Background: Pancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specific...
September 18, 2020
Journal:
BMC Cancer
Author:
Willumsen N, Bager CL, Leeming DJ, Smith V, Karsdal MA, Dornan D, Bay-Jensen AC
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv...
April 9, 2020
Journal:
Liver Int
Author:
Karsdal MA, Daniels SJ, Nielsen SH, Bager CL, Rasmussen DGK, Loomba R, Surabattula R, Villesen IF, Luo Y, Shevell D, Gudmann NS, Nielsen MJ, George J, Christian R, Leeming DJ, Schuppan D
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring...
April 3, 2020
Journal:
Sci Rep
Author:
Nielsen SH, Mortensen JH, Willumsen N, guldager Kring Rasmussen D, Mogensen DJ, Di Sabatino A, Mazza G, Jørgensen LN, giuffrida P, Pinzani M, Klinge LG, Kjeldsen J, Leeming DJ, Karsdal MA, Genovese F
An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify ...
December 28, 2019
Journal:
Cells
Author:
Mazza G, Telese A, Al-Akkad W, Frenguelli L, Levi A, Marrali M, Longato L, Thanapirom K, Vilia MG, Lombardi B, Crowley C, Crawford M, Karsdal MA, Leeming DJ, Marrone G, Bottcher K, Robinson B, Del Rio Hernandez A, Tamburrino D, Spoletini G, Malago M, Hall AR, Godovac-Zimmermann J, Luong TV, De Coppi P, Pinzani M, Rombouts K
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, Ronnow SR, Karsdal MA, Tal-Singer R, Vestbo J, Leeming DJ, Miller BE, bülow Sand JM
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups...
October 25, 2019
Journal:
Nat Med
Author:
Moroni F, Dwyer BJ, Graham C, Pass C, Bailey L, Ritchie L, Mitchell D, Glover A, Lauire A, Doig S, Hargreaves E, Fraser AR, Turner ML, Cambpell JDM, McGowan NWA, Barry J, Moore JK, Hayes PC, Leeming DJ, Nielsen MJ, Musa K, Fallowfield JA, Forbes SJ
Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were...
October 16, 2019
Journal:
Sci Rep
Author:
Nielsen MJ, Villesen IF, Gudmann NS, Leeming DJ, Krag A, Karsdal MA, Zimmermann T, Schuppan D
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:
Schuppan D, Leeming DJ, papakonstantinou E, Kostikas K, Boersma W, Louis R, Milenkovik B, Aerts J, Sand JM, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Tamm M, Karsdal M, Stolz D
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, Sand JMB, Diefenbach C, Sun S, Danielsen A, Karsdal MA, Leeming DJ
BACKGROUND AND AIMS: Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sys...
September 5, 2018
Journal:
PLoS One
Author:
kimer N, Gudmann NS, Pedersen JS, Møller S, Nielsen MJ, Leeming DJ, Karsdal MA, Møller HJ, Bedtsen F, Grønbæk H
BACKGROUND AND AIMS: Macrophages play a significant role in chronic liver disease as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and associated with liver disease severity and prognosis. Extracellular matrix remodelling associated with fibrogenesis may be affected by sys...
September 5, 2018
Journal:
PLoS One
Author:
kimer N, Gudmann NS, Pedersen JS, Møller S, Nielsen MJ, Leeming DJ, Karsdal MA, Møller HJ, Bendtsen F, Grønbæk H
BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with ...
September 3, 2018
Journal:
Aliment Pharmacol Ther
Author:
El Sharkawy R, Thabet K, Lampertico P, Petta S, Mangia A, Berg T, Netwally M, Bayoumi A, Boonstra A, Brouwer WP, Smedile A, Abate ML, Loglio A, Douglas MW, Khan A, Santoro R, Fischer J, Leeming DJ, Liddle C, George J, Eslam M
OBJECTIVE: There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be incl...
August 30, 2018
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Karsdal MA, Hjuler ST, Luo Y, Rasmussen DG, Nielsen MJ, Nielsen SH, Leeming DJ, Goodman ZD, Arch RH, Patel K, Schuppan D
OBJECTIVE: There is a need for non-invasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to anti-fibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be incl...
August 30, 2018
Journal:
Am J Physiol Gastrointest Liver Physiol.
Author:
Karsdal MA, Hjuler ST, Luo Y, Rasmussen DG, Nielsen MJ, Holm Nielsen S, Leeming DJ, goodman Z, Arch RH, Patel K, Schuppan D
OBJECTIVE: Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix (ECM) proteins in the arterial wall. Collagen type I (COL1), a component of the arterial ECM, is cleaved by matrix metalloproteinases (MMPs) and known to be remodelled in atherosclerosis. We explore...
August 28, 2018
Journal:
J Intern Med
Author:
Holm Nielsen S, Tengryd C, Edsfeldt A, Genovese F, Bengtsson E, Karsdal MA, Leeming DJ, Nilsson J, Goncalves I
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...
August 1, 2018
Journal:
Cancer biology therapy
Author:
Kehlet SN, Manon-Jensen T, Sun S, Brix S, Karsdal MA, Leeming DJ, Willumsen N
Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have bioma...
July 20, 2018
Journal:
Cancer Med
Author:
Jensen C, Nielsen SH, Mortensen JH, Kjeldsen J, Klinge LG, Harling H, Jørgensen LN, Karsdal MA, Willumsen N, Leeming DJ
BACKGROUND AND AIM: Given the high global prevalence of non-alcoholic fatty liver disease (NAFLD), the need for relevant non-invasive biomarkers and algorithms to accurately stage disease severity is a critical unmet medical need. Identifying those with advanced fibrosis (≥F3) is the most crucial, a...
July 16, 2018
Journal:
Hepagology
Author:
Daniels SJ, Leeming DJ, Eslam M, Hashem AM, Nielsen MJ, Krag A, Karsdal MA, Grove JI, Guha IN, Kawaguchi T, Torimura T, McLeod D, Akiba J, Kaye P, de Boer B, Aithal GP, Adams LA, George J
BACKGROUND: Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an individual level are currently not established. AIM: To evaluate the prognostic utility of four biomarkers of bas...
July 16, 2018
Journal:
Alimentary pharmacology therapeutics
Author:
Nielsen MJ, Thorburn D, Leeming DJ, Hov JR, Nygård S, Moum B, Saffioti F, Gilja OH, Boberg KM, Mazza G, Røsjø H, Pinzani M, Karlsen TH, Karsdal MA, Vesterhus M
Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two i...
June 20, 2018
Journal:
Int j.cancer, International journal of cancer
Author:
Lipton A, Leitzel K, Polimera HV, Ali SM, Naggabhairu V, Marks E, Richardson AE, Krecko L, Ali A, Koestler W, Esteva FJ, Leeming DJ, Karsdal MA, Willumsen N
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:
Sand JMB, Tanino Y, Karsdal MA, Nikaido T, Misa K, Sato Y, Togawa R, Wang X, Leeming DJ, Munakata M
There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collag...
April 25, 2018
Journal:
Clin Biochem
Author:
Bay-Jensen AC, Kjelgaard-Petersen CF, Petersen KK, Arendt-Nielsen L, Quasnichka HL, Mobasheri A, Karsdal MA, Leeming DJ
Protein cross-links are formed in regulated biochemical processes in many biological systems, but they are also generated inadvertently via the reactions of exogenous or endogenous oxidants. Site-specific identification and characterization of such cross-links is challenging and the goal was therefo...
April 13, 2018
Journal:
J Proteome Res
Author:
Mariotti M, Leinisch F, Leeming DJ, Svensson B, Davies MJ, Hägglund P
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:
Sand JMB, Lamy P, Juhl P, Siebuhr AS, Iversen LV, Nawrocki A, Larsen MR, Domsic RT, Franchimont N, Chavez J, Karsdal MA, Leeming DJ
Patients with end-stage liver disease develop acute decompensation (AD) episodes, which become more frequent and might develop into acute-on-chronic liver failure (ACLF). However, it remains unknown how AD induces acceleration of liver disease. We hypothesized that remodeling of collagen type III pl...
January 18, 2018
Journal:
Hepatol Commun
Author:
Praktiknjo M, Lehmann J, Nielsen MJ, Schierwagen R, Uschner FE, Meyer C, Thomas D, Strassburg CP, Bendtsen F, Møller S, Krag A, Karsdal MA, Leeming DJ, Trebicka J
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, Sand JMB, Bihlet AR, Lange P, Thal-Singer R, Miller BE, Karsdal MA, Vestbo J
OBJECTIVE:Detecting significant fibrosis and cirrhosis remains important in treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The aim of this study was to assess the ability of PRO-C3 to identify significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) both as...
October 25, 2017
Journal:
Scand J Gastroenterol
Author:
Hansen JF, Juul Nielsen M, Nyström K, Leeming DJ, Lagging M, Norkrans G, Brehm Christensen P, Karsdal MA
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
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, Sand JM, Daniels SJ, Mortensen JH, Schuppan D
Matrix metalloprotease (MMP)-mediated tissue remodeling is one of the malignant changes driving colorectal cancer. Measurement of altered MMP expression/activity is not sufficient to fully understand the effect of MMP-mediated tissue remodeling. Biomarkers are required that specifically reflect the ...
May 13, 2017
Journal:
Oncol Lett
Author:
Willumsen N, Bager CL, Bay-Jensen AC, Kehlet SN, Harling H, Leeming DJ, Karsdal MA, Jorgensen LN
Search and find publications that we have published.
Please don't hesitate to contact us if you have any questions or other inquiries.
We use cookies on our site to enable essential services and functionalities, and collect data in regards to visitor information. This is done in order to provide the best possible experience for the visitor. Cookie policy Privacy statement
