Professor Alex Tonks
(he/him)

BSc (Hons), PhD, FHEA

Personal Chair, Division of Cancer and Genetics

: Available for postgraduate supervision

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.

Date
Type

2018

Hassan, N., Ali, A., Withycombe, C., Ahluwalia, M., Al-Nasseri, R. H., Tonks, A. and Morris, K. 2018. TET-2 up-regulation is associated with the anti-inflammatory action of Vicenin-2. Cytokine 108, pp. 37-42. (10.1016/j.cyto.2018.03.016)

2015

Munje, C., Hills, R. K., Whetton, A., Burnett, A. K., Darley, R. L. and Tonks, A. 2015. Cord blood-derived quiescent CD34+ cells are more transcriptionally matched to AML blasts than cytokine-induced normal human hematopoietic CD34+ cells. Gene Expression: International Journal of Molecular and Cellular Science 16(4), pp. 169-175. (10.3727/105221615X14399878166159)
Coles, S. J. et al. 2015. The immunosuppressive ligands PD-L1 and CD200 are linked in AML T-cell immunosuppression: identification of a new immunotherapeutic synapse. Leukemia 29, pp. 1952-1954. (10.1038/leu.2015.62)

2014

Morgan, R. G., Ridsdale, J., Tonks, A. and Darley, R. L. 2014. Factors affecting the nuclear localization of β-Catenin in normal and malignant tissue. Journal of Cellular Biochemistry 115(8), pp. 1351-1361. (10.1002/jcb.24803)
Zabkiewicz, J., Pearn, L., Hills, R., Morgan, R. G., Tonks, A., Burnett, A. K. and Darley, R. 2014. The PDK1 master kinase is over-expressed in acute myeloid leukemia and promotes PKC-mediated survival of leukemic blasts. Haematologica 99(5), pp. 858-864. (10.3324/haematol.2013.096487)

2013

Hole, P. S. et al. 2013. Overproduction of NOX-derived ROS in AML promotes proliferation and is associated with defective oxidative stress signaling. Blood 122(19), pp. 3322-3330. (10.1182/blood-2013-04-491944)
Morgan, R. G., Pearn, L., Liddiard, K., Pumford, S. L., Burnett, A. K., Tonks, A. and Darley, R. L. 2013. γ-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of β-catenin. Leukemia 27(2), pp. 336-343. (10.1038/leu.2012.221)

2012

Daud, S. S. et al. 2012. Identification of the Wnt signalling protein, TCF7L2 as a significantly overexpressed transcription factor in AML [Abstract]. Blood 120(21), article number: 1281.
Coles, S., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Man, S. T., Darley, R. L. and Tonks, A. 2012. Increased CD200 expression in acute myeloid leukemia is linked with an increased frequency of FoxP3+ regulatory T cells [Letter]. Leukemia 26(9), pp. 2146-2148. (10.1038/leu.2012.75)
Coles, S., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Man, S. T., Darley, R. L. and Tonks, A. 2012. Expression of CD200 on AML blasts directly suppresses memory T-cell function [Letter]. Leukemia 26(9), pp. 2148-2151. (10.1038/leu.2012.77)
Liddiard, K., Burnett, A. K., Darley, R. L. and Tonks, A. 2012. RUNX1-ETO deregulates the proliferation and growth factor responsiveness of human hematopoietic progenitor cells downstream of the myeloid transcription factor, MYCT1 [Letter]. Leukemia 26(1), pp. 177-179. (10.1038/leu.2011.188)

2011

Coles, S., Man, S. T., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Darley, R. L. and Tonks, A. 2011. CD200 inhibits memory Th1 cell function in acute myeloid leukaemia (AML)[Abstract]. Immunology 135(S1), pp. 178. (10.1111/j.1365-2567.2011.03534.x)
Coles, S., Wang, E. C. Y., Man, S. T., Hills, R. K., Burnett, A. K., Tonks, A. and Darley, R. L. 2011. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia. Leukemia 25(5), pp. 792-799. (10.1038/leu.2011.1)
Hole, P. S., Darley, R. L. and Tonks, A. 2011. Do reactive oxygen species play a role in myeloid leukemias?. Blood 117(22), pp. 5816-5826. (10.1182/blood-2011-01-326025)

2010

Zabkiewicz, J., Pearn, L., Hills, R. K., Morgan, R. G., Burnett, A. K., Tonks, A. and Darley, R. L. 2010. PDK1 overexpression in acute myeloid leukemia; Clinical significance and potential as a therapeutic target [Abstract]. Blood 116(21), pp. 892-893.
Morgan, R. G., Pearn, L., Liddiard, K., Hills, R. K., Burnett, A. K., Tonks, A. and Darley, R. L. 2010. Distinct regulation of beta- and gamma-Catenin throughout hematopoietic development contrasts with their cooperative roles in acute myeloid leukemia [Abstract]. Blood 116(21), article number: 1573.
Coles, S., Man, S. T., Hills, R. K., Wang, E. C. Y., Burnett, A. K., Darley, R. L. and Tonks, A. 2010. Over-expression of CD200 un acute myeloid leukemia mediates the expansion of regulatory T-lymphocytes and directly inhibits natural killer cell tumor immunity [Abstract]. Blood 116(21), pp. 218-218.
Liddiard, K., Hills, R. K., Burnett, A. K., Darley, R. L. and Tonks, A. 2010. OGG1 is a novel prognostic indicator in acute myeloid leukaemia. Oncogene 29(13), pp. 2005-2012. (10.1038/onc.2009.462)
Hole, P. S., Pearn, L., Tonks, A. J., James, P. E., Burnett, A. K., Darley, R. L. and Tonks, A. 2010. Ras-induced reactive oxygen species promote growth factor-independent proliferation in human CD34+ hematopoietic progenitor cells. Blood 115(6), pp. 1238-1246. (10.1182/blood-2009-06-222869)

2008

Morris, R. H. K., Tonks, A. J., Jones, K. P., Ahluwalia, M. K., Thomas, A. W., Tonks, A. and Jackson, S. K. 2008. DPPC regulates COX-2 expression in monocytes via phosphorylation of CREB. Biochemical and Biophysical Research Communications 370(1), pp. 174-178. (10.1016/j.bbrc.2008.03.052)

2007

Tonks, A., Pearn, L., Musson, M., Gilkes, A. F., Mills, K. I., Burnett, A. K. and Darley, R. L. 2007. Transcriptional dysregulation mediated by RUNX1-RUNX1T1 in normal human progenitor cells and in acute myeloid leukaemia. Leukemia 21(12), pp. 2495-2505. (10.1038/sj.leu.2404961)
Walsby, E. J., Gilkes, A. F., Tonks, A., Darley, R. L. and Mills, K. I. 2007. FUS expression alters the differentiation response to all-trans retinoic acid in NB4 and NB4R2 cells. British Journal of Haematology 139(1), pp. 94-97. (10.1111/j.1365-2141.2007.06756.x)
Tonks, A. J., Dudley, E., Porter, N. G., Parton, J., Brazier, J. S., Smith, E. L. and Tonks, A. 2007. A 5.8KDa component of manuka honey stimulates immune cells via TLR4. Journal of Leukocyte Biology 82(5), pp. 1147-1155. (10.1189/jlb.1106683)
Tonks, A., Hills, R. K., White, P. C., Rosie, B., Mills, K. I., Burnett, A. K. and Darley, R. L. 2007. CD200 as a prognostic factor in acute myeloid leukaemia. Leukemia 21(3), pp. 566-568. (10.1038/sj.leu.2404559)
Tonks, A., Hills, R. K., White, P. C., Rosie, B., Mills, K. I., Burnett, A. K. and Darley, R. L. 2007. CD200 as a prognostic factor in acute myeloid leukaemia [Letter]. Leukemia 21(3), pp. 566-568. (10.1038/sj.leu.2404559)

2006

Tonks, A., Pearn, L., Mills, K. I., Burnett, A. K. and Darley, R. L. 2006. The sensitivity of human cells expressing RUNX1-RUNX1T1 to chemotherapeutic agents. Leukemia 20(10), pp. 1883-5. (10.1038/sj.leu.2404364)

2005

Tonks, A., Parton, J., Tonks, A. J., Morris, R. H. K., Finall, A., Jones, K. P. and Jackson, S. K. 2005. Surfactant phospholipid DPPC downregulates monocyte respiratory burst via modulation of PKC. AJP Lung Cellular and Molecular Physiology 288(6), pp. 1070-80. (10.1152/ajplung.00386.2004)
Tonks, A., Tonks, A. J., Pearn, L., Mohamad, Z., Burnett, A. K. and Darley, R. L. 2005. Optimized retroviral transduction protocol which preserves the primitive subpopulation of human hematopoietic cells. Biotechnology Progress 21(3), pp. 953-958. (10.1021/bp0500314)

2004

Tonks, A. et al. 2004. Expression of AML1-ETO in human myelomonocytic cells selectively inhibits granulocytic differentiation and promotes their self-renewal. Leukemia 18(7), pp. 1238-1245. (10.1038/sj.leu.2403396)
Tonks, A. et al. 2004. Expression of AML1-ETO in human myelomonocytic cells selectively inhibits granulocytic differentiation and promotes their self-renewal. Leukemia 18(7), pp. 1238-1245. (10.1038/sj.leu.2403396)

2003

Tonks, A. et al. 2003. The AML-1 fusion gene promotes extensive self-renewal of human primary erythroid cells. Blood 101(2), pp. 624-632. (10.1182/blood-2002-06-1732)
Tonks, A. J., Tonks, A., Morris, R. H. K., Jones, K. P. and Jackson, S. K. 2003. Regulation of platelet-activating factor synthesis in human monocytes by dipalmitoyl phosphatidylcholine. Journal of Leukocyte Biology 74(1), pp. 95-101. (10.1189/jlb.1202601)
Tonks, A. et al. 2003. The AML1-ETO fusion gene promotes extensive self-renewal of human primary erythroid cells. Blood 101(2), pp. 624-632. (10.1182/blood-2002-06-1732)

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.

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.

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

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

Rehab Alanazi

Research student

Maryam Alanazi

Research student

Maryam Halawi Halawi

Research student

Owen Hughes

Research student

Hind Alqahtani

Research student

Abdulsalam Alruwaili

Research student

Contact Details

TonksA@cardiff.ac.uk
+44 29207 42235

Professor Alex Tonks
(he/him)

BSc (Hons), PhD, FHEA

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Articles