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133 Publications visible to you, out of a total of 133
Transcriptomic profiling identifies immunotherapy-responsive phenotypes in microsatellite-stable metastatic colorectal cancer.

Abstract (Expand)

Conventional immune checkpoint inhibitors (ICIs) remain largely ineffective in microsatellite-stable metastatic colorectal cancer (MSS mCRC), where low tumor immunogenicity and molecular heterogeneity … across metastatic sites underpin therapeutic resistance. We present a comprehensive transcriptomics analysis of metastatic and primary tumor biopsies from MSS mCRC patients treated with botensilimab (BOT; Fc-enhanced anti-CTLA-4) +/- balstilimab (BAL; anti-PD-1). Self-organizing map (SOM) machine learning stratified tumors into four molecular types, including a liver-like (LIV) subtype characterized by metabolic reprogramming and immunosuppressive signatures, and proliferative (PRO), inflammatory (INF), and mesenchymal (MES) types concordant with pan-cancer classifications. PRO, INF, and MES types were enriched for epithelial tumor cells, immune cells, and fibroblasts, respectively, defining immune-depleted, immune-enriched, and fibrotic states along a plasticity gradient. We observed treatment-related transcriptomic shifts toward immune-enriched states via upregulation of antigen presentation, T cell recruitment, and cytotoxicity pathways. INF and MES tumor types exhibited improved clinical responses and survival vs PRO and LIV types. This study identified distinct tumor microenvironment states that align along an immunophenotype axis marked by CD74, interferon-gamma, and APOBEC3 expression identified previously for primary CRC. Our findings provide novel insights into molecular correlates of immunotherapy response in MSS mCRC, potentially informing future therapeutic strategies to expand ICI efficacy to historically unresponsive tumors.

Authors: T. Konecny, N. Zadirako, A. Grigoryan, M. Tamazyan, S. Mnatsakanyan, L. Stepanyan, H. Loeffler-Wirth, S. Bourdelais, G. Mednick, C. Delepine, D. Chand, H. Binder

Date Published: 16th Jun 2026

Publication Type: Journal

Genomic Instability and Clonal Hematopoiesis in the Deep-Space Environment: The Role of Sex-Chromosome Asymmetry and High-LET Radiation

Abstract (Expand)

This paper examines how deep-space conditions in the Artemis program, including radiation, microgravity, and other stressors affect genomic stability in blood-forming cells, with a focus on clonal … hematopoiesis and sex-specific differences in DNA repair and mutation risk. Studies show space conditions promote mutations in hematopoietic stem cells, with sex-specific effects: males are more vulnerable to Y chromosome loss and structural damage, while females may experience increased epigenetic instability despite protective redundancy from the X chromosome; these risks are amplified by combined stressors like radiation, oxidative stress, and circadian disruption. Sex chromosome differences play a key role in radiation-induced mutations and clonal expansion, highlighting the need for personalized, sex-specific medical monitoring and countermeasures rather than a uniform approach for astronauts on long-duration missions.

Authors: Roksana Zakharyan, Ani Stepanyan, Arpine Minasyan, Suren Davitavyan, Gisane Lazaryan, Siras Hakobyan, Agnieszka Brojakowska, Malik Bisserier, Susmita Sahoo, Shihong Zhang, Venkata Naga Srikanth Garikipati, Mary K. Khlgatian, Arsen Arakelyan, David A. Goukassian

Date Published: 23rd Apr 2026

Publication Type: Journal

Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma.

Abstract (Expand)

Lymph node (LN) function requires the organization of cells into higher-order spatial units. However, the principles governing LN architecture in health and disease remain poorly understood. Here, we … used single-cell and spatial mapping to investigate the mechanisms directing immune cell organization in human LNs and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells that triggers stromal remodeling, progressive loss of homeostatic chemokine gradients, and tissue disorganization from a non-malignant state to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives the loss of tissue organization.

Authors: F. Czernilofsky, A. Mathioudaki, L. Jopp-Saile, R. Lutz, D. Vonficht, X. Wang, C. Schniederjohann, H. Voehringer, T. Roider, M. A. Baertsch, C. Rodemer, H. Loffler-Wirth, M. Grau, D. Fitzgerald, J. Mammen, J. Kosla, N. Liebers, P. M. Bruch, D. Ordonez-Rueda, A. Brobeil, G. Mechtersheimer, C. Pabst, C. Muller-Tidow, A. Trumpp, M. Seifert, F. Neumann, M. Heikenwalder, V. Benes, W. Huber, J. Distler, G. Lenz, H. Binder, R. Siebert, G. P. Nolan, M. Gerstung, J. B. Zaugg, D. Hubschmann, S. Haas, S. Dietrich

Date Published: 31st Mar 2026

Publication Type: Journal

Can artificial intelligence transform antiviral drug discovery?

Abstract (Expand)

The development of antiviral therapies is constrained by high costs and extended timelines, often insufficient to address rapidly spreading viral outbreaks. Artificial intelligence (AI) has recently … shown significant progress in identifying and optimizing therapeutic candidates. This review examines the application of AI across four domains in antiviral drug discovery: target identification via host-virus protein-protein interaction prediction and machine-learning analysis of genome-wide CRISPR screens; drug repurposing; de novo molecule design with generative AI; and resistance mutations prediction and phenotypic effects from viral sequence data. We discuss in silico and validated studies, focusing on the limited in vitro and in vivo evidence, and highlight common challenges and key limitations.

Authors: Irina Tirosyan, Yeva Gabrielyan, Vahe Petrosyan, Marco Vignuzzi, Hovakim Zakaryan

Date Published: 22nd Mar 2026

Publication Type: Journal

Multi-target computational pipeline for discovery of pan-influenza neuraminidase inhibitors.

Abstract (Expand)

The continuous evolution of influenza A and B viruses, coupled with the emergence of drug resistance, creates a pressing need for novel antiviral agents with broad-spectrum activity. The viral neuraminidase … enzyme remains a prime target, but its structural variability across different strains complicates the discovery of universal inhibitors. To address this challenge, we developed and implemented a multi-target computational pipeline designed to identify pan-influenza neuraminidase inhibitors. Our strategy involved high-precision molecular docking of a curated library containing 499,721 compounds against three structurally distinct neuraminidase representatives from influenza A (H1N1, H2N2) and influenza B viruses. Hits were prioritized using a cascade of energetic and geometric filters, followed by a rigorous two-tiered validation using extensive molecular dynamics simulations. This validation not only confirmed binding stability on the primary target but also critically assessed whether candidates maintained stable interactions across the other neuraminidase subtypes. This cross-validation approach was essential for eliminating subtype-specific binders, ultimately identifying ten compounds with robust, pan-influenza binding profiles. Notably, the successful identification of a diastereomer of the established drug zanamivir among the top candidates provides strong validation for the pipeline's ability to find biologically relevant scaffolds. Overall, this work demonstrates the integration of multi-target screening with cross-validated molecular dynamics (cross-MD) that overcame target variability and yielded ten promising hits candidates for next-generation anti-influenza therapeutics.

Authors: Smbat Gevorgyan, Marusya Ayvazyan, Levon Kharatyan, Anastasiya Shavina, Narek Abelyan, Hamlet Khachatryan, Hovakim Zakaryan

Date Published: 10th Mar 2026

Publication Type: Journal

Spotting a unicorn: spatial transcriptome analysis of the eyelid reveals gene regulatory networks enriched in Moll glands.

Abstract (Expand)

Moll glands, found in the margin of the eyelid next to the base of the eyelashes, are likely to play an important role in maintaining the tear film and therefore in securing adequate visual function. … However, information about their secretion and its regulation is extremely scarce. Here, we subjected spatial transcriptome data of the human eyelid to bioinformatics workflows incorporating machine learning to shed light on the Moll-specific transcriptional program. We identified Moll-specific genes such as HPD, CYP4Z1, PIP, GLYATL2, or SCGB2A2, which delineate a transcriptional core, i.e. not shared with other eyelid elements. Gene ontology enrichment analyses further depicted the biological functions of the Moll gland transcriptional programs, which include tyrosine metabolism and biosynthesis, extracellular exosome, small molecule metabolism, and erythrose 4-phosphate/phosphoenolpyruvate-family amino acid metabolism. Expression of GLYATL2 and HPD, identified as a specific and sensitive transcripts in the Moll gland transcriptome, was confirmed by immunofluorescence in the eyelid of four different patients, thus supporting the validity of our approach. Collectively, these results indicate that Moll-associated gene sets exhibit distinct but complementary functional programs, reflecting the gland's specialized metabolic capacity and secretory function within the eyelid tissue microenvironment. Our study provides the first in-depth analysis of the human Moll gland transcriptional landscape and identifies novel targets for regulating Moll gland homeostasis in health and disease.

Authors: T. Konecny, H. Binder, U. Hampel, F. Hansmann, H. Pfannkuche, M. R. Schneider

Date Published: 1st Mar 2026

Publication Type: Journal

Population structure of wild and cultivated grapevines in Armenia

Abstract (Expand)

Background: The South Caucasus region, including Armenia, is recognized as a center of early viticulture, home to the oldest known winery and a rich tradition of winemaking. Armenia's topography … has contributed to the preservation of genetically diverse grapevine populations. Cultivated grapevines (Vitis vinifera ssp. vinifera or V.V. ssp. vinifera) and their wild ancestor (V. vinifera ssp. sylvestris or V.V. ssp. sylvestris) exhibit high genetic diversity, making them valuable resources for understanding domestication, adaptation, and breeding. Despite Armenia’s historical and economic importance, the genomic diversity of its wild and cultivated grapevines remains underexplored. We re-analyzed whole-genome sequencing data of 164 grapevine accessions from Armenia, including cultivated and wild individuals, taken from a previous study on worldwide collected vine accessions to characterize genomic diversity, population structure, and domestication history of this gene pool. Results: Our analysis uncovered genetic patterns partly unique to Armenia. Population structure analysis revealed a clear genetic separation between wild and cultivated groups and three distinct ancestral components within the cultivated gene pool, reflecting a west-to-east geographical gradient in Armenia. This genetic cline correlates with a shift in usage, from table to wine grapes, and a transition in berry skin color from white to black. Additionally, we identified four distinct subgroups within wild populations in Syunik, suggesting notable diversity. Evolutionary history analysis indicates that wild and cultivated lineages began to separate ~18.5k years ago, with divergence intensifying ~4k years ago under human cultivation. Comparative genomic scans for divergent selection identified genomic regions associated with domestication traits, including disease resistance and biosynthesis of anthocyanin and flavanol. Genome-wide association, including k-mer-based approach studies, uncovered candidate markers linked to agronomic traits, such as berry skin color and bunch density. These results provide genomic resources and highlight targets for grapevine improvement and conservation. Conclusions: This whole-genome study on the genetic diversity of wild and cultivated grapevines from Armenia provides a valuable resource for identifying candidate genes and domestication-related regions associated with agronomic traits. The results underscore the importance of conserving local grapevine diversity in Armenia, a historically significant and genetically rich viticultural region.

Authors: Maria Nikoghosyan, Emma Hovhannisyan, Nate Zadirako, Shengchang Duan, Armine Asatryan, Arsen Arakelyan, Kristine Margaryan, Anush Baloyan, Tomas Konecny, Hans Binder

Date Published: 11th Feb 2026

Publication Type: Journal

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