Dr Martin Zeidler
School of Biosciences
Reader in Cell Signalling
m.zeidler@sheffield.ac.uk
+44 114 222 6093
+44 114 222 6093
+44 114 222 6094
(Lab phone)
Firth Court
Full contact details
Dr Martin Zeidler
School of Biosciences
Firth Court
Western Bank
Sheffield
S10 2TN
School of Biosciences
Firth Court
Western Bank
Sheffield
S10 2TN
- Profile
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Brief career history
- 2007-present: Reader, University of Sheffield, UK.
- 2006-2007: Senior Lecturer, University of Sheffield, UK.
- 2001-2006: Emmy Noether Independent Group Leader, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
- 1996-2001: Postdoctoral Fellow, Department of Genetics, Harvard Medical School, Boston, MA, USA
- 1991-1996: Pre-doctoral student at the European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
- 1987-1991: BSc in Biology with European Studies (German), The University of Sussex, Brighton, UK.
- Research interests
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Research interests
My lab is interested in identifying and analysing regulators of the JAK/STAT pathway– a signaling cascade frequently misactivated in haematopoietic malignancies.
We use both high throughput RNAi screening technologies and developmental genetic assays in Drosophila to determine the mechanisms of action of pathway regulators and their interactions in vivo.
JAK/STAT signalling in development and disease
My lab studies the regulators and roles of the JAK/STAT signal transduction cascade using a combination of human cell based approaches, Drosophila-based genetic screening and in vivo biology.
This work is aimed at generating insights into human inflammatory and haematopoietic disease.
The JAK/STAT pathway transduces the signals provided by multiple cytokines, growth factors and interferons. As a consequence, it plays a central role in development, cellular proliferation, stem cell maintenance, haematopoiesis and immunity.
In addition, inappropriate pathway activation is also linked to a wide range of human diseases including cancers, leukaemias, myeloproliferative neoplasms (MPNs) and inflammatory diseases such as rheumatoid arthritis.
Conserved throughout evolution, the pathways biological roles have also been largely maintained and as a result, many of the findings made in low complexity model systems such as Drosophila are applicable to humans.
The Zeidler lab has collaborations with a number of high profile groups including that of Tony Green (Cambridge) and Stefan Constantinescu (Brussels).
I have also collaborated and co-supervised joint PhD students with the Strutt and Smythe labs (BMS) and the Bellantuono lab (Human Metabolism).
In the future, I anticipate working more closely on Drosophila haematopoiesis (with lab of Iwan Evans) and on inflammatory aspects of JAK/STAT signalling humans.
In addition, we are also developing Zebrafish models of human myeloproliferative neoplasms in collaboration with the laboratory of Dr Rob Wilkinson (Cardiovascular Science). Insights gained from this work will also inform analysis using patient material which will be undertaken with Sally Thomas and John Snowden (NHS, Haematology).
Finally, ‘drug repurposing’ relating to our discovery of Methotrexate as a potent inhibitor of JAK/STAT pathway signalling will also be pursued.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Low-dose methotrexate in myeloproliferative neoplasm models.. Haematologica, 102, e336-e339. View this article in WRRO
- Methotrexate Is a JAK/STAT Pathway Inhibitor. PLOS ONE, 10(7). View this article in WRRO
- Control of tissue morphology by Fasciclin III-mediated intercellular adhesion.. Development, 140(18), 3858-3868.
- Gα73Β is a downstream effector of JAK/STAT signaling and a regulator of Rho1 in Drosophila hematopoiesis. J Cell Sci.
- Identification of JAK/STAT signalling components by genome-wide RNA interference.. Nature, 436(7052), 871-875.
All publications
Journal articles
- Case report: Effectiveness of low-dose methotrexate monotherapy in post-essential thrombocythemia myelofibrosis. Frontiers in Medicine, 11. View this article in WRRO
- Macrophage subpopulation identity in Drosophila is modulated by apoptotic cell clearance and related signalling pathways. Frontiers in Immunology, 14. View this article in WRRO
- Evaluating the molecular properties and function of ANKHD1, and Its role in cancer. International Journal of Molecular Sciences, 24(16). View this article in WRRO
- Identification of functionally distinct macrophage subpopulations in Drosophila.. Elife, 10.
- Integration of JAK/STAT receptor/ligand trafficking, signalling and gene expression in Drosophila melanogaster cells. Journal of Cell Science, 133.
- How does methotrexate work?. Biochemical Society Transactions, 48(2), 559-567.
- JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy. Journal of Leukocyte Biology, 106(5), 1063-1068. View this article in WRRO
- Low‐dose methotrexate: potential clinical impact on haematological and constitutional symptoms in myeloproliferative neoplasms. British Journal of Haematology, 187(3).
- ZOLEDRONATE EXTENDS LIFESPAN AND HEALTHSPAN IN VIVO. Innovation in Aging, 2(suppl_1), 545-545.
- A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability.. Journal of Cell Science, 131(13). View this article in WRRO
- Ankyrin repeat and Single KH domain 1 (ANKHD1) drives renal cancer cell proliferation via binding to and altering a subset of miRNAs.. The Journal of Biological Chemistry, 293, 9570-9579. View this article in WRRO
- Low-dose methotrexate in myeloproliferative neoplasm models.. Haematologica, 102, e336-e339. View this article in WRRO
- Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran. Molecular Biology of the Cell, 27(3), 421-598. View this article in WRRO
- The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. British Journal of Cancer, 113(3), 365-371. View this article in WRRO
- Methotrexate Is a JAK/STAT Pathway Inhibitor. PLOS ONE, 10(7). View this article in WRRO
- Effect of methotrexate on JAK/STAT pathway activation in myeloproliferative neoplasms. The Lancet, 385, S98-S98.
- G 73B is a downstream effector of JAK/STAT signalling and a regulator of Rho1 in Drosophila haematopoiesis. Development, 141(3), e308-e308.
- Drosophila SOCS36E negatively regulates JAK/STAT pathway signaling via two separable mechanisms.. Mol Biol Cell, 24(18), 3000-3009. View this article in WRRO
- Control of tissue morphology by Fasciclin III-mediated intercellular adhesion.. Development, 140(18), 3858-3868.
- Localised JAK/STAT pathway activation is required for Drosophila wing hinge development.. PLoS One, 8(5), e65076. View this article in WRRO
- The Drosophila JAK-STAT pathway. JAK-STAT, 2(3).
- Gα73Β is a downstream effector of JAK/STAT signaling and a regulator of Rho1 in Drosophila hematopoiesis. J Cell Sci.
- Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway.. BMC Genomics, 13, 506. View this article in WRRO
- Matters of the heart. JAK-STAT, 1(3), 208-210. View this article in WRRO
- Simplified Insertion of Transgenes Onto Balancer Chromosomes via Recombinase-Mediated Cassette Exchange.. G3 (Bethesda), 2(5), 551-553. View this article in WRRO
- Modulation of human JAK-STAT pathway signaling by functionally conserved regulators. JAK-STAT, 1(1), 34-43. View this article in WRRO
- Drosophila SOCS Proteins.. J Signal Transduct, 2011, 894510. View this article in WRRO
- Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3.. Cell Signal, 23(5), 920-927.
- Differential activities of the Drosophila JAK/STAT pathway ligands Upd, Upd2 and Upd3. Cellular Signalling, 23(5), 920-927.
- Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking. Development, 137(21), e2107-e2107.
- Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking.. J Cell Sci, 123(Pt 20), 3457-3466.
- Transcriptional targets of Drosophila JAK/STAT pathway signalling as effectors of haematopoietic tumour formation.. EMBO Rep, 11(3), 201-207.
- Plasticity of Drosophila Stat DNA binding shows an evolutionary basis for Stat transcription factor preferences.. EMBO Rep, 9(11), 1114-1120. View this article in WRRO
- Unphosphorylated STATs go nuclear.. Curr Opin Genet Dev, 18(5), 455-460.
- MsSOCS expression indicates a potential role for JAK/STAT signalling in the early stages of Manduca sexta spermatogenesis.. Insect Mol Biol, 17(5), 475-483.
- Identification of JAK/STAT pathway regulators--insights from RNAi screens.. Semin Cell Dev Biol, 19(4), 360-369.
- JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions.. Development, 133(14), 2605-2616.
- Mutational analysis reveals separable DNA binding and trans-activation of Drosophila STAT92E.. Cell Signal, 18(6), 819-829.
- JAK/STAT signalling in Drosophila controls cell motility during germ cell migration.. Dev Dyn, 235(4), 958-966.
- Identification of Drosophila genes modulating Janus kinase/signal transducer and activator of transcription signal transduction.. Genetics, 172(3), 1683-1697.
- Ken & barbie selectively regulates the expression of a subset of Jak/STAT pathway target genes.. Curr Biol, 16(1), 80-88.
- Characterisation of Upd2, a Drosophila JAK/STAT pathway ligand.. Dev Biol, 288(2), 420-433.
- Identification of JAK/STAT signalling components by genome-wide RNA interference.. Nature, 436(7052), 871-875.
- Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation.. Oncogene, 24(15), 2503-2511.
- Temperature-sensitive control of protein activity by conditionally splicing inteins.. Nat Biotechnol, 22(7), 871-876.
- A sensitized genetic screen to identify novel regulators and components of the Drosophila janus kinase/signal transducer and activator of transcription pathway.. Genetics, 165(3), 1149-1166.
- Cloning and expression of Drosophila SOCS36E and its potential regulation by the JAK/STAT pathway.. Mech Dev, 117(1-2), 343-346.
- Multiple roles for four-jointed in planar polarity and limb patterning.. Dev Biol, 228(2), 181-196.
- Sex determination: co-opted signals determine gender.. Curr Biol, 10(18), R682-R684.
- The roles of the Drosophila JAK/STAT pathway.. Oncogene, 19(21), 2598-2606.
- The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification.. Curr Biol, 9(23), 1363-1372.
- Polarity determination in the Drosophila eye: a novel role for unpaired and JAK/STAT signaling.. Genes Dev, 13(10), 1342-1353.
- six-banded, a novel Drosophila gene, is expressed in 6 segmental stripes during embryonic development and in the eye imaginal disc.. Biol Chem, 378(10), 1119-1124.
- Drosophila TFIIA-S is up-regulated and required during Ras-mediated photoreceptor determination.. Genes Dev, 10(1), 50-59.
- Drosophila TFIIA directs cooperative DNA binding with TBP and mediates transcriptional activation.. Genes Dev, 8(19), 2313-2323.
- Comparative anatomy of serotonin-like immunoreactive neurons in isopods: putative homologues in several species.. J Comp Neurol, 347(4), 553-569.
- Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner. The Journals of Gerontology: Series A.
- Zoledronate extends healthspan and survival via the mevalonate pathway in a FOXO-dependent manner.
Chapters
Conference proceedings papers
- Methotrexate Is a Suppressor of JAK/STAT Pathway Activation Which Inhibits JAK2V617F Induced Signalling. Blood, Vol. 124(21) (pp 4577-4577)
- Examination of cell signalling involved in the convergent extension movements during Drosophila embryonic hindgut development. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S176-S176)
- The University of Sheffield RNAi Screening facility: Genome-wide RNAi screens in Drosophila cells using a 2nd generation in silico optimized library. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S290-S290)
Preprints
- Macrophage subpopulation identity inDrosophilais modulated by apoptotic cell clearance and related signalling pathways, Cold Spring Harbor Laboratory.
- A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability, Cold Spring Harbor Laboratory.
- Identification of functionally-distinct macrophage subpopulations regulated by efferocytosis in Drosophila.
- Low-dose methotrexate in myeloproliferative neoplasm models.. Haematologica, 102, e336-e339. View this article in WRRO
- Grants
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Funding
- CR-UK Fellowship
- UoS Schemes
- Cancer Research UK
- Wellcome Trust
- Teaching activities
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Undergraduate
- BMS109 Lab Skills & Skills Sessions
- BMS242/243 Principles of Developmental Biology
- BMS301 Membrane Receptors
- BMS356 Biomedical Technology & Drug Discovery (Co-ordinator)
Masters (MSc)
- BMS6083 Practical Developmental Genetics
- Professional activities and memberships
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- CR-UK Senior Cancer Research Fellow
- Former Emmy Noether Career Development Fellow and CRUK Senior Cancer Research Fellow
- Founder and academic director of the Sheffield RNAi Screening Facility (SRSF)
- Supervised 13x PhD students
- Journal Editor and reviewer for many journals and grant awarding bodies
- Fellow of the Higher Education Academy (FHEA)
- Teaching at all Undergraduate levels