University College Cork

My research area of interest is using gene editing tools to model and study genetic diseases and to find potential new treatments. My PhD and first post-doc focussed on how to correct cystic fibrosis (CF)-causing mutations using gene editing tools such as zinc finger nucleases, TALENS and the CRISPR/Cas9 system. I was part of the team that developed the world’s first successful gene editing experiment to correct the most common CF-causing mutation, deltaF508 (Lee et al., 2012). 

Cystinosis - bench to bedside 

I emigrated to New Zealand in 2014 and joined Prof Alan Davidson’s lab, to use my skills in gene editing to model cystinosis in induced pluripotent stem cells (iPSCs). Cystinosis is a lysosomal storage disease that is caused by defective cystinosin transporter activity leading to an accumulation of cystine in every cell of the body. The kidney is particularly affected with kidney proximal tubule dysfunction followed by end stage renal disease. My driving goal was to find alternative treatments for this incurable disease. In the first three years working as a postdoc, I developed these techniques and was part of the team that developed a simple, affordable method to differentiate these stem cells into kidney tissue or organoids (Przepiorski et al., 2018). Using fluorescent cell-based assays, I discovered that a basic biochemical pathway, autophagy, is dysfunctional in these cells and organoids and went on to specifically target this pathway with FDA approved drugs and found that a combination treatment of mTOR inhibition and cysteamine could successfully rescue the disease phenotype in these cell models (Hollywood et al., 2020).
I focussed on developing a longer-term strategy to get this treatment to patients and realised that there was pressing need for a good in vivo model of cystinosis to test new therapies. In 2018 I  generated the world’s first CRISPR/Cas9 genetically modified cystinotic rat. I performed a yearlong characterisation of this rat and I found that its disease progression and biochemical dysfunction very closely resembles the human disease making it the best animal model currently available, and an excellent tool to be used in preclinical drug studies. 
My focus now is performing pre-clinical drug studies in this rodent model with 2 potential new therapies progressing to clinical trials in 2025.