Dr Lee Parry

(he/him)

BSc (Hons), PhD, FHEA

Publication

• Date
• Type

Research

Primary research

Colorectal cancer (CRC) is the 4th most frequent type of tumour and the 2nd leading cause of malignancy-related deaths in the Western world. Worldwide CRC incidence is increasing in female patients, those younger than 50 years-old and in low/middle income nations. As ~50% of CRC cases are preventable (WCRF-UK and Cancer Research UK websites) there is a potential to significantly reduce CRC incidence and address this global clinical need. Many of the fundamental mechanisms which link nutritional intake to physiological consequences remain undetermined.     An improved mechanistic understanding would form part of a wider robust evidence base which is important in determining cause-and-effect relationships. There is a need to answer fundamental questions about the mechanisms by which diet impacts upon the normal biological processes and how they link through to influences on health and disease. Primary prevention can be achieved with greater understanding of how the major CRC risk factors of diet and lifestyle impact on the intestinal stem cell from which CRC originates.    Secondary prevention can be achieved with improvements in existing and new techniques for the early detection of the pre-malignant polyps prior to thier progression to carcinoma.

It is well documented that CRCs evolve through loops of deregulated inflammatory stimuli which are sustained by DNA damage signalling pathways and epigenetic re-modelling (DNA methylation). Intensive work in recent years has led to the identification of genes and mechanisms that link diet to changes in the gut microbiota, and the pigenome. These alterations drive epithelial and inflammatory/immune responses which interact with intestinal stem cell and can increase or decrease CRC risk.  As a lab we aim to foster symbiotic relationships with a multidisciplinary team that includes epidemiologists, dietitians, exercise physiologists, translational scientists, basic scientists, clinical researchers, clinicians, statisticians and public health professionals, all of whom bring their individual specialties to the common purpose. As we believe that synergic analysis of all  parameters could provide new biological insights and effective biomarkers that could have applications in prevention, molecular diagnosis, prognosis and treatment of intestinal disease and CRC.

Current projects:

• Molecular and Functional Characterization of the Role of Foxp3+ Regulatory T (Treg) Cells in the Development of Intestinal Cancer
• Molecular and Functional Characterisation of the Nutri-Epigenetic Effects of Chemopreventative Polyphenols in Intestinal Cancer
• Identifying the influence of the microbiome and metabolome on the normal and
  malignant murine intestinal stem cell
• Exploiting oncotropic bacteria for early detection of colorectal cancer

Teaching

Lecturer at Cardiff University

• 2022-23
  • Examination lead and Contributor on BI2332: Concepts of Disease
  • Supervisor on BI3001: Final Year Project
  • Lecturer in immunology on BI3352 Cancer: Cellular and Molecular Mechanisms and Therapeutics
  • Contributor on BI3351: Contemporary topics in disease
  • Supervisor on BI4001: Advanced Research Project
  • Contributor on BI4002: Advanced Research Methods
  • Contributor on BI4003: Frontiers in Biosciences
• 2020-21
  • Co-ordinator: 2nd Year Cancer Biology Workshop
  • Lecturer in immunology on BI3352 Cancer: Cellular and Molecular Mechanisms and Therapeutics
  • Supervisor on BI4001: Advanced Research Project
  • Contributor on BI4002: Advanced Research Methods
  • Contributor on BI4003: Frontiers in Biosciences
  • Supervisor on BI3001: Final Year Project
  • Contributor on BI2332: Concepts of Disease

Occaisonal Lecturer at University of West England

• 2016-present: Lecturer at MSc Rsearch Conference Event

Biography

Honours and awards

2014 Cardiff University Excellence Award For Leadership

Professional memberships

• British Association of Cancer Research 2006-
• European Association of Cancer Research 2006
• Genetics Society 1998-present

Network Memberships

• ECMC UK - Therapeutic Cancer Prevention Network
• STFC Cancer Detection Network+

Academic positions

• 2020 - present: Lecturer, Cardiff University, UK
• 2020 - 2020: Senior Research Fellow, European Cancer Stem Cell Research Institute, Cardiff University, UK
• 2013 - 2020: Research Fellow, European Cancer Stem Cell Research Institute, Cardiff University, UK
• 2005 - 2013: Postdoctoral Research Associate, Cardiff University, UK
• 2002-2005: Postdoctoral Research Fellow, Murdoch Children's Research Institute, Melbourne, Australia

Committees and reviewing

2020-present: Wales Cancer Research Centre Executive Committee Member

2018- present: Review Panel Member, Cardiff University Biobank

Grant Reviewer

• American Institute of Cancer Research
• Medical Research Council
• NC3R
• KiKa Dutch Cancer Council
• Research Council of Norway
• Cancer Research Trust NZ
• Swansea Bay Heath Board

Journal Reviewer

• BMC Cancer
• Clinical and Translational Medicine
• Immunology
• Journal of Pathology
• Journal of Visualised Experiments
• Kidney International
• Oncogene
• PLOS Biology
• Scientific Reports
• Trends in Endocrinology
• Acta Biomaterialia

Supervisions

I have space in my lab and can provide a supportive enviornment for supervising in the areas of:

• Mouse models of disease
• Intestinal stem cells/cancer stem cells
• Cancer prevention
• Cancer early detection
• Any interaction between the microbiome, immune system and epigenome that impacts on the intestine
• Technology to improve prevention and early detection of cancer

I currently supervise/co-supervise the following students:

2021-22 Emma O'Neill & Mohammed Rauf - 4th Year Intergated Masters

2021-24 Non William - PhD

2018-21 Kyle Murphy - PhD & Maria Howland - PhD

Potential Projects

Project Title: Impact of dietary components on the intestinal stem cell homeostasis and cancer risk

Bowel cancer is the 4th most common and second biggest cause of cancer mortality.  Of the ~14,000 new cases of bowel cancer each year in the UK it is estimated 50% could have been prevented through healthy lifestyle changes.  For example, there is strong evidence for a high fibre diet preventing bowel cancer. Fibre provides food for the bacteria which live in the bowel; in turn the bacteria convert fibre into substances called short chain fatty acids (SCFAs) that nourish bowel cells and prevent them becoming cancerous [1].  To improve our understanding of bowel cancer prevention, we focus on understanding how the diet, microbiome, epigenome, immunity, and environment impacts on the intestinal stem cell (ISC), the cell of origin of CRC [2]. The link between dietary fibre and bowel cancer prevention has been partly attributed to the microbial conversion of fibre to the SCFA butyrate[3].  Butyrate is generally considered to be tumour suppressive but discrepancies in research results suggest it may be either an oncometabolite or a tumour-suppressive metabolite[4].  Potentially this is linked to the ability of butyrate at high levels to act as an epigenetic modifier.  Further we have demonstrated in models that the epigenetic modifier Mbd2 can determine whether environmental interactions within the intestine are anti- or pro-tumourigenic[5].  Previous data identified by our team on the role of butyrate and MBD2 potentially explains the confusion over whether these agents are suppressive or oncogenic but has been established using mouse models.  The PhD candidate will make use of an established clinical collaboration to determine the impact of butyrate and Mbd2 regulation on normal and pre-malignant human intestinal tissue.  Translation of their roles on human stem cell biology, chromatin modifications and gene expression will be performed on tissue grown as 3D organoids ex vivo.

Techniques: Ex vivo 3D organoid culture, molecular biology, IHF/IF, genetic/epigenetic analysis, tissue culture

Project Title: Efficacy of enhanced bacterial immunotherapy to treat cancer

Theoretically, RNA interference to reduce oncogene expression is an attractive therapeutic intervention to reduce tumour burden.  Except for delivery of shRNA packaged in nanoparticles to hepatic tumours, the major obstacle to the use of therapeutic RNAi has always been finding a way to deliver interfering RNA molecules to a tumour. To overcome this hurdle, we have focussed on manipulating oncotropic bacteria to stably synthesise shRNA. Conceptually, this approach is designed to ensure that tumour-colonising bacteria continuously synthesise shRNA, enhancing the therapeutic effect of bacterial colonisation which can trigger the host immune system to recognise the tumour. Initial results with a manipulated strain of the oncotropic SL7207 bacterium administered as a single dose to a genetically manipulated mouse model of acute colorectal cancer (CRC)indicated (a) a high degree of tumour tropism; (b) significantly extended survival of treated mice; (c) a reduction in oncogene expression, as outlined below.  Our goal is to provide data to justify subsequent clinical trials and expand the pre-clinical data into other solid tumour types of clincila unmet need e.g breast, pancreas and prostate.   We have developed mouse models which develop single tumours akin to human presentation at clinic and have access to a panel of human cancer cell lines.  Thes  focus will be to develop customised bacteri astrain sto targt genes relevant to different cancer types and provide detailed analyses of (1) immune responses , (2) tissue colonisation by SL7207 – assessing a range of healthy tissues/organs including, for example, spleen obtained from sacrificed animals, (3) responses in the tumours such as size changes and changes in gene expression of target genes, and (4) comparison of survival times among the different cohorts.

Techniques:Immuno-histochemistry of tissue sections, RNAscope ® for stem cell markers, quantitative PCR and RT-PCR, 3D ex vivo oganoid culture, ELISA and immune-assays and flow cytometry.