![Alex Tonks BSc (Hons), PhD, FHEA](https://profiles-cardiff.imgix.net/attachments/4119?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Yr Athro Alex Tonks
(Translated he/him)
BSc (Hons), PhD, FHEA
Senior Lecturer
- Ar gael fel goruchwyliwr ôl-raddedig
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
2024
- Rizzo, S., Varache, M., Sayers, E. J., Jones, A. T., Tonks, A., Thomas, D. W. and Ferguson, E. L. 2024. Modification of the antibiotic, colistin, with dextrin causes enhanced cytotoxicity and triggers apoptosis in myeloid leukemia. International Journal of Nanomedicine 19, pp. 5419-5437. (10.2147/IJN.S449185)
- Sorouri Khorashad, J., Rizzo, S. and Tonks, A. 2024. Reactive oxygen species and its role in pathogenesis and resistance to therapy in acute myeloid leukemia. Cancer Drug Resistance 7, article number: 5. (10.20517/cdr.2023.125)
2023
- Ullah, S. et al. 2023. Whole exome sequence of Pakistani acute lymphocytic leukemia patient from Pakhtuns ancestry reveal the novel genetic variant characterization in the GLDC gene. Journal of Biotechnology and Biomedicine 6(3), pp. 409-420. (10.26502/jbb.2642-91280103)
- Rastogi, N. et al. 2023. Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia. Leukemia 37, pp. 276-287. (10.1038/s41375-022-01801-z)
- Wagstaff, M. et al. 2023. Crosstalk between β-catenin and WT1 signalling activity in acute myeloid leukemia [Letters to the Editor]. Haematologica 108(1) (10.3324/haematol.2021.280294)
2022
- Morgan, H. J. et al. 2022. CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis. Journal of Clinical Investigation 132(21), article number: e150750. (10.1172/JCI150750)
- Menezes, A. C. et al. 2022. Increased expression of RUNX3 inhibits normal human myeloid development. Leukemia 36, pp. 1769-1780. (10.1038/s41375-022-01577-2)
- Ullah, S., Tonks, A., Ullah Khan, A., Alruwaili, A. M. and lodhi, M. A. 2022. A Case report of rare disease Prolidase deficiency in a 15-year-old Pakistan boy. Journal of Rare Diseases Research & Treatment 7(2), pp. 1-4. (10.29245/2572-9411/2022/2.1206)
- Nicholson, R. et al. 2022. Protein kinase C epsilon overexpression is associated with poor patient outcomes in AML and promotes daunorubicin resistance through p-glycoprotein-mediated drug efflux. Frontiers in Oncology 12, article number: 840046. (10.3389/fonc.2022.840046)
- Hillier, J. et al. 2022. The BCAT1 CXXC motif provides protection against ROS in acute myeloid leukaemia cells. Antioxidants 11(4), article number: 683. (10.3390/antiox11040683)
- Menezes, A. C. et al. 2022. RUNX3 overexpression inhibits normal human erythroid development. Scientific Reports 12, article number: 1243. (10.1038/s41598-022-05371-z)
2021
- Abdelfattah, A. M. et al. 2021. Gata2 haploinsufficiency promotes proliferation and functional decline of HSCs with myeloid bias during aging. Blood Advances 5(20), pp. 4285-4290. (10.1182/bloodadvances.2021004726)
- Robinson, A. J., Darley, R. L. and Tonks, A. 2021. Reactive oxygen species in leukemias: maintaining cancer cell proliferation via redox signaling and changing metabolic homeostasis. Oncotarget 12(10), pp. 952-954. (10.18632/oncotarget.27913)
- Rastogi, N. et al. 2021. Use of an anti-CD200 blocking antibody improves immune responses to AML in vitro and in vivo. British Journal of Haematology 193(1), pp. 155-159. (10.1111/bjh.17125)
- Robinson, A. J., Darley, R. L. and Tonks, A. 2021. Reactive oxygen species and metabolic re-wiring in acute leukemias. In: Piccaluga, P. P. ed. Acute Leukemias. IntechOpen, (10.5772/intechopen.94829)
- Robinson, A. J., Davies, S., Darley, R. L. and Tonks, A. 2021. Reactive oxygen species rewires metabolic activity in acute myeloid leukemia. Frontiers in Oncology 11, article number: 632623. (10.3389/fonc.2021.632623)
- Tonks, A. 2021. Make your cake and eat it: refueling of immune fitness in AML post allo-HCT using baking soda. Immunometabolism 3(1), article number: e210005. (10.20900/immunometab20210005)
2020
- Abate, W., Alrammah, H., Kiernan, M., Tonks, A. J. and Jackson, S. K. 2020. Lysophosphatidylcholine acyltransferase 2 (LPCAT2) co-localises with TLR4 and regulates macrophage inflammatory gene expression in response to LPS. Scientific Reports 10(1), article number: 10355. (10.1038/s41598-020-67000-x)
- Robinson, A. J. et al. 2020. Reactive oxygen species drive proliferation in acute myeloid leukemia via the glycolytic regulator PFKFB3. Cancer Research 80(5), pp. 937-949. (10.1158/0008-5472.CAN-19-1920)
- Alanazi, B. et al. 2020. Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. Leukemia 34(2), pp. 427-440. (10.1038/s41375-019-0596-4)
2019
- Menendez Gonzalez, J. B. et al. 2019. Gata2 as a crucial regulator of stem cells in adult hematopoiesis and acute myeloid leukemia. Stem Cell Reports 13(2), pp. 291-306. (10.1016/j.stemcr.2019.07.005)
- Morgan, R. G. et al. 2019. LEF-1 drives aberrant B-catenin nuclear localization in myeloid leukemia cells. Haematologica 104, pp. 1365-1377., article number: 202846. (10.3324/haematol.2018.202846)
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)
Articles
- Rizzo, S., Varache, M., Sayers, E. J., Jones, A. T., Tonks, A., Thomas, D. W. and Ferguson, E. L. 2024. Modification of the antibiotic, colistin, with dextrin causes enhanced cytotoxicity and triggers apoptosis in myeloid leukemia. International Journal of Nanomedicine 19, pp. 5419-5437. (10.2147/IJN.S449185)
- Sorouri Khorashad, J., Rizzo, S. and Tonks, A. 2024. Reactive oxygen species and its role in pathogenesis and resistance to therapy in acute myeloid leukemia. Cancer Drug Resistance 7, article number: 5. (10.20517/cdr.2023.125)
- Ullah, S. et al. 2023. Whole exome sequence of Pakistani acute lymphocytic leukemia patient from Pakhtuns ancestry reveal the novel genetic variant characterization in the GLDC gene. Journal of Biotechnology and Biomedicine 6(3), pp. 409-420. (10.26502/jbb.2642-91280103)
- Rastogi, N. et al. 2023. Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia. Leukemia 37, pp. 276-287. (10.1038/s41375-022-01801-z)
- Wagstaff, M. et al. 2023. Crosstalk between β-catenin and WT1 signalling activity in acute myeloid leukemia [Letters to the Editor]. Haematologica 108(1) (10.3324/haematol.2021.280294)
- Morgan, H. J. et al. 2022. CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis. Journal of Clinical Investigation 132(21), article number: e150750. (10.1172/JCI150750)
- Menezes, A. C. et al. 2022. Increased expression of RUNX3 inhibits normal human myeloid development. Leukemia 36, pp. 1769-1780. (10.1038/s41375-022-01577-2)
- Ullah, S., Tonks, A., Ullah Khan, A., Alruwaili, A. M. and lodhi, M. A. 2022. A Case report of rare disease Prolidase deficiency in a 15-year-old Pakistan boy. Journal of Rare Diseases Research & Treatment 7(2), pp. 1-4. (10.29245/2572-9411/2022/2.1206)
- Nicholson, R. et al. 2022. Protein kinase C epsilon overexpression is associated with poor patient outcomes in AML and promotes daunorubicin resistance through p-glycoprotein-mediated drug efflux. Frontiers in Oncology 12, article number: 840046. (10.3389/fonc.2022.840046)
- Hillier, J. et al. 2022. The BCAT1 CXXC motif provides protection against ROS in acute myeloid leukaemia cells. Antioxidants 11(4), article number: 683. (10.3390/antiox11040683)
- Menezes, A. C. et al. 2022. RUNX3 overexpression inhibits normal human erythroid development. Scientific Reports 12, article number: 1243. (10.1038/s41598-022-05371-z)
- Abdelfattah, A. M. et al. 2021. Gata2 haploinsufficiency promotes proliferation and functional decline of HSCs with myeloid bias during aging. Blood Advances 5(20), pp. 4285-4290. (10.1182/bloodadvances.2021004726)
- Robinson, A. J., Darley, R. L. and Tonks, A. 2021. Reactive oxygen species in leukemias: maintaining cancer cell proliferation via redox signaling and changing metabolic homeostasis. Oncotarget 12(10), pp. 952-954. (10.18632/oncotarget.27913)
- Rastogi, N. et al. 2021. Use of an anti-CD200 blocking antibody improves immune responses to AML in vitro and in vivo. British Journal of Haematology 193(1), pp. 155-159. (10.1111/bjh.17125)
- Robinson, A. J., Davies, S., Darley, R. L. and Tonks, A. 2021. Reactive oxygen species rewires metabolic activity in acute myeloid leukemia. Frontiers in Oncology 11, article number: 632623. (10.3389/fonc.2021.632623)
- Tonks, A. 2021. Make your cake and eat it: refueling of immune fitness in AML post allo-HCT using baking soda. Immunometabolism 3(1), article number: e210005. (10.20900/immunometab20210005)
- Abate, W., Alrammah, H., Kiernan, M., Tonks, A. J. and Jackson, S. K. 2020. Lysophosphatidylcholine acyltransferase 2 (LPCAT2) co-localises with TLR4 and regulates macrophage inflammatory gene expression in response to LPS. Scientific Reports 10(1), article number: 10355. (10.1038/s41598-020-67000-x)
- Robinson, A. J. et al. 2020. Reactive oxygen species drive proliferation in acute myeloid leukemia via the glycolytic regulator PFKFB3. Cancer Research 80(5), pp. 937-949. (10.1158/0008-5472.CAN-19-1920)
- Alanazi, B. et al. 2020. Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. Leukemia 34(2), pp. 427-440. (10.1038/s41375-019-0596-4)
- Menendez Gonzalez, J. B. et al. 2019. Gata2 as a crucial regulator of stem cells in adult hematopoiesis and acute myeloid leukemia. Stem Cell Reports 13(2), pp. 291-306. (10.1016/j.stemcr.2019.07.005)
- Morgan, R. G. et al. 2019. LEF-1 drives aberrant B-catenin nuclear localization in myeloid leukemia cells. Haematologica 104, pp. 1365-1377., article number: 202846. (10.3324/haematol.2018.202846)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
Book sections
- Robinson, A. J., Darley, R. L. and Tonks, A. 2021. Reactive oxygen species and metabolic re-wiring in acute leukemias. In: Piccaluga, P. P. ed. Acute Leukemias. IntechOpen, (10.5772/intechopen.94829)
Ymchwil
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
- Bloodwise Specialist Programme Renewal. Targets for treatment in AML. Targeting the ROS axis. (Co-PI with Prof Darley.
- Leukaemia and Lymphoma Research.Specialist Programme Renewal. Targets for treatment in AML. £657K; 2013-2015(Co-PI with Prof Darley.
- Leukaemia and Lymphoma Research.Specialist Programme. Targets for treatment in AML. £649K; 2010-2013 (Co-PI with Prof Darley).
- Life Sciences Research Network Wales. Development of novel CD200:CD200R blockade cancer immunotherapy. £50K;2015-2016. (Co-applicant with Dr G Patel(PI)).
- 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)).
- Tenovus Cancer Care. PhD studentship. The role of ROS and glycolytic metabolism in leukaemogenesis.£89K; 2013-2016.
- Cancer Research Wales PhD studentship. Mechanisms dysregulating canonical Wnt signalling in acute myeloid leukaemia. £116K; 2013-2016 (co-applicant with Prof Darley (PI))
- NISCHR. NISCHR Cancer ResearchGrouping. ~£75K; 2010-2015. (Co-applicant with Prof Griffiths (PI)).
- Kay Kendall Leukaemia Research. The role of ROS in leukaemogenesis. £129K; 2010-2012. (Co-applicant with Prof Darley (PI)).
- 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
Goruchwyliaeth gyfredol
Maryam Alanazi
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Maryam Halawi Halawi
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Owen Hughes
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Hind Alqahtani
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Abdulsalam Alruwaili
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