I am a Research Fellow working on the biological mechanisms of genetic disease, with the goal of developing novel therapies. In my Kidney Research UK funded Training Fellowship I elucidated the pathophysiology of the devastating congenital bladder disease urofacial syndrome, and began to unravel the function of the implicated genes HPSE2 and LRIG2. My lab now runs preclinical trials of viral vector mediated gene therapy in mutant mouse models, with the eventual goal of translation to the clinic.

I studied for my undergraduate degree at The University of Edinburgh, which I completed in 2005, then moved to The University of Leeds to study for an MSc in Human Genetic. For my PhD at The University of Manchester I investigated the genetic basis of human pancreas development, focusing on the role of the transcription factor SOX9 in the specification of insulin producing cells. As a postdocoral researcher I continued to study genes that cause rare diseases when mutated. I am currently working on Urofacial Syndrome, an autosomal recessive disease that affects bladder function and facial expression. My work, published in Human Molecular Genetics (Roberts et al 2014) and in the Journal of the American Society of Nephrology (Stuart et al 2015), respectively, contained the first descriptions of hpse2 morphant Xenopus embryos and Hpse2 mutant mice. In 2016, I obtained a Kidney Research UK Postdoctoral Research Training Fellowship. I used this Fellowship to provide the first direct evidence that urofacial syndrome features a peripheral neuropathy, describing neuronal patterning and neuro-functional defects in mutant mouse models (Kidney International and Neurourology and Urodynamics). To establish the feasibility of gene therapy for this congenital disease, I obtained a Kidney Research UK project grant and forged a new collaboration with Prof. Simon Waddington, a world-renowned expert in neonatal gene therapy, from whom  I received training in neonatal gene delivery. My promising preliminary data demonstrated the feasibility of reporter gene delivery into baby mouse pelvic ganglia. With Prof. Adrian Woolf (UoM) we have obtained MRC funding for preclinical trials of the technology in mutant mouse models. I have established the technical platform to delivery therpeutic transgenes in vivo, and we successfuly delivered genes to autonomic nerves using the AAV vector. This paves the way to therapeutic gene delivery to treat disease models.

I am interested in rare inherited human diseases and believe that by investigating the genetic causes of these diseases we will gain insights into novel developmental and disease processes. My primary focus is understanding the pathological mechanisms that underlie early-onset bladder disease. To this end I use a battery of molecular, physiological and imaging techqniues in disease models. I developed whole-bladder tissue imaging to analyse muscle and nerve patterning, and this revealed how the bladder is innervated in unprecedented detail. Furthermore, I have established a unique myograph-based system to analyse neurogenic and myogenic bladder function.  We used this system to understand the tissue basis of the devastating bladder disease urofacial syndrome, and the technique also serves as a highly sensitive readout of pathogenic amelioration in treated animals. I am interested more broadly in genetic diseases and closely collaborate with experts in Genomic Medicine to study a wide range of rare diseases.

Affiliated researchers:

Professor Adrian Woolf

Professor Sid Banka

Professor William Newman

Profesor Alison Gurney

Dr Natalie Gardiner

External collaborators:

Professor Karen McCloskey (Queen's University, Belfast)

Professor Ilan Neta (Technion Institute, Israel)

Professor Hakan Hedman (Umeå University, Sweden)

Bladder myograph physiology

Whole tissue fluorescent imaging

Antibody based techniques: western blotting, immunohistochemstry and immunofluorscence on sectioned tissue and whole tissue samples.

Molecular biology: RNASeq and qPCR, vector cloning, transfections and protein overexpression.

Xenopus tropicalis microinjection and morpholino transcript knock down.

Heparanase in vitro assays.

In vitro proteome signalling arrays.

BSc in Genetics from the University of Edinburgh

MSc in Human Genetics from the University of Leeds

PhD from the University of Manchester.