New researcher to use organoids to study oesophageal cancer

 

We would like to welcome Dr Amy Stainthorp to the Leeds Centre for Disease Models. Amy has recently started a postdoctoral researcher position in the lab of Professor John Ladbury. Amy's research aims to advance understanding of Oesophageal cancer - a cancer that currently has rapidly increasing incidence and poor outcomes for patients. We asked Amy a few questions to find out more about her, and the project that she is undertaking...

Could you tell us about your academic/research background?

"For my undergraduate degree, I went to the University of Nottingham and studied Biochemistry. While there, I did a summer placement in a research lab studying actin-based protein transport and carried this project on in my third year. After this, I came to the University of Leeds to do the Wellcome Trust funded PhD scheme on ‘the molecular basis of biological mechanisms'. The first year consisted of 3 research projects, which I did with Prof. Richard Bayliss in Biology, Dr Richard Foster in Chemistry and Prof. John Ladbury. I stayed in John’s lab for my final PhD project, which involved studying a novel mechanism of microRNA biogenesis regulation"

What are the scientific problem/s that you will be addressing in this project?

"Barrett’s oesophagus (BO) is a premalignant condition which precedes oesophageal cancer (OAC). The prevalence of both BO and OAC has risen in recent years, and in high-income countries OAC has one of the most rapidly increasing incidences of all cancers. While only a small proportion of BO patients will go on to develop OAC, the prognosis for these patients is poor, with a predicted 5-year survival of 15%. OAC is frequently diagnosed after the cancer has metastasised and most patients have not had prior diagnosis of BO.

Monitoring of BO is through endoscopy, which has limited success in detecting cancerous cell progression. While several biomarkers have been suggested for OAC, none are yet used in the clinic, and the molecular mechanisms which mediate progression are largely unknown. Receptor tyrosine kinase proteins (RTKs) are frequently overexpressed in BO and OAC but little has been done to elucidate the role of these proteins in driving the disease. For example, both protein overexpression and gene amplification of the RTK, epidermal growth factor receptor (EGFR), has been recorded in BO/OAC. This suggests the potential of EGFR to aid diagnosis and therapy. Therefore, it will be clinically beneficial to ascertain the mechanism of action of EGFR in BO"

How will you be addressing these scientific questions?

"We are using both organoid and cell line models of BO to elucidate the EGFR-mediated mechanism which drives BO progression. EGFR will be depleted in both patient-derived organoids and a BO cell line, which will then be subject to repeated exposures of acidic bile salt which mimics repeated episodes of gastroesophageal reflux. EGFR-dependent changes in signalling will be identified by analysing gene and protein expression, combined with evaluation of cell behaviour, morphology and histology. This work will identify the molecular role of EGFR in OAC pathogenesis and provide insights for use of EGFR as a biomarker or EGFR-targeted therapies for BO/OAC patients"

Why were you drawn to this research topic and the field of disease models?

"The topic appealed to me on multiple levels: the opportunity to work in the exciting and rapidly developing field of organoid technology and to develop our knowledge of oesophageal cancer. Although I loved the mechanistic biology that made up the basis of my PhD project, I have long wanted to participate in more translational research. Furthermore, having used only immortalised cell lines in the past, I am eager to work with more physiologically relevant systems"

What is your favourite laboratory technique and why?

"I’ve enjoyed using CRISPR/Cas9 gene editing as this successfully produced a cell line with homozygous gene knockout. Due to the important role of the gene of interest, good knockdowns had been difficult to achieve with other techniques"

What inspired you to become a Scientist?

"From a young age I had harboured an interest in biology, but had initially wanted to apply to veterinary school. However, after deciding this wasn’t the career for me, I instead accepted a place to study biochemistry at the University of Nottingham. It was instantly clear that this was the right decision. I loved learning about the molecular functioning of the cell, the signalling pathways that govern physiological processes and biochemical basis of disease"

 

Follow Leeds Centre for Disease Models on twitter for all of our latest news and events updates.

Author: Rowan Taylor