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PXD074954

PXD074954 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA human iPSC-derived sensory neuron platform for high-throughput discovery of neuroprotectants against chemotherapy-induced peripheral neuropathy
DescriptionChemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models has hindered therapeutic progress. We have established a scalable model of paclitaxel-induced axon degeneration and neurotoxicity in iPSC-derived sensory neurons, suitable for high-throughput discovery of neuroprotective compounds. Using this platform, we screened 192 kinase inhibitors and identified 19 hits that commonly inhibited three STE20 kinases - MAP4K4, MINK1, and TNIK. Genetic knockdown revealed that multi-kinase inhibition of STE20 kinases is required for neuroprotection against paclitaxel. Moreover, selective pharmacological inhibition of STE20 kinases rescued paclitaxel-induced axon degeneration in iPSC-derived sensory neurons and primary human DRG, as well as preserved intraepidermal nerve fiber density in a mouse model of CIPN. These results establish a translational human sensory neuron platform for target and drug discovery in CIPN.
HostingRepositoryPRIDE
AnnounceDate2026-04-03
AnnouncementXMLSubmission_2026-04-02_19:56:08.479.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMarian Kalocsay
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Ascend
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-02-26 12:53:17ID requested
12026-04-02 19:56:09announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: axon degeneration, iPSC-derived sensory neurons, STE20 kinases, neuroprotective small molecules, high-throughput screening,Chemotherapy-induced peripheral neuropathy
Contact List
Clifford Woolf
contact affiliationDepartment of Neurobiology, Harvard Medical School; Boston, USA.
contact emailclifford.woolf@childrens.harvard.edu
lab head
Marian Kalocsay
contact affiliationThe University of Texas MD Anderson Cancer Center Department of Experimental Radiation Oncology
contact emailmkalocsay@mdanderson.org
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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