Latest publications from CanCell

• Hermansen, Johanne Uthus; Kong, Weikaixin; Brodersen, Andrea M; Yanping, Yin; Urban, Aleksandra & Rein, Idun Dale [Show all 25 contributors for this article] (2026). A functional prognostic model predicts progression‐free survival in patients with relapsed chronic lymphocytic leukemia treated with ibrutinib + venetoclax. HemaSphere. 10(9). doi: 10.1002/hem3.70467. Full text in Research Archive Show summary

  Targeted therapies have improved outcomes for patients with chronic lymphocytic leukemia (CLL); yet, not all achieve durable responses. Existing prognostic models, developed for chemoimmunotherapy, have limited predictive value for newer targeted combinations. Here, we used data from a randomized phase II clinical trial to identify predictors of progression‐free survival (PFS) in response to Bruton tyrosine kinase (BTK) + B‐cell lymphoma 2 (Bcl‐2) inhibitor combination therapy. We studied the functional, genetic, and clinical characteristics of patients with relapsed/refractory (R/R) CLL treated with ibrutinib + venetoclax in the VISION/HO141 clinical trial (NCT03226301). Ex vivo drug sensitivity testing, (phospho)protein profiling, and immunophenotyping were performed on baseline peripheral blood mononuclear cells from 177 patients. Ex vivo drug sensitivity correlated with clinical responses to single‐agent therapies. (Phospho)protein patterns reflected intracellular pathway activity and predicted ex vivo drug sensitivity. Using stringent feature selection and regularized ridge regression to prevent overfitting, we integrated functional, genetic, and clinical data sets and identified six features—sensitivity to VEGFR‐2‐, JAK1/2 + Bcl‐2‐, and BTK + PI3K‐inhibitors; phosphorylation ratios of Bcl‐2:BTK and p90RSK:PLCγ2; and frequency of CD8 + T cells—that together outperformed the International Prognostic Index for CLL (CLL‐IPI) and other clinical scores in predicting PFS. These findings demonstrate that a prognostic model based on the functional features of CLL cell signaling and interaction with the microenvironment has the potential to improve upon conventional prognostic scores, warranting further clinical validation also in the frontline setting.

• Totland, Max Zachrisson; Rasmussen, Nikoline Lander; Elster, Vilde Cecilie Wivestad; Arnesen, Karen Irene; Bergmann, Dina Glømmi & Bergill, Ida [Show all 13 contributors for this article] (2026). Regulation of ubiquitination and degradation of the gap junction channel protein Connexin43 involves the concerted action of multiple members of the NEDD4 family of E3 ubiquitin ligases. Cancer Letters. ISSN 0304-3835. 659, p. 218796–218796. doi: 10.1016/j.canlet.2026.218796. Full text in Research Archive
• Haukaas, Håvard Styrkestad; Carlsson, Sven R. & Lystad, Alf Håkon (2026). Dealing with membrane stress through CASM. Autophagy. ISSN 1554-8627. p. 10–10. doi: 10.1080/15548627.2026.2717033. Full text in Research Archive Show summary

  Compartments of the endolysosomal and secretory pathways encounter diverse insults - from loss of ion gradients and osmotic imbalance to physical membrane disruption - creating a need for rapid, localized surveillance and response systems. Recent work demonstrates that conjugation of ATG8 to single membranes (CASM) provides such specificity via stress-responsive targeting mechanisms that recruit the ATG8 conjugation machinery through pathways distinct from macroautophagy/autophagy. Here, we review recent advances in how membrane stress is sensed, coupled to CASM initiation, and converted into downstream cellular responses.

• Kournoutis, Athanasios & Stenmark, Harald Alfred (2026). Sealing and healing: A two-step model for plasma membrane repair. Developmental Cell. ISSN 1534-5807. 61(7), p. 1345–1346. doi: 10.1016/j.devcel.2026.06.011. Full text in Research Archive Show summary

  Plasma membrane damage can cause cell death and is associated with neurodegeneration. In this issue of Developmental Cell, Heffner et al. show that annexin A11 (ANXA11) first plugs membrane lesions, before ESCRT-III is recruited to extrude the damaged patch-a two-step repair mechanism compromised by ALS- and FTD-linked mutations.

• Nakken, Sigve; Edsjö, Anders; Lehtiö, Janne; Nygaard, Vigdis; Roepman, Paul & Rosenquist, Richard [Show all 69 contributors for this article] (2026). Towards an ecosystem of clinical decision support tools for precision cancer medicine. NPJ precision oncology. doi: 10.1038/s41698-026-01551-6. Full text in Research Archive Show summary

  Molecular tumor boards are supported by clinical decision support system (CDSS) tools for the interpretation of complex molecular data towards personalized treatments. Current CDSS tools are genomics-focused and characterized by tight couplings between data ingestion, guideline-based reasoning logic and curated knowledgebases. Next-generation CDSS solutions should integrate multimodal data and learn from outcomes in an interoperable ecosystem, leveraging explainable, trustworthy output from AI models through rigorous clinical validation processes.

• Nygaard, Vigdis; Zhao, S.; Tamborero, D.; Rosenquist, R.; Stenzinger, A. & Roepman, P. [Show all 23 contributors for this article] (2026). Assessing clinical decision support system tools in precision oncology: piloting ring testing. ESMO Real World Data and Digital Oncology. 13. doi: 10.1016/j.esmorw.2026.100731. Full text in Research Archive
• MK, Starka-Rantina; R,, Ceseiko; M,, Campa; M, Zolovs; GF, Jermolenko & K,, Eglitis [Show all 9 contributors for this article] (2026). Remote HR-guided high-intensity interval training with weekly health monitoring in breast cancer patients during chemotherapy: A moderation analysis of physiological predictors. Baltic Journal of Health and Physical Activity. 12(2). doi: 10.29359/BJHPA.18.2.03. Full text in Research Archive Show summary

  Background: The study aimed to investigate the effects of a six-month remotely monitored heart rate – guided high-intensity interval training (HIIT) program on aerobic capacity, functional performance, and weekly self-reported health outcomes in women with stage II–III breast cancer undergoing neoadjuvant chemotherapy. Materials and methods: Fifty-six women (mean age 47 ± 8 years) were randomly assigned (1:1) to a HIIT group or a control group (CG). Thirty-five participants were included in analyses (HIIT group = 17; CG = 18). HIIT group performed 4 × 4-minute HIIT sessions at the intensity of 85–95% of the peak heart rate, two to three times weekly for six months. Aerobic capacity, time to exhaustion, functional performance, and weekly self-reported health domains were assessed before and after the intervention. Generalized linear mixed-effects models tested group × time interactions, and moderation analyses to test if physiological changes predicted self-reported trends. Results: The HIIT group achieved 79% adherence without adverse events. Peak oxygen uptake was maintained in the HIIT group (p = 0.94) but declined in CG (−13%, p < 0.001). Time to exhaustion (+5%, p = 0.043), 6-minute walking performance (+7%, p = 0.006), 30-second sit-to-stand (+19%, p = 0.003), and five-times sit-to-stand (+20%, p < 0.001) improved in the HIIT group. Significant group × time effects favored the HIIT group for physical functioning (p = 0.003), and both psychological state and sleep (p < 0.001). Reductions in the respiratory exchange ratio predicted improvements in pain, fatigue, social functioning, and sleep (all p < 0.01). Conclusion: Remote HIIT during chemotherapy preserved aerobic capacity and improved functional and patient-reported outcomes. Reductions in the respiratory exchange ratio moderated several patient-reported out-comes, suggesting an association between metabolic efficiency and less severe symptoms during chemotherapy.

• Abdallah, Majd; Nakken, Sigve; Georges, Mikaël; Bierkens, Mariska; Galvis, Johanna & Groppi, Alexis [Show all 15 contributors for this article] (2026). TrialMatchAI: an end-to-end AI-powered clinical trial recommendation system to streamline patient-to-trial matching. Nature Communications. 17(1). doi: 10.1038/s41467-026-70509-w. Full text in Research Archive Show summary

  Patient recruitment remains a major bottleneck in clinical trials, calling for scalable and automated solutions. We present TrialMatchAI, an AI-powered recommendation system that automates patient-to-trial matching by processing heterogeneous clinical data, including structured records and unstructured physician notes. Built on fine-tuned, open-source large language models (LLMs) within a retrieval-augmented generation framework, TrialMatchAI ensures transparency and reproducibility and maintains a lightweight deployment footprint suitable for clinical environments. The system normalizes biomedical entities, retrieves relevant trials using a hybrid search strategy combining lexical and semantic similarity, re-ranks results, and performs criterion-level eligibility assessments using medical Chain-of-Thought reasoning. This pipeline delivers explainable outputs with traceable decision rationales. In real-world validation, 92% of oncology patients had at least one relevant trial retrieved within the top 20 recommendations. Evaluation across synthetic and real clinical datasets confirmed state-of-the-art performance, with expert assessment validating over 90% accuracy in criterion-level eligibility classification - particularly excelling in biomarker-driven matches. Designed for modularity and privacy, TrialMatchAI supports Phenopackets-standardized data, enables secure local deployment, and allows seamless replacement of LLM components as more advanced models emerge. By enhancing efficiency, interpretability and offering lightweight, open-source deployment, TrialMatchAI provides a scalable solution for AI-driven clinical trial matching in precision medicine.

• Eva, Bassols-Citores,; Agnese, Brokāne,; Rūdolfs, Cešeiko,; Jānis, Eglītis,; Kristaps, Eglītis, & Konstantinos, Gkelis, [Show all 21 contributors for this article] (2026). Home-based high-intensity exercise training during neoadjuvant chemotherapy is associated with favorable chemotherapy outcomes and tumor microenvironment remodeling in breast cancer | Cell Communication and Signaling | Springer Nature Link. Cell Communication and Signaling. doi: 10.1186/s12964-026-03053-1. Full text in Research Archive Show summary

  A growing number of studies show that physical exercise is feasible and safe for cancer patients and enhances various physical and cognitive capabilities, thus improving the quality of life and disease outcomes. The molecular mechanisms behind these effects are, however, poorly understood. Here, we present the results from the CancerBeat study, where breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC) were enrolled in a high-intensity interval training (HIIT) program to investigate the effects of exercise on tumor biology and response to NAC. Fifty BC patients were randomized into HIIT and control (CON) groups. Patients were enrolled in the study shortly after diagnosis, and the HIIT group took personalized home-based training sessions for the whole duration of NAC (mean 24 weeks). NAC response was evaluated using the standard Miller-Payne grading system. A retrospective control (Ctrl) group consisted of age, stage and subtype-matched BC patients receiving standard of care during NAC. Acute exercise-induced changes in the plasma proteome were analyzed with the Olink Immuno-Oncology panel. Bulk RNA sequencing analysis was performed on BC and normal breast tissues from 20 patients in the HIIT and Ctrl groups. Tumor-infiltrating immune cell composition was inferred from the bulk RNA-seq data using CIBERSORTx, and findings were validated with a 7-plex immunofluorescence assay. In the HIIT group, the proportion of patients with Miller-Payne grades 4 and 5 was significantly higher compared to CON (80% vs. 47%, p = 0.036) and Ctrl groups (80% vs. 50%, p = 0.047), representing the primary finding of this study. Exploratory plasma proteomic analysis identified 2 and 20 plasma proteins whose levels change after acute exercise in BC patients at diagnosis and after completing the training program/NAC, respectively; five of these had not previously been linked to exercise. Bulk RNA sequencing of post-NAC tumor tissues revealed HIIT/NAC-associated gene expression patterns consistent with less aggressive phenotypes, favorable outcomes, and altered wound-healing and immune-related processes at the tumor site. The findings suggest the possible involvement of fibroblasts, endothelial cells, and other stromal cells in exercise-associated tumor microenvironment remodeling. CIBERSORTx analysis suggested greater infiltration of activated NK cells in HIIT tumors compared to resting NK cells in Ctrl tumors. As an exploratory observation, both plasma and tumor tissue levels of decorin were upregulated in the HIIT group, and this increase was associated with better NAC response and favorable prognosis. These findings warrant further investigation in larger, dedicated studies. Our study provides novel insights into the molecular mechanisms underlying the protective effects of exercise on BC progression. These preliminary results support the further investigation of physical exercise as a component of BC treatment and highlight the need for clinical trials exploring the impact of HIIT on immunotherapy efficacy. retrospectively registered at ClinicalTrials.gov, NCT06522971.

• Maria, Bogdanova,; Daria, Evensen,; Hanne, Haslene-Hox,; Mari-Liis, Kaljusto,; Escobar, Kvitting, John-Peder & Alicia, Llorente, [Show all 11 contributors for this article] (2026). Role of valve endothelial cells and extracellular vesicles in aortic valve calcification in vitro | Scientific Reports. Scientific Reports. doi: 10.1038/s41598-026-66629-4. Full text in Research Archive Show summary

  Aortic valve calcification is mediated by valve interstitial cells (VICs). We hypothesized that valve endothelial cells (VECs) stimulate pro-osteogenic changes in VICs, potentially via extracellular vesicles (EVs). We investigated VECs' pro-osteogenic effects on VICs, compared proteomes of healthy versus calcified VECs, and examined VECs-derived EVs effects on calcification. Human VECs and VICs were co-cultured in 2D and 3D (collagen gel) formats with osteogenic induction. Proteomic analysis compared VECs from healthy and calcified valves. Pro-osteogenic markers were assessed by qPCR, gel contractility was measured, and VECs-derived EVs were added to VICs cultures. In 2D co-cultures, induced calcification almost doubled versus VICs monocultures (p = 0.008). In 3D co-cultures, VECs from calcified valves induced strongest pro-osteogenic marker transcription in healthy VICs and reduced gel contraction. Proteomic analysis identified 3378 proteins with 27 and 8 proteins exclusive to healthy or calcified VECs, respectively. Nitric oxide synthase 3 and Hedgehog-interacting protein increased in calcified VECs (p = 0.005 and 0.002). VECs-derived EVs did not influence VICs calcification. VECs from calcified valves possess enhanced pro-osteogenic properties and promote VICs calcification independently of EVs. Pro-calcification EVs likely originate from other valve cell types.

• Feng, Xin; Sigurdardottir, Fjola Dögg Hugberg; Arnardottir, Erna Sif; Dammen, Toril; Einvik, Gunnar & Korkalainen, Henri [Show all 15 contributors for this article] (2026). Association of major adverse cardiovascular events with the apnea-hypopnea index, desaturation severity parameters, and cardiac troponins in participants of the Akershus Sleep APnea cohort. Sleep. ISSN 0161-8105. 49(8). doi: 10.1093/sleep/zsag013. Full text in Research Archive Show summary

  Study Objectives: To examine the prognostic value of the apnea-hypopnea index (AHI), desaturation severity parameters, and cardiac troponins alone and combined for major cardiovascular events (MACEs). Methods: MACE data were retrieved in 2021 from the Norwegian Patient Registry for 518 participants in the Akershus Sleep APnea (ASAP) cohort. Baseline polysomnography and fasting blood samples were collected between June 2006 and January 2008. Desaturation duration (DesDur) and severity (DesSev) were calculated using Automatic Blood Oxygen Saturation Analysis software. Cox regression models estimated hazard ratios (HRs) for MACE. Predictive properties of combining troponins and obstructive sleep apnea severity were calculated by comparing established clinical thresholds for cardiac troponin I (cTnI) and T (cTnT) with AHI clinical thresholds of ≥15 and ≥30, respectively. Results: High AHI, DesDur, DesSev, cTnI, and cTnT were associated with increased MACE risk. However, only cTnI independently predicted MACE after adjustment (HR: 1.74, 95% CI: 1.32–2.29). The HR for MACE was 2.68 (95% CI: 1.03–6.97) in patients with both high cTnI and AHI ≥30 events/h. Conclusion: In this 15-year follow-up, cTnI was independently associated with risk of MACE, whereas the AHI, desaturation parameters, and cTnT were not independent predictors. cTnI, especially when combined with AHI, was a stronger MACE predictor than cTnT. Provided our findings are validated in clinical obstructive sleep apnea populations, the measurement of cTnI may be considered for cardiovascular risk stratification.

• Nothnagel, Patrizia Maria Christiane; Meslin, Paul-Arthur Richard; Wik, Jonas Aakre; Dufour, Damien; Strøm, Yunna Erika & Bjørås, Magnar [Show all 11 contributors for this article] (2026). Transient SUMOylation inhibition in human pre-adipocytes stably imprints a transcriptional beiging fate. Nucleic Acids Research (NAR). ISSN 0305-1048. 54(6), p. 1–22. doi: 10.1093/nar/gkag232. Full text in Research Archive Show summary

  SUMOylation regulates chromatin states and transcriptional programs that preserve cellular identity, yet how perturbation of the SUMOylation pathway impacts adipocyte plasticity remains unclear. Here, we show that brief pharmacologic inhibition of SUMOylation in human pre-adipocytes using TAK-981 primes stable de novo beige differentiation in the presence of the PPARG agonist rosiglitazone. Transient TAK-981 exposure produces changes in the transcriptome and metabolism of mature adipocytes, including robust induction of canonical beiging markers like UCP1 and increased mitochondrial respiration. Mechanistically, ATAC-seq and RNA-sequencing revealed immediate chromatin remodeling and early mobilization of CEBP family members, followed by stable activation of CEBPA and PPARG regulatory networks. ChIP experiments demonstrated loss of H3K27me3 and gain of H3K27ac at PPAR response elements at thermogenic enhancers, and increased PPARG occupancy across the UCP1 regulatory unit. This mechanism is enforced by enhanced cAMP-PKA-p38 signaling and stabilization of beiging transcription activators. We propose that transient relief of SUMO-mediated repression unlocks dominant regulatory units, notably the UCP1 enhancer cluster, producing a monomorphic reprogramming toward adaptive thermogenesis. These findings identify SUMOylation as a reversible epigenetic barrier to adipocyte beiging and suggest that temporally controlled SUMO pathway inhibition combined with PPARG activation could be exploited to modulate adipose tissue thermogenic capacity.

• Dahl, Anette Kathinka; Mann, Daniel; Lystad, Alf Håkon Lohsen; Sachse, Carsten; Simonsen, Anne Gjøen & Pankiv, Serhiy (2026). Characterizing the membrane recruitment domain of BDCPs and its role in gray platelet syndrome. Journal of Cell Biology. ISSN 0021-9525. 225(10). doi: 10.1083/jcb.202510098. Full text in Research Archive
• Ballina, Laura Rodriguez de la; Walther, Christa G.; Condon, Nicholas D.; Felder, Alessandro A.; Schätz, Martin & Schmerl, Bettina [Show all 18 contributors for this article] (2026). GloBIAS survey results – An insight into the global bioimage analysis community. Journal of Microscopy. ISSN 0022-2720. p. 1–10. doi: 10.1111/jmi.70153. Full text in Research Archive
• Willoch-Allen, Katarina; Zhao, Zhi; Duran, Pilar Ayuda; Mikaeloff, Flora; Struyf, Nona & Österroos, Albin [Show all 13 contributors for this article] (2026). A multi-center study on the consistency of drug sensitivity testing in patients with acute myeloid leukemia. NPJ precision oncology. 10(1). doi: 10.1038/s41698-026-01480-4. Full text in Research Archive Show summary

  Clinical implementation of patient cell-based drug testing is hampered by inconsistencies and irreproducible results. Using linear mixed models and drug response data from four cohorts of patients with acute myeloid leukemia (n = 993 samples), we identified sources of variability in ex vivo drug sensitivity testing across the studies. We identified several experimental factors, including the time until sample was tested, the type of culture media and viability assay, which led to systematic differences in drug sensitivity profiles. We further investigated the effects of sample types (fresh or frozen) and disease status (diagnosis, relapse, or refractory), and observed that peripheral blood samples resulted in higher drug sensitivity levels, compared to those derived from bone marrow. Technical factors, such as the type of plate reader and centrifugation procedure, further contributed to the response variability depending on the chosen drug response metric. These factors need to be standardized for improved consistency in functional precision medicine studies.

• Skotland, Tore & Sandvig, Kirsten (2026). Plasma membranes: does one model fit all? Trends in Cell Biology. ISSN 0962-8924. 36(7), p. 537–544. doi: 10.1016/j.tcb.2026.03.001. Full text in Research Archive Show summary

  Biological membranes consist of a lipid bilayer with a highly asymmetric distribution of lipids in the two leaflets. This asymmetry is maintained by enzymes whose activities depend on cytosolic ATP and Ca2+ concentrations. Recently, a new model for plasma membranes (PMs) was introduced. It is based on studies with human erythrocytes and suggests that there is a 50% overabundance of lipids with two hydrophobic chains in the cytosolic leaflet, compensated by the presence of three times more cholesterol in the outer leaflet. In this opinion article, we discuss the large differences in lipid composition between erythrocytes and other cell types, the assumptions used to reach the new membrane model, and whether this model would fit PMs of other cell types.

• Kostas, Michal Janusz; Munthe, Else; Haugsten, Ellen Margrethe; Mateus, Duarte Nunes de Carvalho; Sørensen, Vigdis & Lærdahl, Jon Kristen [Show all 13 contributors for this article] (2026). Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H<inf>2</inf>O<inf>2</inf>-mediated kinase oxidation. Cell reports. 45(6). doi: 10.1016/j.celrep.2026.117504. Full text in Research Archive
• Balaguera, Nathalia Chica; Andersen, Aram Nikolai; Munoz, Sara Orellana; Llorente, Ignacio Garcia; P, Aurélie Nguéa & Nakken, Sigve [Show all 14 contributors for this article] (2026). Time-resolved functional genomics using deep learning reveals global hierarchical control of autophagy. Nature Cell Biology. ISSN 1465-7392. 28(3), p. 465–479. doi: 10.1038/s41556-025-01837-0. Full text in Research Archive Show summary

  Recycling of cellular components through autophagy maintains homeostasis in changing nutrient environments. Although its core mechanisms are extensively studied, understanding of its systems-wide dynamic regulation remains limited, particularly regarding how autophagy is inactivated once nutrients are restored. Here we mapped the genetic network that controls activation and inactivation of autophagy during nitrogen changes by combining time-resolved high-content imaging, deep learning and latent feature analysis. This dataset, termed AutoDRY, categorizes 5,919 mutants based on nutrient response kinetics and their contributions to autophagosome formation and clearance. Integrating these profiles with functional and genetic network data uncovered hierarchical and multilayered control of autophagy and revealed multiple new regulatory pathways. Notably, we identified the retrograde pathway as a pivotal time-varying modulator that tunes the expression of core autophagy genes and plays a central role in autophagy inactivation. Together, this study establishes a systems-level resource to guide future investigations of autophagy.

• Enserink, Jorrit Martijn & Balaguera, Nathalia Chica (2026). AutoDRY: a genome-wide resource revealing phase-specific control of autophagy activation, amplitude, and termination. Autophagy. ISSN 1554-8627. doi: 10.1080/15548627.2026.2660121. Full text in Research Archive
• Løchen, Arja Katrina Lea Arnesen; Søreng, Kristiane; Veroni, Chiara; Moncho, Laura Cristina Trachsel; Asp, Nagham Theres & Gaupset, Robin [Show all 10 contributors for this article] (2026). Interaction of HS1BP3 with cortactin modulates TKS5 localisation, cell secretion and cancer malignancy. Molecular Oncology. ISSN 1574-7891. doi: 10.1002/1878-0261.70248. Full text in Research Archive Show summary

  The HCLS1-Binding Protein 3 (HS1BP3) interacts with the SH3 domain of cortactin (CTTN), a protein that contributes to a malignant phenotype in cancers. Here, we demonstrate that high expression of HS1BP3 is associated with reduced survival for gastric adenocarcinoma and triple negative breast carcinoma patients and that HS1BP3 is specifically upregulated in these cancers. We mapped the HS1BP3-cortactin interaction site to the third proline-rich region (PRR3.1) of HS1BP3 and show that this interaction is important for cancer cell proliferation, extracellular matrix degradation and secretion. HS1BP3 expression was found to correlate with expression of the invadopodia scaffold protein TKS5 and we show that the localisation of TKS5 inside multivesicular endosomes is increased in cells expressing an HS1BP3 PRR3.1 mutant. Overall, our results highlight the importance of the direct interaction between HS1BP3 and cortactin in cancer development by regulating cell proliferation, secretion and invasion, which may provide an explanation for the negative correlation between HS1BP3 levels and the survival of gastric adenocarcinoma and triple negative breast cancer patients.

• Livia, Bajelan,; Bjarne, Bogen,; Ranveig, Braathen,; Prabhu, Gopalakrishnan, Ramakrishna; Victor, Greiff, & Hu, Xian [Show all 10 contributors for this article] (2026). Idiotype-specific CD4+ T cells chronically stimulate autoreactive B cells to develop into B lymphomas in mice | Nature Communications. Nature Communications. doi: 10.1038/s41467-026-69916-w. Full text in Research Archive Show summary

  The molecular mechanism linking autoimmunity to the development of lymphoma remains unexplained. Here, the authors develop a mouse model and show that chronic Id-driven T-B collaboration initiates autoreactive B cell responses and drives malignant transformation into lymphoma.

• Vo, Nicole; Oñate, Lorena de; Frank, Maximillian; Hu, Xian; Blackburn, Sophie M. & Foss, Dana V. [Show all 13 contributors for this article] (2026). Calcium Shock Enables Efficient and Programmable Particle Delivery for Genome Editing Applications. Advanced Science. 13(21). doi: 10.1002/advs.202510441. Show summary

  ABSTRACT Classical intracellular delivery methods such as transfection and transduction are inefficient, particularly with confluent cells and organoids, and lack cell type‐specific programmability. We demonstrate that an innovative methodology called calcium shock (CaSh) dramatically improves particle delivery into single cells, colonies, and organoids, and enables programmable delivery (CaSh‐Pro) into specific cell types within heterocellular populations. Calcium shock works by increasing endocytotic uptake while simultaneously disarming cell‐cell junctions. CaSh‐Pro further incorporates specific molecular targeting agents and amphiphilic peptides for preferential editing of different cell types. Calcium shock improves expression of plasmid, ribonucleoprotein, or adeno‐associated viral vectors with minimal toxicity in intact organoids representing diverse lineages. CaSh and CaSh‐Pro provide simple, versatile protocols for genome editing in complex systems, to enable biological discovery and therapeutic development.

• Leithner, Alexander; Kvalvaag, Audun Sverre Myrset; Mitra, Tanmay; Valvo, Salvatore; Dada, Hannah & Compeer, Ewoud [Show all 12 contributors for this article] (2026). Mixed-mobility supported lipid bilayers uncover the role of immobilized ICAM1 on T cell activation and immune synapse organization. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 123(11). doi: 10.1073/pnas.2530126123. Full text in Research Archive Show summary

  The immunological synapse (IS) integrates antigen recognition and adhesion to control T cell activation and effector functions. Reductionist systems have been instrumental in dissecting IS organization, but conventional systems constrain all ligands to be either mobile or immobile, unlike antigen-presenting cells where intercellular adhesion molecule 1 (ICAM1) is cytoskeletally anchored while T cell receptor (TCR) ligands remain mobile. Here, we establish mixed-mobility supported lipid bilayers (SLBs) that simultaneously present mobile TCR agonists and immobile ICAM1. Selective immobilization of ICAM1 disrupts centripetal F-actin flow, prevents centralization of TCR microclusters and shifts signaling to peripheral microclusters. This attenuates TCR downregulation through ectocytosis while maintaining recycling, and enhances integrin mechanotransduction, reflected in increased phosphorylation of Focal Adhesion Kinase, Paxillin, and the stretch-sensitive adaptor CasL. Functionally, immobilized ICAM1 augments T cell activation, degranulation, Perforin release, and cytotoxicity. Importantly, these findings were recapitulated in a cell–cell system engineered to express either full-length, cytoskeleton-anchored ICAM1 or a truncated form lacking cytoskeletal association, with full-length ICAM1 consistently promoting stronger effector responses. These findings identify ligand mobility as a key biophysical parameter that shapes IS organization and T cell effector responses and establish mixed-mobility SLBs as a powerful tool for probing receptor mechanics in immunity.

• Lystad, Alf Håkon Lohsen (2025). V-ATPase assembly at leaky lysosomes. Nature Structural & Molecular Biology. ISSN 1545-9993. 32(10), p. 1862–1864. doi: 10.1038/s41594-025-01612-7. Full text in Research Archive
• Chochola, Vaclav; Spustova, Karolina; Lavicky, Josef; Golunova, Anna; Pospisil, Jakub & Dvořáková, Jana [Show all 14 contributors for this article] (2025). TYRAY-Functionalized Alginate Bioinks for 3D Bioprinting Support Stem Cell Culture and Endothelial Network Formation. ACS Biomaterials Science and Engineering. 11(12), p. 7368–7383. doi: 10.1021/acsbiomaterials.5c01132. Full text in Research Archive Show summary

  3D bioprinting is transforming tissue engineering by enabling spatial arrangement of cells and cell aggregates within supportive hydrogels. Among available materials, alginate remains widely used for its biocompatibility, printability, and cost-effectiveness. However, its bioinert nature and lack of adhesive moieties restrict its capacity to support essential processes like cell adhesion, migration, and proliferation. In this study, we propose a comprehensive approach to enhance alginate hydrogels focusing on stem, stromal, and endothelial cell types to support extended growth and vascular network formation. Key innovations include the incorporation of the TYRAY peptide in 3D alginate hydrogels─its first application in this context─to promote cell adhesion and migration, accompanied by Ca(OH)2-modified surfaces for stable hydrogel anchoring and an ultrasonic mist cross-linking to preserve 3D structure fidelity. Functionalization with the TYRAY peptide significantly enhanced cell proliferation, promoted multicellular spheroid fusion, and supported endothelial network development in comparative culture setting. Together, these findings establish this defined, xeno-free alginate system as a versatile bioink material suitable for 3D culture and bioprinting applications.

• Sagini, Krizia; Selvarajah, Mughilan; Romero, Silvana Angelica Troncoso; Bassols, Eva Citores; Gracia, Beatriz Martín & Ramirez, Manuel [Show all 16 contributors for this article] (2025). The Redox Enzyme Thioredoxin Is Increased in Plasma Extracellular Vesicles From Endurance‐Trained Females in Response to Acute Exercise. The FASEB Journal. ISSN 0892-6638. 39(16). doi: 10.1096/fj.202500678r. Full text in Research Archive Show summary

  The effects of exercise are mediated by molecules secreted into the circulation in response to exercise. Extracellular vesicles (EVs) have recently appeared as possible vehicles for some of these molecules, and as mediators of tissue crosstalk during exercise. This study aimed to identify changes in the proteome of EVs released into circulation by endurance running‐trained females after a bout of 60‐min aerobic exercise consisting of incremental treadmill running. Blood samples were collected immediately before and after exercise, and EVs were separated from plasma and characterized by Western blot and electron microscopy. Mass spectrometry‐based proteomics analysis of EV preparations was then performed and showed that the levels of 9 proteins were differentially expressed in response to exercise. Thioredoxin, an enzyme that plays an essential role in the maintenance of redox homeostasis, showed the largest change. The increase in the levels of thioredoxin after exercise was also observed by Western blot analysis. Interestingly, post‐exercise plasma EVs were able to protect cells against oxidative stress. These results support the effect of physical exercise in modulating the levels of molecules involved in the maintenance of redox homeostasis, such as thioredoxin and other antioxidant enzymes, in plasma EVs. Although further studies are needed to fully understand the functional role of these molecules, it is intriguing to consider the protective health effects that exercise‐induced EVs may have against oxidative stressors.

• Lapao, Ana Sofia Da Silva; Johnson, Lauren Sophie; Moncho, Laura Cristina Trachsel; Rodgers, Samuel J; Singh, Sakshi & Ng, Matthew [Show all 9 contributors for this article] (2025). The RAB27A effector SYTL5 regulates mitophagy and mitochondrial metabolism. eLIFE. 14. doi: 10.7554/elife.105541. Full text in Research Archive Show summary

  SYTL5 is a member of the Synaptotagmin-Like (SYTL) protein family that differs from the Synaptotagmin family by having a unique N-terminal Synaptotagmin homology domain that directly interacts with the small GTPase RAB27A. Several SYTL protein family members have been implicated in plasma membrane transport and exocytosis, but the specific function of SYTL5 remains unknown. We here show that SYTL5 is a RAB27A effector and that both proteins localise to mitochondria and vesicles containing mitochondrial material. Mitochondrial recruitment of SYTL5 depends on its interaction with functional RAB27A. We demonstrate that SYTL5-RAB27A positive vesicles containing mitochondrial material, autophagy proteins and LAMP1 form during hypoxia and that depletion of SYTL5 and RAB27A reduces mitophagy under hypoxia mimicking conditions, indicating a role for these proteins in mitophagy. Indeed, we find that SYTL5 interacts with proteins involved in vesicle-mediated transport and cellular response to stress and that its depletion compromises mitochondrial respiration and increases glucose uptake. Intriguingly, SYTL5 expression is significantly reduced in tumours of the adrenal gland and correlates positively with survival for patients with adrenocortical carcinoma.

• Medhus, Astrid; Schink, Kay Oliver; Longva, Ane Sager; Engebråten, Olav; Berg, Kristian & Weyergang, Anette (2025). The mechanisms of HER2 targeted ADCs are dependent on Rab GTPases. Therapeutic Advances in Medical Oncology. ISSN 1758-8340. 17. doi: 10.1177/17588359251332473. Full text in Research Archive Show summary

  Introduction: In the era of personalized cancer therapy, antibody-drug conjugates (ADCs) have become one of the fastest-emerging groups of anticancer drugs. ADCs consist of an antibody coupled to a cytotoxic payload by a chemical linker, designed to be cleaved off intracellularly. Understanding the intracellular trafficking and processing of ADCs is crucial for elucidating their mechanism of action. Objective: This study aimed to compare trastuzumab deruxtecan (T-DXd) to ado-trastuzumab emtansine (T-DM1) with emphasis on Rab GTPase-regulated intracellular trafficking and its impact on ADC efficacy. Methods: The efficacy of T-DXd and T-DM1 was assessed in a panel of HER2-positive cell lines. Correlations between ADC efficacy and the expression of HER2 and Rab GTPases were evaluated. Functional studies, including knockdown (KD), overexpression, and microscopy, were performed to evaluate the impact of Rab GTPases on ADC cytotoxicity. Results: In contrast to T-DM1, T-DXd efficacy was found not to correlate to HER2 expression in a panel of HER2-positive cell lines. However, a correlation to RAB5A expression was found for T-DXd efficacy, although not as strong as for T-DM1. Altering the expression of RAB5 in our model system confirmed RAB5 to have an impact on both T-DXd and T-DM1 cytotoxicity, but more on T-DM1. In addition, RAB4a was found to influence T-DXd sensitivity, but not T-DM1, indicating differences in intracellular processing between T-DXd and T-DM1. Conclusion: The study demonstrates that ADC design significantly influences intracellular trafficking and processing. The linker design, in particular, plays a major role in determining the intracellular fate of an ADC.

• Hurley, James H.; Coyne, Alyssa N.; Miączyńska, Marta & Stenmark, Harald Alfred (2025). The expanding repertoire of ESCRT functions in cell biology and disease. Nature. ISSN 0028-0836. 642(8069), p. 877–888. doi: 10.1038/s41586-025-08950-y. Full text in Research Archive
• Droste, Marvin; Puhka, Maija; Royen, Martin E. van; Ng, Monica S. Y.; Blijdorp, Charles & Alvarez‐Llamas, Gloria [Show all 30 contributors for this article] (2025). Roadblocks of Urinary EV Biomarkers: Moving Toward the Clinic. Journal of Extracellular Vesicles. 14(7). doi: 10.1002/jev2.70120. Full text in Research Archive Show summary

  ABSTRACT Despite remarkable interest in the biomarker potential of urinary extracellular vesicles (uEVs) and the identification of numerous promising candidates, their clinical translation still presents multiple challenges. The opportunities for successful translation are obvious, yet the main roadblocks on the way have hardly been systematically considered and more coordinated approaches are needed to overcome them. In the present review article, we have identified the most relevant roadblocks of clinical translation of urinary EV‐based biomarkers and discuss possible solutions to overcome them. These roadblocks are categorized as fundamental and technical but also related to development of novel biomarker assays and clinical acceptance. In addition, hurdles within the regulatory approval process are discussed. It is clear that various roadblocks to clinical translation of urinary EV biomarkers exist; however, they are addressable by promoting rigor and reproducibility as well as collaboration between basic and clinical scientists, clinicians, industry and regulatory bodies. Moreover, knowledge of obstacles for assay development and regulatory requirements should already be considered when developing a new biomarker to maximize the chance of successful translation. This review presents not only a status quo, but also a roadmap for the further development of the field.

• Lerche, Martina; Mathieu, Mathilde; Hamidi, Hellyeh; Chastney, Megan; Jacquemet, Guillaume & Bruininks, Bart Marlon Herwig [Show all 18 contributors for this article] (2025). Regulation of cell dynamics by rapid integrin transport through the biosynthetic pathway. Journal of Cell Biology. ISSN 0021-9525. 225(2). doi: 10.1083/jcb.202508155. Full text in Research Archive Show summary

  Constitutive integrin endocytosis and recycling control cell movement and morphology. In contrast, the role of newly synthesized integrins delivered via the biosynthetic pathway has been largely overlooked. We used the retention using selective hooks system to monitor the localization of new integrins exiting the endoplasmic reticulum in space and time. We discovered that new integrin delivery to the plasma membrane is polarized and enhances cell protrusion and focal adhesion growth in an extracellular matrix-ligand–dependent manner. Motor-clutch modeling explained the increased adhesion as higher integrin availability driving recruitment of additional receptors. Unexpectedly, live-cell imaging revealed a small subset of fast-emerging integrin vesicles rapidly transported to the cell surface to facilitate localized spreading. This unconventional secretion depended on cell adhesion and correlated with increased surface levels of immature, high-mannose glycosylated integrin, indicating bypass of the canonical Golgi-dependent secretory pathway. Thus, spatial plasma membrane-targeting of new integrins rapidly alters adhesion receptor availability, providing cells with added plasticity to respond to their environment.

• Dillard, Caroline Marie Claude; Reis, Jose Gerardo Belem Teles Roque Dos; Jain, Ashish; Antunes, Marina Manuel Goncalves; Duran, Paula Ruiz & Qi, Yanyan [Show all 9 contributors for this article] (2025). NF-κB signaling driven by oncogenic Ras contributes to tumorigenesis in a Drosophila carcinoma model. PLoS Biology. ISSN 1544-9173. 23(4), p. 1–24. doi: 10.1371/journal.pbio.3002663. Full text in Research Archive Show summary

  Cancer-driving mutations synergize with inflammatory stress signaling pathways during carcinogenesis. Drosophila melanogaster tumor models are increasingly recognized as models to inform conserved molecular mechanisms of tumorigenesis with both local and systemic effects of cancer. Although initial discoveries of the Toll-NFκB signaling pathway in development and immunity were pioneered in Drosophila , limited information is available for its role in cancer progression. Using a well-studied cooperative Ras V12 -driven epithelial-derived tumor model, we here describe functions of Toll-NF-κB signaling in malignant Ras V12 , scrib - tumors. The extracellular Toll pathway components ModSP and PGRP-SA and intracellular signaling Kinase, Pelle/IRAK, are rate-limiting for tumor growth. The Toll pathway NFκB protein Dorsal as well as cactus/I κΒ show elevated expression in tumors with highest expression in invasive cell populations. Oncogenic Ras V12 , and not loss of scribble, confers increased expression and heterogenous distribution of two Dorsal isoforms, DorsalA and DorsalB, in different tumor cell populations. Mechanistic analyses demonstrates that Dorsal, in concert with the BTB-transcription factor Chinmo, drives growth and malignancy by suppressing differentiation, counteracting apoptosis, and promoting invasion of Ras V12 , scrib - tumors.

• Nie, Xin; Sun, Yan; Dijk, David P. J. van; Deng, Min; Brecheisen, Ralph & Wang, Zhaoqi [Show all 9 contributors for this article] (2025). Loss of Skeletal Muscle Mass Is Associated With Reduced Cytotoxic T Cell Abundance and Poor Survival in Advanced Lung Cancer. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 16(5), p. 1–13. doi: 10.1002/jcsm.70063. Full text in Research Archive Show summary

  Background Body composition alterations such as skeletal muscle (SM) loss in cancer patients are associated with poor survival. In turn, immune cell-driven pathways have been linked to muscle wasting. We aimed to investigate the relationship between body composition, tumour-infiltrating lymphocytes and survival in patients with advanced lung cancer. Methods We studied 200 patients with advanced lung cancer receiving immunotherapy (n = 81) or non-immunotherapy regimens (n = 119). Body composition including SM index (SMI) at baseline and longitudinal changes were assessed using computed tomography (CT) scans at the third lumbar vertebra. Associations between body composition parameters and overall survival (OS) were evaluated using Cox regression analysis. The median value of SMI, stratified by sex, was used as the cut-off to define groups with high and low baseline SMI. Stable SMI was defined by any increase or < 2% decrease per 100 days; loss of SMI was defined by ≥ 2% decrease per 100 days. Logistic regression analysis was applied to investigate the association between SMI and peripheral circulating immune cells. Tumour-infiltrating lymphocytes were identified by immunohistochemistry, and their relationship with SMI was evaluated. Results SMI loss was associated with shorter OS (whole cohort: HR = 2.314, 95% CI = 1.388–3.858, p = 0.001; immunotherapy cohort: HR = 3.028, 95% CI = 1.113–8.236, p = 0.03; non-immunotherapy cohort: HR = 2.298, 95% CI = 1.191–4.435, p = 0.013). Low baseline SMI was associated with higher CD3+ T cell abundance (OR = 1.240, 95% CI = 1.080–1.424, p = 0.002) but lower CD3+ CD8+ T cell abundance (OR = 0.862, 95% CI = 0.762–0.974, p = 0.018) in peripheral blood. Subsequent SMI loss during treatment was also significantly associated with higher CD3+ T cell counts (OR = 3.414, 95% CI = 1.301–8.961, p = 0.013) and lower CD3+ CD8+ T cell abundance (OR = 0.666, 95% CI = 0.459–0.968, p = 0.033). Patients with stable SMI had a higher number of CD8+ tumour-infiltrating lymphocytes than patients with SMI loss (15.4% vs. 7.9%, p = 0.036). Conclusion SM loss is an independent predictor for survival in patients with advanced lung cancer and is associated with reduced peripheral and tumour-infiltrating cytotoxic T cell abundance. An inadequate antitumour immune response may contribute to metabolic tissue wasting in cancer.

• Alampi, Manuela Maria; Kozlíková, Magdaléna; Mariangeli, Matteo; Civita, Simone; Delcanale, Pietro & Mussini, Andrea [Show all 14 contributors for this article] (2025). Light-enhanced cytotoxicity and intracellular trafficking of the PD-L1-targeting photoimmunoconjugate EITC-atezolizumab. Biomedicine & Pharmacotherapy. ISSN 0753-3322. 191, p. 118550–118550. doi: 10.1016/j.biopha.2025.118550. Full text in Research Archive
• Bouska, Alyssa; Zhang, Weiwei; Sharma, Sunandini; Holte, Harald; Shah, Rauf A. & Lone, Waseem G. [Show all 44 contributors for this article] (2025). Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T‐Cell Lymphoma. American Journal of Hematology. ISSN 0361-8609. 100(9), p. 1486–1501. doi: 10.1002/ajh.27736. Full text in Research Archive Show summary

  Nodal follicular helper T‐cell ( T FH ) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole‐exome sequencing ( n  = 124), transcriptomic ( n  = 78), and methylation ( n  = 40) analysis, we identified recurrent mutations in known epigenetic drivers ( TET2, DNMT3A, IDH2 R172 ) and novel ones ( TET3, KMT2D ). TET2, IDH2 R172 , DNMT3A co‐mutated AITLs had poor prognosis ( p  < 0.0001). Genes regulating T‐cell receptor (TCR) signaling ( CD28, PLCG1, VAV1 , FYN ) or activation ( RHOA G17V ) or regulators of the PI3K‐pathway (PIK(3)C members, PTEN, PHLPP1, PHLPP2 ) were mutated. CD28 mutation/fusion was associated with poor prognosis ( p  = 0.02). WES of purified, neoplastic T‐cell (CD3 + PD1 + ) demonstrated high concordance with whole tumor biopsies and validated the presence of TET2 and DNMT3A in tumor and non‐lymphoid cells, but other mutations ( CD28 , RHOA G17V , IDH2 R172 , PLCG1 ) in neoplastic cells. Integrated DNA‐methylation and mRNA expression analysis revealed epigenetic alterations in genes regulating TCR, cytokines, PI3K‐signaling, and apoptosis. RNA‐seq analysis identified fusion transcripts regulating TCR‐activation (8%), revealed a restricted TCR‐repertoire (α = 87%, β = 72%), and showed the presence of Epstein–Barr virus transcriptome (73%). GEP demonstrated the association of B‐cells or dendritic cells in the tumor milieu with prognosis ( p  < 0.01). RNA‐seq and WES analysis of 12 AITL‐patient‐derived‐xenografts (PDX) showed that bi‐allelic TET2 and DNMT3A mutations or sub‐clonal mutations ( PLCG1, PHLPP2 ) propagated in sequential passages, and gene signatures related to T FH and T CM (central‐memory) were well‐maintained through passages. Gene expression signatures associated with late PDX passages (3rd–5th) were enriched with proliferation and metabolic reprogramming‐related genes and predicted prognosis in an independent AITL series. Low PHLPP2 mRNA expression predicted poor prognosis ( p  = 0.05) and engineered PHLPP2 or TET2 loss in CD4 + T‐cells showed enhanced PI(3)K activation, thus uncovering a therapeutic target for clinical trials.

• Nita, Alexandru; Abraham, Sara P.; Elrefaay, Eman R.; Fafilek, Bohumil; Cizkova, Eliska & Ursachi, Vlad Constantin [Show all 20 contributors for this article] (2025). FGFR2 residence in primary cilia is necessary for epithelial cell signaling. Journal of Cell Biology. ISSN 0021-9525. 224(7), p. 1–21. doi: 10.1083/jcb.202311030. Full text in Research Archive Show summary

  Primary cilium projects from cells to provide a communication platform with neighboring cells and the surrounding environment. This is ensured by the selective entry of membrane receptors and signaling molecules, producing fine-tuned and effective responses to the extracellular cues. In this study, we focused on one family of signaling molecules, the fibroblast growth factor receptors (FGFRs), their residence within cilia, and its role in FGFR signaling. We show that FGFR1 and FGFR2, but not FGFR3 and FGFR4, localize to primary cilia of the developing mouse tissues and in vitro cells. For FGFR2, we demonstrate that the ciliary residence is necessary for its signaling and expression of target morphogenic genes. We also show that the pathogenic FGFR2 variants have minimal cilium presence, which can be rescued for the p.P253R variant associated with the Apert syndrome by using the RLY-4008 kinase inhibitor. Finally, we determine the molecular regulators of FGFR2 trafficking to cilia, including IFT144, BBS1, and the conserved T429V430 motif within FGFR2.

• Reis, Jose Gerardo Belem Teles Roque Dos; Jain, Ashish; Liu, Dan; Khezri, Rojyar; Antunes, Marina Manuel Goncalves & Micheli, Sofia [Show all 9 contributors for this article] (2025). EyaHOST, a modular genetic system for investigation of intercellular and tumor-host interactions in Drosophila melanogaster. Cell Reports Methods. 5(11), p. 1–16. doi: 10.1016/j.crmeth.2025.101220. Full text in Research Archive Show summary

  Studying intercellular and interorgan interactions in animal models is key to understanding development, physiology, and disease. We introduce EyaHOST, a system for clonal combinatorial loss- and gain-of-function genetics in fluorescently labeled cells under QF2-QUAS eya promoter control. Distinct from mosaic analysis with a repressible cell marker (MARCM), it reserves the use of genome-wide GAL4-UAS tools to manipulate any host tissue. EyaHOST-driven RasV12 overexpression with scribble knockdown recapitulates key cancer features, including systemic catabolic switching and organ wasting. We demonstrate effective tissue-specific manipulation of host compartments, including homotypic epithelial neighbors, immune cells, fat body, and muscle. Organ-specific inhibition of autophagy or stimulation of growth signaling via PTEN knockdown in fat body or muscle prevents cachexia-like wasting. Additionally, tumors trigger caspase-driven apoptosis in the neighboring epithelium, and blocking apoptosis with p35 enhances tumor growth. EyaHOST provides a modular platform to dissect mechanisms of intercellular and interorgan communication under physiological or disease conditions.

• Mlynska, Agata; Dobrovolskiene, Neringa; Suveizde, Karolina; Lukaseviciute, Gabija; Sagini, Krizia & Martin-Gracia, Beatriz [Show all 14 contributors for this article] (2025). Exercise-induced extracellular vesicles delay tumor development by igniting inflammation in an immunologically cold triple-negative breast cancer mouse model. Journal of Sport and Health Science. ISSN 2095-2546. 14. doi: 10.1016/j.jshs.2025.101041. Full text in Research Archive Show summary

  Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth. Rapid release of extracellular vesicles (EVs) during exercise suggests their potential role as mediators of exercise-induced systemic effects and physiological adaptation. This study investigated the impact of exercise-induced plasma EVs on tumor growth and immune tumor microenvironment in murine models of triple-negative breast cancer (TNBC): EO771 (a C57BL/6-derived TNBC cell line) and 4T1 (a BALB/c-derived TNBC cell line). Methods Size exclusion chromatography was used to isolate exercise-induced EVs from plasma of healthy female mice (BALB/c and C56BL/6, n = 30 per strain) that underwent ten 30-min moderate-intensity treadmill running sessions over 2 weeks. Nanoparticle tracking analysis, Western blot, and electron microscopy confirmed the presence of EVs in the samples. Tumor-bearing mice (n = 72 per strain) were administered with exercise-induced EVs before or/and after tumor implantation. Local and systemic immune responses were assessed using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative polymerase chain reaction (qPCR). Results Administration of exercise-induced EVs, particularly before tumor implantation, significantly suppressed tumor growth and reduced tumor burden in both TNBC models. In EO771, endpoint tumor volumes were 278–330 mm³ in treated groups compared to 799 mm³ in untreated (p < 0.0001), while in 4T1, treated groups showed volumes of 287–564 mm³ vs. 696 mm³ in untreated (p = 0.0002). Notable differences in tumor-infiltrating lymphoid and myeloid cell subpopulations indicated immunomodulatory effects of exercise-induced EVs, particularly in the 4T1 model, where their continuous administration significantly increased intratumoral cluster of differentiation 8 (CD8) T lymphocyte proportion (5.77% vs. 0.90% in untreated, p < 0.0001). Similarly, in the EO771 model, exercise-induced EVs administered before tumor implantation led to a marked rise in intratumoral CD8 T lymphocytes (2.24% vs. 1.08% in untreated, p = 0.0181). Conclusion Our findings indicate that exercise-induced EV treatment elicits a pro-inflammatory antitumor immune response, suggesting a shift of immunologically cold TNBC tumors towards a more inflamed phenotype associated with better outcomes. Our study supports the further investigation of EVs as modulators of antitumor immunity and their potential utility in enhancing the efficacy of immunotherapy.

• Jayakumar, Nikhil; Villegas-Hernández, Luis Enrique; Zhao, Weisong; Mao, Hong; Dullo, Firehun Tsige & Tinguely, Jean-Claude [Show all 9 contributors for this article] (2025). Chip-based label-free incoherent super-resolution optical microscopy. Light: Science & Applications (LSA). ISSN 2095-5545. 14(1). doi: 10.1038/s41377-025-01914-x. Full text in Research Archive Show summary

  The photo-kinetics of fluorescent molecules have enabled the circumvention of the far-field optical diffraction limit. Despite its enormous potential, the necessity to label the sample may adversely influence the delicate biology under investigation. Thus, continued development efforts are needed to surpass the far-field label-free diffraction barrier. The statistical similarity or finite coherence of the scattered light off the sample in label-free mode hinders the application of existing super-resolution methods based on incoherent fluorescence imaging. In this article, we present physics and propose a methodology to circumvent this challenge by exploiting the photoluminescence (PL) of silicon nitride waveguides for near-field illumination of unlabeled samples. The technique is abbreviated EPSLON, Evanescently decaying Photoluminescence Scattering enables Label-free Optical Nanoscopy. We demonstrate that such an illumination has properties that mimic the photo-kinetics of nano-sized fluorescent molecules, i.e., such an illumination permits incoherence between the scattered fields from various locations on the sample plane. Thus, the illumination scheme enables the development of a far-field label-free incoherent imaging system that is linear in intensity and stable over time, thereby permitting the application of techniques like structured illumination microscopy (SIM) and intensity-fluctuation-based optical nanoscopy (IFON) in label-free mode to circumvent the diffraction limit. In this proof-of-concept work, we observed a two-point resolution of $$\sim$$ ~ 180 nm on super-resolved nanobeads and resolution improvements between 1.9× to 2.8× over the diffraction limit, as quantified using Fourier Ring Correlation (FRC), on various biological samples. We believe EPSLON is a step forward within the field of incoherent far-field label-free super-resolution microscopy that holds a key to investigating biological systems in their natural state without the need for exogenous labels.

• Rusten, Tor Erik (2025). Autophagy regulation by signaling. Current Opinion in Cell Biology. ISSN 0955-0674. 97. doi: 10.1016/j.ceb.2025.102595. Full text in Research Archive Show summary

  The first identified regulators of autophagy were the hormones Glucagon and Insulin, long before the recognition that they act through receptor-mediated cell signaling pathways. More than two decades since the identification of the autophagy molecular machinery, we appreciate that regulation of autophagy is complex, operates at several levels, and serves many functions to maintain cellular and organismal health. TORC1 remains the best-defined gatekeeper, serving to sense nutrient and energy sufficiency while also integrating systemic growth factor signaling to control cell growth and autophagy autonomously. This review summarizes the current understanding of autophagy regulation by signaling through TORC1-dependent and independent mechanisms and discusses the emerging understanding of control and coordinated response of autophagy at the organism level.

• Bordi, Matteo; Testa, Beatrice; Compagnucci, Claudia; Colasuonno, Fiorella; Cipressa, Francesca & Betterini, Elisabetta [Show all 31 contributors for this article] (2025). ADSL deficiency is a secondary mitochondrial disease affecting organelle homeostasis and ERK2/AKT signaling in a linear genotype-phenotype relation. Cell reports. 44(9). doi: 10.1016/j.celrep.2025.116230. Full text in Research Archive Show summary

  Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production. The severity of mitochondrial impairment correlates with ADSLd pathology, especially in mitochondria-dependent tissues. We also identify defects in mitochondrial dynamics and transport linked to ERK2 and AKT suppression. Notably, overexpressing constitutively active ERK2 or supplementing purine intermediates partially rescues the mitochondrial phenotype. These findings suggest an alternative disease mechanism and highlight mitochondrial metabolism as a potential therapeutic target in ADSLd.

• Bope, Christian Domilongo; Kalyanasundaram, Sumana; Rand, Knut Dagestad; Nakken, Sigve; Lingjærde, Ole Christian & Hovig, Eivind (2025). StarSignDNA: Mutation-to-signature attribution for accurate representation of mutational processes in low-mutation contexts. NAR Genomics and Bioinformatics. 7(4). doi: 10.1093/nargab/lqaf181. Full text in Research Archive Show summary

  All cell lineages accumulate mutations over time, increasing the probability that some lineages eventually become malignant. Many of the processes responsible for generating mutations leave a characteristic footprint in the genome that allows their presence to be detected. However, the mutational pattern in a tumour is usually the combined result of multiple mutational processes being at work simultaneously, and the problem of disentangling the different footprints and their relative impact then becomes a deconvolution problem. Several algorithms have been developed for this purpose, most of them involving a factorisation of the mutation count matrix into two non-negative matrices, representing, respectively, the underlying mutational signatures and the relative exposure to these signatures. Here, we introduce the StarSignDNA algorithm for mutational signature analysis, which offers efficient re-fitting and de novo mutational signature extraction. StarSignDNA performs mutation-to-signature attribution, assigning each mutation to its most probable causative mutational signature(s) based on the mutation’s trinucleotide context and the signature profiles. StarSignDNA demonstrates robust and clinically relevant performance in low-mutation contexts, with particular strengths in re-fitting analysis and balanced performance in de novo signature discovery. The package offers a command-line-based interface and data visualisation routines. The package is available at https://github.com/uio-bmi/StarSignDNA and can be installed via PyPI.

• Croce, Katherine R; Ng, Christopher; Pankiv, Serhiy; Albarran, Eddy; Langfelder, Peter & Jesus, Ana Ramos de [Show all 22 contributors for this article] (2025). A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy - PMC. Neuron. ISSN 0896-6273. 113(22), p. 3780–3797. doi: 10.1016/j.neuron.2025.08.018. Full text in Research Archive Show summary

  The study of disease modifiers is a powerful way to identify patho-mechanisms associated with disease. Using the strong genetic traits of Huntington’s disease (HD), we identified a rare, single-nucleotide polymorphism (SNP) in WDFY3 associated with a delayed age of onset of up to 23 years. Remarkably, the introduction of the orthologous SNP into mice recapitulates this neuroprotection, significantly delaying neuropathological and behavioral dysfunction in two models of HD. The SNP increases expression of the protein autophagy-linked Fab1, YOTB, Vac1, and EEA1 (FYVE) protein (Alfy), an autophagy adaptor protein for the clearance of aggregated proteins, whose ectopic overexpression is sufficient to capture the neuroprotective effects of the variant. Increasing Alfy expression protects not only against HD but also against the toxicity due to phospho-α-synuclein and AT8-positive accumulation. By combining human and mouse genetics, we have uncovered a pathway that protects against multiple proteinopathies, revealing a much-sought-after, shared therapeutic target across a broad range of neurodegenerative diseases.

• Theart, Rensu P.; Levet, Florian; Hernández-Herrera, Paul; Leterrier, Christophe & Ballina, Laura R. de la (2025). Presynaptic actin nanostructures: A reproducibility case study. bioRxiv - the preprint server for biology. doi: 10.64898/2025.12.18.695210. Full text in Research Archive Show summary

  ABSTRACT In an effort to assess the reproducibility of bioimage analyses in current publications, we took part in a Global BioImage Analysts’ Society (GloBIAS) initiative to try and reproduce results from published articles. We attempted to reproduce core findings from the work of Bingham et al. , which investigates the actin organisation in presynaptic structures by using diffraction-limited and super-resolution microscopy. While the original paper unveiled clear biological insight, it lacked sufficient detail in the bioimage analysis methodological approach, limiting the depth of reproducibility we could achieve. Through frequent contacts with the corresponding author, we managed to replicate qualitative aspects of the analysis of actin nanostructures in bead-induced presynapses. We performed image reconstruction from super-resolution microscopy data, automatic image registration and visual inspection, followed by manual annotation of structures of interest in ∼35 images. Our experience with this exercise highlights the importance of transparent data sharing and accessibility, as well as the need to adhere to bioimage analysis standards that ensure the reproducibility of nowadays complex biological image analysis studies. It also shows how crucial interdisciplinary collaboration is, since many biology labs are simply unaware of these standards, which are often easy to implement and would likely be widely adopted if their value was better understood or known.

• Corbat, Agustin Andres; Walther, Christa G; Ballina, Laura R de la; Condon, Nicholas David; Felder, Alessandro A & Schätz, Martin [Show all 17 contributors for this article] (2025). GloBIAS: strengthening the foundations of BioImage Analysis. arXiv. doi: 10.48550/ARXIV.2507.06407. Full text in Research Archive Show summary

  There is a global need for BioImage Analysis (BIA) as advances in life sciences increasingly rely on cutting-edge imaging systems that have dramatically expanded the complexity and dimensionality of biological images. Turning these data into scientific discoveries requires people with effective data management skills and knowledge of state-of-the-art image processing and data analysis, in other words, BioImage Analysts. The Global BioImage Analysts’ Society (GloBIAS) aims to enhance the profile of BioImage Analysts as a key role in science and research. Its vision encompasses fostering a global network, democratising access to BIA by providing educational resources tailored to various proficiency levels and disciplines, while also establishing guidelines for BIA courses. By collaboratively shaping the education of BioImage Analysts, GloBIAS aims to unlock the full potential of BIA in advancing life science research and to consolidate BIA as a career path. To better understand the needs and geographical representation of the BIA community, a worldwide survey was conducted and 291 responses were collected across people from all career stages and continents. This work discusses how GloBIAS aims to address community-identified shortcomings in work environment, funding, and scientific activities. The survey underscores a strong interest from the BIA community in activities proposed by GloBIAS and their interest to actively contribute. With 72% of respondents willing to pay for membership, the community’s enthusiasm for both online and in-person events is set to drive the growth and sustainability of GloBIAS.

• Timmer, Romy; Bellanger, Aurélie Nathalie Pascale; Peeters, Sarah; Kim, Hera; Ballina, Laura Rodriguez de la & Eikvar, Sissel [Show all 11 contributors for this article] (2025). LRRC59 cooperates with nuclear transporters to restrain the nuclear envelope repair machinery and safeguard genome integrity. Nature Communications. 16(1). doi: 10.1038/s41467-025-65994-4. Full text in Research Archive Show summary

  Nuclear envelope (NE) rupture is a hallmark of cancer cells, and persistent NE damage drives genome instability and inflammation. NE repair relies on activation of the endosomal sorting complex required for transport (ESCRT)-III repair machinery by the LEMD2-CHMP7 compartmentalization sensor, but little is known beyond these core factors. Here, we use convergent proximity proteomics to inventorise proteins mobilized to the NE upon assembly of LEMD2-CHMP7 and activation of ESCRT-III. Within this NE repairome, we identify LRRC59 as a critical regulator of LEMD2 accumulation at NE ruptures. We find that LRRC59, together with the nuclear transporters KPNB1 and XPO1, restricts the assembly of LEMD2-CHMP7 complexes to the site of rupture. Disruption of this regulatory axis escalates LEMD2-CHMP7 spreading across the NE, driving torsional DNA damage in ruptured nuclei and micronuclei. Thus, our work identifies a central regulatory layer of NE repair centered on LRRC59 and KPNB1. We propose that altered LRRC59 levels and deregulated nuclear transport coordinately compromise NE repair, driving genome instability and cancer development.

• Radulovic, Maja; Yang, Chonglin & Stenmark, Harald Alfred (2025). Lysosomal membrane homeostasis and its importance in physiology and disease. Nature reviews. Molecular cell biology. ISSN 1471-0072. 27(1), p. 71–87. doi: 10.1038/s41580-025-00873-w. Full text in Research Archive
• Puurand, Marju; Llorente, Alicia; Linē, Aija & Kaambre, Tuuli (2025). Exercise-induced extracellular vesicles in reprogramming energy metabolism in cancer. Frontiers in Oncology. 14. doi: 10.3389/fonc.2024.1480074. Full text in Research Archive
• Rossini, Roberto; Oshaghi, Mohammadsaleh; Nekrasov, Maxim; Bellanger, Aurélie Nathalie Pascale; Domaschenz, Renae & Dijkwel, Yasmin [Show all 13 contributors for this article] (2025). Loss of multilevel 3D genome organization during breast cancer progression. Genome Research. ISSN 1088-9051. p. 1–18. doi: 10.1101/gr.280791.125. Full text in Research Archive Show summary

  Breast cancer entails intricate alterations in genome organization and expression. However, how three-dimensional (3D) chromatin structure changes in the progression from a normal to a breast cancer malignant state remains unknown. To address this, we have conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that although the fundamental properties of topologically associating domains (TADs) are overall maintained, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observe a restructuring of TAD–TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identify a previously unrecognized interchromosomal insertion event, wherein a locus on Chromosome 8 housing the MYC oncogene is inserted into a highly active subcompartment on Chromosome 10. This insertion is accompanied by the formation of de novo enhancer contacts and activation of MYC , illustrating how structural genomic variants can alter the 3D genome during oncogenesis. In summary, our findings provide evidence for the loss of genome organization at multiple scales during breast cancer progression, revealing novel relationships between genome 3D structure and oncogenic processes.

• Tiron, Crina Elena; Luta, Gabriel; Ghiarasim, Razvan; Tiron, Adrian; Nastasa, Valentin & Anita, Dragos Constantin [Show all 11 contributors for this article] (2025). Trastuzumab-Conjugated pH-Sensitive Micelles Exhibit Antitumor Activity and Induce Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer Cell Lines. Pharmaceutics. 17(12). doi: 10.3390/pharmaceutics17121554. Full text in Research Archive Show summary

  Background: Despite improved knowledge on cancer prevention, progression, and treatment, the incidence of cancer is still increasing. Patients with highly aggressive triple-negative breast cancer benefit from chemotherapy as the only systemic therapeutic alternative. Here, we performed studies that demonstrate the effects of trastuzumab linked to nanostructures with pH-dependent release on triple-negative models. Methods: We assessed in vitro cell proliferation, migration, invasion, mammospheres, spheroids, and organoid formation of human and murine cell lines. Balb/c mice were used to investigate the in vivo anti-tumoral effects of functionalized nanostructures. Ex vivo samples and cell lines were used to investigate, using immunohistochemistry and Western blot, the modulation of key molecular pathways. Results: Using a human normal cell line and human and murine triple-negative breast cancer cell lines, we found that trastuzumab exhibits anti-tumoral properties on triple-negative breast cancer cell lines only when linked to pH-sensitive micelles. In addition, the data demonstrates that functionalized micelles induce mesenchymal-to-epithelial transitions, impairing the metastasis. Conclusions: Taken together, these results indicate that functionalization of micelles by linking trastuzumab may open the way of treating triple-negative patients with trastuzumab, a treatment which is currently in use for patients with Her2 overexpression. The functionalized micelles may be loaded with various molecules to further improve the anti-tumoral effects.

• Fosslie, Madeleine Lystad; Ilaslan, Erkut; Skuland, Trine; Choudalakis, Michel; Søegaard, Mirra Louise Cicilie & Halliwell, Jason Alexander [Show all 23 contributors for this article] (2025). Major waves of H2A.Z incorporation during mouse oogenesis and preimplantation embryo development. Nature Communications. 17(1). doi: 10.1038/s41467-025-66919-x. Full text in Research Archive Show summary

  Abstract Epigenomes of mammalian oocytes and embryos undergo major transitions essential for successful development. Here, we provide genome-wide maps of histone variant H2A.Z during twelve stages of mouse oogenesis and preimplantation embryo development and relate it to histone marks and genomic features. This revealed that major waves of H2A.Z incorporation occur early in growing oocytes, forming distinct patterns of maternal, embryonic, and persistent H2A.Z enrichment. Late maternal enrichment is inherited by the zygote and precedes reduced formation of lamina associated domains and early replication in the maternal genome of 2-cell embryos. Persistent H2A.Z enrichment is strongly associated with CpG islands and H3K4me3 near transcription start sites of active genes, but thousands of maternal and embryonic H2A.Z incorporation sites exist elsewhere, frequently at transposable elements. The persisting H2A.Z enrichments across related developmental stages enable preservation of epigenetic information despite major concurrent changes in H3K4me3, H3K27me3, and DNA methylation. Altogether, this advances our understanding of how histone variants contribute to epigenetic reprogramming during mammalian oogenesis and early development.

• Andresen, Siri; Outa, Amani al; Formica, Miriam; Enserink, Jorrit & Knævelsrud, Helene (2025). Improved detection of lipidated Atg8a by immunoblotting in Drosophila melanogaster cells and tissues enables precise investigation of Atg8a flux and its termination. Autophagy. ISSN 1554-8627. 21(11), p. 2497–2517. doi: 10.1080/15548627.2025.2508551. Full text in Research Archive Show summary

  Macroautophagy/autophagy is an essential intracellular catabolic process for maintaining cellularhomeostasis. In Drosophila melanogaster, Atg8a lipidation serves as a key marker for autophagy, yettraditional methods often fail to effectively detect its lipidated state. To overcome this limitation, wedeveloped a refined approach that employs N-ethylmaleimide (NEM) to inhibit Atg4, thereby pre-serving Atg8a lipidation during sample preparation both in vitro and in vivo. We determined theoptimal concentration of the autophagic inhibitors bafilomycin A1 (BafA1) and chloroquine (CQ)required for inhibition of autolysosomal degradation. Furthermore, we investigated the effects ofprolonged nutrient deprivation on autophagic flux and TORC1 signaling. Our findings not onlyvalidate the effectiveness of this new approach to monitor lipidation of Atg8a but also provideinsights into selection of autolysosomal inhibitors and nutrient-dependent regulatory roles of TORC1in Drosophila.

• Presacan, Oriana; Mesa, María Hernández; Aldea, Alexandru C.; Andresen, Siri; Outa, Amani al & Johannessen, Julie Aarmo [Show all 9 contributors for this article] (2025). Explainable AI to unveil cellular autophagy dynamics. PLOS ONE. 20(9). doi: 10.1371/journal.pone.0331045. Full text in Research Archive Show summary

  Autophagy is a fundamental intracellular renovation process vital for maintaining cellular homeostasis through the degradation and recycling of damaged components. It is implicated in numerous pathological conditions, including cancer and neurodegenerative diseases. However, its dynamic nature and complexity pose challenges for manual analysis. In this study, we present a computational pipeline that leverages advanced deep learning models to automate the analysis of autophagic processes in 6,240 fluorescence microscopy images from the CELLULAR dataset. Our framework integrates object detection, cell segmentation, classification by autophagic state, cellular tracking, and explainability methods for interpretability. We achieved optimal results using YOLOv8 for object detection with a mAP50 of 0.80, U-Net++ for segmentation with an IoU of 0.82, and a vision transformer for classification with an accuracy of 0.86. To track cells, we developed a custom algorithm capable of handling complex scenarios such as cell division and morphological changes, all without requiring annotated tracking data. To enhance transparency, we employed explainability techniques based on class activation mappings to analyze model decision-making processes and validate classification outcomes, complemented by t-SNE visualizations for deeper insights into the data. Collaboration with biology experts validated our findings, highlighting the pipeline’s potential to advance autophagy research. This study demonstrates the potential of deep learning and explainable AI to streamline biomedical research, reduce manual effort, and uncover key autophagy dynamics.

• Wang, Yu; Eapen, Vinay V.; Liang, Yaosi; Kournoutis, Athanasios; Sherman, Marc Samuel & Xu, Yanxin [Show all 37 contributors for this article] (2025). WSTF nuclear autophagy regulates chronic but not acute inflammation. Nature. ISSN 0028-0836. 644(8077), p. 780–789. doi: https:/www.nature.com/articles/s41586-025-09234-1.pdf. Full text in Research Archive Show summary

  Acute inflammation is an essential response that our bodies use to combat infections1. However, in the absence of infections, chronic inflammation can have a pivotal role in the onset and progression of chronic diseases, such as arthritis, cancer, autoimmune disorders, metabolic-dysfunction-associated steatohepatitis (MASH), and most ageing-associated pathologies2,3. The underlying mechanisms that distinguish chronic inflammation from its acute counterpart remain unclear, posing challenges to the development of targeted therapies for these major diseases. Here we identify a mechanism that separates the two responses: during chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy, in which the WSTF protein of the ISWI chromatin-remodelling complex interacts with the ATG8 autophagy protein family in the nucleus. This interaction leads to WSTF nuclear export and subsequent degradation by autophagosomes and lysosomes in the cytoplasm. Loss of WSTF leads to chromatin opening over inflammatory genes, amplifying inflammation. Cell-penetrating peptides that block the WSTF-ATG8 interaction do not affect acute inflammation but suppress chronic inflammation in senescence as well as in MASH and osteoarthritis in mouse models and patient samples. The ability to specifically target chronic inflammation without blunting acute inflammation offers an approach for treating common chronic inflammatory diseases.

• Zapata-Muñoz, Juan; Jiménez-Loygorri, Juan Ignacio; Stumpe, Michael; Villarejo-Zori, Beatriz; Alonso-Gil, Sandra & Terešak, Petra [Show all 11 contributors for this article] (2025). The Developing Retina Undergoes Mitochondrial Remodeling via PINK1/PRKN-dependent Mitophagy. Journal of Molecular Biology (JMB). ISSN 0022-2836. 437(18). doi: 10.1016/j.jmb.2025.169263. Full text in Research Archive Show summary

  Mitophagy, the selective degradation of mitochondria, is essential for retinal ganglion cell (RGC) differentiation and retinal homeostasis. However, the specific mitophagy pathways involved and their temporal dynamics during retinal development and maturation remain poorly understood. Using proteomics analysis of isolated mouse retinas across developmental stages and the mitophagy reporter mouse line, mito-QC, we characterized mitophagy throughout retinogenesis. While mitolysosomes were more prevalent in the mature retina, we observed two distinct mitophagy peaks during embryonic development. The first, independent of PTEN-induced kinase 1 (PINK1) activation, was associated with RGCs. The second, PINK1-dependent peak was triggered after an increase in retinal oxidative stress. This PINK1-dependent, oxidative stress-induced mitophagy pathway is conserved in mice and zebrafish, providing the first evidence of programmed, PINK1-dependent mitophagy during development.

• Mauthe, Mario; Beek, Nicole van de; Mari, Muriel; Korsten, Giel; Nobari, Parisa & Castelino, Kennith B. [Show all 17 contributors for this article] (2025). A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy. Nature Cell Biology. ISSN 1465-7392. 27(9), p. 1448–1464. doi: 10.1038/s41556-025-01747-1. Full text in Research Archive Show summary

  Perturbations in protein quality control lead to the accumulation of misfolded proteins and protein aggregates, which can compromise health and lifespan. One key mechanism eliminating protein aggregates is aggrephagy, a selective type of autophagy. Here we reveal that fragmentation is required before autophagic clearance of various types of amorphous aggregates. This fragmentation requires both the 19S proteasomal regulatory particle and the DNAJB6-HSP70-HSP110 chaperone module. These two players are also essential for aggregate compaction that leads to the clustering of the selective autophagy receptors, which initiates the autophagic removal of the aggregates. We also found that the same players delay the formation of disease-associated huntingtin inclusions. This study assigns a novel function to the 19S regulatory particle and the DNAJB6-HSP70-HSP110 module, and uncovers that aggrephagy entails a piecemeal process, with relevance for proteinopathies.

• Croce, Katherine R.; Ng, Christopher; Pankiv, Serihy; Albarran, Eddy; Langfelder, Peter & Jesus, Ana Ramos de [Show all 22 contributors for this article] (2025). A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy. Neuron. ISSN 0896-6273. 113(22), p. 3780–3797. doi: 10.1016/j.neuron.2025.08.018. Full text in Research Archive Show summary

  The study of disease modifiers is a powerful way to identify patho-mechanisms associated with disease. Using the strong genetic traits of Huntington’s disease (HD), we identified a rare, single-nucleotide polymorphism (SNP) in WDFY3 associated with a delayed age of onset of up to 23 years. Remarkably, the introduction of the orthologous SNP into mice recapitulates this neuroprotection, significantly delaying neuropathological and behavioral dysfunction in two models of HD. The SNP increases expression of the protein autophagy-linked Fab1, YOTB, Vac1, and EEA1 (FYVE) protein (Alfy), an autophagy adaptor protein for the clearance of aggregated proteins, whose ectopic overexpression is sufficient to capture the neuroprotective effects of the variant. Increasing Alfy expression protects not only against HD but also against the toxicity due to phospho-α-synuclein and AT8-positive accumulation. By combining human and mouse genetics, we have uncovered a pathway that protects against multiple proteinopathies, revealing a much-sought-after, shared therapeutic target across a broad range of neurodegenerative diseases.

• Ho, Richard David Jun-Geet; Mossige, Joachim; Ponomartcev, Sergei; Natalia, Smirnova,; Sunny, Dai, Keqing & Hu, Xian [Show all 9 contributors for this article] (2025). [2509.08929] Spontaneous elongation of 3D gastruloids from local cell polarity alignment. arXiv. doi: https:/arxiv.org/abs/2509.08929. Full text in Research Archive Show summary

  Gastruloids are 3D stem cell aggregate models for early embryogenesis that provide a unique platform to study how collective cell dynamics drive tissue symmetry breaking and axial elongation. Using 3D light sheet imaging, we show that a pulse of Chiron, a Wnt activator, induces coherent alignment of cell polarity during elongation. While nuclear elongation occurs with or without treatment, only Chiron-treated gastruloids exhibit quasi-long-range alignment of nuclear axes, linking cell polarity coherence to tissue-scale remodeling. A minimal physical model of polarized cells, incorporating alignment-dependent torques and polarity-mediated adhesion, reproduces symmetry breaking and elongation, demonstrating that local cell polarity alignment alone can drive tissue-scale convergence-extension flows.

• Kumari, Remya Valsala; Pandya, Abhilash D.; Pettersen, Solveig; Kvalvaag, Audun Sverre Myrset; Myrann, Anne-Grethe & Ghiarasim, Razvan [Show all 12 contributors for this article] (2025). Evaluation of HER2 Targeted Poly(Ethylene Glycol)-Poly(L-histidine) Copolymer Micelles in Breast Cancer Models. Macromolecular Bioscience. ISSN 1616-5187. p. 1–15. doi: 10.1002/mabi.202500047. Full text in Research Archive Show summary

  Breast cancer positive for human epidermal growth factor receptor-2 (HER2) is challenging to treat due to the development of drug resistance, even with recently developed antibody-mediated therapeutics. However, nanotechnology provides new innovative therapeutic strategies. This study evaluates the efficacy of new HER2-targeted, pH-sensitive poly(ethylene glycol)-poly(L-histidine) copolymer micelles (PEG-PHis micelles), either empty, loaded with the drug doxorubicin (DOX), or the fluorophore Rhodamine-B (RB) for imaging purposes. Cellular association of the micelles, in vitro effects on proliferation and cytotoxicity, as well as ex vivo and in vivo responses on tumor growth are assessed. The results indicate that trastuzumab (TZM) conjugation enhances the specific cellular association of PEG-PHis micelles in HER2 overexpressing cells and improves the cytotoxic effects of the micelles themselves. Although the TZM conjugation of DOX-loaded micelles did not contribute to an enhancement in overall efficacy in cell lines and tumor explant cultures, the findings highlight the potential of TZM conjugation on these micelles in targeting HER2-positive tumors.

• Rosselle, Lea Bernadette; Leray, Thibault Christian; Joaquina, Sandy; Caulier, Benjamin William; Cormack, Emmet Mc & Gelebart, Pascal Francois [Show all 8 contributors for this article] (2025). Protocol for production of tonic CAR T cells with dasatinib. STAR Protocols. 6(1). doi: 10.1016/j.xpro.2024.103529. Full text in Research Archive Show summary

  Chimeric antigen receptors (CARs) are synthetic molecules composed of an extracellular antigen-binding domain and an intracellular signaling domain, leading to tonic signaling and manufacturing challenges. We present a protocol for the expansion of tonic CARs by using a Food and Drug Administration (FDA)-approved kinase inhibitor, dasatinib. We report steps for T cell transduction with retrovirus, expansion and verification of CAR quality using flow cytometry, and killing assay. At only 30 nM, dasatinib improves tonic CAR T cell proliferation and quality after expansion. For complete details on the use and execution of this protocol, please refer to Caulier et al.

• Ullern, Halvor; Schnur, Paulina; Boccara, Charlotte & Knævelsrud, Helene (2025). Rest, Repair, Repeat: The Complex Relationship of Autophagy and Sleep. Journal of Molecular Biology (JMB). ISSN 0022-2836. 437(18). doi: 10.1016/j.jmb.2025.169227. Full text in Research Archive Show summary

  Autophagy and sleep are two evolutionary conserved mechanisms across the animal kingdom. Autophagy is a pathway for the degradation of cytoplasmic material in the lysosome, playing important roles in the homeostasis and health of the organism. On the other hand, sleep is a homeostatically regulated state with numerous presumed essential roles, including the restoration of tissue and physiological functions, such as brain waste clearance via the activation of the glymphatic systems. Given that sleep and autophagy are crucial processes tightly linked to homeostasis and maintenance of good health, understanding how they interact is of great interest, especially as sleep quality decreases in our modern 24-hour societies. Autophagy represents a promising target for therapeutic interventions in this context. Here, we review the contrasted and complementary roles of autophagy and sleep in maintaining homeostasis. Specifically, we focus on recent evidence suggesting that sleep impairment may increase autophagy, while autophagosome levels may modulate the amount of sleep. We discuss outstanding questions at the intersection of these two fields, highlighting methodological shortcomings in the current literature. Overcoming these limitations will be instrumental to design new experiments with the aim of answering one of the greatest mysteries of our time – why do we sleep?

• Tunset, Mette Elise; Haslene-Hox, Hanne; Larsen, Jeanette Brun; Kondziella, Daniel; Nygård, Mona & Pedersen, Sindre Andre [Show all 8 contributors for this article] (2025). Clinical studies of blood-borne Extracellular vesicles in psychiatry: A systematic review. Journal of Psychiatric Research. ISSN 0022-3956. 182, p. 373–390. doi: 10.1016/j.jpsychires.2025.01.037. Full text in Research Archive Show summary

  Biomarkers for the diagnosis and clinical management of psychiatric disorders are currently lacking. Extracellular vesicles (EVs), lipid membrane-encapsulated vesicles released by cells, hold promise as a source of biomarkers due to their ability to carry molecules that reflect the status of their donor cells and their ubiquitous presence in biofluids. This review examines the literature on EVs in biofluids from psychiatric disorder patients, and discuss how the published studies contribute to our understanding of the pathophysiology of these conditions and to the discovery of potential biomarkers. We analyzed 46 studies on blood-borne EVs; no investigations on cerebrospinal fluid-derived EVs were found. A significant number of studies lacked optimal description of the methodology and/or characterization of the isolated EVs. Moreover, many studies aimed to capture brain-derived EVs, but often capture-proteins with low brain specificity were used. Considering biomarkers, miRNAs were the most investigated molecular type, but based on the studies analyzed it was not possible to identify robust biomarker candidates for the investigated disorders. Additionally, we describe the contribution of EV studies in illuminating the pathophysiology of psychiatric disorders, including research on insulin resistance, inflammation, mitochondrial dysfunction, and the microbiota. We conclude that there is a shortage of studies with detailed methodology description and EV sample characterization in psychiatric research. To exploit the potential of EVs to investigate psychiatric disorders and identify biomarkers more studies and validated protocols using capture proteins with high specificity to brain cells are needed. The review protocol was pre-registered in the PROSPERO database under the registration number CRD42021277534.

• Moncho, Laura Cristina Trachsel; Veroni, Chiara; Mathai, Benan John; Lapao, Ana Sofia Da Silva; Singh, Sakshi & Asp, Nagham Theres [Show all 9 contributors for this article] (2025). SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics. Journal of Cell Biology. ISSN 0021-9525. 224(5). doi: 10.1083/jcb.202404009. Full text in Research Archive Show summary

  We here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy of OXPHOS machinery components. In control conditions, SNX10 localizes to early endocytic compartments in a PtdIns3P-dependent manner and modulates endosomal trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX-IV and SAMM50, and the autophagy proteins SQSTM1/p62 and LC3B. The turnover of COX-IV was enhanced in SNX10-depleted cells, with a corresponding reduced mitochondrial respiration and citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show reduced levels of Cox-IV, as well as elevated ROS levels and ROS-mediated cell death in the brain, demonstrating the in vivo relevance of SNX10-mediated modulation of mitochondrial bioenergetics.

• Zhao, Sen; Nakken, Sigve; Vodak, Daniel & Hovig, Eivind (2025). FuSViz—visualization and interpretation of structural variation using cancer genomics and transcriptomics data. Nucleic Acids Research (NAR). ISSN 0305-1048. 53(4). doi: 10.1093/nar/gkaf078. Full text in Research Archive Show summary

  Structural variation (SV) is a frequent category of genetic alterations important for understanding cancer genome evolution and revealing key cancer driver events. With the development of high-throughput sequencing technologies, the ability to detect SVs of various sizes and types has improved, at both the DNA and RNA levels. However, SV calls are still prone to a considerable fraction of false positives, which necessitates visual inspection and manual curation as part of the quality control process. Identification of reliable and recurrent SVs in larger cohorts lends strength to revealing the driving roles of SVs in cancer development and to the discovery of potential diagnostic and prognostic biomarkers. Here, we present FuSViz, an application for visualization, interpretation, and prioritization of SVs. The tool provides multiple data view approaches in a user-friendly interface, allowing the investigation of prevalence and recurrence of SVs and relevant partner genes in a sample cohort. It integrates SV calls from DNA and RNA sequencing datasets to comprehensively illustrate the biological impact of SVs on the implicated genes and associated genomic regions. The functionality of FuSViz is intended for interrogation of both recurrent and private SVs, effectively assisting with pathogenicity evaluation and biomarker discovery in cancer sequencing projects.

• Song, Linlin; Kostas, Michal Janusz; Lærdahl, Jon Kristen; Skálová, Marie; Janská, Tereza & Juzeniene, Asta [Show all 14 contributors for this article] (2025). Preparation and Characterization of an Engineered FGF1 Conjugated to 161 Tb for Targeting of FGFRs. ACS Omega. 10(6), p. 5730–5743. doi: 10.1021/acsomega.4c09179. Full text in Research Archive Show summary

  The fibroblast growth factor receptor family members, FGFR1-4, are frequently overexpressed in various solid tumors, including breast cancer and sarcomas. This overexpression highlights the potential of the family of FGFRs as promising targets for cancer therapy. However, conventional FGFR kinase inhibitors often encounter challenges such as limited efficacy or drug resistance. In this study, we pursue an alternative strategy by designing a conjugate of the FGFR ligand FGF1 with the radioisotope 161Tb, for targeted therapy in FGFR-overexpressing cancer cells. FGF1 was engineered (eFGF1) to incorporate a single cysteine at the C terminus for site-specific labeling with a DOTA chelator. eFGF1-DOTA was mixed with the radioisotope 161Tb under mild conditions, resulting in a labeling efficiency above 90%. The nonradioactive ligands were characterized by mass spectrometry, while radioligands were characterized by thin-layer chromatography. The targeting function of the radioligands was assessed through confocal microscopy, flow cytometry, and Western blot analysis, focusing on binding to cancer cells and the activation of downstream signaling pathways related to FGFR. When compared to MCF-7 and RD cell lines with low FGFR expression, eFGF1-DOTA-Tb[161Tb] radioligands demonstrated significantly higher accumulation in FGFR-overexpressing cell lines (MCF-7 FGFR1 and RMS559), leading to enhanced cytotoxicity. Besides radionuclides, eFGF1 can also deliver doxorubicin (DOX) into cancer cells. Considering these characteristics, eFGF1-DOTA-Tb[161Tb] and eFGF1-DOX emerge as promising candidates for FGFR-targeted cancer therapy, and further evaluation in vivo is warranted.

• Goto, Tatsunori; Okamura, Hiroshi; Ikeda, Takashi; Mori, Yasuo; Shiratori, Souichi & Fujiwara, Shin-Ichiro [Show all 15 contributors for this article] (2025). Vedolizumab for prevention of lower-GI acute GVHD in the Japanese subgroup analysis of the phase 3 GRAPHITE study. International journal of hematology. ISSN 0925-5710. 122(1), p. 93–105. doi: 10.1007/s12185-025-03955-9. Full text in Research Archive Show summary

  In the randomized, double-blind, phase 3 GRAPHITE study (NCT03657160), anti-α4β7 integrin antibody vedolizumab showed greater efficacy than placebo for prevention of lower-gastrointestinal (GI) acute graft-versus-host disease (aGVHD) after unrelated allogenic hematopoietic stem cell transplantation (allo-HSCT). This post hoc analysis assessed the efficacy and safety of vedolizumab versus placebo for lower-GI aGVHD prevention in Japanese and non-Japanese patients, when added to standard GVHD prophylaxis (calcineurin inhibitor + methotrexate/mycophenolate mofetil + / − anti-thymocyte globulin [ATG]). The analysis included 35 (18 vedolizumab-treated, 17 placebo-treated) Japanese and 298 (150 vedolizumab-treated, 148 placebo-treated) non-Japanese patients. Lower-GI aGVHD-free survival by day + 180 after allo-HSCT (primary endpoint) was 94% in vedolizumab-treated versus 81% in placebo-treated Japanese patients (HR 0.36; 95% CI 0.03–4.01; P = 0.2) and 84% in vedolizumab-treated versus 70% in placebo-treated non-Japanese patients (HR 0.47; 95% CI 0.28–0.78; P = 0.002). The number of events for the 5 key secondary endpoints (lower-GI aGVHD-free and relapse-free survival, Grade C–D aGVHD-free survival, non-relapse mortality, overall survival, and Grade B–D aGVHD-free survival) by day + 180 was lower in vedolizumab- versus placebo-treated Japanese patients. No safety concerns were identified for vedolizumab use as lower-GI aGVHD prophylaxis in Japanese patients.

• Bäcker, Nils; Ast, Julia; Martorana, Domenica; Renicke, Christian; Berger, Jil & Mais, Cristopher-Nils [Show all 18 contributors for this article] (2025). Peroxisomal core structures segregate diverse metabolic pathways. Nature Communications. 16. doi: 10.1038/s41467-025-57053-9. Full text in Research Archive Show summary

  Peroxisomes are single membrane-bounded oxidative organelles with various metabolic functions including β-oxidation of fatty acids. Peroxisomes of many species confine certain metabolic enzymes into sub-compartments sometimes visible as electron dense cores. Why these structures form is largely unknown. Here, we report that in the smut fungus Ustilago maydis detergent resistant core structures are enriched for different enzymes excluding several key enzymes of the β-oxidation pathway. This confinement contributes to generation of peroxisome subpopulations that differ in their enzyme content. We identify short amino acid motifs necessary and sufficient for protein self-assembly into aggregates in vitro. The motifs trigger enrichment in cores in vivo and are active in mammalian cells. Perturbation of core assembly via variation of such motifs affects peroxisome function in U. maydis strains challenged with fatty acids. Thus, protein core structures serve to compartmentalize the lumen of peroxisomes thereby preventing interference of biochemical reactions. Metabolic compartmentalization of peroxisomes via assembly of specific proteins may occur in other organisms as well.

• Kaur, Namrita; Carlsson, Sven R. & Lystad, Alf Håkon Lohsen (2025). Lysosome-associated CASM: from upstream triggers to downstream effector mechanisms. Frontiers in Cell and Developmental Biology. 13. doi: 10.3389/fcell.2025.1559125. Full text in Research Archive Show summary

  Lysosomes are dynamic organelles critical for cellular degradation and signaling, safeguarded by a limiting membrane that prevents leakage of harmful contents into the cytoplasm. Upon lysosomal damage, cells deploy defensive mechanisms, including a key process called CASM (conjugation of ATG8 to single membranes), which lipidates ATG8 proteins onto the limiting membrane to support protective pathways. CASM operates through two pathways: VAIL, induced by lysosomal pH changes via V-ATPase and ATG16L1, and STIL, triggered by sphingomyelin exposure and mediated by TECPR1. This review examines CASM’s role in lysosomal damage responses, exploring the mechanisms of damaging agents, distinctions between VAIL and STIL, and the downstream effects of decorating lysosomes with ATG8, including effector recruitment for membrane repair or removal.

• Skotland, Tore; Ekroos, Kim; Llorente, Alicia & Sandvig, Kirsten (2025). Quantitative Lipid Analysis of Extracellular Vesicle Preparations: A Perspective. Journal of Extracellular Vesicles. 14(3). doi: 10.1002/jev2.70049. Full text in Research Archive Show summary

  Quantitative lipidomic analysis performed by mass spectrometry is required for determination of the lipid content of extracellular vesicles (EVs). Such methods can provide information about the total amount of lipids, the lipid species composition, the purity of EV samples as well as the cellular origin of the EVs. There are, however, many pitfalls when performing lipid analyses. Thus, any non-specialist should collaborate with experts in lipidomics. In addition to many good review articles giving advice about lipid analyses, we recommend the information and guidelines published by the Lipidomic Standard Initiative, an interest group affiliated with the International Lipidomics Society.

• Kolapalli, Srinivasa P.; Beese, Carsten J.; Reid, Steven E.; Brynjólfsdóttir, Sólveig H.; Jørgensen, Maria H. & Jain, Ashish [Show all 17 contributors for this article] (2025). Pellino 3 E3 ligase promotes starvation-induced autophagy to prevent hepatic steatosis. Science Advances. 11(3). doi: 10.1126/sciadv.adr2450. Full text in Research Archive Show summary

  Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR). This facilitates PELI3-mediated ubiquitination of ULK1, driving ULK1’s subsequent proteasomal degradation. PELI3 depletion leads to an aberrant accumulation and mislocalization of ULK1 and disrupts the early steps of autophagosome formation. Genetic deletion of Peli3 in mice impairs fasting-induced autophagy in the liver and enhances starvation-induced hepatic steatosis by reducing autophagy-mediated clearance of lipid droplets. Notably, PELI3 expression is decreased in the livers of patients with metabolic dysfunction–associated steatotic liver disease (MASLD), suggesting its role in hepatic steatosis development in humans. The findings suggest that PELI3-mediated control of autophagy plays a protective role in liver health.

• Haukaas, Håvard Styrkestad & Stenmark, Harald Alfred (2025). Phosphoinositides as regulators of membrane contact sites. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. ISSN 1388-1981. 1870(7). doi: 10.1016/j.bbalip.2025.159673. Full text in Research Archive Show summary

  Membrane contact sites (MCSs) between the different compartments of the cell play important roles in lipid, protein and ion transfer. Phosphoinositides are crucial for the functions of many MCSs, either as membrane anchors for MCS proteins, or as part of a countertransport mechanism driven by phosphoinositide dephosphorylation in the endoplasmic reticulum. Here we review the involvement of phosphoinositides in MCSs between the endoplasmic reticulum and other organelles such as the plasma membrane, mitochondria, endosomes, lysosomes, autophagosomes and the Golgi complex. These phosphoinositide-containing MCSs mediate transfer of Ca2+, phospholipids, cholesterol, and a motor protein, and thus are of great importance for cellular physiology.

• Moncho, Laura Cristina Trachsel; Mathai, Benan John; Veroni, Chiara & Simonsen, Anne Gjøen (2025). SNX10 at the crossroad of endocytosis and piecemeal mitophagy. Autophagy. ISSN 1554-8627. 21(9), p. 2077–2079. doi: 10.1080/15548627.2025.2499641. Full text in Research Archive Show summary

  Mitophagy targets damaged or dysfunctional mitochondria for lysosomal degradation. While canonical mitophagy pathways target the whole mitochondria for lysosomal degradation, it has become clear that selected mitochondrial components can be targeted for lysosomal degradation via other pathways, such as piecemeal mitophagy or mitochondria-derived vesicles. In a recent study, we identified the PX domain-containing endosomal protein SNX10 as a negative modulator of piecemeal mitophagy. Endosomal SNX10-positive vesicles dynamically interact with mitochondria and acquire selected mitochondrial proteins upon hypoxia. Zebrafish larvae lacking Snx10 show elevated Cox-IV degradation, increased levels of reactive oxygen species (ROS), and ROS-dependent neuronal death.

• Feith, Marek; Sajib, Saikat Das; Myrann, Anne-Grethe; Høgset, Anders; Garrido, Pablo & Martinez, Alfredo [Show all 11 contributors for this article] (2025). Induction of Cell Death by Combined Treatment with Photosensitizer-Chitosan Nanoparticles and the Ferroptosis Inducer RSL3 in Breast Cancer Cell Lines. Advanced NanoBiomed Research. 5(5). doi: 10.1002/anbr.202400208. Full text in Research Archive Show summary

  Breast cancer, a prevalent malignancy worldwide, includes the triple-negative subtype (TNBC) characterized by poor treatment outcomes. TNBC has been shown to be sensitive to ferroptotic cell death, an iron-dependent cell death mechanism involving reactive oxygen species (ROS) and lipid peroxidation. Herein, biodegradable tetraphenylchlorin-conjugated chitosan nanoparticles (TPC-CS NPs) in combination with the free ferroptosis inducer RSL3 is used in MCF7 (hormone receptor-positive, epithelial) and MDA-MB-231 (hormone receptor-negative, mesenchymal-like) breast cancer cell lines. The results show that RSL3 treatment has no cytotoxic effect in MCF7 and there is no enhanced sensitivity when combined with TPC-CS NPs, while the combination sensitizes MDA-MB-231 cells. Western blot analysis reveals that the combined treatment decreases and differently affects GPX4 levels and the ratio between the two GPX isoforms in the two cell lines. In MDA-MB-231 cells, the combined treatment shows enhanced effects on lipid peroxidation, mitochondrial potential, and basal and maximal respiration, as compared to single treatments. Finally, ferroptosis expression signatures distinguish breast cancer cell lines with an increasing score in mesenchymal-like cells. Moreover, the signatures correlate with breast cancer subtypes, exhibiting the highest scores in subtypes rich in mesenchymal-like cells, particularly basal-like and claudin-low tumors, suggesting their susceptibility to ferroptosis induction.

• Vonk, Christian M.; Grob, Tim; Rijken, Melissa; Kavelaars, François G.; Konijnenburg, Jolinda M.L. & Ossenkoppele, Gert J. [Show all 11 contributors for this article] (2025). Advantages of a genomic DNA-based next-generation sequencing assay for detection of mutant NPM1 measurable residual disease in AML. Blood Advances. ISSN 2473-9529. 9(5), p. 1069–1077. doi: 10.1182/bloodadvances.2024014490. Full text in Research Archive Show summary

  Mutations in the nucleophosmin-1 (NPM1) gene are among the most common molecular aberrations in acute myeloid leukemia (AML). Various studies have established mutant NPM1 (mNPM1) as a faithful molecular measurable residual disease (MRD) marker with prognostic significance. Assessment of prognostic mNPM1 is included in the European LeukemiaNet recommendations on MRD detection in AML. Because of recent advancements of promising drugs targeting mNPM1 AML, monitoring of mNPM1 MRD has gained interest, and is generally done by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). However, these RT-qPCR assays use complementary DNA (cDNA) as input, are based on gene expression levels of mNPM1, and are generally limited to specific mNPM1 gene variants. The main advantages of next-generation sequencing (NGS) using genomic DNA as input are stability, independence of gene expression levels, and the ability to detect any NPM1 variant in a single assay. Here, we comprehensively investigated the applicability of NGS on DNA to detect mNPM1 MRD in a cohort of 119 (cDNA) and 310 (DNA) patients with mNPM1 AML in complete remission after 2 cycles of induction chemotherapy. We demonstrate high correlations in levels and prognostic value between RT-qPCR/cDNA and NGS/DNA approaches, postulating NGS/DNA as an attractive alternative to RT-qPCR. We report that the 2% mNPM1/ABL1 threshold by RT-qPCR/cDNA corresponds to an NGS/DNA variant allele frequency of 0.01%. The NGS/DNA threshold of >0.01% after 2 cycles of induction chemotherapy identifies significantly more patients with AML with an increased relapse risk than current RT-qPCR/cDNA assays. The prognostic significance of mNPM1 MRD appears greatest in patients with AML with FLT3-internal tandem duplications.

• Zhen, Yan & Stenmark, Harald Alfred (2025). Sustained release of cytokines from migrasomes. Extracellular Vesicles and Circulating Nucleic Acids (EVCNA). 6, p. 171–175. doi: 10.20517/evcna.2025.15. Full text in Research Archive Show summary

  Cytokines are released by cells in response to infections and tissue damage. A recent paper by Jiao et al. demonstrates that circulating monocytes release the cytokines tumor necrosis factor and Interleukin-6 encapsulated in large extracellular vesicles called migrasomes, from which the cytokines are secreted locally in a sustained fashion.

• Kumari, Remya Valsala; Feith, Marek; Pettersen, Solveig; Åslund, Karl Olof Andreas; Mørch, Yrr Asbjörg & Skotland, Tore [Show all 9 contributors for this article] (2025). Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells. Pharmaceutics. 17(5), p. 1–20. doi: 10.3390/pharmaceutics17050657. Full text in Research Archive Show summary

  Background: Combination therapies for cancer have gained considerable attention due to their potential for enhancing therapeutic efficacy and decreasing drug resistance. Introducing nanodrug delivery systems in this context may further improve the therapy due to targeted delivery, improved drug stability, sustained drug release, and prevention of rapid clearance from circulation. This study evaluates the combinatorial effects of two cytotoxic drugs, cabazitaxel (CBZ) and RSL3 (RAS-selective lethal 3), in free form as well as encapsulated within poly(2-ethyl butyl cyanoacrylate) (PEBCA) nanoparticles (NPs) in breast cancer cell lines. Methods: Cell proliferation was assessed using IncuCyte technology, and synergistic drug effects were determined with SynergyFinder Plus. Cell viability was measured with the MTT assay. Additionally, we investigated whether the combinatorial effects were reflected in alterations of metabolic activity or reactive oxygen species (ROS) production using Seahorse technology and the CM-H₂DCFDA assay, respectively. Results: The data presented reveal, for the first time, that CBZ and RSL3 exhibit synergistically or additively combinatorial effects on various breast cancer cell lines. The pattern of cytotoxic effects was consistent, whether the drugs were in free form or encapsulated in NPs. Moreover, the combinatorial effects were not observed to be associated with early changes in metabolic activity or ROS production. Conclusion: This study highlights the potential of CBZ and RSL3 in combinatorial nanomedicine as they may act synergistically. Further studies are warranted to better understand the mechanisms behind these combinatorial effects.

• Bjørnerud, Birgitte; Wesche, Jørgen & Haugsten, Ellen Margrethe (2025). A rhabdomyosarcoma cell migration inhibitor screen using phase-contrast microscopy. Experimental Cell Research. ISSN 0014-4827. 449(1). doi: 10.1016/j.yexcr.2025.114582. Full text in Research Archive Show summary

  Rhabdomyosarcoma (RMS) is a malignant soft tissue tumour occurring in young children. Alterations in fibroblast growth factor receptor 4 (FGFR4) signalling pathways are linked to metastasis and poor prognosis in RMS. A critical trait of metastatic disease is the ability of cancer cells to migrate and invade nearby and distant tissues. To study cell migration, we have developed a computational tool that automatically tracks and measures the velocity of migrating cells in phase contrast images. This tool facilitated an inhibitor screen comprising 462 compounds, analysing nearly 2000 videos and tracking approximately 700 000 RMS-derived cells harbouring a constitutively active FGFR4 (RMS559). The highly selective inhibitor screen targeted various signalling pathways, including receptor tyrosine kinases (RTKs), mitogen-activated protein kinases (MAPK), and phosphoinositide 3-kinases (PI3K). Validation of screen hits revealed that inhibiting proteins in the MAPK and PI3K pathway decreased cell migration and, in some cases, cell viability. Inhibiting FGFR4 resulted in decreased RMS559 cell migration, while, surprisingly, inhibitors targeting Rho-associated protein kinase (ROCK) and focal adhesion kinase (FAK) resulted in increased RMS559 cell migration. Mechanistically, the inhibition of ROCK and FAK resulted in fewer focal adhesions, thereby facilitating increased cell velocity. These findings suggest that targeting specific signalling pathways can effectively modulate migration and survival of metastatic RMS559 cells.

• Lamsal, Apsana; Andersen, Sonja Benedikte; Nonstad, Unni; Kurganovs, Natalie Jayne; Skipworth, Richard J.E. & Bjørkøy, Geir [Show all 7 contributors for this article] (2025). A role of arginase-1-expressing myeloid cells in cachexia. Cancer & Metabolism. 13, p. 1–18. doi: 10.1186/s40170-025-00396-0. Full text in Research Archive Show summary

  Background Despite decades of efforts to find successful treatment approaches, cachexia remains a major unmet medical need. This condition, that affects patients with diverse underlying conditions, is characterized by severe muscle loss and is associated with reduced quality of life and limited survival. Search for underlying mechanisms that may guide cachexia treatment has mainly evolved around potential atrophy-inducing roles of inflammatory mediators, and in cancer patients, tumor-derived factors. Recently, a new paradigm emerged as it is becoming evident that specific immune cells inhabit atrophic muscle tissue. Arginase 1 (Arg1) expression is characteristic of these immune cells. Studies of potential contributions of these immune cells to loss of muscle mass and function is in its infancy, and the contribution of ARG1 to these processes remains elusive. Methods Analyses of RNA sequencing data from murine cachexia models and comprehensive, unbiased open approach proteomics analyses of skeletal myotubes was performed. In vitro techniques were employed to evaluate mitochondrial function and capacity in skeletal muscle cells and cardiomyocytes. Functional bioassays were used to measure autophagy activity. ARG1 level in patients’ plasma was evaluated using ELISA, and the association between ARG1 level and patient survival, across multiple types of cancer, was examined using the online database Kaplan-Meier plotter. Results In line with arginine-degrading activity of ARG1, we found signs of arginine restriction in atrophic muscles. In response to arginine restriction, mitochondrial functions and ATP generation was severely compromised in both skeletal muscle cells and in cardiomyocytes. In skeletal muscle cells, arginine restriction enhanced the expression of autophagic proteins, suggesting autophagic degradation of cellular content. Reduction in mitochondria marker TIMM23 supports selective autophagic degradation of mitochondria (mitophagy). In arginine starved cardiomyocytes, mitochondrial dysfunction is accompanied by both increased bulk autophagy and mitophagy. In cancer patients, we found an association between ARG1 expression and accelerated weight loss and reduced survival, further supporting a role of ARG1-producing cells in cachexia pathogenesis. Conclusion Together, our findings point to a mechanism for cachexia which depends on expansion of ARG1-expressing myeloid cells, local restriction of arginine, loss of mitochondrial capacity and induced catabolism in skeletal muscle cells and in the heart. Similar content being viewed by others

• Zoofaghari, Mohammad; Sagini, Krizia; Damrath, Martin; Zargarnia, Azar; Flaten, Håkon & Veletic, Mladen [Show all 8 contributors for this article] (2025). In silico Study of Bloodstream Penetrating Extracellular Vesicles. IEEE Transactions on Molecular, Biological, and Multi-Scale Communications. 11(2), p. 166–175. doi: 10.1109/TMBMC.2025.3550323. Full text in Research Archive
• Caulier, Benjamin William; Joaquina, Sandy; Gelebart, Pascal Francois; Dowling, Tara Helen Steinsland; Kaveh, Fatemeh & Thomas, Moritz [Show all 20 contributors for this article] (2024). CD37 is a safe chimeric antigen receptor target to treat acute myeloid leukemia. Cell Reports Medicine. 5(6). doi: 10.1016/j.xcrm.2024.101572. Full text in Research Archive Show summary

  Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the peripheral blood. Nearly half of the AML patients relapse after standard induction therapy, and new forms of therapy are urgently needed. Chimeric antigen receptor (CAR) T therapy has so far not been successful in AML due to lack of efficacy and safety. Indeed, the most attractive antigen targets are stem cell markers such as CD33 or CD123. We demonstrate that CD37, a mature B cell marker, is expressed in AML samples, and its presence correlates with the European LeukemiaNet (ELN) 2017 risk stratification. We repurpose the anti-lymphoma CD37CAR for the treatment of AML and show that CD37CAR T cells specifically kill AML cells, secrete proinflammatory cytokines, and control cancer progression in vivo. Importantly, CD37CAR T cells display no toxicity toward hematopoietic stem cells. Thus, CD37 is a promising and safe CAR T cell AML target.

• Sandvig, Kirsten; Iversen, Tore Geir & Skotland, Tore (2024). Entry of nanoparticles into cells and tissues: status and challenges. Beilstein Journal of Nanotechnology. ISSN 2190-4286. 15, p. 1017–1029. doi: 10.3762/bjnano.15.83. Full text in Research Archive Show summary

  In this article we discuss how nanoparticles (NPs) of different compositions may interact with and be internalized by cells, and the consequences of that for cellular functions. A large number of NPs are made with the intention to improve cancer treatment, the goal being to increase the fraction of injected drug delivered to the tumor and thereby improve the therapeutic effect and decrease side effects. Thus, we discuss how NPs are delivered to tumors and some challenges related to investigations of biodistribution, pharmacokinetics, and excretion. Finally, we discuss requirements for bringing NPs into clinical use and aspects when it comes to usage of complex and slowly degraded or nondegradable NPs.

• Zhen, Yan & Stenmark, Harald Alfred (2024). A dual-purpose fusion complex in autophagy. Cell Research. ISSN 1001-0602. doi: 10.1038/s41422-023-00925-w. Full text in Research Archive
• Janssen, Mathijs Adriaan; Liese, Susanne; Al-Izzi, Sami Cameron & Carlson, Andreas (2024). Stability of a biomembrane tube covered with proteins. Physical Review E (PRE). ISSN 2470-0045. 109(4). doi: 10.1103/PhysRevE.109.044403. Full text in Research Archive Show summary

  Membrane tubes are essential structural features in cells that facilitate biomaterial transport and inter- and intracellular signaling. The shape of these tubes can be regulated by the proteins that surround and adhere to them. We study the stability of a biomembrane tube coated with proteins by combining linear stability analysis, out-of-equilibrium hydrodynamic calculations, and numerical solutions of a Helfrich-like membrane model. Our analysis demonstrates that both long- and short-wavelength perturbations can destabilize the tubes. Numerical simulations confirm the derived linear stability criteria and yield the nonlinearly perturbed vesicle shapes. Our study highlights the interplay between membrane shape and protein density, where the shape instability concurs with a redistribution of proteins into a banded pattern.

• Zhen, Yan & Stenmark, Harald Alfred (2024). Exosome regulation by Rubicon in ageing. Nature Cell Biology. ISSN 1465-7392. 26, p. 1380–1381. doi: 10.1038/s41556-024-01482-z. Full text in Research Archive
• Wu, Chenyu; Gunnarsson, Einar Bjarki; Myklebust, Even Moa; Luque, Alvaro Kohn; Tadele, Dagim Shiferaw & Enserink, Jorrit [Show all 9 contributors for this article] (2024). Using birth-death processes to infer tumor subpopulation structure from live-cell imaging drug screening data. PLoS Computational Biology. ISSN 1553-734X. 20(3). doi: 10.1371/journal.pcbi.1011888. Full text in Research Archive Show summary

  Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor a variety of subpopulations with distinct therapeutic response characteristics. Characterizing this heterogeneity by determining the subpopulation structure within a tumor enables more precise and successful treatment strategies. In our prior work, we developed PhenoPop, a computational framework for unravelling the drug-response subpopulation structure within a tumor from bulk high-throughput drug screening data. However, the deterministic nature of the underlying models driving PhenoPop restricts the model fit and the information it can extract from the data. As an advancement, we propose a stochastic model based on the linear birth-death process to address this limitation. Our model can formulate a dynamic variance along the horizon of the experiment so that the model uses more information from the data to provide a more robust estimation. In addition, the newly proposed model can be readily adapted to situations where the experimental data exhibits a positive time correlation. We test our model on simulated data (in silico) and experimental data (in vitro), which supports our argument about its advantages.

• Wenzel, Eva; Pedersen, Nina Marie; Elfmark, Liv Anker; Ling, Wang; Kjos, Ingrid & Stang, Espen [Show all 10 contributors for this article] (2024). Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding. Nature Communications. 15. doi: 10.1038/s41467-024-45558-8. Full text in Research Archive Show summary

  Overexpression of the transmembrane matrix metalloproteinase MT1-MMP/MMP14 promotes cancer cell invasion. Here we show that MT1-MMP-positive cancer cells turn MT1-MMP-negative cells invasive by transferring a soluble catalytic ectodomain of MT1-MMP. Surprisingly, this effect depends on the presence of TKS4 and TKS5 in the donor cell, adaptor proteins previously implicated in invadopodia formation. In endosomes of the donor cell, TKS4/5 promote ADAM-mediated cleavage of MT1-MMP by bridging the two proteases, and cleavage is stimulated by the low intraluminal pH of endosomes. The bridging depends on the PX domains of TKS4/5, which coincidently interact with the cytosolic tail of MT1-MMP and endosomal phosphatidylinositol 3-phosphate. MT1-MMP recruits TKS4/5 into multivesicular endosomes for their subsequent co-secretion in extracellular vesicles, together with the enzymatically active ectodomain. The shed ectodomain converts non-invasive recipient cells into an invasive phenotype. Thus, TKS4/5 promote intercellular transfer of cancer cell invasiveness by facilitating ADAM-mediated shedding of MT1-MMP in acidic endosomes.

• Egeland, Eivind Valen; Vasiliauskaite, Kotryna; Skourti, Eleni; Øy, Geir Frode; Pettersen, Solveig & Pandya, Abhilash D. [Show all 13 contributors for this article] (2024). The SRC-family serves as a therapeutic target in triple negative breast cancer with acquired resistance to chemotherapy. British Journal of Cancer. ISSN 0007-0920. 131, p. 1656–1667. doi: 10.1038/s41416-024-02875-5. Full text in Research Archive Show summary

  BACKGROUND: Resistance to chemotherapy, combined with heterogeneity among resistant tumors, represents a significant challenge in the clinical management of triple negative breast cancer (TNBC). By dissecting molecular pathways associated with treatment resistance, we sought to define patient sub-groups and actionable targets for next-line treatment.<p> <p>METHODS: Bulk RNA sequencing and reverse phase protein array profiling were performed on isogenic patient-derived xenografts (PDX) representing paclitaxel-sensitive and -resistant tumors. Pathways identified as upregulated in the resistant model were further explored as targets in PDX explants. Their clinical relevance was assessed in two distinct patient cohorts (NeoAva and MET500). <p>RESULTS: Increased activity in signaling pathways involving SRC-family kinases (SFKs)- and MAPK/ERK was found in treatment resistant PDX, with targeted inhibitors being significantly more potent in resistant tumors. Up-regulation of SFKs- and MAPK/ERKpathways was also detected in a sub-group of chemoresistant patients after neoadjuvant treatment. Furthermore, High SFK expression (of either SRC, FYN and/or YES1) was detected in metastatic lesions of TNBC patients with fast progressing disease (median disease-free interval 27 vs 105 months). <p>CONCLUSIONS: Upregulation of SFK-signaling is found in a subset of chemoresistant tumors and is persistent in metastatic lesions. Based on pre-clinical results, these patients may respond favorably to treatment targeting SFKs.

• Brugger, Melanie; Lauri, Antonella; Zhen, Yan; Gramegna, Laura L.; Zott, Benedikt & Sekulic, Nikolina [Show all 40 contributors for this article] (2024). Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy. American Journal of Human Genetics. ISSN 0002-9297. 111(3), p. 594–613. doi: 10.1016/j.ajhg.2024.02.005. Full text in Research Archive Show summary

  The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile). In patient-derived fibroblasts, bi-allelic SNF8 variants cause loss of ESCRT-II subunits. Snf8 loss of function in zebrafish results in global developmental delay and altered embryo morphology, impaired optic nerve development, and reduced forebrain size. In vivo experiments corroborated the pathogenicity of the tested SNF8 variants and their variable impact on embryo development, validating the observed clinical heterogeneity. Taken together, we conclude that loss of ESCRT-II due to bi-allelic SNF8 variants is associated with a spectrum of neurodevelopmental/neurodegenerative phenotypes mediated likely via impairment of the autophagic flux.

• Pankiv, Serhiy; Dahl, Anette Kathinka; Aas, Aleksander; Andersen, Rosa Linn; Brech, Andreas & Holland, Petter [Show all 9 contributors for this article] (2024). BEACH domain proteins function as cargo-sorting adaptors in secretory and endocytic pathways. Journal of Cell Biology. ISSN 0021-9525. 223(12). doi: 10.1083/jcb.202408173. Full text in Research Archive Show summary

  We identify BEACH domain–containing proteins (BDCPs) as novel membrane coat proteins involved in the sorting of transmembrane proteins (TMPs) on the trans-Golgi network and tubular sorting endosomes. The seven typical mammalian BDCPs share a predicted alpha-solenoid-beta propeller structure, suggesting they have a protocoatomer origin and function. We map the subcellular localization of seven BDCPs based on their dynamic colocalization with RAB and ARF small GTPases and identify five typical BDCPs on subdomains of dynamic tubular-vesicular compartments on the intersection of endocytic recycling and post-Golgi secretory pathways. We demonstrate that BDCPs interact directly with the cytosolic tails of selected TMPs and identify a subset of TMPs, whose trafficking to the plasma membrane is affected in cells lacking BDCP. We propose that the competitive binding of BDCPs and clathrin coat adaptors to the cytosolic tails of TMPs, followed by their clustering to distinct subdomains of secretory/recycling tubules function as a mechanism for sorting of TMPs in pleomorphic tubular-vesicular compartments that lack a clathrin coat.

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• A., Barreiro, Karina; Dylan, Burger,; Uta, Erdbrügger,; Cristina, Grange,; Morgan, Greig, & Alicia, Llorente, [Show all 13 contributors for this article] (2026). Analysis of Urinary Extracellular Vesicles | Springer Nature Link. Humana Press. ISBN 9781071649053. doi: 10.1007/978-1-0716-4905-3_7. Full text in Research Archive Show summary

  After blood, urine is the second most studied biofluid, because it is easy to collect and available in large quantities. However, urine is also the most dynamic biofluid with large variations in concentration of its diverse content. Separation, storage, and...

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• Telumyan, Elen; Gracia, Beatriz Martín; Sagini, Krizia; Andersen, Maria K.; Tessem, May-Britt & Llorente, Alicia [Show all 7 contributors for this article] (2026). NOR-EV annual meeting 2026. doi: https:/www.norev.org/. Full text in Research Archive
• Hu, Xian; Margadant, Felix & Bakke, Oddmund (2026). Micro-stepping extended focus reduces photobleaching and preserves structured illumination super-resolution features. Show summary

  Despite the progress made in fast scan units, confocal systems still have insufficient temporal resolution for many volume imaging requirements, such as tracking movement of membrane vesicles in live cells. Researchers might sacrifice certain imaging modalities to achieve better performance in temporal resolution. This may result in imaging artifacts such as undersampling artifacts and limit the amount of analyzable data. We propose a imaging modality producing fast projections from the field of depth which will shorten the imaging time by approximately an order of magnitude compared to volume imaging. The implementation requires merely a minimum two synchronized control signals that drive a piezo stage and trigger the camera exposure, a third, optional signal, blanks the laser output when the stage is in motion which mildly improves the stability and repeatability of the exposure. The device generating the signals has been tested on spinning disk confocal as well as on instant structured- illumination-microscopy (iSIM) microscopes. Our calibration images show that the approach provides highly repeatable and stable imaging conditions and does enable photometric measurements of the acquired data, in both the regular spinning disk setup as well as in the iSIM configuration.While light sheet microscopes can provide even faster projections of the same volume, the presented method provides more homogeneous optical sectioning and maintains the structured illumination characteristics.

• Jemterud, Torkild; Roberts, Aubrey Jane; Sandve, Geir Kjetil Ferkingstad & Vestre, Katharina (2026). Hva er greia med hestesko? - Abels tårn - NRK Radio. [Radio]. NRK. Full text in Research Archive Show summary

  Når vet en stamcelle hva den skal bli? Hvordan belønne KI? Er jeg mer av min mormor enn av min mor? Hadde dinosaurene pandemier? Hvor fargeblinde er hunder?

• Feith, Marek; Pandya, Abhilash D.; Hyldbakk, Astrid; Høgset, Anders; Sandvig, Kirsten & Skotland, Tore [Show all 8 contributors for this article] (2025). Photodynamic therapy in breast cancer by photosensitizer-chitosan particles inducing ferroptosis. Cancer Research. ISSN 0008-5472. 85(8_Supplement_1), p. 4483–4483. doi: 10.1158/1538-7445.am2025-4483. Full text in Research Archive Show summary

  Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with poor prognosis and limited treatment options. While chemotherapy has traditionally been the main treatment, resistance frequently emerges, reducing its effectiveness. Recently, a range of immunotherapy strategies, including combinations of chemotherapy and immunotherapy, have expanded treatment possibilities. To further enhance the therapeutic efficacy, there is a desire to combine chemotherapy with other currently used modalities such as photodynamic therapy (PDT) or to encapsulate drugs into nanoparticles (NPs). Ferroptosis has been described as a highly immunogenic type of cell death, characterized by increased ROS and lipid peroxidation. Mesenchymal cancer cells have been reported to be more sensitive to ferroptosis than epithelial cells. We have previously shown that tetraphenylchlorin-conjugated chitosan nanoparticles (TPC-CS NPs) loaded with mertansine and cabazitaxel induce ferroptosis in TNBC.1 In this project, we investigated the effect of TPC-CS NPs together with free RSL3, a ferroptosis inducer. We show that such treatment induces cell death in a mesenchymal breast cancer cell line but not in an epithelial one. The combined treatment also significantly affects lipid peroxidation and mitochondrial function. Based on these results, we encapsulated RSL3 into TPC-CS NPs and used them in two different breast cancer cell lines. We explored the photodynamic effect of empty and RSL3 loaded TPC-CS NPs upon illumination on cell viability by using an MTS assay. Since we have not observed any beneficial effect of TPC-CS NPs-RSL3, we explored the uptake of only empty TPC-CS NPs by using fluorescence microscopy and flow cytometry in these two cell lines. Currently, a biodistribution study in immunocompetent animals bearing 4T1 tumors is being performed. We will perform the maximum tolerable dose experiments for illumination to determine the light dose for further experiments. Moreover, we will perform efficacy studies of TPC-CS NPs and investigate the immune cell composition of tumors and tumor microenvironment using a flow cytometry panel of 25 markers. 1.Pandya AD, Øverbye A, Sahariah P, et al. Drug-Loaded Photosensitizer-Chitosan Nanoparticles for Combinatorial Chemo- and Photodynamic-Therapy of Cancer. Biomacromolecules. 2020/04/13 2020;21(4):1489-1498. This project has received funding from the Europe Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 956544. Citation Format: Marek Feith, Abhilash D. Pandya, Astrid Hyldbakk, Anders Høgset, Kirsten Sandvig, Tore Skotland, Tore-Geir Iversen, Gunhild Mari Mælandsmo. Photodynamic therapy in breast cancer by photosensitizer-chitosan particles inducing ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4483.

• Knævelsrud, Helene & Tooze, Sharon A. (2025). Autophagy Across Scales – From Molecules to Physiology. Journal of Molecular Biology (JMB). ISSN 0022-2836. 437(18), p. 169300–169300. doi: 10.1016/j.jmb.2025.169300. Full text in Research Archive
• Telumyan, Elen; Gracia, Beatriz Martín; Sagini, Krizia; Andersen, Maria K.; Tessem, May-Britt & Rye, Morten Beck [Show all 7 contributors for this article] (2025). Optimizing Protocols for Seminal Extracellular Vesicle Isolation in Prostate Cancer Research. Full text in Research Archive
• Vestre, Katharina (2024). Vidunderlige nye organer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(10). doi: 10.4045/tidsskr.24.0351. Full text in Research Archive
• Vestre, Katharina (2024). Frihet til å formidle. Full text in Research Archive
• Vestre, Katharina (2024). X og y-kromosomer. [Radio]. Ekko NRK P2. Full text in Research Archive
• Telumyan, Elen; Rye, Morten Beck; Tessem, May-Britt; Llorente, Alicia & Andersen, Maria K. (2026). From Tissue to Liquid Biopsy: Multi-Omics Analysis of Extracellular Vesicles in Prostate Cancer. Norges teknisk-naturvitenskapelige universitet. ISSN 9788235303400. Full text in Research Archive Show summary

  This PhD project investigates molecular approaches to the study of prostate cancer using both body fluids and prostate tissue. A central focus is on extracellular vesicles (EVs) - small membrane-bound particles released by cells that carry molecular information reflecting their cells and tissues of origin. By characterising EVs derived from semen, the project examines the extent to which their molecular profiles reflect changes within the prostate and their potential to provide insight into prostate cancer. The project also evaluates how different laboratory and analytical methods may influence the molecular profiles observed in EVs. In addition, it includes PRECAST, a gene expression-based test using prostate tissue to improve prostate cancer risk assessment. Overall, the project seeks to advance our understanding of the molecular features of prostate cancer and to assess how information derived from body fluids and prostate tissue may contribute to improved disease characterisation and risk assessment.

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