SKIN INFLAMMATION

Keratinocyte stress responses and inflammation

The relationship between keratinocyte stress responses and inflammation in human skin is not well known. In this study, we explore the effect of various stress conditions on keratinocyte immune function with special emphasis on interleukin-33 and its regulation by osmotic stress.

Project leader: Olav Sundnes. Collaborators: Guttorm Haraldsen, Department of Pathology, K. G. Jebsen Inflammation Research Centre.


Early gene expression changes as predictors of therapeutic response to narrow-band UVB in atopic dermatitis

Atopic dermatitis (AD) is a common, chronic inflammatory skin disease with increasing prevalence. There is a large unmet need for better treatment modalities, and the therapeutic repertoire when compared to that of psoriasis is appalling. UV-treatment is an effective and safe treatment modality, yet we know surprisingly little about the exact molecular mechanisms driven by this type of treatment. A better understanding of this could shed light on the pathophysiology behind AD and lead to more efficient treatment protocols in the future.

PhD-project: Astrid Lossius. Main supervisor: Jan-Øivind Holm. Co-supervisors: Teresa Løvold Berents, Olav Sundnes, Guttorm Haraldsen. Collaborators: Department of Pathology, K. G. Jebsen Inflammation Research Centre.


Moderate to Severe Atopic Dermatitis: Evaluation of Upadacitinib in Combination with Topical Corticosteroids in Adolescent and Adult Subjects. 

A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Combination with Topical Corticosteroids in Adolescent and Adult Subjects with Moderate to Severe Atopic Dermatitis. AbbVie Inc.

Local project leader: Teresa Løvold Berents. Co-workers: Guro Sunniva Bjørnevaagen, Eva Astrid Tønsberg.


Skin and amniotic fluid microbiome and atopic dermatitis

In the recent years, skin microbiome studies are emerging, and there is increasing evidence of a lower microbial diversity in the atopic skin.  It is still uncertain if a dysbiosis occurs before the development of atopic dermatitis or if it is a consequence of it. New sequencing methods are suggesting a unique microbiome also in the amniotic fluid that resembles the placenta and the infants’ meconium. In this PhD project of PreventADALL, we will investigate both the microbiome of the amniotic fluid as well as that in the skin in relation to early development of atopic dermatitis.

PhD-project: Eva Maria Rehbinder. Main supervisor: Karin C. Lødrup Carlsen. Co-supervisor: Linn Landrø. Collaborators: PreventADALL.


A NORwegian multicentre trial assessing the effectiveness of tailoring infliximab treatment by therapeutic DRUg Monitoring (NOR-DRUM)

Biological treatment with cytokine-neutralizing antibodies such as the anti-TNF antibody infliximab (INX) is highly effective for treatment of a wide range of autoimmune  diseases, including inflammatory bowel disease, rheumatoid arthritis and psoriasis. However, optimal response to INX treatment may depend on individual dosage. Furthermore, several patients eventually develop anti-drug antibodies (ADAb) against INX, making the treatment ineffective. The NOR-DRUM trial is a prospective randomized clinical algorithm study that investigates whether monitoring INX serum levels and INX ADAb leads to better treatment or not in terms of minimizing under-treatment, reduce over-treatment, prevent hypersensitivity and detect treatment failures prior to a clinical flare.

Øystein Sandanger (MD, PhD, national study coordinator for dermatology), Kristin Halvorsen Hortemo (MD. PhD), Siri Kratter  Abrahamsen (MD), Elisabeth Schrumpf (MD. PhD), Cato Mørk (MD, PhD). Collaborators: Silje Watterdal Syversen (project leader)1, Guro Goll (MD. PhD, national study coordinator for rheumatology)1,prof. Espen A. Haavardsholm1, prof. Tore K. Kvien1, Kristin Kaas Jørgensen (MD, PhD, national study coordinator for gastroenterology), prof. Jørgen Jahnsen2, David J. Warren3and Nils Bolstad3. 1) Department of Rheumatology, Diakonhjemmet Hospital. 2) Department of gastroenterology, Akershus University Hospital. 3) Department of Medical Chemistry, Oslo University Hospital Radiumhospitlaet


A novel mutation decreases innate immune responses

Three siblings struggled with atopic dermatitis as well as increased tendency of warts and upper respiratory tract infections. In the process of diagnosis, exome sequencing revealed a previously uncharacterized mutation in a gene coding for a protein involved in negative regulation of inflammatory responses. In this project, we investigate the patients’ phenotype at the cellular and molecular levels in terms of cytokine profiling and protein expression of innate immune receptors. Induced pluripotent stem cells obtained from the patients and healthy controls will be a major tool. We hypothesize a gain-of-function mutation that leads to impaired innate immune responses and subsequently a Th2 bias.

Project leader: Børre Fevang, MD PhD, Seksjon for klinisk immunologi og infeksjonsmedisin og Institutt for indremedisinsk forskning, OUS Rikshospitalet. Others:  Øystein Sandanger. Collaborators: Institutt for indremedisinsk forskning, OUS Rikshospitalet ved Børre Fevang, Pål Aukrust og Arne Yndestad, Seksjon for klinisk immunologi og infeksjonsmedisin, OUS Rikshospitalet ved Børre Fevang og Pål Aukrust, Avdeling for nyfødtscreening, OUS Rikshospitalet ved Asbjørg Stray Pedersen, og Norsk senter for molekylærmedisin, UiO ved Kjetil Tasken.


PreventADALL

This prospective multicenter birth cohort study will test if primary prevention of allergic diseases is possible by simple and low cost strategies, and secondary to assess the impact of xenobiotic exposure and microbiota in and on the body and the environment on allergic disease development.

Project leader: Karin Lødrup Carlsen. Others: Linn Landrø, Eva Maria Rehbinder, Kim Endre. Collaborators: OUS, Karolinska University Hospital,  Østfold Hospital Trust, University Hospital Lausanne, National Skin and Allergy Hospital Helsinki, Nowegian Institute of Public Health.


Project: Parental, pregnancy and early risk factors for infant atopic dermatitis

This study aims to identify early risk factors for infant atopic dermatitis (AD). Identifying those with high risk of AD is important in order to provide targeted prevention strategies. Factors that will be investigated includes hereditary risk, gender associations and different variables at childbirth. The project is a part of the PreventADALL study, a 2x2 factorial intervention trial aiming to prevent atopic disease. 

PhD-project: Kim A. Endre. Main supervisor: Linn Landrø. Co-supervisors: Karin Lødrup Carlsen, Håvard Skjerven, Kai-Håkon Carlsen. Collaborators: The PreventADALL study, Extrastiftelsen.


Whole exome sequencing for diagnosis of inherited ichthyoses

A gene panel applying whole exome sequencing (WES) in the routine investigation of patients with ichthyoses was introduced at the Oslo University Hospital in 2013. The diagnostic outcome of WES, including a description and evaluation of novel pathogenic mutations in a cohort of 34 consecutive patients, is now being analyzed.

Project leader: Jan Cezary Sitek. Collaborators: Department of Medical Genetics, OUS


Keratolytic winter erythema – genetic and functional studies

We have recently identified the genetic cause for keratolytic winter erythema (KWE) and are now pursuing functional investigations to elucidate pathogenetic mechanisms underlying the disease. In addition, we aim to define possible therapeutic approaches based on the knowledge from our investigations.

Project leader: Torunn Fiskerstrand, Haukeland University Hospital, Norway. Others: Jan Cezary Sitek, Olav Sundnes. Collaborators: Nijmegen University Hospital, The Netherlands;  Michele Ramsay, University of the Witwatersrand, South Africa; and University of Halifax, Canada. 


Genetic causes for inherited ichthyoses applying next-generation sequencing

Since 2013, patients with ichthyoses have been investigated with gene panels using next-generation sequencing (NGS) to identify the molecular cause for their disease. Approximately 20% of such patients have a negative gene test. These patients will be studied further by investigating their total exome, aiming at identifying new causes for their ichthyosis.

Project leader: Jan C Sitek. Collaborators: Department of Medical Genetics, OUS


Treatment of genital lichen planus in women

Genital erosive lichen planus (GELP) is a chronic inflammatory skin disease characterized by painful vulval and vaginal erosions and limited treatment options. 

The study is investigator-initiated, double-blinded, randomized andplacebo-controlled  on oral treatment with the phosphodiesterase 4-inhibitor aprimelast for genital erosive lichen planus in 40 women, assessing the effect on clinical, immunohistochemical and  patient-registered changes

PhD project : Kristin Skullerud, Olafia Clinic. Main supervisor: Anne Lise Ording Helgesen. Co-supervisor: Petter Gjersvik, Co-supervisor: Erik Qvigstad. Collaborators: Department of Obstetrics and Gynecology, Ullevål Hospital, Norwegian National Advisory Unit on Women’s Health.


Quality of life in women with genital erosive lichen planus.

Using three validated questionnaires,, quality of life in women with genital erosive lichen planus will be documented in patients visiting the Vulva Clinic at OUS.

Project leader: Anne Lise Ording Helgesen. Others: Kristin Skullerud, Petter Gjersvik. Collaborators: Department of Obstetrics and Gynecology, Ullevål Hospital, Norwegian National Advisory Unit on Women’s Health.


Effect of somatocognitive therapy vs treatment as usual in provoked vestibulodynia – a randomized controlled trial.

Provoked vestibulodynia (PVD) is the most common subtype of vulvodynia comprising 65-80% of all cases and affecting around 8-12% of women in the general population. The study seeks to validate multimodal physical therapy approach for PVD, and provide further insights into the working mechanisms behind treatment outcomes and predictors of treatment success or failure.

PhD project. Main supervisor Gro Killi Haugstad, co-supervisor Anne Lise Helgesen, co-supervisor Slawomir Wojniusz. Collaborators: Department of Gynecology, Vulva Clinic, OUS, Department of Physiotherapy (HiOA). 


Study of the efficacy of early intervention with secukinumab compared to UVB in patients with new onset moderate to severe plaque psoriasis.An international, multicenter, phase IV study

Project leader: Joar Austad. Other: Olav Sundnes. Collaborators: Novartis

 
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