Melanie J Welham

Summary

Affiliation: University of Bath
Country: UK

Publications

  1. doi request reprint Controlling embryonic stem cell proliferation and pluripotency: the role of PI3K- and GSK-3-dependent signalling
    Melanie J Welham
    Centre for Regenerative Medicine, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Biochem Soc Trans 39:674-8. 2011
  2. ncbi request reprint Phosphoinositide 3-kinases and regulation of embryonic stem cell fate
    M J Welham
    Department of Pharmacy and Pharmacology and The Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, UK
    Biochem Soc Trans 35:225-8. 2007
  3. ncbi request reprint Insulin receptor substrate-2 is the major 170-kDa protein phosphorylated on tyrosine in response to cytokines in murine lymphohemopoietic cells
    M J Welham
    The Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    J Biol Chem 272:1377-81. 1997
  4. ncbi request reprint Tyrosine phosphatase SHP-1 acts at different stages of development to regulate hematopoiesis
    Nicholas R D Paling
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY United Kingdom
    Blood 105:4290-7. 2005
  5. pmc Regulation of interleukin-3-induced substrate phosphorylation and cell survival by SHP-2 (Src-homology protein tyrosine phosphatase 2)
    Helen Wheadon
    Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Biochem J 376:147-57. 2003
  6. ncbi request reprint Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling
    Nicholas R D Paling
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
    J Biol Chem 279:48063-70. 2004
  7. pmc Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis
    Heather K Bone
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    J Cell Sci 120:1752-62. 2007
  8. ncbi request reprint Ligation of CD28 stimulates the formation of a multimeric signaling complex involving grb-2-associated binder 2 (gab2), SRC homology phosphatase-2, and phosphatidylinositol 3-kinase: evidence that negative regulation of CD28 signaling requires the gab2 pl
    Richard V Parry
    Lymphocyte Activation Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
    J Immunol 176:594-602. 2006
  9. ncbi request reprint The coupling of TEL/PDGFbetaR to distinct functional responses is modulated by the presence of cytokine: involvement of mitogen-activated protein kinases
    Helen Wheadon
    Department of Pharmacy and Pharmacology, University of Bath, United Kingdom
    Blood 102:1480-9. 2003
  10. pmc Role of the protein tyrosine phosphatase SHP-1 (Src homology phosphatase-1) in the regulation of interleukin-3-induced survival, proliferation and signalling
    Nicholas R D Paling
    Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Biochem J 368:885-94. 2002

Collaborators

  • Stephen Ward
  • Julie Letchford
  • Elsa Abranches
  • Luca Orlando
  • David Tosh
  • Richard V Parry
  • M Lee
  • Karina Stewart
  • C E Edmead
  • Heather K Bone
  • Michael P Storm
  • Nicholas R D Paling
  • Helen Wheadon
  • Yolanda Sanchez-Ripoll
  • Belinda A N Thompson
  • Benjamin Kumpfmueller
  • Adam S Nelson
  • Teresa Damiano
  • Mike P Storm
  • H Bone
  • Tom Crabbe
  • B L Craddock
  • Bridget C Fox
  • Tom Owen
  • Ana M V Guedes
  • Ruth V Spriggs
  • Domingos Henrique
  • Amanda B Mackenzie
  • Sarah Hogg
  • N Patel
  • James Hewinson
  • Christopher E Goldring
  • Craig B Orchard
  • Julian B Chaudhuri
  • Yolanda Sanchez Ripoll
  • Belinda Thompson
  • Stephen Bartlett
  • Alexis Perry
  • Oliver Hummel
  • Raivo Kolde
  • Herbert Schulz
  • Jaak Vilo
  • Pierre Savatier
  • Pierre Yves Bourillot
  • Adam Nelson
  • Valerie Schreiber
  • Craig G Beck
  • Tracey E Crew
  • J N Staniforth
  • J Hobbs
  • M J Tobyn
  • J W Schrader
  • F Jirik
  • U Dechert
  • V Duronio
  • S Abraham
  • P Dryden

Detail Information

Publications30

  1. doi request reprint Controlling embryonic stem cell proliferation and pluripotency: the role of PI3K- and GSK-3-dependent signalling
    Melanie J Welham
    Centre for Regenerative Medicine, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Biochem Soc Trans 39:674-8. 2011
    ....
  2. ncbi request reprint Phosphoinositide 3-kinases and regulation of embryonic stem cell fate
    M J Welham
    Department of Pharmacy and Pharmacology and The Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, UK
    Biochem Soc Trans 35:225-8. 2007
    ..In the present paper, we review the evidence that PI3K (phosphoinositide 3-kinase)-dependent signalling plays a role in regulation of both ES cell pluripotency and proliferation...
  3. ncbi request reprint Insulin receptor substrate-2 is the major 170-kDa protein phosphorylated on tyrosine in response to cytokines in murine lymphohemopoietic cells
    M J Welham
    The Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    J Biol Chem 272:1377-81. 1997
    ....
  4. ncbi request reprint Tyrosine phosphatase SHP-1 acts at different stages of development to regulate hematopoiesis
    Nicholas R D Paling
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY United Kingdom
    Blood 105:4290-7. 2005
    ....
  5. pmc Regulation of interleukin-3-induced substrate phosphorylation and cell survival by SHP-2 (Src-homology protein tyrosine phosphatase 2)
    Helen Wheadon
    Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Biochem J 376:147-57. 2003
    ..These findings indicate that SHP-2 plays an important role in mediating the anti-apoptotic effect of IL-3 and raises the possibility that PECAM-1 participates in the modulation of cytokine-induced signals...
  6. ncbi request reprint Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling
    Nicholas R D Paling
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
    J Biol Chem 279:48063-70. 2004
    ..Our studies support a role for PI3Ks in regulation of self-renewal and increase our understanding of the molecular signaling components involved in regulation of stem cell fate...
  7. pmc Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis
    Heather K Bone
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    J Cell Sci 120:1752-62. 2007
    ..These data demonstrate that PI3K-dependent signals play important roles at different stages of haemopoietic development...
  8. ncbi request reprint Ligation of CD28 stimulates the formation of a multimeric signaling complex involving grb-2-associated binder 2 (gab2), SRC homology phosphatase-2, and phosphatidylinositol 3-kinase: evidence that negative regulation of CD28 signaling requires the gab2 pl
    Richard V Parry
    Lymphocyte Activation Group, Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
    J Immunol 176:594-602. 2006
    ..Furthermore, the inhibitory capacity of Gab2 is strictly dependent upon the integrity of its PH domain, suggesting phosphoinositide-mediated membrane recruitment is important to Gab2 function in T cells...
  9. ncbi request reprint The coupling of TEL/PDGFbetaR to distinct functional responses is modulated by the presence of cytokine: involvement of mitogen-activated protein kinases
    Helen Wheadon
    Department of Pharmacy and Pharmacology, University of Bath, United Kingdom
    Blood 102:1480-9. 2003
    ..Given that in vivo hematopoietic cells are in contact with a variety of cytokines, our results have important implications for cellular responses in the pathogenesis of CMML...
  10. pmc Role of the protein tyrosine phosphatase SHP-1 (Src homology phosphatase-1) in the regulation of interleukin-3-induced survival, proliferation and signalling
    Nicholas R D Paling
    Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Biochem J 368:885-94. 2002
    ..These results demonstrate that SHP-1 acts to negatively regulate IL-3-driven survival and proliferation, potentially via regulation of tyrosine phosphorylation of Aic2A and STAT5...
  11. ncbi request reprint The pleckstrin homology domain of Gab-2 is required for optimal interleukin-3 signalsome-mediated responses
    Christine E Edmead
    Department of Pharmacy and Pharmacology, The University of Bath, Bath, BA2 7AY, UK
    Cell Signal 18:1147-55. 2006
    ..Taken together, these findings suggest that once Gab-2 is tyrosine phosphorylated its PH domain is required for the optimal stabilisation of the signalsome, enabling full activation of downstream signals...
  12. ncbi request reprint Interleukin (IL)-3 and granulocyte/macrophage colony-stimulating factor, but not IL-4, induce tyrosine phosphorylation, activation, and association of SHPTP2 with Grb2 and phosphatidylinositol 3'-kinase
    M J Welham
    Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    J Biol Chem 269:23764-8. 1994
    ..These results suggest that SHPTP2 may play an important role in integrating signals from the IL-3 and GM-CSF receptors to both Ras and PI 3'-kinase...
  13. ncbi request reprint Phosphoinositide 3-kinase-dependent regulation of interleukin-3-induced proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2
    B L Craddock
    Department of Pharmacy and Pharmacology, The University of Bath, Bath BA2 7AY, United Kingdom
    J Biol Chem 276:24274-83. 2001
    ..These results imply that the regulation of Erks by class I(A) phosphoinositide 3-kinase may contribute to IL-3-driven proliferation and that both SHP2 and Gab2 are possibly involved in this regulation...
  14. pmc Differential coupling of self-renewal signaling pathways in murine induced pluripotent stem cells
    Luca Orlando
    Centre for Regenerative Medicine, Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
    PLoS ONE 7:e30234. 2012
    ....
  15. pmc A novel chemically directed route for the generation of definitive endoderm from human embryonic stem cells based on inhibition of GSK-3
    Heather K Bone
    Centre for Regenerative Medicine and Department of Pharmacy and Pharmacology, University of Bath, Bath BA27AY, UK
    J Cell Sci 124:1992-2000. 2011
    ..These findings describe, for the first time, the utility of GSK-3 inhibition, in a chemically directed approach, to a method of DE generation that is robust, potentially scalable and applicable to different hESC lines...
  16. ncbi request reprint Phosphoinositide 3-kinases can act independently of p27Kip1 to regulate optimal IL-3-dependent cell cycle progression and proliferation
    Bridget C Fox
    Department of Pharmacy and Pharmacology, The University of Bath, Claverton Down, Bath BA2 7AY, UK
    Cell Signal 17:473-87. 2005
    ....
  17. ncbi request reprint Molecular interactions of SHP1 and SHP2 in IL-3-signalling
    Helen Wheadon
    Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY, Bath, UK
    Cell Signal 14:219-29. 2002
    ..These studies suggest that SH2-domain interactions are important for targetting these phosphatases to their substrates...
  18. ncbi request reprint Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains
    H Bone
    Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, UK
    Cell Signal 12:183-94. 2000
    ..PTB binding to IL-3R beta chains was of highest affinity, and appeared to play the primary role in binding. These findings suggest that Shc may play an important role in coordinately integrating IL-3 signalling pathways...
  19. pmc A novel role for P2X7 receptor signalling in the survival of mouse embryonic stem cells
    Belinda A N Thompson
    Department of Pharmacy and Pharmacology, University of Bath, Bath, UK
    Cell Signal 24:770-8. 2012
    ..Together, these data demonstrate a novel role for P2X7 receptors in regulation of ES cell behaviour where they can mediate either a pro-survival or pro-death signal depending on the mode of activation...
  20. doi request reprint Characterization of the phosphoinositide 3-kinase-dependent transcriptome in murine embryonic stem cells: identification of novel regulators of pluripotency
    Michael P Storm
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Bath, United Kingdom
    Stem Cells 27:764-75. 2009
    ..Further gain-of-function analyses demonstrate the importance of Zscan4c in regulation of ES cell pluripotency...
  21. ncbi request reprint Isolation of C15: a novel antibody generated by phage display against mesenchymal stem cell-enriched fractions of adult human marrow
    Julie Letchford
    Department of Pharmacy and Pharmacology and Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom
    J Immunol Methods 308:124-37. 2006
    ....
  22. pmc p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein
    V Duronio
    Biomedical Research Centre, University of British Columbia, Vancouver, Canada
    Proc Natl Acad Sci U S A 89:1587-91. 1992
    ..Attempts to demonstrate tyrosine phosphorylation of the p21ras GTPase-activating protein (GAP) were negative, suggesting that phosphorylation of GAP may not be the major mechanism for regulation of p21ras activity by tyrosine kinases...
  23. pmc Glycogen synthase kinase-3 inhibition enhances translation of pluripotency-associated transcription factors to contribute to maintenance of mouse embryonic stem cell self-renewal
    Yolanda Sanchez-Ripoll
    Centre for Regenerative Medicine and Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom
    PLoS ONE 8:e60148. 2013
    ....
  24. doi request reprint Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal revealed by a series of bisindolylmaleimides
    Heather K Bone
    Department of Pharmacy and Pharmacology, Centre for Regenerative Medicine, University of Bath, Bath, UK
    Chem Biol 16:15-27. 2009
    ..Our study clarifies the functional importance of GSK-3 in regulation of ESC self-renewal and provides tools for investigating its role further...
  25. ncbi request reprint SHP1 and SHP2 protein-tyrosine phosphatases associate with betac after interleukin-3-induced receptor tyrosine phosphorylation. Identification of potential binding sites and substrates
    H Bone
    School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom
    J Biol Chem 272:14470-6. 1997
    ..Binding of these protein-tyrosine phosphatases to the IL-3 receptor may regulate IL-3 signal transduction pathways, both through their catalytic activity and through the recruitment of other molecules to the receptor complex...
  26. pmc Three-dimensional culture systems for the expansion of pluripotent embryonic stem cells
    Michael P Storm
    Centre for Regenerative Medicine, Departments of Pharmacy and Pharmacology, University of Bath, Bath, UK
    Biotechnol Bioeng 107:683-95. 2010
    ..Our study highlights the importance of optimization of initial seeding parameters and provides proof-of-concept data demonstrating the utility of microcarriers and bioreactors for the expansion of hESCs...
  27. ncbi request reprint Regulation of Nanog expression by phosphoinositide 3-kinase-dependent signaling in murine embryonic stem cells
    Mike P Storm
    Department of Pharmacy and Pharmacology and Centre for Regenerative Medicine, The University of Bath, Bath BA2 7AY, United Kingdom
    J Biol Chem 282:6265-73. 2007
    ..Regulation of GSK-3 activity by PI3Ks appears to play a key role in this process...
  28. ncbi request reprint Spray-dried insulin particles retain biological activity in rapid in-vitro assay
    N Patel
    Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, UK
    J Pharm Pharmacol 53:1415-8. 2001
    ..The assay may be of use as a more rapid and economic means to screen insulin formulations for inhalation and other purposes as opposed to conventional monitoring of blood glucose levels in animals...
  29. ncbi request reprint The PI3K inhibitor arsenal: choose your weapon!
    Tom Crabbe
    UCB Celltech, Slough, UK
    Trends Biochem Sci 32:450-6. 2007
    ..However, challenges remain for the efforts to pharmacologically target this enzyme family in a successful manner...
  30. ncbi request reprint PI3K comes of age
    Stephen G Ward
    Nat Immunol 4:2. 2003