Publications

Abstract BACKGROUND Tissue released blood-based biomarkers can provide insight into drug mode of action and response. To understand the changes in extracellular matrix turnover, we analyzed biomarkers associated with joint tissue turnover from a phase 3, randomized, placebo-controlled study of baricitinib in patients with active rheumatoid arthritis (RA). METHODS Serum biomarkers associated with synovial inflammation […]

Abstract The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO […]

Abstract OBJECTIVE Dysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase-degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulation, we have performed a genome-wide screening of the genetic factors related […]

Abstract BACKGROUND Immune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) receptor induce a response in only a subgroup of patients with metastatic melanoma. Previous research suggests that transforming growth factor beta signaling and a collagen-rich peritumoral stroma (tumor fibrosis), may negatively interfere with the interaction between T cells and tumor cells […]

Abstract PURPOSE Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State-of-the-art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was undertaken to evaluate the potential for detecting the earliest alterations in fibrogenesis using a […]

Abstract BACKGROUND Over half of children with rare genetic diseases remain undiagnosed despite maximal clinical evaluation and DNA-based genetic testing. As part of an Undiagnosed Diseases Program applying transcriptome (RNA) sequencing to identify the causes of these unsolved cases, we studied a child with severe infantile osteopetrosis leading to cranial nerve palsies, bone deformities, and […]

Abstract A T-cell permissive tumor microenvironment, characterized by the presence of activated T cells and low fibrotic activity is crucial for response to immune checkpoint inhibitors (ICIs). Granzyme B has been shown to promote T-cell migration through the basement membrane by the degradation of type IV collagen. In this study, we evaluated the biomarker potential […]

Abstract The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between […]

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Abstract INTRODUCTION Anti-tumor necrosis factor (TNF) therapy is effective in inducing remission in Crohn’s disease in 60% of patients. No serological biomarkers are available, which can predict response to anti-TNF. We aimed to investigate serological markers of collagen turnover reflecting tissue inflammation as predictors of response to anti-TNF. METHODS In 2 retrospective observational cohorts, markers […]