Dr Lee Parry

(e/fe)

BSc (Hons), PhD, FHEA

Cyhoeddiad

• Date
• Type

Ymchwil

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

Addysgu

Darlithydd ym Mhrifysgol Caerdydd

• 2022-23
  • Arweinydd yr arholiad a chyfrannwr ar BI2332: Cysyniadau Clefydau
  • Goruchwyliwr ar BI3001: Prosiect Blwyddyn Derfynol
  • Darlithydd imiwnoleg ar Ganser BI3352: Mecanweithiau Cellog a Moleciwlaidd a Therapeutics
  • Cyfrannwr ar BI3351: Pynciau cyfoes mewn clefyd
  • Goruchwyliwr ar BI4001: Prosiect Ymchwil Uwch
  • Cyfrannwr ar BI4002: Dulliau Ymchwil Uwch
  • Cyfrannwr ar BI4003: Ffiniau yn y Biowyddorau
• 2020-21
  • Cydlynydd: Gweithdy Bioleg Canser yr 2il Flwyddyn
  • Darlithydd imiwnoleg ar Ganser BI3352: Mecanweithiau Cellog a Moleciwlaidd a Therapeutics
  • Goruchwyliwr ar BI4001: Prosiect Ymchwil Uwch
  • Cyfrannwr ar BI4002: Dulliau Ymchwil Uwch
  • Cyfrannwr ar BI4003: Ffiniau yn y Biowyddorau
  • Goruchwyliwr ar BI3001: Prosiect Blwyddyn Derfynol
  • Cyfrannwr ar BI2332: Cysyniadau Clefydau

Darlithydd Ocsiwn ym Mhrifysgol Gorllewin Lloegr

• 2016-presennol: Darlithydd yn y Digwyddiad Cynhadledd Rsearch MSc

Bywgraffiad

Anrhydeddau a dyfarniadau

2014 Cardiff University Excellence Award For Leadership

Aelodaethau proffesiynol

• 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+

Safleoedd academaidd blaenorol

• 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

Pwyllgorau ac adolygu

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

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

Meysydd goruchwyliaeth

Mae gen i le yn fy labordy a gallaf ddarparu amgylchedd cefnogol ar gyfer goruchwylio yn y meysydd:

• Modelau llygoden o glefyd
• Bôn-gelloedd coluddyn/bôn-gelloedd canser
• Atal canser
• Canfod canser yn gynnar
• Unrhyw ryngweithio rhwng y microbiome, y system imiwnedd a'r epigenom sy'n effeithio ar y coluddyn
• Technoleg i wella atal canser a chanfod canser yn gynnar

Prosiectau Posibl

Teitl y Prosiect: Effaith cydrannau dietegol ar homeostasis bôn-gelloedd coluddyn a risg canser

Canser y coluddyn yw'r 4ydd achos mwyaf cyffredin a'r ail achos mwyaf o farwolaethau canser.  O'r ~14,000 o achosion newydd o ganser y coluddyn bob blwyddyn yn y DU, amcangyfrifir y gellid atal 50% trwy newidiadau iach i'w ffordd o fyw.  Er enghraifft, mae tystiolaeth gref o ddeiet ffibr uchel yn atal canser y coluddyn. Mae ffibr yn darparu bwyd i'r bacteria sy'n byw yn y coluddyn; yn ei dro mae'r bacteria yn trosi ffibr yn sylweddau o'r enw asidau brasterog cadwyn fer (SCFAs) sy'n maethu celloedd y coluddyn ac yn eu hatal rhag dod yn ganseraidd [1].  Er mwyn gwella ein dealltwriaeth o atal canser y coluddyn, rydym yn canolbwyntio ar ddeall sut mae'r diet, microbiome, epigenom, imiwnedd a'r amgylchedd yn effeithio ar y bôn-gell berfeddol (ISC), cell tarddiad CRC [2]. Mae'r cysylltiad rhwng ffibr dietegol ac atal canser y coluddyn wedi'i briodoli'n rhannol i drosi ffibr microbaidd i'r butyrad SCFA[3].  Yn gyffredinol, ystyrir bod butyrad yn atal tiwmor, ond mae anghysondebau yng nghanlyniadau ymchwil yn awgrymu y gallai fod naill ai'n oncometabolit neu'n metabolit sy'n atal tiwmorau[4].  O bosibl mae hyn yn gysylltiedig â gallu butyrate ar lefelau uchel i weithredu fel addasydd epigenetig. Ymhellach,  rydym yn wedi dangos mewn modelau y gall yr addasydd epigenetig Mbd2 benderfynu a yw rhyngweithiadau amgylcheddol o fewn y coluddyn yn wrth- neu'n pro-tiwmorigenig[1].  Mae data blaenorol a nodwyd gan ein tîm ar rôl butyrate a MBD2 o bosibl yn esbonio'r dryswch ynghylch a yw'r asiantau hyn yn ataliol neu'n oncogenig ond mae wedi'i sefydlu gan ddefnyddio modelau llygoden.  Bydd yr ymgeisydd PhD yn defnyddio cydweithrediad clinigol sefydledig i bennu effaith rheoleiddio butyrate a Mbd2 ar feinwe coluddyn dynol arferol a chyn-malaen.  Bydd cyfieithu eu rolau ar fioleg bôn-gelloedd dynol, addasiadau cromatin a mynegiant genynnau yn cael ei berfformio ar feinwe a dyfir fel organoidau 3D ex vivo.

Technegau: Diwylliant organoid 3D ex vivo, bioleg foleciwlaidd, IHF / IF, dadansoddiad genetig / epigenetig, diwylliant meinwe

Teitl y Prosiect: Effeithiolrwydd imiwnotherapi bacteriol gwell i drin canser

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 focused on manipulating oncotropic bacteria to stably synthesise shRNA. Conceptually, this approach is designed to ensure that tumour-colonising bacteria continuous synthesise shRNA, enhancing the therapeutic effect of bacterial colonisation which can trigger the host immune system to recognize the tumour. Initial results with a manipulated strain of the oncotropic SL7207 bacterium administrated 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) gostyngiad mewn mynegiant oncogene, fel yr amlinellir isod.  Ein nod yw darparu data i gyfiawnhau treialon clinigol dilynol ac ehangu'r data cyn-glinigol i fathau eraill o diwmor solet eraill o anghenion clincila heb eu diwallu e.e. y fron, y pancreas a'r prostad.   Rydym wedi datblygu modelau llygoden sy'n datblygu tiwmorau sengl sy'n debyg i gyflwyniad dynol yn y clinig ac mae ganddynt fynediad at banel o linellau celloedd canser dynol.     Bydd ffocws ar ddatblygu genynnau STO Targt wedi'u teilwra sy'n berthnasol i wahanol fathau o ganser a darparu dadansoddiadau manwl o (1) ymatebion imiwnedd, (2) gwladychu meinwe gan SL7207 – gan asesu ystod o feinweoedd/organau iach gan gynnwys, er enghraifft, dueg a gafwyd o anifeiliaid a aberthwyd, (3) ymatebion yn y tiwmorau megis newidiadau maint a newidiadau ym mynegiant genynnau genynnau targed, a (4) cymharu amseroedd goroesi ymhlith y gwahanol garfannau.

Technegau: Imiwno-histocemeg adrannau meinwe, RNAscope ® ar gyfer marcwyr bôn-gelloedd, PCR meintiol ac RT-PCR, diwylliant 3D ex vivo oganoid, ELISA a phrofion imiwnedd a sytometreg llif.

Goruchwyliaeth gyfredol

Alexander Incledion

Billy Hughes

Kian Quest

Ymgysylltu

News articles

Gwella'r dull o wneud diagnosis o ganser y colon a’r rhefr

20 February 2019

Datblygu profion diogel a chost-effeithiol ar gyfer canser y colon a’r rhefr