Biology subjects

Ji, J.-H.

Publications and source records attributed to Ji, J.-H..

4 recordsLinked to original sources

bioRxiv2026

SpatialDataAgent: Autonomous Spatial Omics Data Curation at Decade Scale

Fragmented metadata in spatial omics archives has rendered large volumes of multimodal molecular-histological data inaccessible as dark data. Here, we introduce SpatialDataAgent, an agentic workflow for autonomous spatial omics data curation, combining schema-constrained evidence evaluation with a self-refining standardization agent. Applied to a decade of GEO records, SpatialDataAgent identified 769 paired H&E-spatial transcriptomics (ST) datasets, representing a 6.4-fold scale expansion over existing manually curated baselines. Within the benchmarking window, the framework achieved a 141% increase in high-confidence Class A paired datasets. We further assembled a recent high-confidence subset into HESRT, a standardized datalake containing 29.2 million spots/cells, establishing a blueprint for evidence-grounded autonomous curation of multimodal biomedical archives.

bioinformatics↗

bioRxiv2025

GCN5-TADA2B in the SAGA complex provide constitutive fine-tuning control of XRCC1 recruitment and focal retention at DNA damage sites.

The scaffolding protein XRCC1 orchestrates base excision repair (BER) and DNA single strand break repair (SSBR) through extensive protein-protein interactions, and its disruption contributes to human neurological diseases such as SCAR26. Recruitment to DNA damage sites has been traditionally understood to depend exclusively on interaction with PARP1 and PARP1 mediated PARylation. Here, we report for the first time the discovery of GCN5 and TADA2B, components of histone acetyltransferase module of SAGA complex, as novel XRCC1 binding partners that provide critical fine-tuning control over repair site localization. We demonstrate that these SAGA complex components bind XRCC1 constitutively via distinct BRCT domain interactions -- GCN5 mainly to BRCT I and TADA2B mainly to BRCT II -- independent of DNA damage status or GCN5s acetyltransferase activity. Depletion of either protein significantly impairs XRCC1 recruitment efficiency, while paradoxically rescuing focal retention defects in BRCT II deficient XRCC1 mutants. This dual regulatory behavior reveals a regulatory mechanism where constitutive protein interactions optimize normal XRCC1 function but become counterproductive when XRCC1 is structurally compromised, particularly in the BRCT II domain. Analysis of the SCAR26 associated variant, which disrupts TADA2B binding while maintaining LIG3 interaction, confirms this dual regulatory model and provides molecular insights into potential disease pathophysiology. Our findings establish a ready-for-action model of DNA repair coordination where protein complexes pre-organize repair machinery for immediate deployment upon damage detection, expanding our understanding of BER regulation.

cell biology↗

bioRxiv2025

HIV-1 Vpr drives epigenetic remodeling to enhance virus transcription and latency reactivation

Despite decades of research, the primary proviral function of the HIV-1 Vpr accessory protein remains enigmatic. Vpr is essential for pathogenesis in vivo and for virus replication in myeloid cells, but the underlying cause-and-effect mechanism(s) driving these phenomena are poorly understood. Canonically, Vpr hijacks a cellular ubiquitin ligase complex to target several dozen host proteins for proteasomal degradation. Many of these substrates were recently revealed to be involved in DNA damage repair (DDR), which rationalizes the longstanding observation that Vpr induces constitutive activation of DDR signaling. Here, we use a combination of functional, biochemical, and genetic approaches establish a clear mechanistic link between Vpr-induced DDR signaling and remodeling of the epigenetic landscape to enhance HIV-1 promoter activity during acute infection and virus reactivation from latency. Functional, genetic, and bimolecular fluorescence complementation experiments reveal that Vpr utilizes degradation-dependent and -independent mechanisms to induce epigenetic remodeling and that Vpr segregates into two discrete pools with dedicated activities--A multimeric pool in the nucleus that is associated with chromatin and a monomeric pool associated with DCAF1 in the cytoplasm. Vpr function in remodeling the nuclear environment is present in common HIV-1 subtypes worldwide and provides a mechanistic rationale for its essentiality in virus replication. Author summaryWhile HIV-1 Vpr plays an essential role in virus replication, the molecular mechanisms underlying its essentiality remain enigmatic. Vprs best characterized function is the ability to induce the depletion of several dozen host proteins by hijacking a cellular E3-ubiquitin ligase complex. Here, we establish that Vpr promotes global epigenetic remodeling to enhance HIV-1 promoter activity during acute infection and virus reactivation from latency. We demonstrate that epigenetic remodeling activity is linked to Vprs ability to induce constitutive DNA damage repair signaling, and that it occurs through both degradation-dependent and -independent mechanisms. Moreover, this Vpr function is present in common HIV-1 subtypes circulating globally. This study provides novel mechanistic insights into how HIV-1 exploits host DNA repair pathways and sheds light on Vprs proviral function.

microbiology↗

bioRxiv2018

Pellino 1 Communicates Intercellular Signaling in Chronic Skin Inflammatory Microenvironment

Chronic skin inflammation including psoriasis is a multisystem disease, affecting more than 5% of the general population. Here we show that Pellino 1 (Peli1), a signal-responsive ubiquitin E3 ligase, is highly up-regulated in human psoriatic skin lesions and that increased Peli1 expression correlates with the immunopathogenesis of psoriasis-like chronic skin inflammatory disease. Interestingly, Peli1 directly interacts with interferon regulatory factor 4 (IRF4, a transcription factor that plays pivotal roles in proliferation and cytokine production) and induces lysine 63-mediated ubiquitination. Peli1-mediated IRF4 ubiquitination appears to be a common systemic signaling mechanism shared by lesional keratinocytes, dendritic cells, macrophages, and T cells, generating a feedback relationship between keratinocyte and Th17 cell responses. Conversely, inhibition of Peli1 interferes with IRF4 induction and attenuates immunopathogenic signaling in the psoriasis. In summary, Peli1-mediated ubiquitination is a common immunopathogenic intercellular signaling in psoriasis-like chronic skin inflammatory microenvironment. Thus, targeting Peli1 could be used as a potential strategy for psoriasis treatment.

immunology↗