Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was ass...
July 12, 2019
Journal:
Respir Res.
Author:
Orlan LA, Duggan AR, Oballa E, Taggart SC, Simpson JK, Kangombe AR, Braybrooke R, Molyneaux PL, North B, Karkera Y, Leeming DJ, Karsdal MA, Nanthakumar CB, Fahy WA, Marshall RP, Jenkins RG, Maher TM
OBJECTIVES: Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which h...
February 12, 2019
Journal:
Transl Oncol
Author:
Holm Nielsen S, Willumsen N, Leeming DJ, Daniels SJ, brix s, Karsdal MA, Genovese F, Nielsen MJ
Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluatio...
January 2, 2019
Journal:
Nature Communications
Author:
Woodcock HV, Eley JD, Platé M, Manthakumar CB, Martufi M, Peace S, Joberty G, Poeckel D, Good RB, Taylor AR, Zinn N, Redding M, Forty EJ, Hynds RE, Santon C, Karsdal MA, Maher TM, Bergamini G, Marshall RP, Blanchard AD, Mercer PF, Chambers RC
Background: Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue ho...
August 9, 2017
Journal:
BMC Pulm Med.
Author:
Karsdal MA, Leeming DJ, Brix S, Curran M, Brodmerkel C, Dasgupta B, Willumsen N, Bager CL, Kehlet SN
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant ...
August 1, 2016
Journal:
Thorax
Author:
Mercer PF, Woodcock HV, Eley JD, Platé M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y2, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Arbit E, Marshall RP, Lukey PT, Chambers RC
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, Sand JM, Larsen L, Karsdal MA, Leeming DJ
Background: The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination of...
July 5, 2016
Journal:
Respir Res.
Author:
Hansen NU, Karsdal MA, Brockbank S, Cruwys S, Rønnow S, Christiansen C
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, Sand JM, Willumsen N, Knox AJ, Bolton CE, Johnson SR, Hägglund P, Svensson B, Leeming DJ
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, Sand JM, Willumsen N, Diefenbach C, Svensson B, Hägglund P, Oersnes-Leeming DJ
Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a...
October 3, 2014
Journal:
Cancer Med
Author:
Willumsen N, Bager CL, Leeming DJ, Smith V, Christiansen C, Karsdal MA, Dornan D, Bay-Jensen AC
Objectives: Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will rel...
December 13, 2013
Journal:
PLoS One
Author:
Sand JM, Larsen L, Hogaboam CM, Martinez F, Han M, Røssel Larsen M, Nawrocki A, Zheng Q, Karsdal MA, Leeming DJ
Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two diffe...
June 21, 2013
Journal:
PLoS One
Author:
Skjøt-Arkil H, Clausen RE, Rasmussen LM, Wang W, Wang Y, Zheng Q, Mickley H, Saabye L, Diederichsen ACP, Lambrechtsen J, Martinez FJ, Hogaboam CM, Han M, Larsen MR, Nawrocki A, Vainer B, Krustrup D, Bjørling-Poulsen M, Karsdal MA, Leeming DJ
The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance...
November 8, 1983
Journal:
Cancer biology therapy
Author:
Kehlet SN, Manon-Jensen T, Sun S, Brix S, Karsdal MA, Leeming DJ, Willumsen N
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 8, 1983
Journal:
Biochem Biophys Rep
Author:
Leeming DJ, Willumsen N, Sand JM, Holm Nielsen S, Dasgupta B, Brodmerkel C, Bager CL, Karsdal MA
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant ...
November 8, 1983
Journal:
Thorax
Author:
Mercer PF, Woodcock HV, Eley JD, Platé M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y2, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Arbit E, Marshall RP, Lukey PT, Chambers RC
OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums...
November 8, 1983
Journal:
Transl Oncol
Author:
Nielsen SH, Willumsen N, Brix S, Sun S, Manon-Jensen T, Karsdal MA, Genovese F
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...
November 8, 1983
Journal:
Clin Biochem
Author:
Hansen NU, Willumsen N, Sand JM, Larsen L, Karsdal MA, Leeming DJ
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