Prof Andrew Copp
Glaxo-Wellcome Professor of Developmental Neurobiology
ICH Development Bio & Cancer Prog
UCL GOS Institute of Child Health
- Joined UCL
- 1st Oct 1992
My research is concerned with the embryonic mechanisms underlying central nervous system development and congenital disorders. The laboratory is known internationally for its expertise in animal models of birth defects, particularly neural tube defects (e.g. spina bifida). It is the first lab in the world to take a potential new therapy for a birth defect, worked out in mouse models (i.e. inositol for prevention of folic acid-resistant neural tube defects), and to apply it to human pregnancy through a pilot clinical trial, the PONTI study (Br J Nutr, 2016, 115, 974-83). A positive outcome of a full-scale trial would be the first innovation in primary prevention of a significant human birth defect since the research on folic acid in the late 1980s. My research team is supported by funding from the Wellcome Trust, Medical Research Council, SPARKS (Sport Aiding Medical Research in Kids), Newlife Foundation for Disabled Children and the Bo Hjelt Spina Bifida Foundation.
Significant research landmarks have included:
(i) Identification of inositol as an adjunct to folic acid for preventing spina bifida in the mouse (Nature Medicine, 1997; Human Molecular Genetics, 2004) with translation of these findings into a recent pilot clinical trial (Br J Nutr, 2016);
(ii) Identification of a mouse model of folic acid-preventable neural tube defects (Science, 1998), and the finding of an inborn error of folate metabolism in human fetuses with neural tube defects (Brain, 2007). We have gone on to identify missense mutations in mitochondrial folate metabolic genes in patients with neural tube defects (Human Molecular Genetics, 2012) and demonstrated prevention of such defects in a mouse model using formate therapy (Nat Comms 2015);
(iii) Elucidation of genetic and developmental mechanisms, including key roles for sonic hedgehog and BMP signalling, in the regulation of neural tube closure (Development, 2002, 2007), identification of mechanisms of neuroepithelial bending and the role of the actin cytoskeleton (Developmental Biology, 2015; Journal of Cell Science, 2015) and demonstration that neural fold fusion requires Rac1-dependent cell protrusions (eLife, 2016);
(iv) Demonstration that the planar cell polarity (PCP) pathway is crucial for the initiation of neural tube closure. In its absence a range of neural tube defects result (Human Molecular Genetics, 2001,2003; Current Biology, 2003; Development, 2013; Disease Models & Mechanisms, 2014). We identified PCP mutations in a series of human fetuses with severe NTDs (Human Mutation, 2013) and found a key role for PCP signalling in bone development (Journal of Bone & Mineral Research, 2015);
(v) Resolution of a controversy over the role of programmed cell death (apoptosis) in neural tube closure, which the Copp laboratory recently showed to be non-essential (Proceedings of the National Academy of Sciences USA, 2009).
(vi) Publication of a series of highly cited review articles on the development of the neural tube and NTDs (Progress in Neurobiology, 1990; Nature Reviews Genetics, 2003; Lancet Neurology, 2013; Annual Reviews of Neuroscience, 2014; Nature Reviews Disease Primers, 2015).
Research student supervision at PhD level, together with supervision of laboratory and library projects for MSc and BSc students at UCL and beyond. Co-organiser of the Wellcome Trust 4 year PhD programme in Stem Cell & Developmental Biology. Supervisor on Wellcome Trust 4-year PhD programme in Neuroscience.
Lectures on normal and abnormal development of the CNS, with specific reference to neural tube defects in:
(i) MSc in Organogenesis & Fetal Development;
(ii) MBBS, 2nd year course in Neuroscience & Behaviour;
(iii) BSc in Biomedical Sciences (ANAT1003).
- University of London
- MBBS, Medicine/Surgery | 1983
- University of Oxford
- BM, Pre-clinical Medicine | 1979
- University of Oxford
- DPhil, Experimental Embryology | 1978
- University of Oxford
- BA Hons, Zoology | 1975
I began my career as a scientist with a BA in Zoology and a DPhil
in experimental embryology from Oxford University. I saw how my scientific training could
be clinically relevant to healthcare, but I needed to gain a deeper
understanding of health problems. Hence, after my DPhil, I applied for medical
training at Guy’s Hospital, London. At this time, my plans could be summarised
“The challenge of birth defects had been largely approached from a clinical perspective. We know little of the processes in the embryo and fetus that cause disabling childhood disorders. My aim is to use the embryology knowledge I have gained, together with clinical training, to make inroads into the questions of pathogenesis and prevention of congenital malformations”.
Throughout my clinical course, I moonlighted in research within the Paediatric Research Unit at Guy’s Hospital. I began working on a mouse model of spina bifida, which I am still studying today! I found the period of medical training both varied and stimulating, as I moved seamlessly between learning how to manage patients on the ward and studying mouse embryos that failed to close their neural tube in the lab.
After graduating in medicine, I completed my house officer jobs at Guy’s and Newcross Hospitals, and then returned to full-time academic research. I went to the Department of Pediatrics at Stanford University, USA where I gained valuable postdoctoral experience. Then, I returned to UK and ran a small team at the Imperial Cancer Research Fund’s Developmental Biology Unit, University of Oxford. I moved to the Institute of Child Health in 1992, initially as Senior Lecturer and from 1996 as Professor of Developmental Neurobiology. I became Institute Director in 2003 and stepped down from this role in September 2012.
My latest enthusiasm is heading our new Birth Defects Research Centre, which opened in 2012 at the Institute of Child Health. This Centre is the first of its kind in Europe, and provides a focus, and critical research mass, for scientists and clinicians studying the causes and developmental mechanisms underlying congenital disorders in children. As part of this effort, my own team is working to understand the genetic basis of spina bifida, to unravel the events in the embryo that underlie this disorder, and to pursue new therapies that may enter clinical practice in the coming years.