Biology subjects

Luo, V.

Publications and source records attributed to Luo, V..

7 recordsLinked to original sources

bioRxiv2026

Evaluating Spike Antigenicity across Endemic Human Coronavirus Models using Flow Virometry

While SARS-CoV-2 research has advanced rapidly since COVID-19, endemic human coronaviruses (HCoVs) remain comparatively understudied. Tools to phenotype spike (S), the primary antigenic target on coronaviruses, at the single-virion level could improve vaccine design by capturing variation in epitope availability and spike abundance. Here, we establish a calibrated flow virometry (FV) platform to quantify S antigenicity on native endemic (HCoV-229E, HCoV-OC43) and epidemic (SARS-CoV-2) coronaviruses directly in cell culture supernatants. FV revealed cell line-dependent differences in S antigenicity, including receptor-induced changes in epitope accessibility. Comparison of virion-associated S with recombinant stabilized S by ELISA and biolayer interferometry showed consistent binding for HCoV-OC43, MERS-CoV, and SARS-CoV-2, but differences for HCoV-229E, with FV resolving heterogeneity not captured by bulk assays. Finally, FV showed that HCoV-229E from patient-derived air-liquid interface cultures exhibited reduced antibody binding and distinct S antigenicity compared to cell line-derived virions. Together, these findings establish FV as a platform for single-virion analysis of HCoV antigenicity.

microbiology↗

bioRxiv2024

DOCK8 regulates a mechanosensitive actin redistribution that maintains immune cell cohesion and protects the nucleus during migration

Immune cells navigate through complex 3-dimensional tissue architectures, utilizing an amoeboid mode of migration, characterized by extensive cellular deformation, low adhesion, and high cell velocities. In the absence of expression of Dedicator of Cytokinesis 8 (Dock8), a gene identified with loss-of-function mutations in immunodeficiency, cells become entangled during migration through dense, confined environments and consequently undergo catastrophic cell rupturing, while migration on 2D surfaces remains entirely intact. Here we investigated the specific cytoskeletal defect of Dock8-deficient activated T cells, showing that even prior to entanglement they display a striking difference in F-actin distribution compared to wild type (WT) cells. We describe a central pool of F-actin in WT murine and human T cells which is absent in Dock8 KO T cells, and determine that the relocalization of F-actin is a mechanoresponsive circuit, emerging only when cells are very confined. Our works shows that the central actin pool is nucleo-protective, reducing nuclear deformation and DNA damage during confined migration. We identify the Hippo-pathway kinase Mst1 as a co-mediator of this mechanosensitive pathway in conjunction with Dock8, allowing for cell cohesion and survival during migration through complex environments.

immunology↗

bioRxiv2022

C1orf112 is a novel regulator of interstrand crosslink that decreases FIGNL1-RAD51 interaction

Interstrand DNA crosslinks (ICLs) represent complex lesions that block essential biological processes, including DNA replication, recombination, and transcription. Several pathways have been involved in ICL repair, in particular nucleotide excision repair (NER), translesion DNA synthesis (TLS), Fanconi anemia (FA), and homologous recombination (HR). Still, the extent of factors involved in the resolution of ICL-induced DNA double-strand breaks (DSBs) remains poorly defined. Using CRISPR-based genome-wide screening, we identified the poorly characterized C1orf112 (also known as Apolo1) as a novel sensitizer to the clinically relevant ICL-inducing agent mafosfamide. Consistently, we noted that low expression of C1orf112 correlates with increased sensitivity to a series of ICL agents and PARP inhibitors in a panel of cell lines. We showed that lack of C1orf112 does not impact the initial recruitment and ubiquitylation of FANCD2 at the ICL site but rather impairs the resolution of RAD51 from ICL-induced DSBs, thereby compromising homology-directed DNA repair pathways. Our proximal mapping of C1orf112 protein neighbours coupled to structure-function analysis revealed that C1orf112, through its WCF motif, forms a complex with the N-terminal domain of the AAA+ ATPase FIGNL1 and regulates the interaction of FIGNL1 with RAD51. Our work establishes the C1orf112-FIGNL1 complex as an integral part of the HR-mediated response to ICLs by regulating the unloading of RAD51 during ICL repair.

molecular biology↗

bioRxiv2021

POGZ modulates the DNA damage response in a HP1-dependent manner

The heterochromatin protein HP1 plays a central role in the maintenance of genome stability, in particular by promoting homologous recombination (HR)-mediated DNA repair. However, little is still known about how HP1 is controlled during this process. Here, we describe a novel function of the POGO transposable element derived with ZNF domain protein (POGZ) in the regulation of HP1 during the DNA damage response in vitro. POGZ depletion delays the resolution of DNA double-strand breaks (DSBs) and correlates with an increased sensitivity to different DNA damaging agents, including the clinically-relevant Cisplatin and Talazoparib. Mechanistically, POGZ promotes homology-directed DNA repair pathways by retaining the BRCA1/BARD1 complex at DSBs, in a HP1-dependent manner. In vivo CRISPR inactivation of Pogz is embryonically lethal and Pogz haplo-insufficiency (Pogz+/{Delta}) results in a developmental delay, impaired intellectual abilities, a hyperactive behaviour as well as a compromised humoral immune response in mice, recapitulating the main clinical features of the White Sutton syndrome (WHSUS). Importantly, Pogz+/{Delta} mice are radiosensitive and accumulate DSBs in diverse tissues, including the spleen and the brain. Altogether, our findings identify POGZ as an important player in homology-directed DNA repair both in vitro and in vivo, with clinical implications for the WHSUS.

molecular biology↗

bioRxiv2019

Graph Embedding Method Based Genetical Trajectory Reveals Migration History Among East Asians

An important issue in human population genetics is the ancestry. By extracting the ancestral information retained in the single nucleotide polymorphism (SNP) of genomic DNA, the history of migration and reproduction of the population can be reconstructed. Since the SNP data of population are multidimensional, their dimensionality reduction can demonstrate their potential internal connections. In this study, the graph and structure learning based Graph Embedding method commonly used in single cell mRNA sequencing was applied to human population genetics research to decrease the data dimension. As a result, the human population trajectory of East Asia based on 1000 Genomes Project was reconstructed to discover the inseparable relationship between the Chinese population and other East Asian populations. These results are visualized from various ancestry calculators such as E11 and K12B. Finally, the unique SNPs along the psudotime of trajectory were found by differential analysis. Bioprocess enrichment analysis was also used to reveal that the genes of these SNPs may be related to neurological diseases. These results will lay the data foundation for precision medicine.

genetics↗

bioRxiv2018

FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice.

DNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle. Using a mass spectrometry (MS)-based approach, we identify 11 high-confidence REV7 interactors and elucidate the role of a previously undescribed factor, FAM35A/SHDL2, as a novel effector of REV7 in the NHEJ pathway. FAM35A depletion impairs NHEJ-mediated DNA repair and compromises antibody diversification by class switch recombination (CSR) in B-cells. FAM35A accumulates at DSBs in a 53BP1-, RIF1- and REV7-dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM35A is part of a larger complex composed of REV7 and another previously uncharacterized protein, C20orf196/SHDL1, which promotes NHEJ and limits HR. Together, these results establish FAM35A as a novel effector of REV7 in controlling the decision-making process during DSB repair.

cancer biology↗

bioRxiv2018

The impact of endogenous retroviruses on nuclear organization and gene expression

BackgroundThe organization of chromatin in the nucleus plays an essential role in gene regulation. When considering the mammalian genome it is important to take into account that about half of the DNA is comprised of transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation.\n\nResultsUsing adapted PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of TE interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual TE insertions that interact with, and potentially regulate target genes.\n\nConclusions4Tran provides new insight into the manner in which transposons contribute to chromosome architecture and identifies target genes that transposable elements can potentially control.

genomics↗