Biology subjects

Hudak, A.

Publications and source records attributed to Hudak, A..

5 recordsLinked to original sources

bioRxiv2025

CBM KG: A Comorbidity-Centric Knowledge Graph Uncovering Causal Pathomechanisms Between COVID-19 and Neurodegenerative Diseases

SummaryCOVID-19 is increasingly recognized as a potential trigger or accelerator of neurodegenerative diseases such as Alzheimers and Parkinsons. To systematically explore the putative molecular and clinical associations between them, we present CBM KG (Causal Biological Mechanisms Knowledge Graph)--a manually curated, comorbidity-centric resource developed within the EU-funded COMMUTE project. CBM KG integrates over 2,800 cause-and-effect or correlative relationships from 63 peer-reviewed publications, highlighting key mechanisms such as viral entry routes, blood-brain barrier alteration, microglial activation, neuroinflammation, and APOE {varepsilon}4-associated susceptibility. Each relationship in the graph is fully traceable to its source evidence, ensuring transparency and reproducibility. Unlike general-purpose or single disease-focused knowledge graphs, CBM KG is specifically designed to represent causal biological mechanisms spanning both infectious and neurodegenerative processes. By encoding directional, cause-and-effect relationships, it supports the interpretation of clinical co-occurrences through plausible mechanistic links between overlapping disease pathways, offering high-resolution insights at both molecular and clinical levels. Availability and implementationThe BEL files, Neo4j database, and Cytoscape visualization files are publicly available at: https://github.com/SCAI-BIO/CBM-Comorbidity-KG.

bioinformatics↗

bioRxiv2025

Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACONs) for Mucosal Vaccination Against Genital Herpes

Genital herpes, caused by herpes simplex virus-2 (HSV-2), remains a prevalent sexually transmitted infection with no available vaccine. Effective local immunity--including tissue-resident memory T cells (TRMs) and luminal antibodies--provides immediate viral control. Here, we developed Bioactive Enhanced Adjuvant Chemokine Oligonucleotide Nanoparticles (BEACON) formed via electrostatic interactions between CpG oligodeoxynucleotides (CpG ODN) and the chemokine CXCL9. This adjuvant enhances antigen-presenting cell engagement and innate immune signaling, promotes CD8+ T cell recruitment, and reduces local neutrophilic inflammation relative to CpG ODN. Co-administered vaginally with HSV-2 glycoproteins following intramuscular priming, BEACON improved protection against HSV-2 by increasing local CD8+ TRM populations and mucosal IgG and IgA responses. Vaccine-mediated protection required local delivery of both antigen and adjuvant, and was significantly reduced by CD8+ T cell or B cell depletion. These findings highlight the potential of engineered mucosal adjuvants for vaccines targeting genital herpes and other sexually transmitted infections. One-sentence summaryWe developed BEACON, a mucosal adjuvant that elicits protective immunity against genital herpes simplex virus 2 infection in mice.

immunology↗

bioRxiv2024

Intranasal hemagglutinin protein boosters induce robust mucosal immunity and cross-protection against influenza A viral challenge

Licensed parenteral influenza vaccines induce systemic antibody responses and alleviate disease severity but do not efficiently prevent viral entry and transmission due to the lack of local mucosal immune responses. Here, we describe intranasal booster strategy with unadjuvanted recombinant hemagglutinin (HA) following initial mRNA-LNP vaccination, Prime and HA. This regimen establishes highly protective HA-specific mucosal immune memory responses in the respiratory tract. Intranasal HA boosters provided significantly reduced viral replication compared to parenteral mRNA-LNP boosters in both young and old mice. Correlation analysis revealed that slightly increased levels of nasal IgA are significantly associated with a reduced viral burden in the upper respiratory tract. Intranasal boosting with an antigenically distinct H1 HA conferred sterilizing immunity against heterologous H1N1 virus challenge. Additionally, a heterosubtypic intranasal H5 HA booster elicited cross-reactive mucosal humoral responses. Our work illustrates the potential of a nasal HA protein booster as a needle- and adjuvant-free strategy to prevent infection and disease from influenza A viruses. One Sentence SummaryAdjuvant-free nasal booster induces protective immunity against influenza infection.

immunology↗

bioRxiv2022

Remodeling of human colon plasma cell repertoire in ulcerative colitis

Plasma cells (PCs) constitute a significant fraction of cells in colonic mucosa and contribute to inflammatory lymphocytic infiltrates in ulcerative colitis (UC). While gut PCs secrete 3-5 g of immunoglobulins daily, including IgA antibodies that target colitogenic bacteria, their role in UC is not known. Here, we combined B cell sorting with single-cell VDJ- and RNA-seq and monoclonal antibody (mAb) testing to characterize the colonic PC repertoire in healthy individuals and patients with UC. We show that a large fraction of B cell clones is shared between different colon regions and that inflammation in UC disrupts this landscape, causing clonal expansion and isotype skewing from IgA1 and IgA2 to IgG1. mAbs produced from expanded PC clones show low polyreactivity and autoreactivity and target specific bacterial strains. Expression profiles of individual PCs from inflamed and non-inflamed colon regions indicate that inflammation is associated with up-regulation of the unfolded protein response (UPR) and antigen presentation genes. Together, our results characterize the microbiome-specific PC response in the colon, its disruption in UC and how PCs might contribute to inflammation in UC.

immunology↗

bioRxiv2019

Simulating groundcover community assembly in a frequently burned ecosystem using a simple neutral model

Fire is a global process that drives patterns of biodiversity. In frequently burned fire-dependent ecosystems, surface fire regimes allow for the coexistence of high plant diversity at fine-scales even where soils are uniform. The mechanisms on how fire impacts groundcover community dynamics are however, poorly understood. Because fire can act as a stochastic agent of mortality, we hypothesized that a neutral mechanism might be responsible for maintaining plant diversity. We used the demographic parameters of the Unified Neutral Theory of Biodiversity (UNTB) as a foundation to model groundcover species richness, using a southeastern U.S. pine woodland as an example. We followed the fate of over 7,000 individuals of 123 plant species for four years and two prescribed burns in frequently burned Pinus palustris sites in NW FL, USA. Using these empirical data and UNTB-based assumptions, we developed two parsimonious autonomous agent models, which were distinct by spatially explicit and implicit local recruitment processes. Using a parameter sensitivity test, we examined how empirical estimates, input species frequency distributions, and community size affected output species richness. We found that dispersal limitation was the most influential parameter, followed by mortality and birth, and that these parameters varied based on scale of the frequency distributions. Overall, these nominal parameters were useful for simulating fine-scale groundcover communities, although further empirical analysis of richness patterns, particularly related to fine-scale burn severity is needed. This modeling framework can be utilized to examine our premise that localized groundcover assemblages are neutral communities at high fire frequencies, as well as examine the extent to which niche-based dynamics determine community dynamics when fire frequency is altered and spatial fire intensity patterns differ.

ecology↗