![Martin Ruthardt](https://profiles-cardiff.imgix.net/attachments/2592?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Martin Ruthardt
Senior Lecturer
- RuthardtM@caerdydd.ac.uk
- Prif Adeilad yr Ysbyty, Ystafell Room 183, 7th floor B-C link, Ysbyty Athrofaol Cymru, Parc y Mynydd Bychan, Caerdydd, CF14 4XN
Cyhoeddiad
2022
- Chiriches, C. et al. 2022. Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia. Annals of Hematology 101, pp. 2179-2193. (10.1007/s00277-022-04905-9)
- Chiriches, C. et al. 2022. Understanding a high-risk acute myeloid leukemia by analyzing the interactome of its major driver mutation. PLoS Genetics 18(10), article number: e1010463. (10.1371/journal.pgen.1010463)
2021
- Mian, A. A. et al. 2021. Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR/ABL1 and its resistance and compound mutants BCR/ABL1T315I and BCR/ABL1T315I-E255K. Annals of Hematology 100, pp. 2023-2029. (10.1007/s00277-020-04357-z)
- Regev, O., Kidan, N., Nicola, M., Khamisie, H., Ruthardt, M. and Mahajna, J. 2021. Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells. Archives of Medical Science 17(1), pp. 266–274. (10.5114/aoms.2020.101042)
2019
- Mian, A. A. et al. 2019. The phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis. Leukemia 33, pp. 2319-2323. (10.1038/s41375-019-0468-y)
2017
- Kidan, N. et al. 2017. Ectopic expression of snail and twist in Ph+ leukemia cells upregulates CD44 expression and alters their differentiation potential. Journal of Cancer 8(19), pp. 3952-3968. (10.7150/jca.19633)
2016
- Ratzon, E., Najajreh, Y., Salem, R., Khamaisie, H., Ruthardt, M. and Mahajna, J. 2016. Platinum (IV)-fatty acid conjugates overcome inherently and acquired Cisplatin resistant cancer cell lines: an in-vitro study. BMC Cancer 16, article number: 140. (10.1186/s12885-016-2182-8)
- Haberbosch, I., Rafiei, A., Oancea, C., Ottmann, O., Ruthardt, M. and Mian, A. 2016. BCR: a new target in resistance mediated by BCR/ABL-315I?. Genes & Cancer 7(1-2), pp. 36-46.
2015
- Mian, A. A. et al. 2015. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation. Leukemia 29(5), pp. 1104-1114. (10.1038/leu.2014.326)
- Rafiei, A. et al. 2015. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive Acute Lymphatic Leukemia. PLOS Genetics 11(4), article number: e1005144. (10.1371/journal.pgen.1005144)
- Mian, A. A. et al. 2015. Potential use of allosteric inhibitors as strategy to overcome drug resistance in Ph-positive leukemia. International Journal of Molecular Medicine 36, pp. S26-S26.
2014
- Mian, A., Rafiei, A., Oancea, C., Ottmann, O. and Ruthardt, M. 2014. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome positive Acute Lymphatic Leukemia. Blood 124(21), article number: 2402.
- Roos, J. et al. 2014. 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia. Cancer Research 74(18), pp. 5244-5255. (10.1158/0008-5472.CAN-13-3012)
2008
- Beissert, T., Hundertmark, A., Kaburova, V., Travaglini, L., Mian, A. A., Nervi, C. and Ruthardt, M. 2008. Targeting of the N-terminal coiled coil oligomerization interface by a helix-2 peptide inhibits unmutated and imatinib-resistant BCR/ABL. International Journal of Cancer 122(12), pp. 2744-2752. (10.1002/ijc.23467)
Articles
- Chiriches, C. et al. 2022. Activation of signaling pathways in models of t(6;9)-acute myeloid leukemia. Annals of Hematology 101, pp. 2179-2193. (10.1007/s00277-022-04905-9)
- Chiriches, C. et al. 2022. Understanding a high-risk acute myeloid leukemia by analyzing the interactome of its major driver mutation. PLoS Genetics 18(10), article number: e1010463. (10.1371/journal.pgen.1010463)
- Mian, A. A. et al. 2021. Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR/ABL1 and its resistance and compound mutants BCR/ABL1T315I and BCR/ABL1T315I-E255K. Annals of Hematology 100, pp. 2023-2029. (10.1007/s00277-020-04357-z)
- Regev, O., Kidan, N., Nicola, M., Khamisie, H., Ruthardt, M. and Mahajna, J. 2021. Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells. Archives of Medical Science 17(1), pp. 266–274. (10.5114/aoms.2020.101042)
- Mian, A. A. et al. 2019. The phosphatase UBASH3B/Sts-1 is a negative regulator of Bcr-Abl kinase activity and leukemogenesis. Leukemia 33, pp. 2319-2323. (10.1038/s41375-019-0468-y)
- Kidan, N. et al. 2017. Ectopic expression of snail and twist in Ph+ leukemia cells upregulates CD44 expression and alters their differentiation potential. Journal of Cancer 8(19), pp. 3952-3968. (10.7150/jca.19633)
- Ratzon, E., Najajreh, Y., Salem, R., Khamaisie, H., Ruthardt, M. and Mahajna, J. 2016. Platinum (IV)-fatty acid conjugates overcome inherently and acquired Cisplatin resistant cancer cell lines: an in-vitro study. BMC Cancer 16, article number: 140. (10.1186/s12885-016-2182-8)
- Haberbosch, I., Rafiei, A., Oancea, C., Ottmann, O., Ruthardt, M. and Mian, A. 2016. BCR: a new target in resistance mediated by BCR/ABL-315I?. Genes & Cancer 7(1-2), pp. 36-46.
- Mian, A. A. et al. 2015. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation. Leukemia 29(5), pp. 1104-1114. (10.1038/leu.2014.326)
- Rafiei, A. et al. 2015. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive Acute Lymphatic Leukemia. PLOS Genetics 11(4), article number: e1005144. (10.1371/journal.pgen.1005144)
- Mian, A. A. et al. 2015. Potential use of allosteric inhibitors as strategy to overcome drug resistance in Ph-positive leukemia. International Journal of Molecular Medicine 36, pp. S26-S26.
- Mian, A., Rafiei, A., Oancea, C., Ottmann, O. and Ruthardt, M. 2014. The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome positive Acute Lymphatic Leukemia. Blood 124(21), article number: 2402.
- Roos, J. et al. 2014. 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia. Cancer Research 74(18), pp. 5244-5255. (10.1158/0008-5472.CAN-13-3012)
- Beissert, T., Hundertmark, A., Kaburova, V., Travaglini, L., Mian, A. A., Nervi, C. and Ruthardt, M. 2008. Targeting of the N-terminal coiled coil oligomerization interface by a helix-2 peptide inhibits unmutated and imatinib-resistant BCR/ABL. International Journal of Cancer 122(12), pp. 2744-2752. (10.1002/ijc.23467)
Ymchwil
My collaborators and Ihave an interdisciplinary approach on mechanisms of leukemogenesis with a focus on high risk acute leukemia. Our aim is to understand resistance mechanisms and how to hit the weak points of these leukemias for an improvement of already existing therapy concepts. This is always accompanied by the development of novel hypothesis driven molecular therapy approaches. The final goal of all this is to substitute therapy schemes e.g. in acute myeloid leukemia that are in place nearly unchanged for the last thirty years and only profited from improved care and the advances of heterologeous stem cell transplantation.
Interdisciplinary for us is not only a buzz word but something that we believe to be indispensable to achieve our aims Therefore we are able to integrate leukemia stem cell biology with drug development, all types of proteomic approaches, high profile bioinformatics, and clinical risk stratification based on big next generation sequencing data sets.
My collaborators and I contributed successfully to
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understanding all trans retinoic acid (ATRA) response/resistance in acute promyelocytic leukemia (APL/AML-M3).
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understanding of leukemic stem cells as targets of Arsen Trioxyde (ATO) in APL and thereby of the mechanisms on that the novel "chemotherapy free" approach to treat APL by ATRA/ATO is based on.
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determining the importance of leukemic stem cells for the initiation and maintenance of AML and the role of key factors of the WNT-signaling pathway in leukemic stem cells.
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disclosing the contribution of reciprocal translocation products such as ABL-BCR in the t(9;22) to the induction and maintenance of acute and chronic leukemia.
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establishing novel compounds (e.g. PF114) for the treatment of resistant acute and chronic leukemia.
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determining the target cell of t(6;9)DEK-NUP214 mediated transformation and thus the cells to be hit in order to eradicate this high risk acute leukemia.
My collaborators and I are developing our research further by integrating genomics and proteomics (e.g. phospho-proteomics, interactomics) and the bioinformatics needed for a correct elaboration of these big data sets in the solution of our scientific questions.
In addition, we elaborate NSG data sets from big AML and MDS patient cohorts (targeted sequencing, whole exome sequencing and whole genome sequencing) by different algorithms to answer questions about risk stratification, therapy response, and pathogenetic mechanisms. Final aim is to expand the application of these algorithms to other subtypes of cancer.
Bywgraffiad
Instruction
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1975 - 1984 |
Baccalaureate (humanistic/scientific), Humboldt-Gymnasium, Ulm, Germany |
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1985 - 1993 |
Graduation in Medicine, Università degli Studi, Perugia, Italy |
Research and Professional Experiences
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1990 |
Stage in the Institute of Biochemistry, Medical School of the University Strasbourg, France: „Characterization of the DNA-binding domain of ETS (P. Chambon, B. Wasylyk). |
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1991 – 1993 |
MD thesis: „Acute promyelocytic leukaemia: evaluation of the response to therapy by RT-PCR“ in the Laboratory of Molecular Biology (P.G. Pelicci), Università di Perugia, Italy |
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1993 – 1996 |
Postdoctoral in the Laboratory of Molecular Biology (P.G. Pelicci) at the Institute of Oncological Sciences, Università di Perugia, Italy |
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1996 - 2001 |
Group Leader „The molecular biology of leukemogenesis“, Department of Hematology, Medical School of the Goethe University, Frankfurt, GermanyV-MR |
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2002-2015 |
Head of the Laboratory of Tumor Stem Cell Biology, Department of Hematology, University Medical School, Frankfurt, Germany |
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since 2015 |
Senior Lecturer in Haematology, Department of Haematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, UK |
Anrhydeddau a dyfarniadau
Fellowships and Awards
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1990 |
Student Fellowship „Erasmus“by the EU – Strasbourg, France |
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1994 - 1996 |
Dr. Mildred Scheel International Fellowship (German Cancer Aid) |
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2005 |
Alfred und Angelika Gutermuth-Award for Leukaemia Research |
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2010 |
Heinrich und Erna Schauffler Award for Translational Tumor Research |
Safleoedd academaidd blaenorol
Degrees/Qualifications
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February 1993 |
Graduation in Medicine (grade 108/110), Università Perugia, Italy |
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February 1993 |
Doctoral degree (M.D.), Università Perugia, Italy |
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April 1993 |
Approbation as Physician by the Italian Ministry of Public Health, Rome, Italy, and the Landesprüfungsamt Baden Württemberg, Germany |
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May 2003 |
Habilitation for Experimental Medicine at Goethe University, Frankfurt, Germany |
Pwyllgorau ac adolygu
I led an International DFG funded Collaboration Research Group (German Israel Palestine) and was involved in setting up both National (German) Collaborative Research Groups (funding bodies: DFG; German Cancer Aid, Federal German and Regional Hesse Governments) as well International Collaboration (EU funded European Leukemia Network).
Journal Editing: Member of the Editorial Board of BMC Cancer (2010-2015).
Routinely Reviewing Manuscripts: Blood, Leukemia, Cancer Research, Clinical Cancer Research, Oncogene and several others.
Routinely Reviewing Grants: National (CR-UK, KKLF, Bloodwise) and International funding bodies (Deutsche Forschungsgemeinschaft – DFG, German Cancer Aid, José Carreras Leukemia Foundation, Wilhelm-Sander Foundation (all German), Associazione Ricerca e Lotta contro il Cancro (AIRC, Italy); INSERM (France), Austrian Academy of Science (Austria).