Dr Paul Shaw

Dr Paul Shaw

Senior Lecturer

School of Biosciences

Research overview

I am based in Prof Alan Clarke's laboratory in the European Cancer Stem Cell Research Institute. My research continues to explore and utilise genetically engineered mouse models of colorectal cancer and the therapeutic role of molecularly targeted novel anti-cancer agents against PI3K/mTOR and RAS/RAF/MEK/ERK signaling. This work complements the recognised strengths in personalised medicine (Stratified Medicine Programme, CRUK) and cancer genetics at Cardiff University. This research is now being extended to incorporate small animal PET imaging and novel tracer agents as predictive biomarkers of response to tailored anti-cancer agents (NISCHR funding, £217K over 2 years). I have recently secured funding from Cardiff CRUK Experimental Cancer Medicine Centre, to support a full-time research assistant in Prof. Trevor Dales' laboratory to develop colorectal cancer organoids as an 'ex vivo' model system. A Cancer Research Wales PhD Studentship will further this work from October 2013. I am planning to extend this technique to include other solid tumours in particular lung cancer. Given the direction of my clinical work I am also seeking funding opportunities locally to develop a genetically engineered mouse model of lung cancer.

I am currently funded by NISCHR for research sessions, prior to this I was a Walport Clinical Lecturer and CRUK Bobby Moore Clinical Research Fellow.

My current research takes advantage of local expertise in bioscience, chemistry and the PETIC facility at Cardiff University to explore PET biomarkers of response to novel anti-cancer agents. The benefit of this approach to future patients will be the potential to optimise therapeutic benefit whilst minimising harm and economic costs. We have recently demonstrated a marked anti-tumour effect giving rise to a three fold increased in median survival as a consequence of PI3K/mTOR inhibition  in a pre-clinical model of colon cancer.

The findings from this model have been used to investigate PET as a biomarker to identify antagonism of the PI3K-mTOR pathway. As cyclin D1 mRNA levels are markedly elevated in our model system, this has been used as a target biomarker in the construction of a tracer molecule capable of hybridising to Cyclin D1 via a cell entry protein (Tat). We plan to link this probe to Zerconium-89 for future PET CT studies to identify signal changes associated with therapeutic response.

We are establishing the PETCT platform using FDG and have identified FDG avidity in intestinal tumours

Affiliated staff

Grants

  1. Co-Principal Investigator (with Prof T Dale and Prof Alan Clarke) £104,280 Cancer Research Wales PhD studentship. Developing cancer stem cell containing organoids from human primary and secondary colorectal cancers for preclinical testing of stratified ant-cancer therapeutics (Oct 2013-2016)
  2. Principal Investigator (with Prof A. Clarke and Dr Stephen Daniels) £217,000 National Institute for Social Care and Health Research (NISCHR). PET bio-marker imaging in response to novel targeted anti-cancer therapy in a clinically applicable mouse model of colon cancer. (Feb 2013-2015)
  3. Co-Principal Investigator (with Prof Trevor Dale and Alan Clarke) Post-doctoral support (two years full time) funded by CRUK Experimental Cancer Medicine Centre, Cardiff. Title: Developing stem-cell containing organoids for preclinical studies of colorectal cancer therapeutics. (October 2012-2014).
  4. Co-Investigator (Principal Investigator Prof John Chester) £5K Cardiff CRUK Cancer Centre Development fund. Correlation of functional imaging (PET-CT) and molecular biomarkers of response to chemo-radiotherapy in head and neck cancers (2012-2013)
  5. Principal Investigator (with Dr Nader Omidvar, Dept Haematology, UHW) £5K Cardiff CRUK Cancer Centre, small grants bursary. Pilot study examining the therapeutic effect of a novel pvax1flipper DNA vaccine in a colon cancer mouse model. (2011-2012)
  6. Co-Applicant (with Prof A. Clarke) £90,000 Tenovus Charity (PhD.     Studentship). Investigating PI3K/mTOR inhibition in a mouse model of colorectal cancer mutant for both Apc and Pten. (2009-2012)
  7. Co-Investigator (with Prof C. McGuigan/Alan Clarke) £500,000 MRC DPFS Grant. Developing new agents for colorectal cancer using genetically defined autochthonous models. (2009-2011)
  8. Co-Principal Investigator (with Prof Trevor Dale, Prof Alan Clarke Dr Andrew Hollins, Dr Ken Ewan and Dr Keren Paz) £6K. Extending the development of organoid technology to lung malignancy. Cardiff CRUK Centre development fund.

Research links