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Sujata is a DPhil student in the  Leedham Group

tgu-researcher-photo-sb.jpg1.  How did you become interested in translational gastroenterology?

I have been a Gastroenterology trainee in the Oxford deanery since 2011 and was fortunate to be exposed to the breadth of research available here from an early stage. I became interested in colorectal polyposis syndromes after an audit on the prevalence of Serrated Polyposis Syndrome in the Oxford Bowel Cancer Screening Programme. I wanted to learn more about the molecular pathology of polyps and cancer, and was fortunate to come across Simon Leedham’s lab at the Wellcome Centre for Genetics after seeing him present at a TGU seminar.

I started my DPhil two years ago and although it was a steep learning curve (learning to pipette again after ten years etc!) it has been fantastic. The lab is rapidly expanding and works well together. I have had the opportunity to remain involved in endoscopy and clinics which, as well as keeping up skills, has reminded me of the translational impact of my work.

 

2.  What are you currently working on and what importance does your work hold for current patients with gastrointestinal issues?

The lining of the gastrointestinal tract contains the most rapidly proliferating cells in the body so is an ideal place to study stem cell behaviour. Stem cells reside at the base of intestinal crypts, with daughter cells proliferating and differentiating as they pass along the crypt-villus axis. An interacting network of morphogen signalling pathways controls this complex system. My hypothesis is that disrupted morphogen gradients predispose to epithelial stem cell plasticity – the development of stem cell-like properties away from the crypt base stem cell niche - where proliferation without niche control can lead to mutation and carcinogenesis. A marker of these ectopic stem cells is Sox9, a transcription factor, and I am trying to further elucidate its role in colorectal cancer and colitis. I am using human tissue, in vitro culture systems and in vivo models.

My study will provide insight into the mechanisms that regulate intestinal stem cell homeostasis and the pathogenesis of pre-cancerous lesions, which may contribute to the future development of molecular biomarkers of cancer risk and identification of potential therapeutic targets.

I have also written the ethics and coordinated the collection of several hundred colorectal polyps from patients at colonoscopy as part of the multicentre S-CORT trial. We are using DNA and RNA sequencing to generate a comprehensive molecular signature for each histologically defined polyp subtype. The ability to relate molecular signature back to polyp phenotype will help to identify early molecular events that may be important in disease development.

 

3.  What do you enjoy most about scientific research?

The excitement of designing my own experiments that nobody in the world is doing (hopefully!) and following through results with plans that are constantly changing. The concept of new discovery and changing management in the future for patients, as well as the flexibility and autonomy I have over my own work.

 

4. What’s the best part of being an Oxford University TGU member?

The unit works together cohesively. My work involves collecting endoscopic biopsies and whenever I go to the Endoscopy department the whole clinical team are incredibly helpful. The process of consent in Oxford has been optimised and patients are more aware of research involvement than ever before. The research nurses are a well-run team and work together to ensure as many patients as possible are consented. Communication is excellent and it feels we are all working together towards a common goal.