- Cervical Cancer and HPV Research
- Hippo pathway signaling and YAP/TAZ
- Cancer-related Molecular Pathways
- Antimicrobial Peptides and Activities
- Antimicrobial Resistance in Staphylococcus
- Genital Health and Disease
- interferon and immune responses
- Cancer-related gene regulation
- Probiotics and Fermented Foods
- Wnt/β-catenin signaling in development and cancer
- Bacterial biofilms and quorum sensing
- Biochemical and Structural Characterization
- T-cell and Retrovirus Studies
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related molecular mechanisms research
- Hepatitis B Virus Studies
- Ovarian cancer diagnosis and treatment
- Virus-based gene therapy research
- Cellular Mechanics and Interactions
- Nonmelanoma Skin Cancer Studies
- Influenza Virus Research Studies
- Infant Nutrition and Health
- RNA Interference and Gene Delivery
- Respiratory viral infections research
- Antifungal resistance and susceptibility
Oslo University Hospital
2024
Norwegian University of Life Sciences
2020-2024
University of Cambridge
2015-2019
The Francis Crick Institute
2017
International Centre for Genetic Engineering and Biotechnology
2008-2015
University of Freiburg
1995
The E6 proteins from high-risk, cancer-causing types of human papillomavirus (HPV) are characterized by the presence a PDZ (PSD95/Dlg/ZO-1) binding motif in their extreme carboxy termini, through which they interact with number cellular domain-containing substrates. In order to ascertain how many these degraded vivo, we performed an extensive analysis effects ablation on expression levels previously reported Using HPV type 16 (HPV-16)-positive CaSKi cells and HPV-18-positive HeLa cells, have...
Cancer genome sequencing has implicated the cytosine deaminase activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) genes as an important source mutations in diverse cancers, with APOBEC3B (A3B) expression especially correlated such cancer mutations. To better understand processes directing A3B over-expression cancer, and possible therapeutic avenues for targeting A3B, we have investigated regulation gene expression. Here, show that is inversely related to p53...
Transcription factor NF-kappa B is a central regulator of inflammatory, immune and acute phase reactions. It rapidly initiates the transcription wide variety target genes in response to various pathogenic stimuli. Because predominantly controlled at posttranscriptional level through association with inhibitory I kappa subunits, its activation cannot be monitored directly cellular by means detecting new mRNA or protein synthesis. In this study, we describe monoclonal antibody, designated...
A subset of high-risk Human Papillomaviruses (HPVs) are the causative agents a large number human cancers, which cervical is most common. Two viral oncoproteins, E6 and E7, contribute directly towards development maintenance malignancy. characteristic feature oncoproteins from cancer-causing HPV types presence PDZ binding motif (PBM) at its C-terminus, confers interaction with cellular proteins harbouring domains. Here we show that this allows Sorting Nexin 27 (SNX27), an essential component...
The emergence of antibiotic-resistant pathogens has caused a serious worldwide problem in infection treatment recent years. One the is methicillin-resistant Staphylococcus aureus (MRSA), which major cause skin and soft tissue infections. Alternative strategies novel sources antimicrobials to solve antibiotic resistance problems are urgently needed. In this study, we explored potential two broad-spectrum bacteriocins, garvicin KS micrococcin P1, treatments. bacteriocins acted synergistically...
Abstract Antibiotic-resistant and biofilm-associated infections brought about by methicillin-resistant Staphylococcus aureus (MRSA) strains is a pressing issue both inside as well outside nosocomial environments worldwide. Here, we show that combination of two bacteriocins with distinct structural functional characteristics, garvicin KS, micrococcin P1, showed synergetic antibacterial activity against biofilms produced in vitro S. , including several MRSA strains. In addition, this...
The cancer-causing high-risk human papillomavirus (HPV) E6 oncoproteins target a number of cellular proteins that contain PDZ domains. However, the role many these interactions in either HPV life cycle or HPV-induced malignancy remains to be defined. Previous studies had shown MAGI-1 was one most strongly bound domain-containing substrates E6, and consequence this interaction appeared facilitate perturbation tight junctions (TJs) by E6. In study, we describe generation mutation, K499E,...
In stratified epithelia such as the epidermis, homeostasis is maintained by proliferation of cells in lower epithelial layers and concomitant loss differentiated from surface. These differentiating keratinocytes progressively stratify form a self-regenerating multi-layered barrier that protects underlying dermis. tissue, continual replacement also limits accumulation oncogenic mutations within tissue. Inactivating key driver genes, TP53 NOTCH1, reduce proportion allowing for long-term...
The Influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor with several protein-protein interaction domains, involved in preventing apoptosis of the infected cell and evading interferon response. In addition, majority influenza NS1 proteins have class I PDZ-binding motif at C-terminus, this itself has been shown to be determinant.In human consensus RSxV: avian it ESxV. Of few strains that motif, all were from very high mortality outbreaks disease. Previous...
Human papillomaviruses (HPV) have genotype-specific disease associations, with high-risk alpha types causing at least 5% of all human cancers. Despite these conspicuous differences, our data show that high- and low- risk HPV use similar approaches for genome maintenance persistence. During the phase, viral episomes host cell are replicated synchronously, both low-risk types, E1 helicase is non-essential. virus amplification, replication switches from an E1-independent to E1-dependent mode,...
Abstract Bacteriocins are ribosomally-synthesized antimicrobial peptides, showing great potential as novel treatment options for multidrug-resistant pathogens. In this study, we designed a hybrid bacteriocin, Hybrid 1 (H1), by combing the N-terminal part and C-terminal of related bacteriocins enterocin K1 (K1) EJ97 (EJ97), respectively. Like parental bacteriocins, H1 used membrane-bound protease RseP receptor, however, it differed from others in inhibition spectrum. Most notably, showed...
The ever-increasing use of exogenous materials as indwelling medical devices in modern medicine offers to pathogens new ways gain access human body and begin, some cases, life threatening infections. Biofouling such with bacteria or fungi is a major concern during surgeries, since this often associated biofilm formation difficult treat, recalcitrant Intense research efforts have therefore developed several strategies shield the devices' surface from colonization by pathogenic microorganisms....
Previous studies have shown that the cell polarity regulator hScrib interacts with, and consequently controls, ERK signaling pathway. This interaction occurs through two well-conserved Kinase Interacting Motifs, which allow to bind ERK1 directly, resulting in a reduction levels of phospho-ERK. suggests might recruit phosphatase regulate this Using proteomic approach we now show Protein Phosphatase 1γ (PP1γ) is major interacting partner hScrib. direct conserved PP1γ motif on protein, appears...
Antibiotic-resistant bacterial pathogens have become a serious threat worldwide. One of these is methicillin-resistant Staphylococcus aureus (MRSA), major cause skin and soft tissue infections. In this study we identified strain equorum producing substance with high antimicrobial activity against many Gram-positive bacteria, including MRSA. By mass spectrometry whole genome sequencing the was as thiopeptide bacteriocin micrococcin P1 (MP1). Based on its properties developed one-step...
The ability of high-risk HPV E6 oncoproteins to target cellular proteins which harbor PDZ domains is believed play an important role in the virus life cycle and influence these viruses bring about malignant transformation. Whilst many are potential tumour suppressors, involved control cell polarity cell-contact, recent studies suggest that mislocalisation or overexpression might result emergence oncogenic functions. This has been shown most clearly for two targets, hDlg hScrib. In this study...
Scribble is a potential tumor suppressor protein, whose loss frequent event in late stage cancer development. In both Drosophila and mammalian model systems, has been shown capable of regulating cell polarity, proliferation apoptosis. Although several interacting partners, including βPiX, have identified that help to explain how can regulate polarity migration, little known about control proliferation. Recent work from our laboratory directly the ERK signaling pathway. This mediated by...
The high risk Human Papillomavirus (HPV) E6 oncoproteins play an essential role in the development of cervical malignancy. Important cellular targets include p53 and PDZ domain containing substrates such as hScrib Dlg. We recently showed that activity was mediated part through recruitment protein phosphatase 1γ (PP1γ). Expression patterns PP1γ were assessed by immunohistochemistry HPV-16 positive intraepithelial neoplasm (CIN), classified CIN1 (n = 4), CIN2 8), CIN3 carcinoma tissues 11),...