Ewch i’r prif gynnwys
Dr Alex Tonks

Dr Alex Tonks

Senior Lecturer

Yr Ysgol Meddygaeth

Email:
tonksa@cardiff.ac.uk
Telephone:
+44 29207 42235
Location:
UHW Main Building

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.

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).

Ymrwymiadau siarad cyhoeddus

35th French Society of Haematology Annual Congress: 31.3.14 -3.4.14

Alex Tonks. Reactive oxygen species and alered metabolism in haematological malignancies.

52nd American Society of Haematology, San Francisco, USA. December 2-7th, 2014.

Paul S. Hole, Sara Davies, Chinmay Munje, Sandra Kreuser, Robert K. Hills, Nader Omidvar, Steve Knapper, Alan K. Burnett, Alex Tonks & Richard L. Darley PhD.   A subpopulation of blasts with attenuated p38MAPK response is seen in virtually all AML patients and AML cell lines and is defined by cells with augmented lipid-associated anti-oxidant defense.

Newcastle Scientific Seminar Series:, June 1st, 2014.

Alex Tonks. New targets in AML.

The European Cancer Stem Cell Research Institute: Targeting Cancer. Newport, UK, July 24th-26th, 2013.

Paul S. Hole* & Joanna Zabkiewicz, Chinmay Munje, Zarabeth Newton, Robert K. Hills, Alan K. Burnett, Alex Tonks#, and Richard L. Darley#.   Overproduction of NOX-derived ROS in AML promotes proliferation and is associated with defective p38MAPK stress signalling. #Equal contribution.

International RUNX meeting, San Diego, USA, Aug 11th-14th, 2011.

Alex Tonks, Steve Coles, Stephen Man, Eddie Wang, Alan K Burnett and Richard L Darley. CD200 expression in AML inhibits memory Th1 cell function and is associated with increased frequencies of regulatory T-cells.

International RUNX meeting, Hiroshima, Japan. July 11th-14th, 2010.

Alex Tonks, Steve Coles, Stephen Man, Eddie Wang, Alan K Burnett and Richard L Darley. RUNX1-ETO target genes; the role of CD200 mediated tumour immunity in AML.

Rhys Morgan, Lorna Pearn, Kate Liddiard, Rob Hills, AK Burnett, Alex Tonks and Richard L Darley. A distinct role for the Wnt signalling protein γ-catenin in normal haematopoiesis and its deregulation in AML.

52nd American Society of Haematology, Orlando, Florida, USA.   December 2-7th, 2010.

Steven Coles, Stephen Man, Eddie Wang, Alan K Burnett, Richard L Darley and Alex Tonks. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumour response in AML.

Wales Cancer Conference. Cardiff. April 13th-14th, 2010.

 

Steven Coles, Stephen Man, Eddie Wang, Alan K Burnett, Richard L Darley and Alex Tonks. RUNX1-ETO target genes; the role of CD200 mediated tumour immunity in AML.

Paul S. Hole, Joanna Zabkiewicz, Lorna Pearn, Amanda J. Tonks, Philip E. James, Alan K. Burnett, Richard L. Darley and Alex Tonks. Increased Production of Reactive Oxygen Species Promotes the Proliferation of Human Haematopoietic Progenitor Cells Expressing Activated Ras.

Pwyllgorau ac adolygu

External Committee

  • 2015 - current: I am board member of the HealthCare Research Wales Awards Panel;
  • 2014 - current; Lead member of the HCRW faculty;
  • 2014 - current: I am part of the WAG “College of Experts”
  • 2006 - 2014: various NISCHR review panels for projects and PhD studentships

2019

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2003

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).