A5089946710- Renal and related cancers
- Renal cell carcinoma treatment
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Genetic and Kidney Cyst Diseases
- RNA Interference and Gene Delivery
- Tissue Engineering and Regenerative Medicine
- BRCA gene mutations in cancer
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Birth, Development, and Health
- Congenital heart defects research
- Wnt/β-catenin signaling in development and cancer
- Animal Genetics and Reproduction
- Urological Disorders and Treatments
- Cancer-related gene regulation
- Childhood Cancer Survivors' Quality of Life
- Cancer Genomics and Diagnostics
- Immune Response and Inflammation
- CAR-T cell therapy research
Leiden University Medical Center
2001-2024
Roslin Institute
2013-2023
University of Edinburgh
2014-2023
Leiden University
2023
Western General Hospital
2007-2017
Medical Research Council
2004-2017
Institute of Genetics and Cancer
2004-2015
MRC Human Genetics Unit
2003-2014
Easterseals
2014
Biotechnology and Biological Sciences Research Council
2014
Abstract The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. mammalian Csf1r locus contains a highly conserved super-enhancer, fms -intronic regulatory element (FIRE). Here we show that genomic deletion FIRE in mice selectively impacts CSF1R expression tissue development specific tissues. Deletion ablates murine embryonic stem cells. ΔFIRE/ΔFIRE lack macrophages embryo, brain microglia...
Wt1 is a tumour suppressor gene, mutation of which cause Wilms' tumour, childhood renal nephroblastoma. expressed in rich pattern during development suggesting that it acts at three stages: determination the kidney area, differentiation nephrons and maturation glomeruli. Wt1−/− mice confirm essential for inception development; cells ought to form kidneys die by apoptosis instead. Specific human WT1 mutations defects glomerular (Denys–Drash Frasier syndromes), providing circumstantial...
The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA) results from low levels of survival motor neuron (SMN) protein; however, it is unclear how reduced SMN promotes SMA development. Here, we determined that ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse models SMA, observed widespread perturbations ubiquitin homeostasis, including ubiquitin-like modifier activating enzyme 1 (UBA1). physically interacted with UBA1 neurons, and...
Markers of cell cycle stage allow estimation dynamics in culture and during embryonic development. The Fucci system incorporates genetically encoded probes that highlight G1 S/G2/M phases the allowing live imaging. However available mouse models incorporate are beset by problems with transgene inactivation, varying expression level, lack conditional potential and/or need to maintain separate transgenes—there is no transgenic model solves all these problems. To address shortfalls we...
There is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for Wilms' tumour gene, Wt1, lack kidneys, gonads, spleen die at mid-gestation due defective coronary vasculature. Wt1 vital maintaining mesenchymal–epithelial balance these tissues required epithelial-to-mesenchyme transition (EMT) generates vascular progenitors. Although only expressed rare cell populations adults including...
The different segments of the nephron and glomerulus in kidney balance processes water homeostasis, solute recovery, blood filtration, metabolite excretion. When segment function is disrupted, a range pathological features are presented. Little known about patterning during embryogenesis. In this study, we demonstrate that early patterned by gradient β-catenin activity along axis tubule. By modifying activity, force cells within nephrons to differentiate according imposed level, thereby...
Abstract Synthetic biology provides an opportunity for the construction and exploration of alternative solutions to biological problems - different from those chosen by natural life. To this end, synthetic biologists have built new sensory systems, cellular memories genetic codes. There is a growing interest in applying approaches multicellular especially relation self-organization. Here we describe system that confers large-scale de novo patterning activity on 2-D 3-D populations mammalian...
Abstract The proliferation, differentiation, and survival of cells the mononuclear phagocyte system (MPS; progenitors, monocytes, macrophages, classical dendritic cells) are controlled by signals from M-CSF receptor (CSF1R). Cells MPS lineage have been identified using numerous surface markers transgenic reporters, but none is both universal restricted. In this article, we report development characterization a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with C...
Sex determination in mammals depends on the differentiation of supporting lineage gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although Y-linked testis-determining gene Sry has been identified, ovarian-determining factor remains unknown. In this study, we identified -KTS, a major, alternatively spliced isoform Wilms tumor suppressor WT1, as key determinant female sex determination. Loss -KTS variants blocked gonadal mice, whereas increased...
A number of Wnt genes are expressed during, and known to be essential for, early kidney development. It is typically assumed that their products will act through the canonical β-catenin signalling pathway. We have found evidence suggests not active in nephrogenic metanephric mesenchyme, but instead provide expressional functional implicates non-canonical Calcium/NFAT pathway nephrogenesis. Members NFAT (Nuclear Factor Activated T cells) transcription factor gene family throughout murine...
The renal vasculature is required for blood filtration, pressure regulation, and pH maintenance, as well other specialised kidney functions. Yet, despite its importance, many aspects of development are poorly understood. To provide a detailed spatiotemporal analysis vascularisation, we collected images embryonic mouse kidneys at various developmental time-points. Here describe the first stages vascularisation demonstrate that polygonal networks vessels (endothelial plexuses) form in cycles...
ABSTRACT Arterial calcification is an important hallmark of cardiovascular disease and shares many similarities with skeletal mineralization. The bone-specific protein osteocalcin (OCN) established marker vascular smooth muscle cell (VSMC) osteochondrogenic transdifferentiation a known regulator glucose metabolism. However, the role OCN in controlling arterial unclear. We hypothesized that regulates VSMCs sought to identify underpinning signaling pathways. Immunohistochemistry revealed...
The origins and functions of kidney macrophages in the adult have been explored, but their roles during development remain largely unknown. Here we characterise macrophage arrival, localisation, heterogeneity, organogenesis. Using genetic approaches to ablate macrophages, identify a role for nephron progenitor cell clearance as mouse begins. Throughout renal organogenesis, most are perivascular express F4/80 CD206. These enriched mRNAs linked developmental processes, such blood vessel...