Dr Lee Parry

Lecturer

School of Biosciences

: parryl3@cardiff.ac.uk
: +44 (0)29 2068 8017
: 1.23, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ

: Media commentator
: Available for postgraduate supervision

Lecturer/Darlithydd

Prevention and Early Detection of Cancer

Wales Cancer Research Centre Lead for Early Detection

Wales Cancer Research Centre Lead for Personalised Prevention

Human Tissue Officer, School of Biosciences

Research overview

Colorectal cancer (CRC) leads to approximately 600,000 deaths globally each year and is one of the major causes of death in the western world. In the UK it is the fourth most common cancer with around 40,000 new cases diagnosed each year (Cancer Research UK). At least half of these cases are thought to be preventable, as diet and lifestyle choices play a significant role in altering a person’s risk of developing cancer.

Perhaps unsurprisingly bowel cancer is strongly linked to dietary choices, for example a high fibre diet is associated with a lower cancer risk. However, the reasons for these links remain unknown. To gain a better understanding we need to study the intestinal stem cells that are responsible for maintaining a healthy bowel, as it is damage to these cells which can cause cancer.

However, in comparison to cancer there is little work performed on the normal bowel, partly due to the difficulty of obtaining samples from healthy people and lack of research teams capable of understanding the complete effect of diet on the bowel. The group is working to identify how the bacteria, immune system, epigenome and stem cells in the normal and cancerous bowel respond to different food types. The focus of the research is to improve our understanding of diet and health to provide accurate public advice and develop ways of preventing or detecting bowel cancer.

FOR POSTION AND STUDENTSHIP OPPORTUNITES PLEASE CHECK SUPERVISION TAB

Originally from the South Wales valleys, my undergraduate training was completed in Cardiff University, followed by a PhD at the Institute of Medical Genetics at (what was then) the University of Wales College of Medicine. My Cancer Research Wales funded PhD was completed in the laboratory of Professors Julian Sampson and Jeremy Cheadle on the "Molecular and Functional Analysis of the Human Tumour Suppressor Genes TSC1 and TSC2". Upon completing my PhD in 2002 I took up a Postdoctoral Fellow position at the Murdoch Children's Research Institute (MCRI) in the Royal Children's Hospital in Melbourne, Australia. My work there was a change of focus from the cancer genetics of my PhD as I worked in the research groups of A/Prof Henrik Dahl and David Thorburn on Complex I deficiency in mitochondria. Upon completing this post I returned to Cardiff University and to cancer genetics, working on a Cancer Research UK funded project in the laboratory of Prof Alan Clarke. In July 2013 I took up a fellowship at the European Cancer Stem Cell Research Institute where my research focused on understanding and therapeutically exploiting the mechanisms that links the environment (diet & gut bacteria) to inflammation and colorectal cancer. In 2020 I became a lecturer at Cardiff University's School of Biosciences, where I lead the Prevention and Early Detection of Cancer group and have been included in Cancer Research UK's 2021 promotional video on cancer research during COVID-19.

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

Speaking engagements

2020

European Cancer Stem Cell Research Institute, 4th Symposium, Cardiff, UK

2019

Current Methods in Biomedical Research Summer School, Kuopio, Finland

2018

Genetics Society - 4th Mammalian Gene, Disease and Devlopment Meeting, Bristol, UK
Royal Society of Biology - Public Lecture, Cardiff, UK

2016

Beatson International Cancer Conference - Modelling the Mechanisms of Malignancy - In Vivo Veritas, Glasgow, UK
British Association Cancer Research - Therapeutic Interventions for Cancer Prevenmtion Meeting, Bristol, UK

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

2014

Koh, D. -. et al. 2014. KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes. Proceedings of the National Academy of Sciences of the United States of America 111(42), pp. 15078-15083. (10.1073/pnas.1318780111)

2013

Parry, L., Young, M., El Marjou, F. and Clarke, A. R. 2013. Evidence for a crucial role of Paneth Cells in mediating the intestinal response to injury. Stem Cells 31(4), pp. 776-785. (10.1002/stem.1326)
Jarde, T. et al. 2013. In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89β-catenin system. Oncogene 32(7), pp. 883-893. (10.1038/onc.2012.103)
Meniel, V. et al. 2013. Cited1 deficiency suppresses intestinal tumorigenesis. PLoS Genetics 9(8), article number: e1003638. (10.1371/journal.pgen.1003638)

2012

Smartt, H. J. M. et al. 2012. β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells. Gut 61(9), pp. 1306-1314. (10.1136/gutjnl-2011-300817)

2011

Parry, L. and Clarke, A. R. 2011. The roles of the methyl-CpG binding proteins in cancer. Genes & Cancer 2(6), pp. 618-630. (10.1177/1947601911418499)

2010

Cole, A. et al. 2010. p21 loss blocks senescence following Apc loss and provokes tumourigenesis in the renal but not the intestinal epithelium. EMBO Molecular Medicine 2(11), pp. 472-486. (10.1002/emmm.201000101)

2008

Phesse, T., Parry, L., Reed, K. R., Ewan, K. B. R., Dale, T. C., Sansom, O. J. and Clarke, A. R. 2008. Deficiency of Mbd2 attenuates Wnt induced tumourigenesis via deregulation of a novel Wnt inhibitor, Lect.2. Molecular and Cellular Biology 28(19), pp. 6094-6103. (10.1128/MCB.00539-08)

2005

Wilson, C. H. et al. 2005. A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma. Human Molecular Genetics 14(13), pp. 1839-1850. (10.1093/hmg/ddi190)

2004

Kirby, D. M. et al. 2004. NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency. The Journal of Clinical Investigation 114(6), pp. 837-845. (10.1172/JCI200420683)

2003

Dixon, P. F. et al. 2003. Four years of monitoring for viral haemorrhagic septicaemia virus in marine waters around the United Kingdom. Disease of Aquatic Organisms 54(3), pp. 175-186. (10.3354/dao054175)

2001

Hodges, A. K. et al. 2001. Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Human Molecular Genetics 10(25), pp. 2899-9205. (10.1093/hmg/10.25.2899)
Parry, L. et al. 2001. Analysis of the TSC1 and TSC2 genes in sporadic renal cell carcinomas. British Journal of Cancer 85, pp. 1226-1230. (10.1054/bjoc.2001.2072)

2000

Parry, L., Maynard, J. H., Patel, A., Hodges, A., von Deimling, A., Sampson, J. R. and Cheadle, J. P. 2000. Molecular analysis of the TSC1 and TSC2 tumour suppressor genes in sporadic glial and glioneuronal tumours. Human Genetics 107(4), pp. 350-356. (10.1007/s004390000390)

1997

Dixon, P., Feist, S., Kehoe, E., Parry, L., Stone, D. and Way, K. 1997. Isolation of viral haemorrhagic septicaemia virus from Atlantic herring Clupea harengus from the Atlantic herring Clupea harengus from the English channel. Diseases of Aquatic Organisms 30(2), pp. 81-89.
Parry, L. and Dixon, P. F. 1997. Stability of nine viral haemorrhagic septicaemia virus (VHSV) isolates in seawater. Bulletin of the European Association of Fish Pathologists 17(1), pp. 31-36.

Lecturer at Cardiff University

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

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

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.

Current supervision

Kyle Murphy

Research student

Past projects

PhD

2019
- Supervisor for Ana Padhila - "Molecular and Functional Characterization of the Role of Foxp3+ Regulatory T (Treg) Cells in the Development of Intestinal Cancer"
2018
- Co-supervisor (50%) for Stephanie May-"Molecular and Functional Characterisation of the Nutri-Epigenetic Effects of Chemopreventative Polyphenols in Intestinal Cancer"
- Co-supervisor (20%) for William Hill - " Heterotypic cell-cell interactions between KrasG12D cells and normal neighbours in early pancreatic cancer"

Mres

2014 Supervisor for Christopher Towers - "Understanding the anti/pro tumourigenic role of Ifnγ in intestinal cancer"

Intergrated Masters

2021
- Bethan Phillips - "Enhanced bacterial immunotherapy delivering therapeutic RNA interference to treat colorectal cancer"
2020
- Supervisor for Cerian Thomas -"The impact of different eating mechanisms on gene expression profiles in intestinal stem cells and differentiated cell types.

Professional Training Year

2018
- Matilda Worthy - "Characterisation of a novel RNAi based therapy for solid tumours "
2017
- Riddhi Thanky - "Dietary components influence the behavior of the Apc deficient intestinal stem cell"

Final Year Undergraduate Project students

2021 Emma Clarke - "Defining the requirements and estimating the benefits of producing single sex offspring"

2020 - Contributor to Techniquest After Hours - Rogue Cells

2018 - present: Contributor to Wales Gene Park Gentics Roadshow

2013 - present: CRUK representative and volunteer

2013 - present: - Wales STEM Ambassador