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Dr Jane Goodall

Dr Jane Goodall

Arthritis Research UK Senior Research Fellow

Jane Goodall is available for consultancy.


Departments

Department of Medicine:
Arthritis Research UK Senior Research Fellow

Research Interests

Role of ER stress in inflammation

My work has identified that the response of innate immune cells to pathogens can be modified by the activation of cellular stress pathways.  This was clearly shown by the requirement for the ER stress induced transcription factor, CHOP, in the expression of the pro-inflammatory cytokine, IL-23. We are currently embarking on a 5 year research programme funded by Arthritis UK, to investigate whether collagen induced arthritis (an inflammatory condition that is highly dependent on IL-23) can be modulated by changes in the quality of the ER stress response.

The ER stress pathway allows the cell to adapt to stimuli that alter the protein folding capacity of the ER. Under homeostatic conditions this pathway may subtly modulate ER function. Stimuli that induce differentiation or physiological and infectious insults can induce acute changes in the ER stress signalling response. Defects in the ER stress pathway or potent ER stress signals may alter the balance between between the cell survival and pro-apoptotic pathways evoked during this response.

Induction of ER stress by pathogens

The role of stress signals in pathogen responses was clearly emphasized by experiments using the obligate intracellular pathogen, Chlamydia trachomatis. We identified that IL-23 expression induced by this bacterial infection was dependent on both toll like receptor activation but also on the expression of ER stress proteins including CHOP. This suggests that ER stress pathways play an important role in inflammatory responses to pathogens. A recently awarded Medical Research Council funded grant will addressing some fundamental mechanistic questions that will identify how microorganisms such as chlamydia and salmonella activate these cellular stress pathways.

ER stress in the atherosclerotic plaque

ER stress pathways instigated in macrophages as a result of cholesterol loading play an important role in the development of the atherosclerosis plaque. We are currently investigating in collaboration with Ziad Mallat (Division of Cardiovascular medicine) how modulation of stress pathways may modify the induction of apoptosis and macrophage differentiation.

Keywords

T helper cells ; IL-23 ; T cells ; CHOP ; inflammation ; monocytes ; Toll-like receptors ; ER stress

Topics

  • rheumatoid arthritis
  • spondyloarthritis

Key Publications

Wu, C., Goodall, J.C., Busch, R. & Gaston, J.S. Relationship of CD146 expression to secretion of interleukin-17, interleukin-22, and interferon-gamma by CD4 T cells in patients with inflammatory arthritis. Clinical and experimental immunology (2014).

van Galen P, Kreso A, Mbong N, Kent DG, Fitzmaurice T, Chambers JE, Xie S, Laurenti E, Hermans K, Eppert K, Marciniak SJ, Goodall JC, Green AR, Wouters BG, Wienholds E, Dick JE. (2014) The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress. Nature. 510(7504):268-72. 510, 268-272 (2014).


Goodall, J.C. & Yeo, G.S. PP2Ce: Fat and stressed out? Molecular metabolism 2, 325-326 (2013).


Ellinghaus, D., et al. Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies. Gastroenterology 145, 339-347 (2013).


Benham, H., et al. Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis research & therapy 15, R136 (2013).

Goodall, JC., Changxin W., Zhang, Y., Ellis, L. O’Brien., L. Saudek, V and Gaston, JSH.  ER stress signals are integrated by dendritic cells to enhance IL-23 responses to Toll-like receptor . PNAS, 2012;107(41):17698-703

Shen H, Goodall JC, Gaston JS. Frequency and Phenotype of T Helper 17 Cells in Peripheral Blood and Synovial Fluid of Patients with Reactive Arthritis. J Rheumatol 2010 Oct;37(10):2096-9.

Shen, H., Goodall, J. and Gaston J.S.H. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis and Rheumatism.  2009 60:1647-56.

Gaston JS. Jarvis LB, Zhang L, Goodall JC. Dendritic cell:T cell interactions in spondyloarthritis. Adv Exp Med Biol. 2009 649:263-76.

Goodall, JC., Ellis, L. Yeo, G.S.H and J.S.H Gaston. Does HLA-B27 modify the monocyte inflammatory response to LPS? Rheumatology  2007 46:232-237.

Goodall, J.C., Ellis, L. and Gaston, J.S.H. Spondyloarthritis-associated and non-spondyloarthritis associated B27 subtypes differ in their dependence upon tapasin for surface expression and their incorporation into the peptide loading complex. Arthritis and Rheumatism 2005 54, 138-147.