Publications
Find an abstract and a link to most of the publications produced by Nordic Bioscience
Background Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of ...
August 4, 2022
Journal:
Respiratory Research
Author:
Hesse C, Beneke V, Konzok S, Diefenbach C, Bülow Sand JM, Rønnow S, Karsdal MA, Jonigk D, Sewald K, Braun A, Leeming DJ, Wollin L
Objectives: There is a need for precision medicine and an unspoken promise of an optimal approach for identification of the right patients for value-based medicine based on big data. However, there may be a misconception that measurement of proteins is more valuable than measurement of fewer selecte...
August 26, 2021
Journal:
Clin Biochem
Author:
Karsdal MA, Rasmussen DGK, Bay-Jensen AC, Mortensen JH, Holm Nielsen S, Willumsen N, Jensen C, Manon-Jensen T, Jennings L, Reese-Petersen AL, Henriksen K, Leeming DJ, Bager CL, Genovese F, Bülow Sand JM
Abstract Background: Asthma is a heterogeneous syndrome substantiating the urgent requirement for endotype-specific biomarkers. Dysbalance of fibrosis and fibrolysis in asthmatic lung tissue leads to reduced levels of the inflammation-protective collagen 4 (COL4A3). Objective: To delineate the degra...
July 29, 2021
Journal:
Eur Respir J
Author:
Weckmann M, Bahmer T, Rønnow S, Pech M, Vermeulen C, Faiz A, Karsdal MA, Lunding L, Oliver B, Wegmann M, Ulrich-Merzenich G, Juergens U, Duhn J, Laumonnier Y, Danov O, Sewald K, Zissler U, Jonker M, König I, Hansen G, Mutius E, Fuchs O, Dittrich AM, Schaub B, Happle C, Rabe K, de Berge M, Burgess J, Kopp M, Leeming DJ, Bülow Sand JM
Abstract Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of fibrillar collagens in the alveolar space resulting in reduced pulmonary function and a high mortality rate. Biomarkers measuring the turnover of type I and III collagen could provide valuable informa...
July 15, 2021
Journal:
Respir Res.
Author:
Leeming DJ, Jessen H, Hoyer N, Prior TS, Frederiksen P, Karsdal MA, Bendstrup E, Bülow Sand JM, Shaker SB
Background and objective: Prediction of idiopathic pulmonary fibrosis (IPF) progression is vital for the choice and timing of treatment and patient follow-up. This could potentially be achieved by prognostic blood biomarkers of extracellular matrix (ECM) remodelling. Methods: Neoepitope biomarkers ...
April 9, 2021
Journal:
Respirology
Author:
Hoyer N, H Jessen, Leeming DJ, Karsdal MA, Åttingsberg KAE, Vangsgaard KMG, Bendstrup E, Shaker SB, Prior TS, Bülow Sand JM
Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biom...
February 5, 2021
Journal:
Respir Res.
Author:
Leeming DJ, Rasmussen DGK, Christiansen C, Jenkins G, Mahrer TM, Vestbo J, Karsdal MA, Genovese F, Bülow Sand JM
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair resulting in a hypercoagulable state with intra-alveolar accumulation of fibrin and alveolar basement membrane destruction. This study aimed to investigate if the combination of two serological bi...
November 19, 2020
Journal:
Lancet Respir Med
Author:
Langholm LL, Karsdal MA, Manon-Jensen T, Miller BE, Vestbo J, Leeming DJ, Thal-Singer R, Bülow Sand JM, Rønnow S
Background: Lung epithelial damage, activation of the wound healing cascade, and remodeling of the extracellular matrix (ECM) play a major role in chronic obstructive pulmonary disease (COPD). The pro-peptide of type VI collagen has been identified as the hormone endotrophin. Endotrophin has been sh...
July 30, 2020
Journal:
Respir Res.
Author:
Rønnow S, Langholm LL, Karsdal MA, Manon-Jensen T, Miller BE, Vestbo J, Leeming DJ, Bülow Sand JM, Thal-Singer R
Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es...
March 11, 2020
Journal:
Sci Rep
Author:
Rønnow S, Langholm LL, Leeming DJ, Manon-Jensen T, Miller BE, Karsdal MA, Vestbo J, Thal-Singer R, Thoracius-Ussing J, Bülow Sand JM
Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and lung tissue deterioration. Given the high vascularity of the lung, von Willebrand factor (VWF), a central component of wound healing initiation, has previously been assessed in COPD. VWF processing,...
March 9, 2020
Journal:
Int J Chron Obstruct Pulmon
Author:
Langholm LL, Rønnow S, Leeming DJ, Miller BE, Vestbo J, Karsdal MA, Manon-Jensen T, Bülow Sand JM, Thal-Singer R
PURPOSE OF REVIEW: Biomarkers of remodeling represent a loose collection of features referring to several biological adaptations of the lung to cope with stressing factors. In addition, remodelling infers a dynamic process that would require a spatiotemporal resolution. This review focuses on differ...
Background: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized that...
December 2, 2019
Journal:
Lancet Respir Med
Author:
Manon-Jensen T, Langholm LL, Karsdal MA, Vestbo J, Leeming DJ, Miller BE, Thal-Singer R, Bülow Sand JM, Rønnow S
OBJECTIVES: Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation. DESIGN ...
November 30, 2018
Journal:
Biochem Biophys Res Commun.
Author:
Leeming DJ, Willumsen N, Holm Nielsen S, Dasgupta B, Brodmerkel C, Bager CL, Karsdal MA, Bülow Sand JM
BACKGROUND: The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of ty...
October 1, 2018
Journal:
chest
Author:
Kostikas K, Boersma W, Louis R, Aerts J, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Tamm M, Stolz D, Schumann D, Karsdal MA, Papakonstantinou E, Bülow Sand JM, Leeming DJ, Milenkovic B
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio...
September 10, 2018
Journal:
Biochem Biophys Res Commun
Author:
Gudmann NS, Manon-Jensen T, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ, Bülow Sand JM
BACKGROUND: Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exac...
May 4, 2018
Journal:
Respir Res
Author:
Tanino Y, Karsdal MA, Nikaido T, Misa K, Sato Y, Togawa R, Wang X, Leeming DJ, Munakata M, Bülow Sand JM
Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi...
March 1, 2018
Journal:
Assay Drug Dev Technol
Author:
Lamy P, Juhl P, Siebuhr AS, Iversen LV, Nawrocki A, Larsen MR, Domsic RT, Franchimont N, Karsdal MA, Leeming DJ, Chavez JC, Bülow Sand JM
BACKGROUND: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. METHODS: One thousand COPD subjects from the observational,...
December 4, 2017
Journal:
BMC Pulm Med.
Author:
Leeming DJ, Byrjalsen I, Bihlet AR, Lange P, Miller BE, Karsdal MA, Vestbo J, Thal-Singer R, Bülow Sand JM
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or...
July 21, 2017
Journal:
Adv Drug Deliv Rev
Author:
Karsdal MA, Nielsen SH, Leeming DJ, Langholm LL, Nielsen MJ, Manon-Jensen T, Siebuhr AS, Gudmann NS, Rønnow S, Daniels SJ, Mortensen JH, Schuppan D, Bülow Sand JM
Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elast...
January 19, 2017
Journal:
Respir Res.
Author:
Bihlet AR, Karsdal MA, Leeming DJ, Roberts M, Bowler R, White WI, Bülow Sand JM
A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore...
BACKGROUND: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortalit...
October 4, 2016
Journal:
Respir Res.
Author:
Leeming DJ, Byrjalsen I, Bihlet AR, Lange P, Miller BE, Karsdal MA, Vestbo J, Thal-Singer R, Bülow Sand JM
OBJECTIVES: hronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been a...
September 7, 2016
Journal:
Clin Biochem
Author:
Lange P, Leeming DJ, Karsdal MA, Midjord AK, Martinez G, Bülow Sand JM
BACKGROUND: Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD. METHODS: I...
August 26, 2016
Journal:
Chest
Author:
Leeming DJ, Karsdal MA, Stolz D, Kristensen JH, Boersma W, Louis R, Milenkovic B, Kostikas K, Blasi F, Aerts J, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Papakonstantinou E, Tamm M, Bülow Sand JM, Rothe M
OBJECTIVES: Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...
August 1, 2016
Journal:
Clin Biochem
Author:
Hansen NU, Willumsen N, Larsen L, Karsdal MA, Leeming DJ, Bülow Sand JM
Objectives: Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the ...
July 9, 2015
Journal:
Clin Biochem
Author:
Kristensen JH, Larsen L, Dasgupta B, Brodmerkel C, Curran M, Karsdal MA, Willumsen N, Knox AJ, Bolton CE, Johnson SR, Hägglund P, Svensson B, Leeming DJ, Bülow Sand JM
Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development o...
July 1, 2015
Journal:
Chest
Author:
Bihlet AR, Karsdal MA, Bay-Jensen AC, Read S, Kristensen JH, Leeming DJ, Andersen JR, Lange P, Vestbo J, Bülow Sand JM
Background: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progressi...
June 11, 2015
Journal:
Respir Res.
Author:
Knox AJ, Lange P, Sun S, Kristensen JH, Leeming DJ, Karsdal MA, Bolton CE, Johnson SR, Bülow Sand JM
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential...
May 15, 2015
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Karsdal MA, Manon-Jensen T, Genovese F, Kristensen JH, Nielsen MJ, Brandt-Hansen NU, Bay-Jensen AC, Bager CL, Krag A, Krarup H, Leeming DJ, Schuppan D, Blanchard AD, Bülow Sand JM
Background: During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for ant...
May 3, 2015
Journal:
BMC Pulm Med.
Author:
Kristensen JH, Karsdal MA, Willumsen N, Diefenbach C, Svensson B, Hägglund P, Leeming DJ, Bülow Sand JM
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