We are thrilled to share our latest study, now published on bioRxiv:
👉 https://www.biorxiv.org/content/10.1101/2025.10.24.684372v1
In this work, we report the first phosphoproteomic analysis by mass spectrometry (P-MS) of human induced neurons (iNs) directly reprogrammed from Huntington’s disease (HD) patient fibroblasts, integrated with matched proteomic and transcriptomic data from the same donors.
We identify 177 significantly altered phosphopeptides, revealing widespread signaling changes with enrichments in RNA splicing, autophagy, and stress-response pathways. Strikingly, we find binary phospho-switches (ON-OFF/OFF-ON), including MXRA8, which shows a complete loss of phosphorylation at pS377 in HD-iNs despite increased MXRA8 protein abundance. Kinase analyses and co-IP experiments further implicate autophagy-linked regulators and reveal condition-specific MXRA8 interactors (e.g. LAMP1/TGM2), supporting the role of altered phosphorylation in disrupted proteostasis in human HD neurons.
Led by our amazing shared first authors, Lea Danics and Chandramouli Muralidharan, whose dedication and teamwork drove this study, this work provides a new P-MS resource for the HD community. It represents a collaborative effort across Semmelweis University, HCEMM, and HUN-REN, together with international partners at Lund University, University of Cambridge, and University of Montreal.