Our latest publications

• Sengupta, Poushali; Khadka, Rabindra; Maharjan, Sabita; Eliassen, Frank; Pandey, Shashi Raj & Zhang, Yan [Show all 8 contributors for this article] (2026). Explainability of Complex AI Models with Correlation Impact Ratio. IEEE Transactions on Artificial Intelligence (TAI). p. 14–14. doi: 10.1109/tai.2026.3732283. Full text in Research Archive
• Dyhr, Emma; Pinedo, Lucía Cañete de; Frederiksen, Nicki; Bojer, Martin Saxtorph; Ingmer, Hanne & Sæbø, Ingvill Pedersen [Show all 11 contributors for this article] (2026). Antibacterial peptidomimetics via fragment display on small-molecule scaffolds. RSC Medicinal Chemistry. ISSN 2632-8682. 17(4), p. 1989–2001. doi: 10.1039/d5md00916b. Full text in Research Archive
• Hubers, Lisa Anne; Skjetne, Alexander Myhr; Luna, Luisa; Lefol, Yohan Pierre; Lund, Solveig Osnes & Wågbø, Ane Marit [Show all 15 contributors for this article] (2026). Functional impact of Nth like DNA glycosylase 1 on mitochondrial dynamics. Nucleic Acids Research (NAR). ISSN 0305-1048. 54(17). doi: 10.1093/nar/gkag876. Full text in Research Archive Show summary

  Nth like DNA glycosylase 1 (NTHL1), a key base excision repair enzyme, has long been considered essential for nuclear and mitochondrial genome integrity. Combining in vitro biochemical assays, in cellulo molecular biology, and bioinformatic analyses, we investigated how NTHL1 loss affects mitochondrial DNA (mtDNA) stability and mitochondrial function. Contrary to the conventional view that mtDNA damage is solely detrimental, we find that NTHL1 loss confers a beneficial, mitochondria-initiated phenotype in human cells. Despite accumulating mtDNA lesions, NTHL1 loss unexpectedly increases mtDNA copy number, elevates oxidative phosphorylation protein levels, and enhances mitochondrial respiration. NTHL1−/− cells also show increased mitochondrial mass and higher levels of the biogenesis regulator PGC1α and the fusion protein OPA1, indicating an adaptive response that boosts mitochondrial function and capacity. Consequently, NTHL1−/− cells exhibit resistance to mitochondrial stress, accompanied by increased eIF2α phosphorylation and reduced MYC levels, converging on a broader transcriptional adaptive program. This phenotype depends on mitochondrial NTHL1 and reactive oxygen species (ROS) signaling, since treatment with ROS scavengers or mitochondria-specific reintroduction of NTHL1 rescues it. Together, these findings position NTHL1 as a key modulator of mtDNA stability and mitochondrial function, revealing that loss of this DNA repair enzyme shifts cellular metabolism toward a stress-adaptive state and enhances resilience to oxidative stress.

• Dyhr, Emma; Sæbø, Ingvill Pedersen; Riisnæs, Ida Mathilde Marstein; Bjørås, Magnar; Helgesen, Emily & Booth, James Alexander [Show all 7 contributors for this article] (2026). Antimicrobial Peptides Based on the TisB Toxin: Toward Enhanced Activity and Synergy with Antibiotics. ACS Omega. 11(26), p. 38837–38847. doi: 10.1021/acsomega.6c02137. Full text in Research Archive
• Myhre, Vegard; Kaarbø, Mari; Yang, Mingyi; Fevang, Børre; Sousa, Mirta Mittelstedt Leal de & Reims, Henrik Mikael [Show all 11 contributors for this article] (2026). Altered duodenal N6-methyladenosine levels in common variable immunodeficiency associate with duodenal microbiota. Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1875823. Full text in Research Archive
• Søraas, Arne Vasli Lund; Engvig, Andreas; Alnæs, Dag; Karim, Lana Nagmadin; Danilova, Elena & Istre, Mette Stausland [Show all 17 contributors for this article] (2026). Interstitial fluid rejuvenation through young-donor plasma exchange in cognitively impaired patients: a pilot safety and feasibility study. GeroScience. ISSN 2509-2715. doi: 10.1007/s11357-026-02435-0. Full text in Research Archive Show summary

  Heterochronic parabiosis improves physiological and cognitive function in aging rodents; these benefits appear to be derived from the removal of aged blood plasma components and the addition of younger ones. In humans, removing plasma from older individuals with Alzheimer’s disease (AD) and replacing it with saline and albumin delayed cognitive deterioration in a large clinical trial. However, mimicking heterochronic parabiosis in humans by removing large volumes of a patient’s blood plasma and replacing it with plasma from young and healthy donors has not been tested. Here, we have performed a pilot study to characterize the feasibility and safety of such a procedure, replacing between 16 and 26 L of patient blood plasma with young (ages 18–24) donor blood plasma for twelve patients who recently received a diagnosis of mild cognitive impairment with biomarker evidence of AD. The dose and time interval between plasma exchanges was tailored to maximize equilibration of donor plasma components into the interstitial fluid, with the aim of achieving what we term interstitial rejuvenation. We explored three permutations of a plasma exchange protocol with different treatment intensities and doses, each performed on three to five patients. We present data on safety, feasibility, patient burden, resource use of the treatments, preliminary measurements of clinical variables, and short-term cognitive trajectories in the patients. The procedures were feasible, and the adverse events observed were consistent with known risks of plasma exchange, supporting further investigation of treatment efficacy in a larger controlled trial. This safety and feasibility study was first registered 22 December 2023 at ClinicalTrials.gov and given the identifier NCT06234436.

• Mikkelsen, Thea Falkenberg; Vera-Rodriguez, Maria; Fedorcsák, Zsofia; Greggains, Gareth; Fedorcsak, Peter Zoltan & Hald, Kirsten (2026). Reduced endometrial LIF expression in women with uterine fibroids and its restoration following myomectomy. European Journal of Obstetrics, Gynecology, and Reproductive Biology. ISSN 0301-2115. 326, p. 115340–115340. doi: 10.1016/j.ejogrb.2026.115340. Full text in Research Archive
• Suaste, Veronica; Presterud, Rebecca; Wennerström, Anna Berit; Wang, Heling; Zhang, Jianying & Lund, Solveig Osnes [Show all 16 contributors for this article] (2026). Transcriptional Profiling Shows Dampening of Interferon Gene Signatures by NAD Augmentation in Ataxia-Telangiectasia. International Journal of Molecular Sciences. ISSN 1661-6596. 27(13). doi: 10.3390/ijms27135652. Full text in Research Archive Show summary

  Ataxia-Telangiectasia (A-T) is a multisystem disorder caused by loss of A-T mutated (ATM) protein activity, characterized clinically by immunodeficiency and cerebellar ataxia. ATM is a master regulator of DNA damage responses and loss of ATM function is accompanied by persistent activation of PARP1 leading to depletion of intracellular NAD+ and dysfunction of a series of cellular signalling pathways dependent on NAD+, providing a mechanistic rationale for NAD+ augmentation therapy. We performed a clinical trial of NAD+ augmentation with nicotinamide riboside (NR) over 24 months in A-T patients where we observed improved coordination and eye movements in A-T patients. Here, by using peripheral blood mononuclear cells, we performed longitudinal transcriptome profiling to define molecular signatures of A-T and to assess pathway-level responses to NR supplementation. A-T patients exhibited reproducible transcriptomic alterations involving immune, vascular, and inflammatory pathways. NAD+ augmentation was associated with suppression of interferon response genes and modulation of networks correlated with neurological improvement. These findings establish systemic molecular signatures of A-T and identify potential blood-based biomarkers that reflect disease processes and therapeutic response, supporting the use of NAD+ augmentation as a disease-modifying strategy in A-T by dampening interferon signalling.

• Belhaj, Imen; Åmellem, Ingrid; Tartanoglu, Can H.; Weidemann, Hanne Margrete; Vallenari, Evan Michael & Yang, Mingyi [Show all 10 contributors for this article] (2026). Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer’s and wild-type mice. Scientific Reports. 16(1). doi: 10.1038/s41598-026-48154-6. Full text in Research Archive Show summary

  Lactate, a well-known metabolite and signalling molecule, holds therapeutic potential for neurodegenerative diseases. Here, we investigated the effects of chronic lactate treatment on cognition and molecular biomarkers in the 5XFAD mouse model of Alzheimer’s disease (AD) and in wild-type (WT) controls using behavioural testing alongside proteomic and transcriptomic analyses. Mice received lactate or vehicle injections 4 days per week for 11 weeks, with behavioural testing before and after the treatment period. Lactate improved working memory in late-treated AD mice, without eliciting anxiety-like behaviour. At the molecular level, lactate reduced Il1b expression, and in a sex-dependent manner, normalised NEFL, and enhanced synaptic integrity proteins (OPCML, PPFIA2, STXBP3, SYT1, VGLUT2, VSNL1) in AD mice, while also augmenting mitochondrial regulators (ATP5G2, GRPEL1, SLC25A23) across genotypes. Notably, lactate upregulated low-abundance ionotropic glutamate receptor mRNAs (Grik3, Grin2c, Grid2ip) in female AD mice, indicating enhanced glutamatergic signalling. In WT mice, lactate increased expression of neurotrophic factors (Bdnf, Igf1, Vegfa), anti-inflammatory cytokines (Il4 and Il13), and the neuronal lactate transporter Mct2, suggesting promoted neuronal resilience. Together, these findings indicate that lactate treatment can mitigate cognitive decline and enhance molecular pathways of resilience in AD, warranting larger, age-stratified studies to validate its therapeutic potential and elucidate underlying mechanisms.

• Crisan, Andrea Pop; Ciocan, Cristina; Pirlog, Radu; Necula, Alexandru; Hajjar, Darius Adin Al & Pruteanu, Lavinia Lorena [Show all 11 contributors for this article] (2026). Molecular Signatures and Network Alterations Underlying GBM Progression and Recurrence. Medicina. ISSN 1010-660X. 62(2). doi: 10.3390/medicina62020336. Full text in Research Archive
• Yadav, Ajay; Richartz, Nina; Bhagwat, Sampada; Burman, Marta Maria; Munthe-Kaas, Monica Cheng & Skålhegg, Bjørn Steen [Show all 9 contributors for this article] (2026). Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice. Journal of Biological Chemistry. ISSN 0021-9258. 302(3). doi: 10.1016/j.jbc.2026.111143. Full text in Research Archive Show summary

  Most children with acute lymphoblastic leukemia (ALL) achieve long-term survival due to intensive multimodal chemotherapy. However, the use of cytotoxic DNA-damaging agents is frequently associated with severe long-term side effects, prompting continued efforts to improve treatment strategies. This study explores the potential of starving the leukemic cells to enhance the efficacy of DNA-damaging therapy in ALL. Previous work demonstrated that cAMP signaling attenuates DNA damage-induced apoptosis in ALL cells, both in vitro and in a xenograft model. The current findings show that glucose and serum deprivation reverse the effect of cAMP, converting it from a survival factor to a promoter of DNA damage-induced apoptosis in ALL-derived cell lines and patient-derived leukemic cells in vitro. The starvation-induced sensitization was independent of p53 but was shown to require increased levels of reactive oxygen species (ROS). In turn, the elevated ROS levels enhanced the activation of the mitogen-activated protein kinase p38 (p38 MAPK). The resulting augmented cell death was inhibited both by the ROS scavenger N-acetyl cysteine and the p38 MAPK inhibitor SB 202190. The translational potential of increasing the efficacy of DNA damaging agents in starving ALL cells was supported by in vivo data showing that intermittent fasting, combined with subtherapeutic doses of irradiation, significantly inhibits the leukemia progression in a xenograft model of severe combined immunodeficiency mice.

• Lier, Silje; Markusson, Sara Bachmann; Kocijančič, Anja; Narum, Martine; Lund, Solveig Osnes & Böllering, Bianka [Show all 30 contributors for this article] (2026). CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma. EMBO Molecular Medicine. ISSN 1757-4676. 18, p. 1592–1624. doi: 10.1038/s44321-026-00393-w. Full text in Research Archive Show summary

  Glioblastomas are the most prevalent and aggressive malignant brain tumors, characterized by hypertranscription and dependence on neurodevelopmental transcription factors. The transcriptional cycle is regulated by phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) by transcriptional cyclin-dependent kinases (tCDKs), including CDK7, CDK9, CDK12, and CDK13. Here we find that glioblastoma stem cells (GSCs) are selectively sensitive to CDK12/CDK13 inhibition, whereas CDK7 and CDK9 inhibition cause non-specific cytotoxicity. This selective targeting halts GSC and organoid proliferation, curtails GSC invasion and suppresses tumor growth in a xenograft mouse model. In GSCs, CDK12/CDK13 inhibition leads to a rapid and genome-wide loss of serine-2 phosphorylation (pSer2) of the RNAPII CTD, abolishing transcriptional elongation and a transcriptional program sustained by key neurodevelopmental transcription factors. CDK12/CDK13 inhibition unexpectedly arrests DNA replication and replication fork progression in a manner distinct from the effect of inhibiting other tCDKs. This dramatic arrest precedes DNA damage response activation and cell cycle arrest, directly linking RNAPII elongation to replication fork dynamics and revealing a previously unrecognized dependence of DNA replication on CDK12/CDK13-RNAPII regulation.

• Lagartos, Maria Jose Donate; Doncel, Beatriz Escobar; Zhang, Shi-qi; Pan, Junping; González, Noemí Villaseca & Anisimov, Aleksander [Show all 22 contributors for this article] (2026). Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD+. Brain. ISSN 0006-8950. 149(4), p. 1208–1223. doi: 10.1093/brain/awaf261. Full text in Research Archive Show summary

  Downregulation and inactivation of the Repressor Element 1-Silencing Transcription factor (REST) is shown in Alzheimer’s disease (AD) and likely contributes to its progression, but the exact molecular mechanism linking REST reduction to AD remains unclear. We examined changes in REST expression in the entorhinal cortex and hippocampus across different Braak stages of tauopathy. We show that alterations in REST expression and sub-cellular localization are partially responsible for AD pathology, as REST overexpression improves cognition, reduces amyloid-β and phosphorylated Tau deposition, and restores mitochondrial and synaptic homeostasis. Mechanistically, the NAD+/SIRT1 axis modulates REST expression through chromatin remodelling in the promoter region of REST, leading to changes in the expression of REST target genes involved in mitophagy and synaptic function. These findings reveal a new mechanism of action for NAD+ and highlight REST as a promising therapeutic target for AD therapy.

• Alsøe, Lene; Brackmann, Stephan Andreas; Liu, Yan; Wennerström, Anna Berit; Esbensen, Qin Ying & Kalyanasundaram, Sumana [Show all 10 contributors for this article] (2026). The Role of Nuclear APOBEC Enzymes in Neoplastic Progression of Ulcerative Colitis. Clinical and Experimental Gastroenterology. 19. doi: 10.2147/CEG.S588161. Full text in Research Archive Show summary

  Aberrant expression of the cytidine DNA deaminase AID in enterocytes within inflamed mucosa in ulcerative colitis (UC) patients has been proposed to be involved in progression of UC to colitis-associated colorectal cancer (CA-CRC). Here, we followed the expression of AID and other nuclear cytidine DNA deaminases of the APOBEC family through several stages of progression of UC in a CA-CRC case (UC progressor) and in a cohort of UC progressors and non-progressors. In inflamed and high-grade dysplastic mucosa, AICDA and APOBEC1 mRNAs, but not APOBEC3-family enzyme mRNAs, were overexpressed compared to non-inflamed tissue. Immunohistochemical staining did not show expression of AID or APOBEC3 enzymes in the enterocytes, neither in specimens from the CA-CRC case nor in biopsies from the progressor and non-progressor cohort. APOBEC1 was highly expressed in the enterocytes throughout the colorectum from the CA-CRC case and in most biopsies examined from the progressor and non-progressor cohort. The expression was not correlated with the histology of the mucosa or the progression status of the patients. In the CA-CRC case, we identified AID- and APOBEC3-associated mutation signatures in inflamed, high-grade dysplasia and cancer genomes. In conclusion, our findings suggest that AID or other nuclear APOBECs are unlikely to drive the progression of UC to CA-CRC late during course of UC. However, we cannot exclude the possibility that bursts of AID and nuclear APOBEC3 activity may contribute to formation of genome instability in early phases of disease development.

• Fossmark, Reidar; Hjorth-Hansen, Henrik; Lirussi, Lisa; Lüders, Torben; Visnovska, Martina & Liu, Yan [Show all 9 contributors for this article] (2026). Telomere Length in Celiac Disease in a Population-Based Cohort: A HUNT Study. Clinical and Translational Gastroenterology. 17(6). doi: 10.14309/ctg.0000000000001020. Full text in Research Archive Show summary

  INTRODUCTION: Celiac disease (CeD) occurs in genetically predisposed individuals who are exposed to dietary gluten proteins. Genome-wide association studies have found CeD to be associated with a genetic predisposition to shorter telomere length. It was therefore of interest to measure leukocyte telomere length in a large cohort of patients with CeD. METHODS: This study was population-based and included a defined cohort of patients with CeD in the Trøndelag Health Study. Leukocyte telomere length was measured by quantitative polymerase chain reaction (PCR) in patients and controls 1:2 matched for age, sex, alcohol, and tobacco use. RESULTS: The study population consisted of 58.7% women, with mean age 43 (SD 14.5) years, where half were never smokers, and the majority consumed little or no alcohol. Telomer length in 1,077 patients with CeD did not differ significantly from 2,147 matched controls, 10.39 kb (SD 2.21) vs 10.52 kb (SD 2.25), P = 0.088. In a mixed linear model, we found higher age and alcohol consumption, but not tobacco use or sex, to be associated with shorter telomere length. The telomere length did not differ between patients with newly diagnosed and known CeD. DISCUSSION: This large population-based study provides evidence that CeD is not associated with clinically meaningful telomere shortening.

• Følling, Ivar; Selle, Maria Lie; Nilsen, Hogne Røed; Wennerström, Anna Berit; Nilsen, Hilde & Eide, Tor Jacob (2026). Distribution of glucagon-like peptide 1 receptor and insulin in phaeochromocytomas. Endocrine Connections. 15(1). doi: 10.1530/ec-25-0338. Full text in Research Archive Show summary

  Introduction Most phaeochromocytomas produce insulin, and some produce glucagon-like peptide 1 receptor (GLP-1R). In pancreatic β-cells, stimulation of GLP-1R causes insulin release. A few phaeochromocytoma patients experience hypoglycaemic attacks. Therefore, we studied the distribution of GLP-1R-containing and insulin-containing phaeochromocytoma cells and their relation. Methods In 20 phaeochromocytomas, we performed sequential double staining with anti-insulin and anti-GLP-1R antibodies and, in selected cases, staining with anti-insulin alone. We quantified tumour cells with positive staining and compared their distribution to that of randomly distributed cells using simulations. We obtained GLP-1R transcript data from 182 such tumours from The Cancer Genome Atlas (TCGA) Research Network. Results GLP-1R-containing cells were found in six of the 20 tumours, and insulin-containing cells were found in fifteen. Moreover, in the TCGA cohort, almost half of the tumours produce GLP-1R transcripts, and patients with the highest number of transcripts show longer disease-free survival. In the tumours, we found that cells expressing insulin were present in the cytoplasm and GLP-1R in the membrane, with a frequency of 2.59 and 1.34%, respectively. These cells showed clustering, and one tumour showed a large clonal expansion. Interestingly, we found deposits of insulin, which we suggest naming insulin bodies in two tumours. Very few cells contained both proteins. Conclusion Most phaeochromocytomas contain tumour cells producing insulin. About half produce GLP-1R. The producing cells show clustering, and clonal expansion occurs. Insulin release might cause hypoglycaemia. Increased GLP-1R levels might induce less aggressive tumours.

• Zhu, Hengyi; Eide, Dag Markus; Maremonti, Erica; Nilsen, Hilde & Brede, Dag Anders (2026). Mechanistic insight into the reprotoxic effects of chronic gamma radiation on spermatogenesis in Caenorhabditis elegans. Science of the Total Environment. ISSN 0048-9697. 1016. doi: 10.1016/j.scitotenv.2026.181444. Full text in Research Archive Show summary

  Ionizing radiation is a potent genotoxic agent that may cause detrimental effects on reproductive processes. This study investigated cellular events and transcriptomic alterations underlying reproductive defects caused by chronic gamma (γ) radiation in Caenorhabditis elegans (C. elegans). Continuous exposure (100 mGy/h; total dose: 4.8 Gy) throughout larval development reduced spermatid counts (38.8%) and total brood size (26.4%). It also resulted in delayed and attenuated residual body (RB) formation (22.8%), implicating reduced number of spermatocytes or failed meiosis. Targeted exposure of early L3 to L4 (24-h, total dose 2.4 Gy) after the establishment of the primary spermatocyte population resulted in 26% reduction in brood size, thus implicating damage inflicted during meiosis as detrimental to spermatogenesis. The reprotoxic defects were markedly exacerbated by rad-51 RNAi or polq-1 deletion, confirming the crucial roles for homologous recombination (HR) and polymerase theta-mediated end joining (TMEJ) in mitigating radiation-induced reproductive damage. Phenotypical investigation of the male gonad revealed genotoxic effects including shortened mitotic zone and increased cell-cycle arrest. However, the postmeiotic stage assessed as the quantity of RB-containing phagosomes remained unaffected by ionizing radiation. Transcriptomic profiling of irradiated males showed comprehensive enhanced stress response and mitophagy accompanied by alterations of energy metabolism. Comparative transcriptomic analysis revealed large differences between sexes, where the only shared enrichment term was mitochondrial translation termination. Collectively, our results show that detrimental effects to hermaphrodite spermatogenesis occur during the meiotic phase, which leads to fewer RBs and spermatids, with a corresponding reduction in reproduction.

• Kamyshnyi, Oleksandr; Kamyshna, Iryna; Petakh, Pavlo; Halabitska, Iryna; Bjørås, Magnar & Oksenych, Valentyn [Show all 8 contributors for this article] (2025). Towards molecular diagnostics of parental alienation. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 82(1). doi: 10.1007/s00018-025-05895-3. Full text in Research Archive Show summary

  High-conflict parental divorce can result in parental alienation (PA), leading to chronic psychological stress in children that adversely affects their mental and physical health. This stress may manifest as anxiety, depression, eating disorders, immune dysfunction, and cardiovascular, neurological, endocrine, or gastrointestinal issues. The inconsistent legal recognition of PA highlights the need for objective diagnostic tools to inform judicial decisions. We propose a panel of molecular biomarkers, derived from well-established indicators of chronic stress, to address the limited data specific to PA. This panel targets hypothalamic-pituitary-adrenal (HPA) axis activation, neurotransmitter dysregulation, inflammation, oxidative stress, epigenetic modifications, and gut microbiota dysbiosis. Interdisciplinary collaboration among researchers, general practitioners, and legal professionals is crucial to validate and implement this panel, ultimately enhancing child welfare through early intervention.

• Ravlo, Erlend; Ianevski, Aleksandr; Wolska, Waleria; Schjølberg, Jørn-Ove; Quilez, Maria Camara & Nordli, Ine Emilie Olsen [Show all 23 contributors for this article] (2025). Combination of vemurafenib, pleconaril, and AG7404 attenuates enterovirus replication in vitro and in vivo. NAR Molecular Medicine. 3(1). doi: 10.1093/narmme/ugaf046. Full text in Research Archive Show summary

  Enteroviruses infect multiple human tissues and cause diseases including meningitis, the common cold, myocarditis, pancreatitis, hepatitis, poliomyelitis, sepsis, type 1 diabetes, hand, foot, and mouth disease. Despite this burden, no antiviral therapy has been approved to date. Progress has been limited by the structural and topical diversity of enteroviruses because many variants are intrinsically insensitive to candidate agents and sensitive strains develop resistance rapidly. Here, we report that the approved anticancer drug vemurafenib inhibited replication of some tested enteroviruses in cell cultures. Passage of echovirus EV1 and coxsackievirus CVB5 for six cycles in cell culture yielded vemurafenib-resistant virus variants harboring mainly missense mutations in the viral 3A and VP1 proteins, underscoring the need for combination therapy. We therefore evaluated cocktails, combining vemurafenib with the VP1 inhibitor pleconaril and the 3C protease inhibitor AG7404. In cell culture, the cocktails suppressed replication of all seven tested enteroviruses. The combination was also effective in human pancreatic, retinal, and brain organoids. In infected mice, the triple regimen reduced viral titers in the pancreas. These findings support multi-stage targeting of the enterovirus life cycle as a promising path toward broadly active therapeutic cocktails.

• Kaarbø, Mari; Yang, Mingyi; Meyer-Myklestad, Malin Holm; Sundaram, Arvind; Sousa, Mirta & Sharma, Animesh [Show all 13 contributors for this article] (2025). Transcriptomic and proteomic profiling reveal immune and metabolic dysregulation in the colonic mucosa of people living with HIV with incomplete immune recovery. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1635523. Full text in Research Archive Show summary

  Background People living with HIV are called immunological non-responders (INR) when their CD4+ T cell count is not restored to immunocompetent levels, despite successful viral suppression. INR have increased risk of progression to AIDS, non-AIDS related morbidity, and death. Impaired mucosal barrier function is a prevailing hypothesis for why INR among people with HIV (PWH) have persistently low CD4+ T cell counts. Objective To understand the molecular mechanisms behind incomplete immune recovery in INR, we analyzed gene regulation and protein expression in gut tissues from INR, immunological responders (IR) and healthy controls (HC). Methods The transcriptome was assessed by RNA-sequencing (RNA-seq) and the proteome was examined using shotgun proteomic mass spectrometry in mucosal biopsies from the sigmoid colon and terminal ileum. Results In INR compared to IR, we identified 3326 differentially expressed genes (DEGs) in the colon while no DEGs were observed in the ileum. Gene ontology (GO) analyses revealed that the DEGs in colon of INR, compared to IR, predominantly involved pathways related to immune response, metabolism, and cellular processes. Notably, GO analysis highlighted downregulation of genes associated with B cell-mediated immunity and adaptive responses in INR. Deconvolution analysis indicated that these transcriptomic changes were not solely due to shifts in immune cell composition. Proteomic analysis supported these findings, showing more differential protein composition between INR and IR in colon than ileum. These proteins are associated with the regulation of adaptive immune signaling and essential cellular processes, including cell signaling, tissue repair, and growth, all of which are characteristic features of inflammatory bowel disease (IBD). Conclusion Our findings suggest that incomplete immune recovery during anti-retroviral therapy in PWH is associated with specific dysregulations in the molecular environment of the sigmoid colon, which may share mechanisms with IBD. The identified macromolecules may serve as potential targets for adjuvant treatment to improve the prognosis for INR.

• Starheim, Eirin Johannessen; Manaf, Adeel; Hashim, Adnan; Andersen, Niklas Nonboe; Ravlo, Erlend & Wang, Wei [Show all 12 contributors for this article] (2025). Rapid DNA and RNA isolation from few or single cells using low-cost NAxtra magnetic nanoparticles. Scientific Reports. 15(1). doi: 10.1038/s41598-025-05770-y. Full text in Research Archive
• Berg, Sigrid Ravn; Brambilla, Alessandro; Hagen, Lars; Sharma, Animesh; Vågbø, Cathrine Broberg & Liabakk, Nina-Beate [Show all 11 contributors for this article] (2025). Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells. International Journal of Molecular Sciences. ISSN 1661-6596. 26(18). doi: 10.3390/ijms26189075. Full text in Research Archive Show summary

  Isocitrate dehydrogenase 1 (IDH1) mutations are key drivers of glioma biology, influencing tumor aggressiveness and treatment response. To elucidate their molecular impact, we performed proteome analysis on patient-derived (PD) and U87MG glioma cell models with either mutant or wild-type IDH1. We quantified over 6000 protein groups per model, identifying 1594 differentially expressed proteins in PD-AS (IDH1MUT) vs. PD-GB (IDH1WT) and 904 in U87MUT vs. U87WT. Both IDH1MUT models exhibited enhanced MHC antigen presentation and interferon signaling, indicative of an altered immune microenvironment. However, metabolic alterations were model-dependent: PD-AS cells shifted toward glycolysis and purine salvage, while U87MUT cells retained oxidative phosphorylation, potentially due to D2-hydroxyglutarate (2OHG)-mediated HIF1A stabilization. We also observed a predominance of downregulated DNA repair proteins in IDH1MUT models, particularly those involved in homologous recombination. In contrast, RB1 and ASMTL were strongly upregulated in both IDH1MUT models, implicating them in DNA repair and cellular stress responses. We also found distinct expression patterns of proteins regulating histone methylation in IDH1MUT cells, favoring increased methylation of H3K4, H3K9, and H3K36. A key driver of this may be the upregulation of SETD2 in PD-AS, an H3K4 and H3K36 trimethyltransferase linked to the recruitment of HIF1A as well as DNA mismatch repair proteins. This study uncovers candidate biomarkers and pathways relevant to glioma progression and therapeutic targeting, but also underscores the complexity of predicting glioma pathogenesis and treatment responses based on IDH1 mutation status. While proteome profiling provides valuable insights, a comprehensive understanding of IDH1MUT gliomas will likely require integrative multi-omics approaches, including DNA/RNA methylation profiling, histone and protein post-translational modification analyses, and targeted DNA damage and repair assays.

• Skuland, Trine; Fosslie, Madeleine Lystad; Khodeer, Sherif; Alemu, Endalkachew Ashenafi; Johansen, Jens Vilstrup & Indahl, Marie [Show all 12 contributors for this article] (2025). Broad H3K4me3 domains support oocyte genome silencing and maturation but are dispensable for repression in early embryos. Development. ISSN 0950-1991. 152(21), p. 1–15. doi: 10.1242/dev.204638. Full text in Research Archive Show summary

  Epigenetic reprogramming and embryonic genome activation (EGA) are crucial events during early development. Establishment of distinctive broad histone H3 lysine 4 trimethylation (H3K4me3) domains in the oocyte is necessary for genome silencing, and their removal in the 2-cell embryo is crucial for EGA and development in mice. However, the stage-specific requirement for broad H3K4me3 domains is unclear. Here, we show that inducing broad H3K4me3 removal in mouse oocytes can relieve genome silencing, impair oocyte maturation timing, and may cause transcriptional reactivation in resulting parthenogenetic 1-cell embryos. We further demonstrate that broad H3K4me3 demethylation precedes EGA but, surprisingly, premature depletion in zygotes or early 2-cell embryos does not alter the transcriptional program. Our findings suggest that broad H3K4me3 domains are required for oocyte genome silencing, timely maturation and post-fertilisation silencing, but onward pre-EGA transcriptional repression is not dependent on the original mark. This work contributes to the understanding of events and mechanisms involved in genome silencing and activation in early development, providing insight into potential modes of failure that may contribute to infertility.

• Angheluta, Luiza; Lång, Anna Ulrika; Lång, Emma & Bøe, Stig Ove (2025). Full-Integer Topological Defects in Polar Active Matter: From Collective Migration to Tissue Patterning. Annual Review of Condensed Matter Physics. doi: 10.1146/annurev-conmatphys-031620-105420. Full text in Research Archive Show summary

  Polar active matter—including animal herds, aggregates of motile cells, and active colloids—often forms coordinated migration patterns, such as flocking. This orderly motion can be disrupted by full-integer topological defects representing localized disturbances in which directional alignment is lost. Such polar defects can serve as key organizing centers across scales, sustaining collective behavior such as swirling motion and other large-scale coherent states. Although significant progress has been made in understanding active matter principles in recent years, a quantitative understanding of how topological defects influence active polar matter is still needed. We present a brief overview of recent experimental observations in synthetic active colloids and various biological systems. We describe how polar defects mediate dynamical transitions and contribute to the spontaneous emergence of large-scale coherent states. We also discuss theoretical advances in the physical modeling of coupled processes involving polar defects and collective behavior in active polar matter.

• Berrocal, Marion Silvana Fernández; Døskeland, Dagny Sanden; Saasen, Vidar Langseth; Bugaj, Anna Maria; Kunath, Nicolas & Heggedal, Mina [Show all 12 contributors for this article] (2025). NEIL3 shapes hippocampal network dynamics and fear memory through modulation of PV+ interneurons. Progress in Neurobiology. ISSN 0301-0082. 253. doi: 10.1016/j.pneurobio.2025.102832. Full text in Research Archive Show summary

  The dynamic balance between excitatory and inhibitory (E/I) signaling is critical for hippocampal network function and memory processing. Here, we uncover a novel role for the DNA glycosylase Endonuclease VIII-like 3 (NEIL3) in maintaining this E/I balance through its impact on parvalbumin-positive (PV⁺) GABAergic interneurons. NEIL3 deficiency leads to a selective reduction in PV⁺ interneurons and impaired perineuronal net (PNN) integrity, likely contributing to further PV⁺ neuron dysfunction. These changes result in altered hippocampal oscillatory dynamics, including increased beta and low gamma power, and reduced high gamma and ripple activity. These network alterations are accompanied by distinct effects on fear memory, as demonstrated using contextual and trace fear conditioning paradigms. NEIL3-deficient mice exhibited enhanced extinction of contextual fear memory but impaired extinction of trace fear memory. These findings suggest that the integrity of inhibitory networks plays differential roles in the spatial versus temporal aspects of fear memory extinction. Transcriptomic analysis further reveals dysregulation of genes involved in glutamatergic and GABAergic signaling. Among these, Gabra2 showed a marked downregulation, potentially driven by changes in promoter DNA methylation. This work identifies NEIL3 as an important regulator of the hippocampal inhibitory network, linking PV+ interneuron integrity and oscillatory coordination to distinct memory outcomes, and offers potential mechanistic insight into processes that may contribute to cognitive deficits in disorders characterized by E/I imbalance.

• Arczewska, Katarzyna D; Sys, Dorota; Nilsen, Hilde L & Piekiełko-Witkowska, Agnieszka (2025). DNA Damage and Repair in Thyroid Physiology and Disease. Endocrine reviews. ISSN 0163-769X. 47(1), p. 121–157. doi: 10.1210/endrev/bnaf035. Full text in Research Archive Show summary

  The thyroid is exposed to DNA damage induced by normal physiological processes (eg, oxidative stress resulting from thyroid hormone synthesis or mitochondrial respiration) or through environmental insults (eg, environmental pollutants, ionizing radiation exposure). Robust antioxidative stress defense and DNA repair mechanisms protect thyrocyte genome integrity, but defective or dysregulated DNA repair pathways have been implicated in thyroid pathology, including autoimmune thyroid disease and thyroid malignancy. In thyroid cancer, disturbed antioxidative stress defense, Mismatch Repair, Non-Homologous End-Joining, or DNA damage response pathways contribute to both the onset and progression of the disease. The insight into mechanisms governing thyrocyte genome integrity may help to gain better understanding of the pathology and suggest novel therapeutic regimens, urgently needed in treatment-refractory disease. In the current review, we provide comprehensive description of the exogenous and endogenous factors, as well as DNA repair mechanisms influencing thyrocyte genome integrity. Moreover, we pinpoint major research avenues that should be pursued in future research. This information will be valuable in directing new discoveries to better understand thyroid disease pathomechanisms, as well as aid development of novel diagnostic and therapeutic tools.

• Bø, Ragnhild; Jonassen, Rune; Harmer, Catherine; Øverli, Øyvind; Nilsen, Hilde & Esbensen, Qin Ying [Show all 13 contributors for this article] (2025). 5-HTTLPR does not moderate the effect of attention bias modification for depression: a randomized sham-controlled trial. Translational Psychiatry. 15, p. 1–6. doi: 10.1038/s41398-025-03581-3. Full text in Research Archive Show summary

  Abstract The 5-HTTLPR polymorphism in the serotonin transporter gene SLC6A4 has previously been dubbed a plasticity marker. Within the 5-HTTLPR polymorphism, a SNP (rs25531) in the L-allele in the promoter region, affects the transcription efficacy of the SCL6A4 , leading to functionally important differences related to serotonin transporter availability in the synapses. 5-HTTLPR has been implicated in magnitude of negative attentional bias, a causal risk factor for depression, and the modifiability of attentional biases both in positive and negative directions. Hence, this genotype may moderate the outcomes of attention bias modification (ABM) targeted at reducing depressive symptoms. We conducted a registered randomized sham-controlled trial of ABM in a sample of 301 participants with a history of Major Depressive Disorder (MDD) who had residual symptoms. They were randomized and underwent 14 days of two daily session of either ABM or sham at home. Of these, 264 provided genetic samples for determining the functionally important variant of the gene SLC6A4 . We investigated if the SNP ( rs25531 ) moderated the effect of ABM on symptoms of depression (HDRS, BDI-II) and anxiety (BAI), and attention bias post-intervention. None of the outcomes were moderated by the allelic variation in the promoter region of 5-HTTLPR . Limitations include low level of depressive symptoms, lack of data on ethnicity, current and prenatal level of stress, and early traumatic experiences. The 5-HTTLPR polymorphism did not moderate the effect of ABM on the symptom scales, nor attentional bias. Combination or interactions with other genes may be required for prescribing personalized interventions.

• Rudolfova, Natalie; Skjetne, Alexander Myhr; Montaldo, Nicola Pietro; Visnes, Torkild; Nilsen, Hilde & Michel, Maurice (2025). What is in a name? Rethinking SMUG1 in genome maintenance. NAR Cancer. 7(4), p. 1–12. doi: 10.1093/narcan/zcaf050. Full text in Research Archive Show summary

  Small base lesions in DNA are primarily repaired through the base excision repair pathway, which is initiated by DNA glycosylases. This review focuses on single-strand selective monofunctional uracil–DNA glycosylase (SMUG1), an enzyme whose name incompletely captures its broader biological roles. SMUG1 excises a wide range of substrates beyond uracil, shows a preference for double-stranded DNA, and has been reported to be a bifunctional DNA glycosylase with a weak lyase activity. Moreover, SMUG1 plays roles extending beyond DNA repair, including functions in RNA quality control and RNA biogenesis. Recently, genetic interactions have been described between SMUG1 and proteins that safeguard stressed replication forks, implicating a function for SMUG1 in cancer cell biology. Understanding SMUG1’s full repertoire is key to uncovering its role in genome maintenance and unlocking its potential as a therapeutic target. Here, we review the biochemical properties reported for SMUG1 and its distinct functions from other uracil–DNA glycosylases in vivo. We also highlight the emerging role of SMUG1 in cancer cells and its potential as a therapeutic target, emphasizing the need to define the genetic and molecular contexts in which its modulation may be beneficial.

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• Cuminetti, Vincent & Arranz, Lorena (2026). Control of acute myeloid leukemia by metabolites. Full text in Research Archive
• Heugel, Marcel & Arranz, Lorena (2026). Exploring the transformation potential of hematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Full text in Research Archive
• Arranz, Lorena (2026). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Full text in Research Archive
• Heugel, Marcel & Arranz, Lorena (2026). Exploring the transformation potential of human hematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Full text in Research Archive
• Cuminetti, Vincent & Arranz, Lorena (2026). Control of hematopoiesis by Succinate receptor 1 in the stem cell niche. Full text in Research Archive
• Arranz, Lorena (2026). Knowledge in use: NOK 4,9 million to innovative UiO researchers. [Internet]. /https://www.uio.no/ . doi: https:/www.uio.no/english/about/news-and-events/news/2026/uio-innovation-funds-2026.html. Full text in Research Archive
• Arranz, Lorena (2026). ISEH 5th Annual Virtual Career Fair. Full text in Research Archive Show summary

  New Investigators Committee Presents: ISEH 5th Annual Virtual Career Fair Thank you for a successful Career Fair! Are you searching for a new position in the field of hematology? Or are you seeking to recruit talented scientists for your research groups? Join us for the New Investigator Committee virtual career fair! The New Investigator Committee of the International Society for Experimental Hematology (ISEH) is excited to announce our fifth annual FREE virtual career fair. This unique event aims to connect trainees with hiring faculty from around the world. Using a "speed networking" format, hiring faculty will have the chance to engage in one-on-one conversations with individuals currently in the job market. Our goal is to assist trainees in finding valuable training opportunities in hematology labs, while also helping faculty identify talented scientists to join their teams.

• Arranz, Lorena; Carlsten, Mattias & Newman, Rhiannon (2026). Life After YERM: How the Young EHA Research Meeting Shaped Careers. doi: https:/open.spotify.com/episode/0VtPZopANNt1RDlMH3ZaXI. Full text in Research Archive
• Arranz, Lorena; Carlsten, Mattias & Newman, Rhiannon (2026). Life After YERM: How the Young EHA Research Meeting Shaped Careers. doi: https:/www.youtube.com/watch?v=VD8eLSrDR1w. Full text in Research Archive
• Arranz, Lorena; Cuminetti, Vincent & Doeland, Elin Martine (2026). Vil bekjempe leukemi ved å stoppe stamceller fra å bli til kreftceller. [Internet]. https://www.uio.no/. doi: https:/www.uio.no/forskning/forskningsnytt/artikler/2026/vil-bekjempe-leukemi-stoppe-stamceller-fra-bli-til-kreftceller.html. Full text in Research Archive
• Arranz, Lorena; Cuminetti, Vincent & Doeland, Elin Martine (2026). Aim to combat leukaemia by stopping stem cells from becoming cancer cells. [Internet]. /https://www.uio.no/ . doi: https:/www.uio.no/english/research/research-news/articles/2026/aim-to-combat-leukaemia-by-stopping-stem-cells-cancer-cells.html. Full text in Research Archive
• Arranz, Lorena & Øksne, Rannveig (2026). 9 millioner til forskning på målrettede blodkreftbehandlinger. [Internet]. https://www.blodkreftforeningen.no/. doi: https:/www.blodkreftforeningen.no/om-oss/nyhetsarkiv/tildeling-neurotarget. Full text in Research Archive
• Henriquez, Daniela Cabrera & Arranz, Lorena (2026). Mapping succinate receptor 1 expression and function in the bone marrow niche. Full text in Research Archive
• Arranz, Lorena (2026). Neuropathy of the stem cell niche in myeloid leukemias – potential for therapeutic targeting. Full text in Research Archive
• Arranz, Lorena (2026). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Full text in Research Archive
• Arranz, Lorena (2026). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Full text in Research Archive Show summary

  Our research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Our goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies. We will give an overview of our research and present unpublished observations accepted in principle in Nature Communications, where we have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Our work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.

• Arranz, Lorena (2026). Potential for therapeutic targeting of stem cells and their niches in myeloid malignancies. Full text in Research Archive Show summary

  Lorena Arranz's research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Their goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies. Dr Arranz will give an overview of her research and present their group's recent work, where they have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Their work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.

• Holub, Elina; Jochems, Reina; Zeremichael, Teklu Tewoldebrhan; Klungland, Arne & Kommisrud, Elisabeth (2026). Reduced in vitro maturation time of bovine oocytes may increase blastocyst yield. Full text in Research Archive
• Muri, Pia; Wågbø, Ane Marit; Degnes, Kristin Fløgstad; Klinkenberg, Geir; Pandey, Deo Prakash & Visnes, Torkild (2026). Phenotypic drug profiling. doi: https:/www.ntnu.no/kalender/detaljer/-/event/e47637ae-b126-38c8-bfbc-b0f84a93dd55. Full text in Research Archive
• Cuminetti, Vincent (2025). What to do when your PhD project doesn’t progress (?). Full text in Research Archive
• Arranz, Lorena (2025). Neuropathy of the stem cell niche in myeloid leukemias – potential for therapeutic targeting. Full text in Research Archive
• Vikedal, Krister; Skarstad, Kirsten; Bjørås, Magnar; Helgesen, Emily & Booth, James Alexander (2026). DNASupercompaction: A Novel Orchestrated Response to Severe DNA Damage in Bacteria. Universitetet i Oslo. ISSN 9788234807695. Full text in Research Archive Show summary

  Bacteria respond to antibacterial drug exposure by activating stress responses. These responses can promote survival and drive resistance development, thereby compromising antibacterial drug effectiveness. Studying bacterial stress responses is therefore essential for guiding measures that help ensure treatments remain effective. The aim of this thesis was to investigate how bacteria rearrange their chromosome when exposed to severe DNA damage caused by antibacterial drugs. Using Escherichia coli exposed to the antibacterial drug ciprofloxacin as a model system, live-cell microscopy revealed an ordered two-step nucleoid rearrangement that culminates in a dense and persistent midcell compaction. This response, termed DNA supercompaction, was also observed after exposure to other DNA-damaging agents and across bacterial species, including clinical isolates, underscoring its broader biological relevance. The genetic landscape of DNA supercompaction was explored through a genome-wide screening combined with machine learning-assisted analysis of compaction phenotypes. Key DNA repair proteins, RecA, RecBCD, and RecN, emerged as essential orchestrators of the response. Additionally, single-cell fluorescence imaging revealed a dynamic interplay between RecA and RecN at nucleoid-associated positions during DNA supercompaction. Overall, this work identifies DNA supercompaction as an important and conserved component of the bacterial DNA damage response and provides a framework for future studies of this newly recognized layer of bacterial stress adaptation, which may prove relevant for preserving antibacterial drug effectiveness.

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