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).