Current position
- 2017 - present: Head of the High-Throughput Chemical Biology Screening Platform
Background
Research
- 2013 - 2016: Researcher, Taskén Group, funded by the K. G. Jebsen Centre for Cancer Immunotherapy.
- 2011 - 2013: Researcher, Taskén Group, funded by “MARINE FUNGI - natural products from marine fungi for the treatment of cancer.”
- 2008 - 2011: Postdoctoral research fellow, Taskén Group, Biotechnology Centre of Oslo, funding by FUGE.
Education
- 2007: PhD (Dr. rer. nat.), Institute of Zoology, University of Regensburg, Germany.
PhD thesis: “Studies on the clock proteins PERIOD and TIMELESS in the fruit fly Drosophila melanogaster.”
Tags:
Cell signalling,
High-throughput screening,
Flow cytometry
Publications
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Wei, Qian; Hajjar, Ehsan; Cornillot‐Clément, Selma; Solli, Elise; Diaz, Nuria Garcia & Landskron, Johannes
[Show all 9 contributors for this article]
(2026).
High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells.
ACS Chemical Biology.
ISSN 1554-8929.
21(4),
p. 764–778.
doi:
10.1021/acschembio.5c01019.
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FoxP3+ regulatory T cells (Tregs) maintain immune homeostasis by suppressing excessive antiself-immunity of effector T cells (Teffs) and thereby regulate autoimmunity and inhibit antitumor immune responses. Thus, Treg-targeting is a popular therapeutic strategy for both autoimmune diseases and cancer treatment. However, specific regulators of Tregs are needed to bypass adverse effects elicited by strategies that target molecules with overlapping expression between Tregs and other T cell subsets. We aim to identify small molecules that specifically target the key Treg lineage-defining transcription factor FoxP3. Here, we describe a high-throughput, flow-cytometry-based phenotypic screening assay, its data processing pipeline, and downstream methods for compound validation. We developed a set of algorithms to easily exclude compounds with high toxicity and to filter out autofluorescent compounds. Our screening assay is performed on human primary T cells by measuring FoxP3 levels in CD4+ T cells, using an automated liquid handling pipeline. Selected hit candidates from the screening were validated and assessed through functional analyses. From screening a library of approved drugs, we identified several candidates that regulate Treg functions through FoxP3. Seventeen chemical analogs of one hit compound were identified and characterized in cell-based assays, revealing structure–activity relationships and identifying compounds with more potent effects on the regulation of FoxP3 levels and Treg function. We conclude that this novel screening method could successfully identify FoxP3 regulators with an effect on Treg functions.
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Wei, Qian; Foyn, Håvard; Landskron, Johannes; Wang, Shixiong; Rye, Inga Hansine & Skånland, Sigrid S
[Show all 10 contributors for this article]
(2025).
Identification of a group of 9-amino-acridines that selectively downregulate regulatory T cell functions through FoxP3.
iScience.
28(3).
doi:
10.1016/j.isci.2025.111931.
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FoxP3+ regulatory T cells (Tregs) are responsible for immune homeostasis by suppressing excessive anti-self-immunity. Tregs facilitate tumor growth by inhibiting anti-tumor immunity. Here, we explored the targeting of FoxP3 as a basis for new immunotherapies. In a high-throughput phenotypic screening of a drug repurposing library using human primary T cells, we identified quinacrine as a FoxP3 downregulator. In silico searches based on the structure of quinacrine, testing of sub-libraries of analogs in vitro, and validation identified a subset of 9-amino-acridines that selectively abrogated Treg suppressive functions. Mechanistically, these acridines interfered with the DNA-binding activity of FoxP3 and inhibited FoxP3-regulated downstream gene regulation. Release from Treg suppression by 9-amino-acridines increased anti-tumor immune responses both in cancer patient samples and in mice in a syngeneic tumor model. Our study highlights the feasibility of screening for small molecular inhibitors of FoxP3 as an approach to pursuing Treg-based immunotherapy.
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Diaz, Nuria Garcia; Solli, Elise; Hajjar, Ehsan; Cornillot‐Clément, Selma; Landskron, Johannes & Ahmad, Rafi
[Show all 8 contributors for this article]
(2025).
MAPK and STAT3 Inhibitors Modulate FoxP3 Expression and Regulatory T Cell Function.
European Journal of Immunology.
ISSN 0014-2980.
55(2).
doi:
10.1002/eji.202451225.
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Regulatory T cells (Tregs) are a subset of T cells defined by the expression of Forkhead box protein P3 (FoxP3) playing a crucial role in regulating effector T cell activity. Tregs accumulate in the tumor microenvironment facilitating tumor growth. Thus, targeting FoxP3+ Tregs could improve cancer immunotherapies. Here, we conducted a high-throughput, phenotypic screening of a drug repurposing library to identify compounds downregulating FoxP3 expression in human primary T cells. We identified the tyrosine kinase inhibitor bosutinib and the STAT3 inhibitor nifuroxazide effectively downregulating FoxP3 expression. To identify more potent compounds, structural analogs of these two compounds were searched and validated. These analogs were found to reduce FoxP3 expression in a similar- or more potent manner than the original hits. All compounds inhibited Treg suppressive functions and reduced the expression of Treg activation markers. Importantly, bosutinib disrupted FAK and CaMKII signaling more potently in Tregs, whilst nifuroxazide and its analog NA16 targeted STAT3 protein levels more effectively in Tregs. Additionally, bosutinib and NA16 targeted effector Tregs more effectively than other Treg subsets. In summary, bosutinib, nifuroxazide, and their analogs inhibited FoxP3 expression, Treg suppressive abilities, and Treg activation effectively, which could serve as tools for the improvement of current cancer immunotherapies.
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Bischof, Katharina; Cremaschi, Andrea; Eroukhmanoff, Lena; Landskron, Johannes; Flage-Larsen, Lise-Lotte & Gade, Alexandra
[Show all 9 contributors for this article]
(2024).
Patient-derived acellular ascites fluid affects drug responses in ovarian cancer cell lines through the activation of key signalling pathways.
Molecular Oncology.
ISSN 1574-7891.
19(1).
doi:
10.1002/1878-0261.13726.
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Malignant ascites is commonly produced in advanced epithelial ovarian cancer (EOC) and serves as unique microenvironment for tumour cells. Acellular ascites fluid (AAF) is rich in signalling molecules and has been proposed to play a role in the induction of chemoresistance. Through in vitro testing of drug sensitivity and by assessing intracellular phosphorylation status in response to mono- and combination treatment of five EOC cell lines after incubation with AAFs derived from 20 different patients, we investigated the chemoresistance-inducing potential of ascites. We show that the addition of AAFs to the culture media of EOC cell lines has the potential to induce resistance to standard-of-care drugs (SCDs). We also show that AAFs induce time- and concentration-dependent activation of downstream signalling to signal transducer and activator of transcription 3 (STAT3), and concomitantly altered phosphorylation of mitogen-activated protein kinase kinase (MEK), phosphoinositide 3-kinase (PI3K)–protein kinase B (AKT) and nuclear factor NF-kappa-B (NFκB). Antibodies targeting the interleukin-6 receptor (IL6R) effectively blocked phosphorylation of STAT3 and STAT1. Treatments with SCDs were effective in reducing cell viability in only a third of 30 clinically relevant conditions examined, defined as combinations of drugs, different cell lines and AAFs. Combinations of SCDs and novel therapeutics such as trametinib, fludarabine or rapamycin were superior in another third. Notably, we could nominate effective treatment combinations in almost all conditions except in 4 out of 30 conditions, in which trametinib or fludarabine showed higher efficacy alone. Taken together, our study underscores the importance of the molecular characterisation of individual patients' AAFs and the impact on treatment resistance as providing clinically meaningful information for future precision treatment approaches in EOC.
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Bengtsen, Mads; Winje, Ivan Myhre; Eftestøl, Einar; Landskron, Johannes; Sun, Chengyi & Nygård, Kamilla Børve
[Show all 10 contributors for this article]
(2021).
Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle.
PLoS Genetics.
ISSN 1553-7390.
17:e1009907(11).
doi:
10.1371/journal.pgen.1009907.
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Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.
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Meås, Hany Zakaria; Haug, Markus; Beckwith, Marianne Sandvold; Louet, Claire; Ryan, Liv & Hu, Zhenyi
[Show all 12 contributors for this article]
(2020).
Sensing of HIV-1 by TLR8 activates human T cells and reverses latency.
Nature Communications.
11:147,
p. 1–16.
doi:
10.1038/s41467-019-13837-4.
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During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.
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Brennecke, Philip; Rasina, Dace; Catevilla, Oscar Aubi; Herzog, Katja; Landskron, Johannes & Cautain, Bastien
[Show all 42 contributors for this article]
(2019).
EU-OPENSCREEN: A novel collaborative approach to facilitate chemical biology.
SLAS Discovery.
ISSN 2472-5552.
24(3),
p. 398–413.
doi:
10.1177/2472555218816276.
Full text in Research Archive
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Compound screening in biological assays and subsequent optimization of hits is indispensable for the development of new molecular research tools and drug candidates. To facilitate such discoveries, the European Research Infrastructure EU-OPENSCREEN was founded recently with the support of its member countries and the European Commission. Its distributed character harnesses complementary knowledge, expertise, and instrumentation in the discipline of chemical biology from 20 European partners, and its open working model ensures that academia and industry can readily access EU-OPENSCREEN’s compound collection, equipment, and generated data. To demonstrate the power of this collaborative approach, this perspective article highlights recent projects from EU-OPENSCREEN partner institutions. These studies yielded (1) 2-aminoquinazolin-4(3H)-ones as potential lead structures for new antimalarial drugs, (2) a novel lipodepsipeptide specifically inducing apoptosis in cells deficient for the pVHL tumor suppressor, (3) small-molecule-based ROCK inhibitors that induce definitive endoderm formation and can potentially be used for regenerative medicine, (4) potential pharmacological chaperones for inborn errors of metabolism and a familiar form of acute myeloid leukemia (AML), and (5) novel tankyrase inhibitors that entered a lead-to-candidate program. Collectively, these findings highlight the benefits of small-molecule screening, the plethora of assay designs, and the close connection between screening and medicinal chemistry within EU-OPENSCREEN.
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Goodridge, Jodie; Jacobs, Benedikt Marcel; Sætersmoen, Michelle Lu; Clement, Dennis; Hammer, Quirin & Clancy, Trevor
[Show all 24 contributors for this article]
(2019).
Remodeling of secretory lysosomes during education tunes functional potential in NK cells.
Nature Communications.
10:14,
p. 1–15.
doi:
10.1038/s41467-019-08384-x.
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Inhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation; however, the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. Secretory lysosomes are part of the acidic lysosomal compartment that mediates intracellular signalling in several cell types. Here we show that educated NK cells expressing self-MHC specific inhibitory killer cell immunoglobulin-like receptors (KIR) accumulate granzyme B in dense-core secretory lysosomes that converge close to the centrosome. This discrete morphological phenotype is independent of transcriptional programs that regulate effector function, metabolism and lysosomal biogenesis. Meanwhile, interference of signaling from acidic Ca2+ stores in primary NK cells reduces target-specific Ca2+-flux, degranulation and cytokine production. Furthermore, inhibition of PI(3,5)P2 synthesis, or genetic silencing of the PI(3,5)P2-regulated lysosomal Ca2+-channel TRPML1, leads to increased granzyme B and enhanced functional potential, thereby mimicking the educated state. These results indicate an intrinsic role for lysosomal remodeling in NK cell education.
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Landskron, Johannes; Kraggerud, Sigrid M.; Wik, Elisabeth; Dørum, Anne; Bjørnslett, Merete Pauline & Melum, Espen
[Show all 11 contributors for this article]
(2017).
C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease.
PLOS ONE.
12:e0182030(7),
p. 1–12.
doi:
10.1371/journal.pone.0182030.
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The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4–6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon’s differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive. An incidental finding in an ovarian cancer patient cohort from West Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs. 1.8% allele frequency). However, this finding could not be validated in a larger patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian population. However, its frequency was increased in patients with FIGO stage II, endometrioid histology or an age at diagnosis of 60 years or older indicating a possible association with a less aggressive cancer type.
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Eriksen, Agnete Bratsberg; Indrevær, Randi Larsen; Holm, Kristine Lillebø; Landskron, Johannes & Blomhoff, Heidi Kiil
(2012).
TLR9-signaling is required for turning retinoic acid into a potent stimulator of RP105 (CD180)-mediated proliferation and IgG synthesis in human memory B cells.
Cellular Immunology.
ISSN 0008-8749.
279(1),
p. 87–95.
doi:
10.1016/j.cellimm.2012.09.003.
Full text in Research Archive
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Saunders, Threrese Solstad; Bains, Simer Jit; Landskron, Johannes; Aandahl, Einar Martin; Thiede, Bernd & Tasken, Kjetil
[Show all 7 contributors for this article]
(2011).
CD147 (Basigin/Emmprin) identifies FoxP3(+)CD45RO(+)CTLA4(+)-activated human regulatory T cells.
Blood.
ISSN 0006-4971.
118(19),
p. 5141–5151.
doi:
10.1182/blood-2011-02-339242.
Full text in Research Archive
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Human CD4(+)FoxP3(+)T cells are functionally and phenotypically heterogeneous providing plasticity to immune activation and regulation. To better understand the functional dynamics within this subset, we first used a combined strategy of subcellular fractionation and proteomics to describe differences at the protein level between highly purified human CD4(+)CD25(+) and CD4(+)CD25(+) T-cell populations. This identified a set of membrane proteins highly expressed on the cell surface of human regulatory T cells Tregs), including CD71, CD95, CD147, and CD148. CD147 (Basigin or Emmprin) divided CD4(+)CD25(+) cells into distinct subsets. Furthermore, CD147, CD25, FoxP3, and in particular CTLA-4 expression correlated. Phenotypical and functional analyses suggested that CD147 marks the switch between resting (CD45RA(+)) and activated (CD45RO(+)) subsets within the FoxP3(+) T-cell population. Sorting of regulatory T cells into CD147(-) and CD147(+) populations demonstrated that CD147 identifies an activated and highly suppressive CD45RO(+) Treg subset. When analyzing CD4(+) T cells for their cytokine producing potential, CD147 levels grouped the FoxP3(+) subset into 3 categories with different ability to produce IL-2, TNF-alpha, IFN-gamma, and IL-17. Together, this suggests that CD147 is a direct marker for activated Tregs within the CD4(+)FoxP3(+) subset and may provide means to manipulate cells important for immune homeostasis. (Blood. 2011;118(19):5141-5151)
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Haug, Markus; Meås, Hany Zakaria; Beckwith, Marianne Sandvold; Louet, Claire; Ryan, Liv & Hu, Z.
[Show all 12 contributors for this article]
(2019).
Sensing of HIV-1 by TLR8 in human CD4+ T cells.
Full text in Research Archive
Show summary
Cell-to-cell transmission of HIV can result in endosomal uptake of HIV by CD4+ T cells with possible exposure of viral ssRNA genome to endolysosomal Toll-like receptors (TLRs). TLRs are central in activating inflammatory responses in innate immune cells, but their function in CD4+ T cells is less well understood.
Here we show that combined TLR8 ligand and T cell receptor (TCR) stimulation boosted CD4+ T cell activation by enhancing NF-B and MAPK signaling. This led to increased production of inflammatory cytokines and surface activation marker expression. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, promoted interleukin (IL)-17 and interferon (IFN)- effector cytokine production, indicating lineage commitment towards the pro-inflammatory T helper (Th)1 and Th17 axis.
Using a cell-to-cell transmission model, we found that endosomal HIV induced cytokine secretion from CD4+ T cells, which could be significantly reduced by a TLR8 specific inhibitor. TLR8 engagement also enhanced HIV replication in CD4+ T cells and potentiated the reversal of latency in patient-derived CD4+ T cells. Taken together, our results reveal a previously unknown function of TLR8 in human primary CD4+ T cells in shaping immunity and modulating HIV-1 infection. This adjuvant TLR8 activity can contribute to low-grade inflammation seen in HIV patients and may also have implications for therapeutic targeting and vaccine development.
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Bengtsen, Mads; Winje, Ivan; Eftestøl, Einar; Domanska, Diana Ewa; Landskron, Johannes & Gundersen, Kristian
(2019).
The Epigenetic landscape of two phenotypic extreme skeletal muscles - soleus and EDL.
Acta Physiologica.
ISSN 1748-1708.
doi:
10.1111/apha.13414.
Full text in Research Archive
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Haug, Markus; Meås, Hany Zakaria; Beckwith, Marianne Sandvold; Louet, Claire; Ryan, Liv & Hu, Z.
[Show all 12 contributors for this article]
(2019).
Sensing of HIV-1 nucleic acids by TLR8 in human CD4+ T cells.
Full text in Research Archive
Show summary
During HIV-infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endolysosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood.
Here we show that combined TLR8 ligand and T cell receptor (TCR) stimulation boosted CD4+ T cell activation by enhancing NF-kB and MAPK signaling. This led to increased production of inflammatory cytokines and surface activation marker expression. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, promoted interleukin (IL)-17 and interferon (IFN)-g effector cytokine production, indicating lineage commitment towards the pro-inflammatory T helper (Th)1 and Th17 axis. Using a cell-to-cell transmission model, we found that endosomal HIV-1 induced cytokine secretion from CD4+ T cells, which could be significantly reduced by a TLR8 specific inhibitor. TLR8 engagement also enhanced HIV-1 replication in CD4+ T cells and potentiated the reversal of latency in patient-derived CD4+ T cells.
Taken together, our results reveal a previously unknown function of TLR8 in human primary CD4+ T
cells in shaping immunity and modulating HIV-1 infection. This adjuvant TLR8 activity can contribute to low-grade inflammation seen in HIV patients and may have broad implications for therapeutic targeting and vaccine development.
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Bengtsen, Mads; Winje, Ivan; Landskron, Johannes; Meza-Zepeda, Leonardo A. & Gundersen, Kristian
(2019).
The Epigenetic landscape of two phenotypic extreme skeletal muscles.
Full text in Research Archive
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Bengtsen, Mads; Winje, Ivan; Landskron, Johannes; Meza-Zepeda, Leonardi A & Gundersen, Kristian
(2019).
The Epigenetic landscape of two phenotypic extreme skeletal muscles.
Full text in Research Archive
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Bengtsen, Mads; Winje, Ivan; Landskron, Johannes; Meza-Zepeda, Leonardo A. & Gundersen, Kristian
(2018).
The Epigenetic landscape of two phenotypic extreme skeletal muscles.
Full text in Research Archive
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Johnsen, Guro Mørk; Landskron, Johannes; Tasken, Kjetil & Staff, Anne Cathrine
(2011).
CHARACTERIZATION OF PLACENTAL AND CIRCULATING REGULATORY T-CELLS.
Placenta.
ISSN 0143-4004.
32(9),
p. A122–A122.
Full text in Research Archive
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Johnsen, Guro Mørk; Landskron, Johannes; Tasken, Kjetil & Staff, Anne Cathrine
(2011).
Characterization of Placental and Circulating Regulatory T-Cells.
Full text in Research Archive
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Johnsen, Guro Mørk; Landskron, Johannes; Tasken, Kjetil & Staff, Anne Cathrine
(2011).
Characterization of Subsets of T cells and NK cells in Pregnancy and Preeclampsia.
Full text in Research Archive
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Published
Dec. 17, 2015 10:21 AM
- Last modified
Feb. 25, 2026 4:03 PM
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