Ewch i’r prif gynnwys
Alex Tonks  BSc (Hons), PhD, FHEA

Yr Athro Alex Tonks

(Translated he/him)

BSc (Hons), PhD, FHEA

Senior Lecturer

Yr Ysgol Meddygaeth

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Trosolwyg

I lead a multi-disciplinary research group focused on abnormalities affecting haematopoietic (blood cell) development which leads to haematological malignancies (blood cancer).  More recently, through the funding of three consecutives Bloodwise Programmes my work has focused on the identification of novel targets, biomarkers and potential drug targets for the treatment of one of these cancers - acute myeloid leukaemia (AML).

In particular, I investigate the roles of a number of candidate genes including RUNX1-ETO, CD200, Wnt signalling, S100 proteins and the production of reactive oxygen species (ROS) in leukamogenesis. I am interested in how the process of haematopoietic development in stem and progenitor populations is dysregulated by these genes in AML.

Cyhoeddiad

2023

2022

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2003

Articles

Book sections

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Research Overview

Acute myeloid leukaemia (AML) still has a generally poor outcome particularly for those over sixty.  Hope for the future comes in the form of treatments which target key abnormalities that are the “Achilles’ heel” of the disease; unfortunately AML is a highly variable disease and only one subtype of the disease is currently treated in this way.  I investigate the roles of a number of candidate genes including RRUNX1-ETO, CD200, Wnt signalling, S100 and the production of reactive oxygen species (ROS) in leukamogenesis. In particular I am interested in how the process of haematopoietic development in stem and progenitor populations is dysregulated by these genes in AML.

Research Description

Translocations affecting the RUNX1 transcription factor are amongst the most common in AML and preleukaemia. Knockout models have demonstrated the importance of this gene for haematopoietic development, however, at present we understand little of the effect of translocated RUNX1 genes such as RUNX1-ETO on the development of primary human cells. The aim of our studies have been to gain a detailed understanding of the effect of RUNX1-ETO on the development of primitive human primary cells. We have achieved this by ectopically expressing RUNX1-ETO in CD34+ using a retroviral vector which co-expressed green fluorescent protein. This enabled the identification of infected cells in 'real-time', and allowed us to study the effects of RUNX1-ETO on primitive cells and on their subsequent ability to complete their differentiation down the myeloid and erythroid lineages. Using this approach we showed that expression of RUNX1-ETO strongly inhibited the differentiation of both myeloid and erythroid cells as well as promoting their self-renewal. We have subsequently used microarray technology to identify target genes of RUNX1-ETO. We are currently investigating these genes and their ability to recapitulate the RUNX1-ETO phenotype.

We have also identified an abnormality that is common to the majority of AML patients, which is the over-production of reactive oxygen species (ROS). While ROS are damaging to normal blood cells, AML cells have developed resistance to them and moreover depend on ROS to promote their growth. We are currently investigating approaches that can be effective against AML cells by using agents that are much more easily tolerated than conventional chemotherapy.

Knowing which genes, proteins (and ROS) are linked to abnormal blood production enables us to develop new treatments which are critically needed for patients with AML.

Grants held in last 5 years

  1. Bloodwise Specialist Programme Renewal. Targets for treatment in AML. Targeting the ROS axis. (Co-PI with Prof Darley.
  2. Leukaemia and Lymphoma Research.Specialist Programme Renewal. Targets for treatment in AML. £657K; 2013-2015(Co-PI with Prof Darley.
  3. Leukaemia and Lymphoma Research.Specialist Programme. Targets for treatment in AML. £649K; 2010-2013 (Co-PI with Prof Darley).
  4. Life Sciences Research Network Wales. Development of novel CD200:CD200R blockade cancer immunotherapy. £50K;2015-2016. (Co-applicant with Dr G Patel(PI)).
  5. British Skin Foundation.Project Grant. Targeting CD200 signalling to overcome human basal cell carcinoma immune-evasion; £81K; 2014-2016 (Co-applicant with G Patel(PI)).
  6. Tenovus Cancer Care. PhD studentship. The role of ROS and glycolytic metabolism in leukaemogenesis.£89K; 2013-2016.
  7. Cancer Research Wales PhD studentship. Mechanisms dysregulating canonical Wnt signalling in acute myeloid leukaemia. £116K; 2013-2016 (co-applicant with Prof Darley (PI))
  8. NISCHR. NISCHR Cancer ResearchGrouping. ~£75K; 2010-2015. (Co-applicant with Prof Griffiths (PI)).
  9. Kay Kendall Leukaemia Research. The role of ROS in leukaemogenesis. £129K; 2010-2012. (Co-applicant with Prof Darley (PI)).
  10. NISCHR. Identification of therapeutic targets in acute myeloid leukaemia expressing the mutant RASoncogene (PhD studentship). £60K; 2010-2013 (PI).

Addysgu

  • I am a Fellow of the Higher Education Acadamy.
  • I am post graduate research lead for the Division of Cancer and Genetics.  Looking after the student life cycle, welfare and development of PGR students within the Division.
  • I contribute to teaching associated with several courses and modules across the School and Colleges within Cardiff University.
  • I provide several laboratory based projects for undergraduate, postgraduate taught, MRes and PTY students to train within my laboratory. 
  • I am an external lecturer for several UK universities and guest speaker internationally.
  • I am external examiner for PGR students.
  • I am external examiner for BSc/MSi courses. 

Bywgraffiad

Education and significant professional training courses

2014: Fellow of the Higher Education Academy

2012-2014: ILM endorsed course for Practical Leadership for University Management, Cardiff University, Cardiff, UK

2012-2013: CPD in Medical Education Orientation Programme, School of Medicine, Cardiff University, Cardiff UK

1997-2000: PhD – Pulmonary immunology/ROS, Cardiff University / University of Wales Institute Cardiff (UWIC)

1996: HPC Registration for Biomedical Sciences, Health Professions Council, UK

1993-1997: BSc (Hons) Biomedical Sciences (Ist Class),  UWIC, Cardiff, UK

Career Overview

**Present - Senior Lecturer, Department of Haematology, Cardiff University, UK

2003-2009 - Lecturer, Department of Haematology, Cardiff University, UK

2000-2003 - Post-doctoral Research Fellow, Department of Haematology, Cardiff University, UK

2000-2002 - Part time Lecturer, School of Applied Sciences, UWIC, Cardiff, UK          

1997-2000 - Research Assistant, School of Applied Sciences, UWIC, Cardiff, UK          

1995-1996, 1997 - Biomedical Scientist, Royal Gwent Hospital, Pathology Department, Newport, UK          

Aelodaethau proffesiynol

  • I am an associate fellow of the American Society of Haematology
  • I am a Fellow of Higher Education Academy (2014).

Safleoedd academaidd blaenorol

Career Overview

Present - Professor in Haematology, Department of Haematology, Cardiff University, UK

2016-2020 - Reader, Department of Haematology, Cardiff University, UK

2009-2016 - Senior Lecturer, Department of Haematology, Cardiff University, UK

2003-2009 - Lecturer, Department of Haematology, Cardiff University, UK

2000-2003 - Post-doctoral Research Fellow, Department of Haematology, Cardiff University, UK

2000-2002 - Part time Lecturer, School of Applied Sciences, UWIC, Cardiff, UK

1997-2000 - Research Assistant, School of Applied Sciences, UWIC, Cardiff, UK

1995-1996, 1997 - Biomedical Scientist, Royal Gwent Hospital, Pathology Department, Newport, UK

Meysydd goruchwyliaeth

I have a track research record centred on understanding how molecular abnormalities associated with leukaemia contribute to the pathogenesis of these conditions. I am an experienced mentor with an excellent successful PGR supervision record including ECR development.  I have supervised over 15 PGR students to successul completion. I am currently supervising six PhD students.

I have the role of Divisional PGR Director/lead responsible for the progress monitoring and PGR environment of ~45 students across all years of study within my Divsion. Over the last 20 y I have supervised numerous medical SSC/pharmacological BSc students, BSc Medical intercalated degrees and MPhil/MSc/MRes students. I have been internal/external examiner or chair of viva voce examinations on numerous occasions.  My international reputation in this area is evidenced by external examinations in the UK and Europe. 

I am interested in supervising PGR students in the areas of

  • Haematological malignancy
  • Targeted therapies and precision medicine in blood cancer
  • Oxidative stress and REDOX signalling in cancer

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