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Dr Jane Goodall

Dr Jane Goodall

Lecturer

Jane Goodall is available for consultancy.


Departments

Department of Medicine:
Lecturer

Research Interests

Role of ER stress in inflammation

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.

 

Relevance to 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 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 role of Thymic stromal lymphopoietin (TSLP) expression by dendritic cells.

TSLP produced by epithelial cells acts on dendritic cells (DC) to drive differentiation of TH2 cells, and is therefore important in allergic disease pathogenesis. However, we have identified that DC make significant amounts of TSLP in response to microbial products in an autocrine fashion. We have recently identified the critical signals that induce TSLP secretion and the role of TSLP in the regulation of proinflammatory cytokine expression such as IL-1beta, IL-6 and IL-23. This work has revealed a novel pathway of IL-1beta regulation. Autocrine TSLP production is likely to play a role in mDC-controlled immune responses at sites removed from epithelial cell production of the cytokine, such as lymphoid tissue.

 

 

 

The dynamic interaction of Chlamydia trachomatis with host cells.

Chlamydia trachomatis (CT) infection imparts a large burden on the human population, particularly amongst young adults, contributing significantly to the prevalence of sexually transmitted diseases, infertility and preventable blindness.  CT is an obligate intracellular bacterium that is exquisitely adapted to manipulate the environment of the host cell. In contrast to gene expression studies, there is no information on the global protein changes that occur during the infectious process. New work in my laboratory recently funded by a MRC project grant is utilising a powerful multiplexed proteomic technique that allows the relative abundance of chlamydia and host proteins to be determined accurately over the course of the infectious life cycle in both human epithelial and dendritic cells. This approach will provide the first opportunity to interrogate the chlamydia and host protein responses in tandem and provide a dynamic insight into the chlamydia-host interaction.

 

Induction of inflammation by the pathogen Chlamydia trachomatis

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 recent Medical Research Council funded grant has enabled my laboratory to address some fundamental mechanistic questions regarding how chlamydia activates these cellular stress pathways.

 

ER stress in the atherosclerotic plaque

ER stress pathways instigated in macrophages as a result of cholesterol loading or mechanical forces play an important role in the development of the atherosclerosis plaque and aneurysm. 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 differentiation in critical cells subsets in disease development.

Keywords

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

Topics

  • rheumatoid arthritis
  • spondyloarthritis

Key Publications

Webster SJ, Brode S, Ellis L, Fitzmaurice TJ, Elder MJ, Gekara and Goodall JC.(2017) Detection of a microbial metabolite by STING regulates inflammasome activation in response to Chlamydia trachomatis infection. PLoS pathogens, 13 (6.) e1006383

Elder MJ, Webster SJ, Chee R, Williams DL, Hill Gaston JS, Goodall JC. (2017) β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production.. Frontiers in immunology. 8. 79.

Clément M, Basatemur G, Masters L, Baker L, Bruneval P, Iwawaki T, Kneilling M, J Goodall and Mallat Z. (2016). Necrotic Cell Sensor Clec4e Promotes a Proatherogenic Macrophage Phenotype Through Activation of the Unfolded Protein Response. Circulation, 134 (14), pp. 1039.

TSLP production by dendritic cells is modulated by IL-1β and components of the endoplasmic reticulum stress response. Matthew J. Elder, Steven J. Webster, David L. Williams, J. S. Hill Gaston, Jane C. Goodall. European J Imunol.

TCR usage, gene expression and function of two distinct FOXP3+Treg subsets within CD4+CD25hiT cells identified by expression of CD39 and CD45RO. Ye L, Goodall JC, Zhang L, Putintseva EV, Lam B, Jiang L, Liu W, Yin J, Lin L, Li T, Wu X, Yeo G, Shugay M, Chudakov DM, Gaston H, Xu H. Immunol Cell Biol. 2015 Oct 15. doi: 10.1038/icb.2015.90. [Epub ahead of print]

http://www.ncbi.nlm.nih.gov/pubmed/26467610

The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress. 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) Nature. 510(7504):268-72. 510, 268-272 (2014).

http://www.ncbi.nlm.nih.gov/pubmed/24776803

ER stress signals are integrated by dendritic cells to enhance IL-23 responses to Toll-like receptor .Goodall, JC., Changxin W., Zhang, Y., Ellis, L. O’Brien., L. Saudek, V and Gaston, JSH.  PNAS, 12;107(41):17698-703

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

Frequency and Phenotype of T Helper 17 Cells in Peripheral Blood and Synovial Fluid of Patients with Reactive Arthritis. Shen H, Goodall JC, Gaston JS. (2010 J Rheumatol . Gaston JS. Jarvis LB, Zhang L, Goodall JC.

Dendritic cell:T cell interactions in spondyloarthritis. (2009). Adv Exp Med Biol. 649:263-76.

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

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.Goodall, J.C., Ellis, L. and Gaston, J.S.H. (2005). Arthritis and Rheumatism 54, 138-147.

 

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, 12;107(41):17698-703

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

Shen H, Goodall JC, Gaston JS. (2010). Frequency and Phenotype of T Helper 17 Cells in Peripheral Blood and Synovial Fluid of Patients with Reactive Arthritis. J Rheumatol in press. Gaston JS. Jarvis LB, Zhang L, Goodall JC. Dendritic cell:T cell interactions in spondyloarthritis. (2009). Adv Exp Med Biol649:263-76.

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

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