Sarah McCuaig

Graduate Research Prize Winner 2016

Sarah McCuaig

As a high school student, a handful of rudimentary microbiology experiments in my bedroom in which I attempted to understand the effects of ingesting antibacterial toothpaste on probiotic bacteria in the gastrointestinal tract, spurred my fascination with immunology and interest in research. My first exposure to a “real” lab came when I worked in a group studying the immune system of teleost fish in my final year of high school. As an undergraduate majoring in immunology at McGill University, Canada, my research focused on oxidative damage to the airway epithelium and inflammation-induced airway remodeling in asthma.

I have since made the journey into the gut with Professor Powrie as a DPhil student at Oxford with the support of the Rhodes Trust. However, I continue to be interested in the consequences of immune-mediated epithelial repair processes going awry and becoming pathogenic.

Specifically, my work has focused on interleukin 22 (IL-22), an IL-10 cytokine superfamily member, which plays a critical role in epithelial repair, but is also indispensable for primary tumourigenesis in selected murine models of colorectal cancer (CRC). My challenge upon joining the lab was to determine the relevance of the IL-22 pathway to human disease. This work has brought together two distinct understandings of cancer as we have discovered a novel synergy between the cytokine IL-22 and the oncogenic driving mutation, KRAS, and have developed a novel strategy to stratify CRC patients to immunomodulatory IL-22 pathway blockade. Thanks to close ties with the Translational Gastroenterology Unit in the NDM, I have been able to develop a unique ex vivo culture system involving patient derived organoids and expanded tumour infiltrating lymphocytes to explore mechanistic biological questions in primary human tissue.

As a basic science immunologist, I have benefited immensely from new interdisciplinary links between immunology and oncology at Oxford. Moreover, I have had the honour of working with a multidisciplinary team of scientists, clinicians, biobankers, and statisticians to secure funding for a novel Phase 0 window trial with biological endpoints of immunomodulatory therapy in CRC.

My time as a doctoral student has been enriched by opportunities to find creative ways to relay complex scientific concepts to children and the general public through exhibiting an interactive “Build Your Own Gut” display at numerous public engagement events and through hosting GCSE and A Level students in the lab. When not in the lab I can be found running around Oxford with the University’s Varsity Cross Country and Athletics Teams. 

 

Recent Achievements:

  1. Defining interactions between the cytokine IL-22 and oncogenic KRAS as a new therapeutic target in colorectal cancer. (£1,200,000). MRC Experimental Medicine Pathfinder Award, 2016. *primary grant author
  2. IL-22 signalling and KRAS synergize to promote malignancy and poor prognosis in colorectal cancer (£12,250). CRUK Oxford Centre Development Fund Grant, 2015. *primary grant author
  3. West NR*, McCuaig S*, Franchini F, Powrie F. Emerging cytokine networks in colorectal cancer. Nature Reviews Immunology 15, 615–629 (2015). *co-first authors
  4. Provisional UK Patent (Application no. 1508841.2) filed May 22, 2015: Cytokine-oncogene interactions as prognostic and therapeutic tools in cancer. *co-inventor