Publications

Abstract OBJECTIVES Menopause is often characterized by detrimental metabolic changes, such as obesity, insulin resistance, and impaired glucose tolerance, often requiring treatment. KeyBioscience Peptides (KBPs) are Dual Amylin and Calcitonin Receptor Agonists which have shown promising metabolic effects in rats. The objective of this study was to investigate the in vivo effect of KBP on […]

Abstract Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic […]

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 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 […]

Abstract INTRODUCTION Hepatic fibrosis is the excessive synthesis and deposition of extracellular matrix including collagen in the tissue. Chronic liver insult leads to progressive parenchymal damage, portal hypertension, and cirrhosis. Determination of hepatic collagen by invasive liver biopsy is the gold standard to estimate severity and stage of fibrosis. However, this procedure is associated with […]

Abstract Osteoarthritis (OA) is associated with cartilage breakdown, brought about by ADAMTS-5 mediated aggrecan degradation followed by MMP-derived aggrecan and type II collagen degradation. We investigated a novel anti-ADAMTS-5 inhibiting Nanobody (M6495) on cartilage turnover ex vivo. Bovine cartilage (BEX, = 4), human osteoarthritic – (HEX, = 8) and healthy-cartilage (hHEX, = 1) explants and […]

Abstract Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients. Prolargin-an extracellular matrix (ECM) protein present in cartilage and tendon-has been previously shown elevated in serum of patients with psoriasis. ECM protein fragments can reflect tissue turnover and pathological changes; thus, this study aimed to develop, validate […]

Abstract Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent the additional benefits reside in their higher potency […]

Abstract Non-alcoholic steatohepatitis (NASH) is characterized by lipotoxicity, inflammation and fibrosis, ultimately leading to end-stage liver disease. The molecular mechanisms promoting NASH are poorly understood, and treatment options are limited. Here, we demonstrate that hepatic expression of bone morphogenetic protein 8B (BMP8B), a member of the transforming growth factor beta (TGFβ)-BMP superfamily, increases proportionally to […]

Abstract BACKGROUND Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. METHODS IMO iPSCs were generated from a patient carrying a homozygous c.11279G>A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing […]