Håvard T. Lindholm

ORCID: 0000-0003-4403-4387
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About
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Research Areas
  • IL-33, ST2, and ILC Pathways
  • Epigenetics and DNA Methylation
  • Cancer Cells and Metastasis
  • RNA modifications and cancer
  • Immune Cell Function and Interaction
  • interferon and immune responses
  • RNA Research and Splicing
  • Extracellular vesicles in disease
  • Gut microbiota and health
  • Neonatal Respiratory Health Research
  • Parasites and Host Interactions
  • Immune responses and vaccinations
  • RNA regulation and disease
  • Digestive system and related health
  • RNA and protein synthesis mechanisms
  • Parasitic Infections and Diagnostics
  • MicroRNA in disease regulation
  • Helicobacter pylori-related gastroenterology studies
  • Ferroptosis and cancer prognosis
  • Cancer, Lipids, and Metabolism
  • Cancer Research and Treatments
  • HIV Research and Treatment
  • Childhood Cancer Survivors' Quality of Life
  • Cytomegalovirus and herpesvirus research
  • Cancer-related gene regulation

Norwegian University of Science and Technology
2020-2024

Princess Margaret Cancer Centre
2022-2024

University Health Network
2022-2024

Oslo University Hospital
2024

The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes immune defense. epithelium has pivotal role in both initiation effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, IL-22. Here, we studied epithelial responses using organoid image analysis based on convolutional neural network, transcriptomic analysis, vivo infection models. We found that IL-13 IL-22 induce genes...

10.1126/sciimmunol.abl6543 article EN Science Immunology 2022-05-13

Viral mimicry describes the immune response induced by endogenous stimuli such as double-stranded RNA (dsRNA) from retroelements. Activation of viral has potential to kill cancer cells or augment anti-tumor responses. Here, we systematically identify mechanisms adaptation associated with cell dependencies. Among top hits is decay protein XRN1 an essential gene for survival a subset lines. dependency mediated mitochondrial antiviral signaling and kinase R activation higher levels cytosolic...

10.1016/j.celrep.2024.113684 article EN cc-by-nc-nd Cell Reports 2024-01-22

Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade host type 2 response. In intestinal niche, epithelium is crucial for initiating immunity via tuft cells, which together with goblet cells expand dramatically in response cytokines IL-4 and IL-13. However, it not known whether helminths modulate these epithelial cell populations. vitro, small organoids, we found that excretory/secretory products (HpES) from Heligmosomoides polygyrus blocked...

10.1084/jem.20211140 article EN cc-by The Journal of Experimental Medicine 2021-11-15

Abstract Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic segmentation movements. However, very little known about other putative roles that smooth cells may have. Here, we show be dominant suppliers BMP antagonists, which are niche factors for intestinal stem cell maintenance. Furthermore, muscle-derived render epithelium reparative fetal-like, includes heightened YAP activity. Mechanistically, find membrane-bound matrix...

10.1038/s41467-021-26904-6 article EN cc-by Nature Communications 2021-11-18

Intestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth appear after birth in the neonatal period. We aimed to identify regulators of development testing a small library epigenetic modifier inhibitors cell-skewed organoid cultures. found that lysine-specific demethylase 1A (Kdm1a/Lsd1) absolutely required for cell differentiation. Lsd1-deficient crypts, devoid are still able form organoids without requirement exogenous or endogenous Wnt....

10.1126/sciadv.abc0367 article EN cc-by-nc Science Advances 2020-09-11

Colorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which present liquid biopsies. Here, we characterised proteome landscape sEVs and their cells origin three CRC cell lines HCT116, HT29 SW620 to explore molecular traits that could be exploited as biomarker candidates how can assessed sEV analysis...

10.3390/proteomes11010003 article EN cc-by Proteomes 2023-01-11

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying noninvasive biomarkers body fluids such as blood and urine. A source of these biofluids are extracellular vesicles (EVs), nanosized that contain a wide array molecular cargo, including small noncoding RNA transfer RNA-derived fragments (tRF) microRNA. Here, we performed small-RNA next-generation sequencing from EVs urine serum, well...

10.3390/cancers16081588 article EN Cancers 2024-04-20

Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of intestinal epithelium towards protective effector state is important to manage inflammation immunity can be therapeutically targeted. The role epigenetic regulatory enzymes within these processes not yet defined. Here, we use mouse model that has an intestinal-epithelial specific deletion histone demethylase Lsd1 (cKO mice), which maintains fixed reparative state. Challenge...

10.1371/journal.ppat.1009476 article EN cc-by PLoS Pathogens 2021-03-31

Intestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated screening method, which applied library highly specific chemical probes identify epigenetic regulators intestinal The role modifiers in adult stem cell systems, such as epithelium, is still undefined. Based on this resource dataset, identified several targets that affected...

10.3389/fcell.2020.618552 article EN cc-by Frontiers in Cell and Developmental Biology 2021-01-21

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers body fluids such as blood and urine. A source of these biofluids are extracellular vesicles (EVs), nanosized that contain a wide array molecular cargo, including small non-coding RNA microRNA transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs...

10.20944/preprints202404.0041.v1 preprint EN 2024-04-01

Postnatal development of the gastrointestinal tract involves establishment commensal microbiota, acquisition immune tolerance via a balanced cell composition, and maturation intestinal epithelium. While studies have uncovered an interplay between first two, less is known about role maturing Here we show that intestinal-epithelial intrinsic expression lysine-specific demethylase 1A (LSD1) necessary for postnatal epithelium maintenance this developed state during adulthood. Using...

10.1038/s41467-024-47815-2 article EN cc-by Nature Communications 2024-04-22

ABSTRACT An emerging hallmark across human diseases – such as cancer, autoimmune and neurodegenerative disorders is the aberrant transcription of typically silenced repetitive elements. Once active, a subset repeats may be capable “viral mimicry”: display pathogen-associated molecular patterns (PAMPs) that can, in principle, bind pattern recognition receptors (PRRs) innate immune system trigger inflammation. Yet how to quantify landscape viral mimicry it shaped by natural selection remains...

10.1101/2021.11.04.467016 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2021-11-04

Abstract The intestinal tract is a common site for infection, and it relies on an appropriate immune response to defend against pathogens. epithelium has important role in effector responses, which coordinated by immune-type specific cytokines. It incompletely understood how cytokines drive epithelial responses. Here, using organoid-cytokine co-cultures, we provide comprehensive analysis of key affect the epithelium, relate this vivo infection models. We use imaging, based convolutional...

10.1101/2020.06.19.160747 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-06-20

Abstract Intestinal organoids are an excellent model to study epithelial biology. Yet, the selection of analytical tools accurately quantify heterogeneous organoid cultures remains limited. Here, we developed a semi-automated screening method, which applied library highly specific chemical probes identify epigenetic regulators intestinal The role modifiers in adult stem cell systems, such as epithelium, is still undefined. Based on this resource data, identified several targets that affected...

10.1101/2020.07.23.217414 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2020-07-24

Intestinal epithelial homeostasis is maintained by intrinsic and extrinsic signals. The signals include those provided mesenchymal cell populations that surround intestinal crypts further facilitated the extracellular matrix (ECM), which modulated proteases such as metalloproteinases (MMPs). Extrinsic ensure an appropriate balance between proliferation differentiation. This study explores role of MMP17, preferentially expressed smooth muscle cells in intestine, during immunity to infection....

10.3389/fimmu.2023.1243528 article EN cc-by Frontiers in Immunology 2023-10-06

ABSTRACT Intestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth appear after birth in the neonatal period. We aimed to identify new regulators of development testing a small library epigenetic modifier inhibitors cell-skewed organoid cultures. found that Lysine-specific demethylase 1A ( Kdm1a/Lsd1 ) absolutely required for cell differentiation. Lsd1 -deficient crypts, devoid are still able form organoids without requirement exogenous or...

10.1101/2020.02.20.958363 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-02-23

Abstract Viral mimicry describes the immune response induced by endogenous stimuli such as dsRNA formed retroelements. Activation of viral has potential to kill cancer cells or augment anti-tumor response. Paradoxically, frequently present a dysregulated epigenome, leading increased expression We previously found that ADAR1 p150 upregulation is an adaptation mechanism tolerate high retroelement-derived levels, druggable dependency. Here, we systematically identified novel mechanisms...

10.1101/2023.03.30.531699 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2023-03-30

ABSTRACT Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of intestinal epithelium towards protective effector state is important to manage inflammation immunity. The role epigenetic regulatory enzymes within these processes not yet defined. Here, we use mouse model that has an intestinal-epithelial specific deletion histone demethylase Lsd1 (cKO mice), which maintains fixed reparative state. Challenge cKO mice with...

10.1101/2020.07.09.186114 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-07-10

SUMMARY Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic segmentation movements. However, very little known about other putative roles that smooth may have. Here, we show dominant supplier BMP antagonists, which are niche factors for intestinal stem cell maintenance. Furthermore, muscle-derived can render epithelium reparative fetal-like, includes heightened YAP activity. Mechanistically, find matrix metalloproteinase MMP17,...

10.1101/2020.06.18.147769 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-06-18

ABSTRACT Intestinal epithelial homeostasis is maintained by intrinsic and extrinsic signals. The signals include those provided mesenchymal cell populations that surround intestinal crypts further facilitated the extracellular matrix (ECM), which modulated proteases such as metalloproteinases (MMPs). Extrinsic ensure an appropriate balance between proliferation differentiation. This study explores role of MMP17, expressed cells, in during immunity to infection. Mice lacking MMP17 high levels...

10.1101/2023.07.10.548379 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2023-07-10

ABSTRACT Postnatal development of the gastrointestinal tract involves establishment commensal microbiota, maturation intestinal epithelium, and acquisition immune tolerance via a balanced cell composition. While studies have uncovered an interplay between microbiota system development, less is known about role maturing epithelium. Here, we comprehensively show that intestinal-epithelial intrinsic expression lysine-specific demethylase 1A (LSD1) necessary for postnatal epithelium as well...

10.1101/2023.09.08.556818 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2023-09-12
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