Daniel Brayson

University College London | UCL · Institute of Child Health

The lamin A precursor, prelamin A, requires extensive processing to yield mature lamin A and effect its primary function as a structural filament of the nucleoskeleton. When processing is perturbed, nuclear accumulation of prelamin A is toxic and causes laminopathic diseases such as Hutchinson–Gilford progeria syndrome and cardiomyopathy. However,...

The thermoneutral zone (TNZ) defines the range of ambient temperatures at which resting metabolic rate (MR) is at a minimum. While the TNZ lower limit has been characterized, it is still unclear whether there is an upper limit, that is, beyond which MR during rest increases, and if so, what physiological upregulations explain this. We take the firs...

ΔR4-R23/ΔCT micro-dystrophin (μDys) is a miniaturized version of dystrophin currently evaluated in a Duchenne muscular dystrophy (DMD) gene therapy trial to treat skeletal and cardiac muscle disease. In pre-clinical studies, μDys efficiently rescues cardiac histopathology, but only partially normalizes cardiac function. To gain insights into factor...

Cardiomyopathies are progressive diseases of heart muscle often caused by mutations in genes encoding sarcomeric, cytoskeletal and nucleoskeletal proteins though in many cases the cause of disease is not identified. Whilst nucleus hypertrophy has been described, it is not known whether nucleus shape changes are a general feature of cardiomyopathy....

Background Patients with repair of tetralogy of Fallot (rToF) who are approaching adulthood often exhibit pulmonary valve regurgitation, leading to right ventricle (RV) dilatation and dysfunction. The regurgitation can be corrected by pulmonary valve replacement (PVR), but the optimal surgical timing remains under debate, mainly because of the poor...

Regulation of the genome is viewed through the prism of gene expression, DNA replication and DNA repair as controlled through transcription, chromatin compartmentalisation and recruitment of repair factors by enzymes such as DNA polymerases, ligases, acetylases, methylases and cyclin-dependent kinases. However, recent advances in the field of muscl...

Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues yet its impact u...

New findings: What is the main observation in this case? Ultra-endurance cycle racing is known to lead to suppressed heart rates as a product of time spent racing. This case report identifies a racer who experienced this phenomenon initially, but then uniquely experienced an overall increase in heart rate late in the race. What insight does it rev...

Cardiomyopathies are heart muscle diseases in which the causes are complex and for which, the treatment strategies often insufficient. Mutations in the LMNA gene, encoding lamins A/C are known to cause severe dilated cardiomyopathy but it is not known how the lamin A precursor, prelamin A might contribute to this. Additionally, prelamin A may be im...

In this issue, Wang et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708137) show that disruption to different mechanical domains of muscle cells converge at the linker of nucleoskeleton to cytoskeleton complex to affect DNA endoreplication potentially via barrier to autointegration factor–mediated epigenetic mechanisms.

The nuclear lamina is a critical structural domain for the maintenance of genomic stability and whole-cell mechanics. Mutations in the LMNA gene, which encodes nuclear A-type lamins lead to the disruption of these key cellular functions, resulting in a number of devastating diseases known as laminopathies. Cardiomyopathy is a common laminopathy and...

Proceedings of The Physiological Society Heart & Cardiac Muscle Abstracts Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB087 Poster Communications Transcriptomic and histological analysis of right ventricular myocardium in patients with tetralogy of Fallot repair undergoing pulmonary valve replacement D. Brayson1, S. Holohan1, M...

Introduction Mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamins A and C, lead to a number of premature ageing syndromes, including Hutchinson Gilford Progeria syndrome (HGPS) and Emery Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM). Some causal mutations disrupt lamin A processing...

The nuclear envelope (NE) is a double membrane bilayer, which serves to compartmentalise the nuclear environment from the cytoplasm and regulate the movement of molecules in and out of the nucleus. Another important role of the NE is to physically mediate communication between the nuclear and cytoplasmic domains, which is facilitated by the linker...

Ageing is a potent risk factor for cardiovascular (CV) disease. Mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamins A & C, lead to a number of premature ageing syndromes, e.g. Emery Dreifuss muscular dystrophy (EDMD), which can lead to dilated cardiomyopathy (DCM) and heart failure. Some of these mutations af...

Rnd proteins are atypical Rho family proteins that do not hydrolyse GTP and are instead regulated by expression levels and post-translational modifications. Rnd1 and Rnd3/RhoE induce loss of actin stress fibres and cell rounding in multiple cell types, whereas responses to Rnd2 are more variable. Here we report the responses of endothelial cells to...