Immunology and the Ageing B-Cell

The Immunology North East December meeting will take place on Thursday 11^th December at 5pm (refreshments from 4.30pm) in the Research Beehive, Newcastle University room 2.21.   

 

Dr. Deborah Dunn-Walters, Division of Immunology, Infection and Inflammatory Disease; Chair of Mechanisms of Ageing section of Ageing Research At King's (ARK), King’s College London, will present  a talk entitled,

 

"The ageing B cell repertoire"

 

 

 

Research Interests

We have extensive experience in B cell repertoire analysis, and molecular events involving the immunoglobulin gene during B cell development. We combine traditional molecular biology techniques with novel mathematical analyses to devise new ways of investigating the humoral immune system.

Our particular interest is in research into ageing. Loss of immune system function with age results in the phenomenon termed “Immunosenescence.” This is associated with increased infectious disease morbidity and mortality, poor responses to vaccination, declines in established protective immunity, and increased incidence of autoimmune disorders. Until recently, most age-associated immune failures had been attributed to changes in T cell populations. However, there are many other changes in the immune system and, as data accumulate to show that B cells have a critical role in antigen presentation and regulation - in addition to their role as antibody producers - B cells and humoral immunity becomes highly significant.

More details on Deborah’s research can be found at http://www.kcl.ac.uk/lsm/research/divisions/diiid/departments/immunobiology/research/DunnWalters/index.aspx

 

Recent Publications:

Immunoglobulin gene repertoire diversification and selection in the stomach - from gastritis to gastric lymphomas.

Michaeli M, Tabibian-Keissar H, Schiby G, Shahaf G, Pickman Y, Hazanov L, Rosenblatt K, Dunn-Walters DK, Barshack I, Mehr R. Front Immunol. 2014 Jun 3;5:264. doi: 10.3389/fimmu.2014.00264. eCollection 2014.

Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity.

Sabouri Z, Schofield P, Horikawa K, Spierings E, Kipling D, Randall KL, Langley D, Roome B, Vazquez-Lombardi R, Rouet R, Hermes J, Chan TD, Brink R, Dunn-Walters DK, Christ D, Goodnow CC. Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):E2567-75. doi: 10.1073/pnas.1406974111. Epub 2014 May 12.

Immunogenetics and transplantation.

Davenport MP, Dunn-Walters DK. Curr Opin Immunol. 2013 Oct;25(5):606-7. doi: 10.1016/j.coi.2013.09.001. Epub 2013 Sep 26. No abstract available.

Human lymphocyte repertoires in ageing.

Boyd SD, Liu Y, Wang C, Martin V, Dunn-Walters DK. Curr Opin Immunol. 2013 Aug;25(4):511-5. doi: 10.1016/j.coi.2013.07.007. Epub 2013 Aug 28. Review.

BCR CDR3 length distributions differ between blood and spleen and between old and young patients, and TCR distributions can be used to detect myelodysplastic syndrome.

Pickman Y, Dunn-Walters D, Mehr R. Phys Biol. 2013 Oct;10(5):056001. doi: 10.1088/1478-3975/10/5/056001. Epub 2013 Aug 22.

Yersinia enterocolitica provides the link between thyroid-stimulating antibodies and their germline counterparts in Graves' disease.

Hargreaves CE, Grasso M, Hampe CS, Stenkova A, Atkinson S, Joshua GW, Wren BW, Buckle AM, Dunn-Walters D, Banga JP. J Immunol. 2013 Jun 1;190(11):5373-81. doi: 10.4049/jimmunol.1203412. Epub 2013 Apr 29.

Granulocyte colony stimulating factor exacerbates antineutrophil cytoplasmic antibody vasculitis.

Freeley SJ, Coughlan AM, Popat RJ, Dunn-Walters DK, Robson MG. Ann Rheum Dis. 2013 Jun;72(6):1053-8. doi: 10.1136/annrheumdis-2012-202160. Epub 2012 Oct 19.

A novel chronic lymphocytic leukemia subset expressing mutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient.

Hoogeboom R, Wormhoudt TA, Schipperus MR, Langerak AW, Dunn-Walters DK, Guikema JE, Bende RJ, van Noesel CJ. Leukemia. 2013 Mar;27(3):738-40. doi: 10.1038/leu.2012.238. Epub 2012 Aug 20. No abstract available.

Age-Related Changes in Human Peripheral Blood IGH Repertoire Following Vaccination.

Wu YC, Kipling D, Dunn-Walters DK. Front Immunol. 2012 Jul 9;3:193. doi: 10.3389/fimmu.2012.00193. eCollection 2012.

B cell immunosenescence: different features of naive and memory B cells in elderly.

Buffa S, Bulati M, Pellicanò M, Dunn-Walters DK, Wu YC, Candore G, Vitello S, Caruso C, Colonna-Romano G. Biogerontology. 2011 Oct;12(5):473-83. doi: 10.1007/s10522-011-9353-4. Epub 2011 Aug 31.

Vaccination-induced changes in human B-cell repertoire and pneumococcal IgM and IgA antibody at different ages.

Ademokun A, Wu YC, Martin V, Mitra R, Sack U, Baxendale H, Kipling D, Dunn-Walters DK. Aging Cell. 2011 Dec;10(6):922-30. doi: 10.1111/j.1474-9726.2011.00732.x. Epub 2011 Aug 10.

The relationship between CD27 negative and positive B cell populations in human peripheral blood.

Wu YC, Kipling D, Dunn-Walters DK. Front Immunol. 2011 Dec 26;2:81. doi: 10.3389/fimmu.2011.00081. eCollection 2011.

B cells and immunosenescence: a focus on IgG+IgD-CD27- (DN) B cells in aged humans.

Bulati M, Buffa S, Candore G, Caruso C, Dunn-Walters DK, Pellicanò M, Wu YC, Colonna Romano G. Ageing Res Rev. 2011 Apr;10(2):274-84. doi: 10.1016/j.arr.2010.12.002. Epub 2010 Dec 23. Review.

B cell repertoire and ageing.

Dunn-Walters DK, Ademokun AA. Curr Opin Immunol. 2010 Aug;22(4):514-20. doi: 10.1016/j.coi.2010.04.009. Epub 2010 May 25. Review.

 

 

Biomarkers in inflammatory disease. Speaker Dr Mary Keir Monday 1st December.

 

 

 

 

 

 

 

 

Speaker: Dr Mary Keir PhD, Genetech Inc, South San Francisco

 

Venue: L2.6, 2^ND Floor, William Leech Building, Medical School

Date and time: Monday 1^st December 2014 at 1.00pm

 

Dr Mary Keir will present

 

“Predictive biomarkers for response to etrolizumab therapy in IBD”

 

Biog: Mary Keir received her Ph.D. in Biomedical Sciences at the University of California, San Francisco, where her thesis work focused on innate responses to HIV infection in the human thymus. Following completion of her Ph.D, she undertook postdoctoral training at Harvard Medical School, where she studied the role of PD-1:PD-L1 interactions in T cell tolerance and autoimmunity. Mary next moved to Genentech to join the Immunology Diagnostic Discovery group and focus on biomarker identification and utility in clinical trials. At Genentech, she has led biomarker efforts in both systemic lupus erythematosus and inflammatory bowel disease (IBD). Her current research focus is on predictive biomarkers of inflammatory subgroups in IBD as well as prognostic biomarkers of disease.

 

 

 

Jenna Ho

PA to:

Professor John Isaacs, Director of the Institute of Cellular Medicine

Professor Neil Sheerin, Professor of Nephrology

4th Floor William Leech Building

Medical School

Newcastle University

Framlington Place

Newcastle Upon Tyne

NE2 4HH

 

Tel: 0191 208 6227

Fax: 0191 208 5066

 

Email: jenna.ho@newcastle.ac.uk

Web:    http://www.ncl.ac.uk/

 

Don't Miss: Emma Rogers on 'A functional genetic study of the osteoarthritis-associated SNP rs4836732'

 

 

 

Institute Research Student Seminars

Speakers:  Eleana Pappa, Emma Rogers & Keith Wu

 

Venue: Seminar room L2.5, 2^nd floor, William Leech Building, Medical School

Date and time:  Wednesday 26^th November 2014 at 12.30

 

Eleana Pappa will present:

“Transcriptional and Phenotypic Characterization of Hepatic Stellate Cells”

(Derek Mann: Fibrosis Group)

 

Correlation of liver stiffness with fibrosis progression has been observed in many liver diseases. Hepatic stellate cells (HSC) are the main scaring forming cells in liver fibrosis. Activation of HSC from quiescent to myofibroblasts is the initial step for fibrosis development. In this project we evaluate the importance of substrate stiffness as driving force for HSC activation.

 

Key words: Liver fibrosis, Hydrogels, HSC 

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Emma Rogers will discuss:

“'A functional genetic study of the osteoarthritis-associated SNP rs4836732'”

(John Loughlin: Osteoarthritis Research Group)

 

A recent genome wide association scan identified the region defined by the intronic SNP rs4836732 to be associated with female hip osteoarthritis. This project intends to identify the functional SNP within this region and investigate how the SNP is mediating increased osteoarthritis susceptibility.

 

Key words: Osteoarthritis, genetics, SNP

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Keith Wu will speak on:

“The Role of Epigenetics, including BET bromodomains, in the Control of Inflammatory Skin Disease”

(Nick Reynolds: Dermatology Group)

 

Psoriasis is a common inflammatory skin disease, often with systemic involvement, affecting up to 3% of the adult population.  Despite its prevalence there is an unmet need for new therapies and the pathophysiology is not fully understood.  Here we discuss the role of BET bromodomains in the control of inflammatory cytokines and their potential as a novel therapeutic target.

 

Key words: epigenetics, inflammation, therapeutics

 

Chair:  Irene del Molino del Barrio

 

 

 

 

 

 

Rheumatoid Arthritis Seminar: John Isaacs Tuesday 25 November at 1 pm

 

 

 

 

PI Seminar Series

 

Speaker: Professor John Isaacs, Director of the Institute of Cellular Medicine and Professor of Clinical Rheumatology

 

Venue: Lecture Theatre D, Dental School

Date and Time: Tuesday 25^th November 2014 at 13.00

 

Professor John Isaacs will present:

‘’Breaking through the therapeutic ceiling: Novel strategies and biomarkers in rheumatoid arthritis management’’

 

Brief summary:

My group’s work is focussed on the identification of novel biomarkers and testing of novel therapeutic strategies in patients with rheumatoid arthritis. In this seminar I will describe our work in the early arthritis clinic and in the refractory arthritis clinic, and highlight how this work addresses some of the unmet needs that our patients face.

 

Key themes:

STAT-3 signalling as a biomarker in early arthritis

The AuToDeCRA study

The RA-MAP project

CDK inhibition for rheumatoid arthritis

 

Chair: Professor Steve Yeaman

 

 

 

 

 

 

 

 

Mitochondria, immunity, and monocytic cells in immune inflammatory responses.

 

 

Institute Research Student Seminars

Speaker:  John Widdrington

 

Venue: Seminar room L2.5, 2^nd floor, William Leech Building, Medical School

Date and time:  Wednesday 12^th November 2014 at 12.30

 

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John Widdrington will discuss:

 

"The effect of mtDNA depletion on immune functions in THP-1 cells"

 

Adverse outcomes in sepsis have been associated with both impaired immunity and depletion of mitochondrial DNA (mtDNA) in monocytes. This study assesses the link between these findings by determining the effects of depleting mtDNA copy number on the ability of THP-1 cells to produce immune responses to inflammatory stimuli.

 

Keywords: mitochondria, immunity, monocytic cells

 

Chair: Sadaf Atarod

 

 

 

 

 

 

 

MRG LAB MEETING 7.11.14 Osteoarthritis and Lymphocyte Apoptosis

Friday 7th November 2014 at 9.00am in DENTAL LECTURE THEATRE E.

 

Chair

 

Angie Habgood (PhD Student – PI Drew Rowan)

 

Speakers

 

David Wilkinson (Research Associate - PI Drew Rowan) Title of Talk – "Inhibition of Matriptase: Implications for Osteoarthritis"

 

Siti Mohamad (PhD Student – PI Sophie Hambleton) Title of Talk – "Disease mechanism in a novel disorder of lymphocyte apoptosis"

 

Fiona Gee (Research Associate – PI John Loughlin) Title of Talk – "Investigating the role of NCOA3 and SULF2 in osteoarthritis susceptibility"

 

 

 

Arthritis, HER2 and Atrial Fibrillation: Tomorrow : 12:30

 

 

 

 

Institute Research Student Seminars

Speakers:  Nishanthi Thalayasingam, Anna-Lena Dittrich

& Sarah Anne Kane

 

Venue: Seminar room L2.5, 2^nd floor, William Leech Building, Medical School

Date and time:  Wednesday 5^th November 2014 at 12.30

 

Nishanthi Thalayasingam will present:

 

"A microarray analysis of peripheral blood B cells from early arthritis patients"

 

In Rheumatoid Arthritis (RA) chronic inflammation leads to joint damage and so it is vital treatment is commenced promptly to prevent this. There is increasing interest in the role of B cells in the pathogenesis of RA following the effectiveness of selective B cell depletion. The purpose of this project is to identify potential diagnostic biomarkers by comparing the gene expression profiles of B cells from newly diagnosed RA patients to that of patients diagnosed with other types of arthritis.

Key words: Rheumatoid Arthritis, microarray, B cells

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Anna-Lena Dittrich will discuss:

 

"HER2: Regulation of alternative splicing and novel splice variants"

 

With more than 11000 deaths annually in the UK from breast cancer much effort has been made to provide optimal treatment. Our focus is on HER2, a proto-oncogene in breast cancer. Different splice variants of HER2 can have positive or negative effects on disease progression and therapy efficiency. Our aim is to identify additional splice variant and to understand the regulatory mechanisms underlying the alternative splicing.

Key words: Alternative splicing, ErbB2, Breast Cancer​

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Sarah Anne Kane will speak on:

 

"The Detection of Atrial Fibrillation During 24-hour Blood Pressure Measurement"

 

Atrial Fibrillation (AF) is a cardiac arrhythmia that affects around 2% of the population. Early detection allows patients to begin potentially life-saving therapies so a simple, effective method for screening is required. One method is the use of modified blood pressure monitors that can pick up AF through incorporated pulse detection algorithms. In this project we aim to take this one step further and determine if it is feasible to screen for AF during 24 hour blood pressure measurements.

Keywords: Blood Pressure, Atrial Fibrillation, Clinical Trial

 

Chair:  Sophie Cassidy

 

 

 

 

 

 

 

'Chronic Inflamation as an Accelator of Ageing and Cancer' Seminar - Tuesday 4th November 2014