Dr Catherine Boulter
My lab is interested in the role of stem/progenitor cells in mammalian organ development, homeostasis, regeneration and disease. The main focus of the lab is on NOV (CCN3) which we and others have identified as a key regulator of stem/progenitor cells. NOV encodes a multi-domain secreted protein which is associated with the extracellular matrix and acts to mediate and modulate the cell’s response to signaling molecules in the extracellular environment. NOV is a member of a family of proteins, the CCN family, which modulates the activities of extracellular signaling molecules and thereby profoundly influences the behaviour of cells in development, wound healing, tissue homeostasis and in a range of diseases including fibrosis and cancer. We are investigating the role of NOV in regulating stem/progenitor cell proliferation, survival and differentiation in mesodermal and embryonic stem cells in cell culture and in organ development and homeostasis using transgenic and knockout technologies. The aim of our work is to understand how NOV regulates stem/progenitor cell behaviour and the mechanisms by which defects in NOV function lead to disease. As developmental mechanisms involving stem and progenitor cells also underpin organ regeneration and repair, our work also has relevance for greater understanding of these processes.
Loss of NOV in primary embryonic fibroblasts (PEFs) from Novdel3 -/- embryos promotes differentiation down the osteogenic lineage, shown by staining with the osteoblast marker, alkaline phosphatase. A,B: PEFs from Novdel3 -/- embryos; C,D PEFs from wild type (+/+) embryos, viewed with (A,C) and without phase contrast (B,D).
Our work on NOV came out of a long-standing interest of my lab in the developmental basis of kidney disease, which focused on the childhood kidney tumour Wilms’ tumour (or nephroblastoma), as well as on Autosomal Dominant Polycystic Kidney Disease (ADPKD). Deregulated expression of NOV is implicated in the formation of nephroblastomas which are characterized by the abnormal proliferation and differentiation of kidney stem (blastemal cells); it is also deregulated in a variety of other tumour types, including musculoskeletal tumours, suggesting a more general involvement in tumourigenesis. We described Nov’s in situ expression pattern which is consistent with it having roles in development of several tissues, including those of the cardiovascular, musculoskeletal and nervous systems. Recently we have generated the first Nov knockouts (Novdel3) which reveal important roles for NOV in development and tissue homeostasis.
Prof. Tariq Enver and Dr Rajeev Gupta, Institute of Molecular Medicine, University of Oxford
Prof. Stewart Fleming, Department of Pathology and Neuroscience, University of Dundee
Prof. Charlie Archer, School of Biosciences, Cardiff University
Prof. Vic Duance, School of Biosciences, Cardiff University