Biology subjects

Homer, R. J.

Publications and source records attributed to Homer, R. J..

4 recordsLinked to original sources

bioRxiv2025

A multicenter spatial transcriptomics atlas of human tuberculosis and non-tuberculous mycobacterial disease

Granulomas are the hallmark of mycobacterial (MB) infections, forming structured immune environments that contain bacteria but also drive disease persistence. However, their spatial and functional organization remains unclear. Using spatial RNA sequencing on 38 patient samples, we identified five distinct granuloma niches: a necrotic core, an immune-activated inner niche, an inflammatory and an extracellular matrix (ECM)-remodeling middle niche, an outer structural niche, and a tertiary lymphoid structure niche supporting antigen presentation. Immune activity peaks in the inner niche, transitioning to fibrosis at the periphery. Lymph node granulomas display reduced fibroblast involvement but stronger JAK-STAT activation. Mycobacterium tuberculosis (MTB) granulomas exhibit heightened JAK-STAT and IFN-{gamma} signaling, while non-tuberculous mycobacteria (NTM) granulomas show increased hypoxia signatures. Compared to sarcoidosis, MB granulomas feature a structured adaptive immune response, marked by the clustering of plasma cells. Our findings, accessible via https://lab-li.ciim-hannover.de/mb-granuloma/, define key disease signatures, guiding biomarker discovery and therapeutic targeting in granuloma-related diseases.

bioinformatics↗

bioRxiv2025

Alveolar epithelial cell plasticity and injury memory in human pulmonary fibrosis

Acute and repetitive lung epithelial injury can lead to irreversible and even progressive pulmonary fibrosis; Idiopathic pulmonary fibrosis (IPF) is a fatal disease and quintessential example of this phenomenon. The composition of epithelial cells in human pulmonary fibrosis - irrespective of disease etiology - is marked by the presence of Aberrant Basaloid cells: an abnormal cell phenotype with pro-fibrotic and senescent features, localized to the surface of fibrotic lesions. Despite their relevance to human pulmonary fibrosis, the exotic molecular profile of Aberrant Basaloid cells has obscured their etiology, preventing insights into how or why these cells emerge with fibrosis. Here we identify cellular intermediaries between Aberrant Basaloid and normal alveolar epithelial cells in human IPF tissue. We track the emergence of Aberrant Basaloid cells from alveolar epithelial cells ex vivo and uncover a role for similar cells in epithelial regeneration under normal conditions. Lastly, we characterize the epigenetic changes that distinguish Aberrant Basaloid cells from their progenitors and identify hallmarks of AP-1 injury memory retention. This study elucidates the phenomenon of maladaptive epithelial plasticity and regeneration in pulmonary fibrosis and re-contextualizes therapeutic strategies for epithelial dysfunction.

cell biology↗

bioRxiv2025

Using Fiji as a simplified tool for assessing alveolar chord length and septal thickness in neonatal pulmonary disease research

Bronchopulmonary Dysplasia (BPD) is a neonatal condition primarily affecting babies born prematurely, who have been exposed to invasive ventilation and/or oxygen supplementation. These therapies predispose the immature developing lungs to inflammation and injury to the alveolar epithelium resulting in loss of the alveolar epithelium and thickening of alveolar septa, the 2 important hallmarks of the pathology of BPD. The expansion and enlargement of the alveolar sacs gives the characteristic feature of alveolar simplification in BPD. To measure this alveolar abnormality, we have modified and developed a custom-made Chord Length Fiji plugin which can easily measure the Chord Length and Septal Thickness on Hematoxylin-Eosin-stained histological lung sections, thus generating an instant morphometry readout for quick interpretation. We validated this plugin in multiple animal experimental models and human neonatal lungs with BPD. We were able to differentiate the morphology under conditions of ventilation or hyperoxia exposure, when compared with untreated controls. We thus conclude that our Chord Length and Septal Thickness plugin can be used in a simplified manner following a less meticulous automated operation. To facilitate global use, we have created a DOI so that any user can access it without any restrictions to complete the morphometric measurements. This plugin will be useful for smaller research laboratories with limited budgets and require no access to complex software.

pathology↗

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↗