Research Topics
Genomes and Genes
| Warren AlexanderSummaryAffiliation: The Walter and Eliza Hall Institute of Medical Research Country: Australia Publications
Research Grants
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Detail Information
Publications
Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 geneWarren S Alexander
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Proc Natl Acad Sci U S A 103:16442-7. 2006..The disease in plt1/plt1 mice suggests that, in addition to immune-mediated effects, intrinsic C1Gal-T1 deficiency in megakaryocytes and the kidney may contribute to pathology...
The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune responseWarren S Alexander
The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Center for Cellular Growth Factors, Parkville, 3052 Victoria, Australia
Annu Rev Immunol 22:503-29. 2004....- SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritisPeter K K Wong
Reid Rheumatology Laboratory, Division of Autoimmunity and Transplantation, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
J Clin Invest 116:1571-81. 2006..These findings provide direct in vivo evidence that endogenous SOCS-3 is a critical negative regulator of multiple cell types orchestrating inflammatory joint disease... - Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelinationBen Emery
Department of Neurobiology, Stanford University, Stanford, CA 94305, USA
Proc Natl Acad Sci U S A 103:7859-64. 2006..These results indicate that modulation of SOCS3 expression could facilitate the endogenous response to CNS injury... - The comparative roles of suppressor of cytokine signaling-1 and -3 in the inhibition and desensitization of cytokine signalingSamuel Wormald
Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medicial Research, Parkville, Victoria, Australia
J Biol Chem 281:11135-43. 2006.... - Socs2 and elf5 mediate prolactin-induced mammary gland developmentJessica Harris
Garvan Institute of Medical Research, St Vincent s Hospital, Darlinghurst, New South Wales 2010, Australia
Mol Endocrinol 20:1177-87. 2006..Thus, Socs2 and Elf5 are key members of the set of prolactin-regulated genes that mediate prolactin-driven mammary development... - Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activityJennifer E Fenner
Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Clayton 3168, Australia
Nat Immunol 7:33-9. 2006..Thus, SOCS1 is an important in vivo inhibitor of type I interferon signaling and contributes to balancing its beneficial antiviral versus detrimental proinflammatory effects on innate immunity... - Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory diseaseLorraine Robb
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Proc Natl Acad Sci U S A 102:16333-8. 2005.... - SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potentialGayle M Davey
The Walter and Eliza Hall Institute of Medical Research, Parkville, 3050 Victoria, Australia
J Exp Med 202:1099-108. 2005..Therefore, impaired deletion of highly autoreactive CD8 T cells, together with uncontrolled activation of naive CD8 T cells by homeostatic survival ligands, may provide a basis for the T cell-mediated disease of SOCS-1-/- mice... - Absence of suppressor of cytokine signalling 3 reduces self-renewal and promotes differentiation in murine embryonic stem cellsAriel Forrai
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Stem Cells 24:604-14. 2006..Its absence perturbs the balance between activation of the JAK-STAT and SHP-2-ERK-1/2-MAPK pathways, resulting in less self-renewal and a greater potential for differentiation into the primitive endoderm lineage... - Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammationMark M W Chong
St Vincent s Institute, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia
Blood 106:1668-75. 2005..A dysregulated cytokine network between T cells and macrophages is thus associated with this inflammatory disease. These findings indicate that SOCS-1 is critical in both T cells and macrophages for preventing uncontrolled inflammation... - Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signalingSandra E Nicholson
The Walter and Eliza Hall Institute of Medical Research, Cooperative Research Centre for Cellular Growth Factors, Parkville, Victoria 3052, Australia
Proc Natl Acad Sci U S A 102:2328-33. 2005..This result suggests that the inhibition of signaling occurs through enhanced proteasomal degradation of the EGF-R through SOCS box recruitment of E3 ubiquitin ligase activity... - A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte maturation and causes thrombocytopeniaIan J Majewski
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Proc Natl Acad Sci U S A 103:14146-51. 2006..Although the equivalent mutation to Gata-1Plt13 in humans results in production of GATA-1s, a short protein isoform initiated from a start codon downstream of the mutated initiation codon, Gata-1s was not detected in Gata-1Plt13/+ mice... 
The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cellsStephen J Loughran
Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
Nat Immunol 9:810-9. 2008..We show that Erg is required for definitive hematopoiesis, adult hematopoietic stem cell function and the maintenance of normal peripheral blood platelet numbers...- Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl-/- miceMaria Kauppi
Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Blood 112:3148-53. 2008.... - Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activityIan J Majewski
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
PLoS Biol 6:e93. 2008..These data suggest that PRC2 is required to maintain a specific gene expression pattern in hematopoiesis that is indispensable to normal stem cell function... - Socs3 maintains the specificity of biological responses to cytokine signals during granulocyte and macrophage differentiationBen A Croker
Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Exp Hematol 36:786-98. 2008..The tight regulation by Socs3 of signal transducer and activator of transcription 3 phosphorylation and gene transcription after cytokine receptor ligation significantly influences the fate of myeloid progenitor cells... - Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cellsHong Qian
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 221 84, Sweden
Cell Stem Cell 1:671-84. 2007..Thus, THPO regulates posttransplantation HSC expansion as well as the maintenance of adult quiescent HSCs, of critical importance to avoid postnatal HSC exhaustion... - Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3Hayley A Croom
Signal Transduction Laboratory, St Vincent s Institute, 9 Princes Street, Fitzroy, Victoria 3065, Australia
Mol Immunol 45:2888-96. 2008..This is the first demonstration of functional redundancy within the SOCS family, and has uncovered a vital role for SOCS1 and SOCS3 during two important checkpoints in early T cell development... - Mechanism of crosstalk inhibition of IL-6 signaling in response to LPS and TNFalphaHiu Kiu
Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia
Growth Factors 25:319-28. 2007..Finally, we have identified an additional, novel mechanism of crosstalk inhibition: a reduction in total cellular levels of gp130 following stimulation with LPS and TNFalpha... - Clonogenic mast cell progenitors and their excess numbers in chimeric BALB/c mice with inactivated GATA-1Donald Metcalf
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Victoria, Australia
Proc Natl Acad Sci U S A 104:18642-7. 2007..No excess tissue mast cells were observed in GATA-1(Plt13/+) mice, suggesting that the excess mast cell progenitors in these mice might be generating mast cells with a defective in vivo proliferative or tissue homing capacity... - Mice rendered severely deficient in megakaryocytes through targeted gene deletion of the thrombopoietin receptor c-Mpl have a normal skeletal phenotypeMark J Perry
Anatomy and Clinical Sciences North Bristol, University of Bristol, Southwell Street, Bristol, BS2 8EJ, UK
Calcif Tissue Int 81:224-31. 2007..These results represent the first in vivo evidence that severe megakaryocyte deficiency does not affect bone formation, suggesting that this process is not dependent on normal megakaryocyte number... - Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27Christine Brender
Signal Transduction Laboratory, St Vincent s Institute, Fitzroy, Victoria, Australia
Blood 110:2528-36. 2007..We conclude that enhanced responses to TCR ligation by SOCS3-deficient CD8 T cells are not caused by aberrant TCR-signaling pathways but, rather, that increased IL-27 signaling drives unregulated proliferation in the absence of SOCS3... - Agm1/Pgm3-mediated sugar nucleotide synthesis is essential for hematopoiesis and developmentKylie T Greig
Division of Molecular Medicine, The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia
Mol Cell Biol 27:5849-59. 2007.... - The SOCS box of suppressor of cytokine signaling-3 contributes to the control of G-CSF responsiveness in vivoKristy Boyle
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Blood 110:1466-74. 2007..Overall, the results establish a role for the SOCS box of SOCS3 in the in vivo regulation of G-CSF signaling and the response to inflammatory stimuli... - Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradationMarlyse A Debrincat
Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
J Biol Chem 282:4728-37. 2007..The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme... - SOCS2 negatively regulates growth hormone action in vitro and in vivoChristopher J Greenhalgh
Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research WEHI and the Cooperative Centre for Cellular Growth Factors, Parkville, Victoria, Australia
J Clin Invest 115:397-406. 2005..Together, the data provide clear evidence that SOCS2 is a negative regulator of GH signaling... - Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb geneDonald Metcalf
Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Blood 105:3480-7. 2005.... - Reduced bone mineral density in SOCS-2-deficient miceMattias Lorentzon
Center for Bone Research at the Sahlgrenska Academy, Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg University, 41345 Gothenburg, Sweden
Pediatr Res 57:223-6. 2005..These effects are not consistent with an augmented GH/IGF-I signaling and, therefore, the mechanism behind the reduced BMD remains to be elucidated... - Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania majorDenise V R Bullen
The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Center for Cellular Growth Factors, Royal Melbourne Hospital, Victoria, Australia
J Immunol 170:4267-72. 2003..These results suggest that SOCS1 plays an important role in the regulation of appropriate inflammatory responses during the resolution of L. major infection... - Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other gamma c-dependent cytokines in peripheral T cellsAnn L Cornish
The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia
J Biol Chem 278:22755-61. 2003..Hypersensitivity to gammac-dependent cytokines may contribute to abnormal T cell function, as well as the pathology observed in mice lacking SOCS-1... - Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activationPaul J Egan
Reid Rheumatology Laboratory, Division of Autoimmunity and Transplantation, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
J Clin Invest 111:915-24. 2003..SOCS-1 is therefore expressed in hematopoietic and nonhematopoietic cell types in vivo and is an important regulator of acute inflammatory arthritis and of CD4(+) T cell activation... - Suppressor of cytokine signaling-1 has IFN-gamma-independent actions in T cell homeostasisAnn L Cornish
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
J Immunol 170:878-86. 2003..Thus, SOCS-1 is a critical regulator of T cell activation and homeostasis, and its influence extends beyond regulating IFN-gamma signaling... - Differential regulation of SOCS genes in normal and transformed erythroid cellsMohinder K Sarna
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Royal Perth Hospital and Centre for Medical Research, The University of Western Australia, Perth, Australia
Oncogene 22:3221-30. 2003..These observations indicate complex, stage-specific regulation of SOCS genes during normal erythroid maturation and in erythroleukemic cells... - Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signalingChristopher J Greenhalgh
Walter and Eliza Hall Institute of Medical Research and the Cooperative Research for Cellular Growth Factors, PO Royal Melbourne Hospital, VIC 3050, Australia
J Biol Chem 277:40181-4. 2002..Together, the data implicate SOCS-2 as having dual effects on GH signaling in vivo... - Suppressors of cytokine signalling (SOCS) in the immune systemWarren S Alexander
The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Victoria, Australia
Nat Rev Immunol 2:410-6. 2002..Evidence is emerging for the involvement of SOCS proteins in diseases of the human immune system, which raises the possibility that therapeutic strategies that are based on the manipulation of SOCS activity might be of clinical benefit... - The SOCS box: a tale of destruction and degradationBenjamin T Kile
The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Parkville, Victoria, Australia
Trends Biochem Sci 27:235-41. 2002..In this way, SOCS proteins regulate protein turnover by targeting proteins for polyubiquitination and, therefore, for proteasome-mediated degradation... - SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardationDanielle L Krebs
The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Victoria 3050, Australia
Mol Cell Biol 22:4567-78. 2002..However, both male and female SOCS-6(-/-) mice weighed approximately 10% less than wild-type littermates... - Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b)Christopher J Greenhalgh
The Cooperative Research Centre for Cellular Growth Factors and The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia
Mol Endocrinol 16:1394-406. 2002..Furthermore, the deletion of SOCS-2 from mice also lacking signal transducer and activator of transcription 5b had little effect on growth, suggesting that the action of SOCS-2 may be the regulation of the GH signaling pathway... - Tyrosine residues of the granulocyte colony-stimulating factor receptor transmit proliferation and differentiation signals in murine bone marrow cellsShiva Akbarzadeh
Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
Blood 99:879-87. 2002..These observations have suggested novel roles for the G-CSF-R tyrosine residues in primary cells that were not observed previously in studies in cell lines... - Polycystic kidneys and chronic inflammatory lesions are the delayed consequences of loss of the suppressor of cytokine signaling-1 (SOCS-1)Donald Metcalf
The Walter and Eliza Hall Institute of Medical Research, and The Cooperative Research Centre for Cellular Growth Factors, Post Office Royal Melbourne Hospital, Victoria 3050, Australia
Proc Natl Acad Sci U S A 99:943-8. 2002..The chronic infections and granulomas of SOCS-1(-/-) IFN-gamma(-/-) mice may be based on autoaggression of SOCS-1(-/-) T lymphoid and related cells or a functional deficiency of these cells when lacking SOCS-1... - Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiationMark M W Chong
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Immunity 18:475-87. 2003..These phenotypes were found to correlate with hypersensitivity to the gamma-common family of cytokines... - SOCS3 negatively regulates IL-6 signaling in vivoBen A Croker
Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, 1G Royal Parade, Parkville, Victoria 3050, Australia
Nat Immunol 4:540-5. 2003..Our data indicate that SOCS3 and SOCS1 have reciprocal functions in IL-6 and IFN-gamma regulation and imply that SOCS3 has a role in preventing IFN-gamma-like responses in cells stimulated by IL-6... - Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptorsJennifer Antonchuk
Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Blood 104:1306-13. 2004..Thus, c-Mpl(-/-) Kit(Wv/Wv) mice reveal nonredundant and synergistic effects of Tpo and SF on primitive hematopoietic cells... - Suppressors of cytokine signalling and regulation of growth hormone actionChristopher J Greenhalgh
Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, 1G Royal Parade, Parkville, Vic. 3050, Australia
Growth Horm IGF Res 14:200-6. 2004..A precise understanding of the actions of SOCS proteins in GH signalling may offer new opportunities for therapeutic intervention in growth disorders and other conditions involving GH action... - Development of hydrocephalus in mice lacking SOCS7Danielle L Krebs
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
Proc Natl Acad Sci U S A 101:15446-51. 2004..In situ hybridization studies revealed prominent expression of Socs7 in the brain, suggestive of an important functional role of SOCS7 in this organ... - Suppressor screen in Mpl-/- mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signalingMarina R Carpinelli
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3052, Australia
Proc Natl Acad Sci U S A 101:6553-8. 2004.... - SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesisBen A Croker
Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Parkville, Victoria 3050, Australia
Immunity 20:153-65. 2004..We conclude that SOCS3 is a key negative regulator of G-CSF signaling in myeloid cells and that this is of particular significance during G-CSF-driven emergency granulopoiesis... - The lack of suppressor of cytokine signalling-1 (SOCS1) protects mice from the development of cerebral malaria caused by Plasmodium berghei ANKADenise V R Bullen
The Walter and Eliza Hall Institute of Medical Research and Cooperative Research Centre for Cellular Growth Factors, 1G Royal Parade, Victoria 3050, Australia
Parasite Immunol 25:113-8. 2003..Understanding the mechanism by which SOCS1 deficiency protects mice from cerebral malaria may allow the manipulation of its activity and alleviate pathology... - The lethal effects of transplantation of Socs1-/- bone marrow cells into irradiated adult syngeneic recipientsDonald Metcalf
Division of Cancer and Hematology, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, 1G Royal Parade, Parkville, Victoria 3050, Australia
Proc Natl Acad Sci U S A 100:8436-41. 2003.... - Thrombopoietin signalling in physiology and diseaseBrooke Fishley
The Walter and Eliza Hall Institute for Medical Research, IG Royal Parade, Parkville, Vic. 3050, Australia
Growth Factors 22:151-5. 2004.... - Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effectsElizabeth Rico-Bautista
Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
Mol Endocrinol 19:781-93. 2005..Our data indicate that SOCS2 deficiency partially mimics a state of increased GH activity, but also results in changes that cannot be related to known GH effects... - SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and functionChristine Brender
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
Mol Cell Biol 24:6094-103. 2004..Therefore, although SOCS5 is expressed in primary B and T cells, it appears to be dispensable for the regulation of lymphocyte function... - A novel mutation in the Nfkb2 gene generates an NF-kappa B2 "super repressor"Elena Tucker
St Vincent s Institute, Fitzroy, Victoria, Australia
J Immunol 179:7514-22. 2007..These findings demonstrate a key role for NF-kappaB2 in the regulation of RelA activation and suggest overlap in the function of NF-kappaB members in canonical and noncanonical pathway signaling... - Genetic heterogeneity of granulocytes for the JAK2 V617F mutation in essential thrombocythaemia: implications for mutation detection in peripheral bloodWilliam S Stevenson
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Pathology 38:336-42. 2006.... - An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and ricketsMarina R Carpinelli
Walter and Eliza Hall Institute of Medical Research, Post Office Royal Melbourne Hospital, Victoria, Australia
Am J Pathol 161:1925-33. 2002.... - c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3Kate D Sutherland
VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
EMBO J 25:5805-15. 2006..Our data establish Socs3 as a critical attenuator of pro-apoptotic pathways that act in the developing mammary gland and provide evidence that c-myc regulates apoptosis during involution...
Research Grants
- REGULATION OF HEMATOPOIESIS BY THROMBOPOIETINWarren Alexander; Fiscal Year: 2001..abstract_text> ..
- Genomic dissection of platelet productionWarren Alexander; Fiscal Year: 2007....
- Genomic dissection of platelet productionWarren Alexander; Fiscal Year: 2009....