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Professor Alex Tonks

Professor Alex Tonks

Personal Chair, Division of Cancer and Genetics

Email
tonksa@cardiff.ac.uk
Telephone
+44 29207 42235
Campuses
UHW Main Building
Users
Available for postgraduate supervision

Overview

I lead a multi-disciplinary research group focused on abnormalities affecting haematopoietic (blood cell) development which leads to haematological malignancies (blood cancer).  With the support of funding of three consecutives Blood Cancer UK Programmes and projects, project grants supported by Charities (Cancer Research Wales), government RCUK and Healthcare Research Wales, 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, metabolic proteins, S100 protiens, Wnt signalling, hnRNP proteins, CD200 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.

Biography

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

Professional memberships

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

Academic positions

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

Publications

2023

2022

2021

2020

2019

2018

2015

2014

2013

2012

2011

2010

2008

2007

2006

2005

2004

2003

Teaching

  • 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. 

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 RUNX1-ETO, RUNX3, hnRNP, 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

HealthCare Research Wales. PhD studentship determining the role of NFIC in AML. Prof Tonks (PI): Dr H WIlliams (Co-app), Prof Darley (Co-app). 2022-2025; £66,000.

Blood Cancer UK. Project grant exploring NOX2 as a component of multi-target therapy for acute myeloid. Prof Tonks (PI): Dr Khorashad (Co-I), Prof Darley (Co-app). 2022-2025; £248,000.

Saudi Arabia Cultural Mission PhD Studentship. The role of hnRNP proteins in leukaemogenesis.PhD Studentship. Prof Tonks (PI), Prof Darley (Co-app). 2021-2025: £146,000.

Saudi Arabia Cultural Mission PhD Studentship. Identification and validation of novel therapeutic targets and biomarkers in acute myeloid leukaemia. Prof Darley (PI), Prof Tonks (Co-app). 2021-2025: £142,000.

Wellcome ISSF Translational kickstart award. PFKFB3 translation in AML. A Tonks (PI), R Darley, S Knaper (Co-app).  2020-2021.  £37,645.

Wellcome ISSF Translational kickstart award. Screening the anticancer activity of novel antibiotic polymer therapeutics.  (Elain Ferguson PI, A Tonks, Co-app and Arwyn Jones Co-app).  2019-2020.  £49,645.

PhD Studentship. The role Wnt signalling in blood stem cell development and in acute myeloid leukaemia Prof Darley (PI), Dr Tonks (Co-app). 2018-2021: £75,000.

PhD Studentship. The Role of Protein Kinase C Epsilon in the Pathogenesis and Treatment Resistance of Acute Myeloid Leukaemia. Prof Darley (PI), Dr Tonks (Co-app). 2017-2020: £75,000.

PhD Studentship. Use of iTRAQ Mass Spectrometry to identify the mechanism of developmental disruption induced by RUNX1-ETO. Dr Tonks (PI), Prof Darley (Co-app). 2017-2020: £75,000

Cancer Research Wales: PhD Studentship. The role of Runx3 in leukaemogenesis. Dr Tonks (PI), Prof Darley (Co-app). 2017-2020: £109,301.

Welsh Government/HEFCW: Project. Evaluation of novel CD200:CD200R blockade cancer immunotherapy. Dr Patel (PI), Dr Tonks (Co-app), Prof Darley (Co-app) et al, 2016-2017: £50,000.

MRC: Project CiC. Development of an in vivo pre-clinical model to test the blockade of CD200-CD200R using a humanised anti-CD200 antibody for the treatment of patients with AML. Dr Tonks (PI), Prof Darley (Co-I), Dr Knapper (Co-I), Dr Afonso (Co-I). 2016-2018: £63,867.

MRC: Project P2D. Biomarker discovery for acute myeloid leukaemia using a proteomic approach. Prof Darley (PI), Dr Tonks (Co-I). 2016-2017. £25,000.

Bloodwise. Specialist Programme Renewal. Targeting the ROS axis. Prof Darley (Co-PI), Dr Tonks (Co-PI), Dr Knapper (Co-app). 2015 – 2018. £657,000K. LLR grant number ref: 15018.

Cancer Research Wales: PhD Studentship. Mechanisms dysregulating canonical Wnt signalling in acute myeloid leukaemia. Prof Darley (PI), Dr Tonks (Co-app). 2013-2017. £116,747.

Tenovus: PhD Studentship. The role of Reactive Oxygen Species (ROS) and glycolytic metabolism in leukaemogenesis. Dr Tonks (PI), Prof Darley (Co-app) 2013 – 2017. £89,953.

Supervision

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

Current supervision

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Rehab Alanazi

Research student

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Maryam Alanazi

Research student

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Maryam Halawi

Research student

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Owen Hughes

Research student

Hind Alqahtani

Research student

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Abdulsalam Alruwaili

Research student

Past projects

2018-2022 Miss Aleksandra Azevedo PhD Use of itraq mass spectrometry to identify the mechanism of developmental disruption induced by RUNX1-ETO Main-supervisor  (with co- supervisor RL Darley)
2020 - 2021 Corey Chapman MRES Role of S100A11 proteins in AML Main-supervisor   
2017 Gabi Wogenstein Erasmus The Role of S100A11 in Leukaemogenesis Main-supervisor   
2017-2021 Miss Ana Catarina Menezes PhD The role of RUNX3 in acute myeloid leukaemia and normal human haematopoietic development Main-supervisor  (with co- supervisor RL Darley)
2017-2021 Miss Rachael Nicholson PhD The role of protein kinase c epsilon in the pathogenesis and treatment resistance of acute myeloid leukaemia Co-supervisor  (with main supervisor RL Darley)
2017-2020 Mr Ali Mahmoud Sharif Abdelfattah PhD Signalling/transcriptional mechanisms regulating haematopoietic and leukaemic stem cells in acute myeloid leukaemia Co-supervisor  (with main supervisor N Rodrigues)
2015-2019 Mr Bader Shayah G. Alanazi PhD The role of S100A proteins in AML Main-supervisor  (with co- supervisor RL Darley, S Knapper)
2014 Christabel Dixon MRES The role of RUNX3 in leukaemogenesis                                                                Main-supervisor  
2014 Esizaze Ozekhome-Mike MRES Generation of a RUNX3 retroviral expression vector and optimisation of RUNX3 protein detection by western blot   Main-supervisor  
2014 Anna Stolz MRES Generating a RUNX3 knock down model in haematological cell lines  Main-supervisor  
2013 Mr Andrew Robinson MRES Does RUNX1-ETO modulate RUNX3 expression ?   Main-supervisor  
2013 Ms Karine Pina MRES The expression of RUNX1-ETO modulates the production of reactive oxygen species in normal primary haematopoeitic cells?  Main-supervisor  
2013-2017 Mr Andrew Robinson PhD The role of Ras and ROS in glycolytic metabolism in AML Main-supervisor  (with co-supervisor RL Darley)
2013-2017 Miss Jenna Ridsdale PhD Mechanisms regulating aberrant Wnt signalling in AML Co-supervisor  (with main supervisor RL Darley)
2010-2014 Miss Lucy Hopkins PhD Identification of therapeutic targets in RAS mediated ROS production in AML Main-supervisor  (with co-main supervisor RL Darley)
2009-2013 Miss Sarah Daud PhD Role of TCF7L2 in AML Main-supervisor  (with co-supervisor RL Darley)
2007-2011 Mr Rhys Morgan PhD The role of g-catenin in normal and malignant haematopoiesis. Co-supervisor  (with main supervisor RL Darley)
2006-2010 Mr Paul Hole PhD The role of Reactive Oxygen Species in AML. Main-supervisor  (with co- supervisor RL Darley)
2003-2006 Mr Nagi Gebril MD The role of arsenic trioxide in the treatment of APL and multiple myeloma Main-supervisor  (with co- supervisor AK Burnett)