National University of Ireland, Maynooth

National University of Ireland, Maynooth
Skip top page links and go directly to the main navigation
The Callan Building
Skip main navigation and go directly to page content

Faculties & Departments

Department of Biology

Paul Moynagh, BA(mod.), PhD (Dublin)
Head of Laboratory; Director Institute of Immunology

 

Molecular Immunology Laboratory

 

Paul Moynagh

Institute of Immunology

Research Interests

Toll-like receptor signalling

Work in the laboratory has focused increasingly on proinflammatory stimuli and the signal transduction pathways that they employ in effecting an inflammatory phenotype. Studies especially concentrate on human Toll-like receptors (TLRs). TLRs recognise pathogen-associated molecules. As examples, TLR2 recognises peptidoglycan and bacterial lipoprotein from Gram-positive bacteria, TLR3 mediates responses to double-stranded RNA, TLR4 is involved in recognition of Gram-negative lipopolysaccharide (LPS), TLR-5 recognises bacterial flagellin and TLR9 functions as a receptor for bacterial DNA containing CpG motifs. The engagement of TLRs by pathogenic components results in induction of co-stimulatory molecules that facilitate T-cell activation and pro-inflammatory proteins that effect elimination of the pathogen from the body. TLRs employ many of the same signalling components as the type I IL-1 receptor (IL-1RI). This is hardly surprising since the intracellular regions of TLRs and IL-1RI share a conserved Toll / IL-1R (TIR) domain that is important in initiating various signalling pathways especially that regulating the transcription factor NFkB. My research group is currently exploring the signal transduction pathways employed by the TLRs. We have identified some novel regulators of the TLR pathways and hope to explore their potential value as therapeutic targets in inflammatory diseases.

Inflammation and the brain

My research group has a continuing interest in characterising the effects of pro-inflammatory cytokines in brain.  This area of research probes the effects of the cytokines interleukin-1 (IL-1) and tumour necrosis factor (TNF) in brain cells. We have shown that both cytokines induce the cell adhesion molecules VCAM-1 and ICAM-1 and chemokines such as IL-8 in glial and neuronal cells. The induction of these genes appears to play important roles in cerebral recruitment of leukocytes which may lead to neuropathology. Indeed IL-1 and TNF promotes sustained expression of these genes and this may underlie the chronic cerebral inflammatory responses seen in neurological disorders such as multiple sclerosis. We are thus very interested in exploring the mechanism by which IL-1 and TNF can cause sustained expression of the genes and we have published findings that show that the sustained expression is likely to be due to prolonged activation of the transcription factor NFkB by IL-1 and TNF. We have also resolved the mechanism underlying this prolonged activation of NFkB. This work is currently being extended in my laboratory with a view to identifying novel agents to block the expression of adhesion molecules and chemokines in brain cells. Such agents include cannabinoids and we have recently published data describing a novel mechanism by which they can produce anti-inflammatory effects in the brain. Such molecules may be of therapeutic value in the treatment of various neuropathological conditions.

Laboratory Personnel

 

Academic coordinator HRB PhD scholars programme in Immunology

  • Dr. Antonio Campos-Torres

Postdoctoral

  • Dr. Paola Atzei
  • Dr. Nezira Delagic
  • Dr. Eric Downer
  • Dr. Mark Mellett
  • Dr. Jakub Siednienko
  • Dr. Lisa Tang
  • Dr. Shuo Yang

Postgraduate

  • Nicholas Bernard (HRB rotational project)
  • Eileen Clifford (HRB rotational project)
  • Siobhan Gargan
  • Alan Horgan
  • Fiachra Humphries
  • Ruaidhrí Jackson (HRB rotational project)
  • Anne Kirwan
  • Bozgana Mangan (HRB rotational project)
  • Ewa Oleszycka (HRB rotational project)
  • Bingwei Wang

Research Assistant

  • Cathy Leonard

Funding Sources

  • Enterprise Ireland
  • European Commission
  • Health Research Board
  • IRCSET
  • Science Foundation Ireland

Recent Publications

  • Moynagh, P.N. (2009) The Pellino family: IRAK E3 ligases with emerging roles in innate immune signalling. Trends in Immunology  30:33-42.

  • Butler, M.P., J.A. Hanly and P.N. Moynagh (2007)  Kinase-active Interleukin-1 Receptor-associated Kinases Promote Polyubiquitination and Degradation of the Pellino Family:  DIRECT EVIDENCE FOR PELLINO PROTEINS BEING UBIQUITIN-PROTEIN ISOPEPTIDE LIGASES. Journal of Biological Chemistry, 282: 29729-29737.

  • Cumiskey, D., M.P. Butler, P.N. Moynagh and J.J. O'Connor (2007)   Evidence for a role for the group I metabotropic glutamate receptor in the inhibitory effect of tumor necrosis factor-alpha on long-term potentiation. Brain Research, 1136: 13-19.

  • Miggin, S.M., E. Palsson-McDermott, A. Dunne, C. Jefferies, E. Pinteaux, K. Banahan, C. Murphy, P.N. Moynagh, M. Yamamoto, S. Akira, N. Rothwell, D.  Golenbock, K.A. Fitzgerald and L.A. O'Neill (2007)  NF-κB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1. Proceedings of National Academy of Sciences, USA, 104: 3372-3377.

  • Carty, M., Goodbody, R., Schröder, M., Stack, J., Moynagh, P.N. and. Bowie, A.G. (2006) The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nature Immunology. 7: 1074 – 1081.

  • Griffin, B.D. and Moynagh, P.N. (2006) In vivo binding of NFkB to the IkBb promoter is insufficient for transcriptional activation. Biochemical Journal. 400: 115-125.

  • Griffin, B.D. and Moynagh, P.N. (2006) Persistent Interleukin-1b Signaling Causes Long Term Activation of NFkB in a Promoter-specific Manner in Human Glial Cells.  Journal of Biological Chemistry 281: 10316-10326.

  • Hassett, S., Moynagh, P. and Reen, D. (2006) TNF-alpha is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome. Pediatric Surgery International 22: 24-30.  

  • Curran, N.M., Griffin, B.D., O’Toole, D.,  Brady, K. J., Fitzgerald, S.N. and Moynagh, P.N. (2005) The synthetic cannabinoid R(+)WIN55,212 inhibits the interleukin-1 signaling pathway in human astrocytes in a cannabinoid-receptor independent manner Journal of Biological Chemistry 280: 35797-35806.

  • Moynagh, P.N. (2005) The NF-kB pathway. Journal of Cell Science, 118: 4589-4592.

  • Moynagh, P.N. (2005) TLR signalling and activation of IRFs: Revisiting old friends from the NF-kB pathway Trends in Immunology 26(9): 469-476.

  • Butler, M.P., Hanly, J.A. and Moynagh, P.N. (2005) Pellino3 is a novel upstream regulator of p38 MAPK and activates CREB in a p38-dependent manner. Journal of Biological Chemistry 280(30): 27759-27768.

  • Moynagh, P.N. (2005) The interleukin-1 signalling pathway in astrocytes: a key contributor to inflammation in the brain. Journal of Anatomy 207: 265-269.

  • Butler, M.P., O’Connor, J.J. and Moynagh, P.N. (2004) Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP. Neuroscience 124: 319-326.

  • Moynagh, P.N. (2003) Toll-like receptor signalling pathways as key targets for mediating the anti-inflammatory and immunosuppressive effects of glucocorticoids. Journal of Endocrinology. 179: 139-144.

  • O'Reilly, SM and Moynagh, PN. (2003) Regulation of Toll-like receptor 4 signalling by A20 zinc finger protein. Biochemical and Biophysical Research Communications 303:586-93.

  • Butler, M., Moynagh, P.N. and O’Connor, J. (2002) Methods of detection of the transcription factor NF-kappaB in rat hippocampal slices. Journal of Neuroscience Methods 119: 185-189.

  • Brady, K., Fitzgerald, S., Ingvarsson, S., Borrebaeck, C.A. and  Moynagh, P.N. (2001) CD40 employs p38 MAP kinase in IgE isotype switching. Biochemical and Biophysical Research Communications 289:276-81.

  • Bourke, E., Kennedy, E.J. and Moynagh, P.N. (2000) Loss of Ikappa B-beta is associated with prolonged NF-kappa B activity in human glial cells. Journal of Biological Chemistry 275:39996-40002.

  • Brady, K., Fitzgerald, S., Moynagh, P.N.(2000) Tumour-necrosis-factor-receptor-associated factor 6, NF-kappaB-inducing kinase and IkappaB kinases mediate IgE isotype switching in response to CD40. Biochemical Journal 350:735-40.

  • Akesson, A., Ingvarsson, S., Brady, K., Moynagh, P., Borrebaeck CA. (2000) Rapid polarization of Th2 cells during induction of antigen-specific IgE antibodies in vitro. Clinical and Experimental Allergy 30(9):1298-306.

  • Bourke, E. and  Moynagh, P.N. (1999) Antiinflammatory effects of glucocorticoids in brain cells, independent of NF-kappa B. Journal of  Immunology 163:2113-9 .

Last edited: Wednesday, 03-Feb-2010 14:54:50 GMT

Biology Department , NUI Maynooth
Tel: +353-1-708 3843 | Fax: +353-1-708 3845| Email: terry.roche@nuim.ie