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Solomon H. Snyder Department of Neuroscience, Department of Molecular Biology and Genetics, Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: donzack@gmail.com.
Johns Hopkins Medicine · USJohns Hopkins University · USNational Center for Advancing Translational Sciences · USNational Institute of Allergy and Infectious Diseases · USSanford Burnham Prebys Medical Discovery Institute · USSmith-Kettlewell Eye Research Institute · USUniversity of California, San Diego · USUniversity of New England · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
RNAi Screening in Hematopoietic CellsZIAAI001106 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$12.4M
Analysis of Innate Immune Signaling NetworksZIAAI001107 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$11.9M
Vision BiostatisticsP30EY022589 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LINDA M ZANGWILL · 2012 to 2026
$10.3M
Visual Science Training ProgramT32EY007143 · NEI · JOHNS HOPKINS UNIVERSITY · PI Laura Ensign, JEREMY NATHANS · 1995 to 2026
$6.2M
A High Content Screening Approach for the Retinal Degenerative DiseasesR01EY024249 · NEI · JOHNS HOPKINS UNIVERSITY · PI BERLINICKE, CYNTHIA · 2015 to 2019
$2.0M
Dual Leucine Zipper Kinase (DLK) as a Mediator of Retinal Ganglion Cell InjuryR01EY023754 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZACK, DONALD J. · 2013 to 2016
$1.6M
NEI NIH HHS P30 EY001765NEI NIH HHS P30 EY022589NEI NIH HHS R01 EY023754NEI NIH HHS R01 EY024249NEI NIH HHS T32 EY007143
6 · The paper itself

Abstract

Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs. Moreover, we identify four transcription factors, JUN, activating transcription factor 2 (ATF2), myocyte-specific enhancer factor 2A (MEF2A), and SRY-Box 11 (SOX11), as being the major downstream mediators through which DLK/LZK activation leads to RGC cell death. Increased understanding of the DLK pathway has implications for understanding and treating neurodegenerative diseases.

Indexed as

AnimalsCell DeathCell SurvivalCyclopropanesDisease Models, AnimalFlow CytometryHuman Embryonic Stem CellsHumansImmunoprecipitationMAP Kinase Kinase KinasesMiceMice, KnockoutNeuritesNeuronsOptic Nerve InjuriesPiperazinesCyclopropanesLzk protein, mouseMAP Kinase Kinase Kinasesmitogen-activated protein kinase kinase kinase 12PiperazinesProtein Kinase InhibitorsPyrazolesPyrimidinestozasertibcell death signalingDLK (dual leucine zipper kinase)glaucomaLZK (leucine zipper kinase)NeuroprotectionRGC (retinal ganglion cell)RNAi screen

Identifiers

PMID28641113
PMCPMC5553555
OpenAlexW2632293652

What OpenQuestion holds

Textmetadata
LicenceTDM
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.