Newcastle University

Introduction

From bedside to bench and back again - my work is all about what children with inherited immunodeficiencies can teach us about the normal immune system, and how that knowledge can help us look after patients better.

Qualifications

BA
BM Bch
MRCP
MRCPCH
DPhil
Cert Clin Ed

Previous Positions

1992-4 Senior House Officer, Paediatrics: Northampton DGH, Queen’s Medical Centre, Nottingham & Great Ormond Street Hospital for Sick Children, London.

1995-6 Registrar, Paediatrics: Birmingham Maternity Hospital & Birmingham Children’s Hospital

1996-2000 Clinical Lecturer: University of Oxford & Honorary Specialist Registrar, Paediatrics, ORH

2001-3 Specialist Registrar, Paediatrics: Oxford Radcliffe Hospitals

2003-5 Postdoctoral Research Fellow: Pediatric Infectious Disease Division, Columbia University, New York, USA

2006-2007 Specialist Registrar, Paediatrics: Newcastle upon Tyne Hospitals NHS Trust

2007-2008 First Assistant, Paediatrics: Newcastle upon Tyne Hospitals NHS Trust

2008-present Clinical Senior Lecturer & Honorary Consultant, Paediatric Immunology & Infectious Diseases: Newcastle University & Newcastle upon Tyne Hospitals NHS Trust

Memberships

Honours and Awards

1991 Pickering Prize, Oxford University
1996-2000 Clinical Training Fellowship, Medical Research Council
2008-2012 Clinician Scientist Fellowship, Medical Research Council

Research Interests

I am a clinical paediatric immunologist with a particular interest in inherited susceptibility to infection. My laboratory research background is in cellular/molecular immunology and herpesvirology. My clinical activities are based in the supra-regional service for children with primary immunodeficiencies, which includes an active stem cell transplantation programme. My research is aimed at understanding the cellular and molecular basis of primary immunodeficiency, and how it informs our knowledge of the normal immune system.

Current Work

Rare individuals with inborn errors of immunity are at high risk of severe infections, autoimmunity and/or malignancy. By understanding the relationship between disease-causing mutations and the patterns of susceptibility that result, we can work out the function of specific elements of the immune system. I am involved in projects that tackle this from a variety of angles, including genetic and immunophenotypic approaches. These studies have so far led to the description of three primary immunodeficiencies that are completely novel in terms of genetic aetiology and phenotype, including a "first in class" example of antigen presenting cell deficiency.

To complement these laboratory-based studies, I have been running a clinical project aimed at improving the prevention of chickenpox in children with cancer. We aim to conduct a pilot randomised controlled trial to compare different preventive approaches.

Future Research

Through collaboration with Prof Eamonn Maher and colleagues in Birmingham, we are mapping novel primary immunodeficiency phenotypes in consanguineous families by homozygosity mapping. This approach can be combined with next generation exome sequencing to identify new disease-causing mutations. I am part of a consortium of clinicians and geneticists implementing exome sequencing in Newcastle. We have set up the Great North Biobank as a further resource for future research into the aetiology of inborn errors.

Postgraduate Supervision

I welcome postgraduate students who are interested in translational immunology research into primary immunodeficiency.

Funding

MRC clinician scientist award 2008-2012

Undergraduate Teaching

Extensive experience of teaching and assessing medical students.

Postgraduate Teaching

I play an active role in postgraduate education within my clinical subspecialty including delivery of registrar training and running study days. I teach "The Immunology of Infection" on the MRes Immunobiology programme.

• Hambleton S, Salem S, Bustamente J, Bigley V, Boisson-Dupuis S, Azevedo J, Fortin A, Haniffa M, Ceron-Gutierrez C, Bacon CM, Menon G, Trouillet C, McDonald D, Carey P, Ginhoux F, Alsina L, Zumwalt TJ, Kong X, Kumararatne D, Butler K, Hubeau M, Feinberg J, Al-Muhsen S, Cant A, Abel L, Chaussabel D, Doffinger R, Talesnik E, Grumach A, Duarte A, Abarca K, Moraes-Vasconcelos D, Burk D, Berghuis A, Geissmann F, Collin M, Casanova J-L, Gros P. IRF8 Mutations and Human Dendritic-Cell Immunodeficiency. New England Journal of Medicine 2011, 365(2), 127-138.
• Bigley V, Haniffa M, Doulatov S, Wang XN, Dickinson R, McGovern N, Jardine L, Pagan S, Dimmick I, Chua I, Wallis J, Lordan J, Morgan C, Kumararatne DS, Doffinger R, van der Burg M, van Dongen J, Cant A, Dick JE, Hambleton S, Collin M. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. Journal of Experimental Medicine 2011, 208(2), 227-234.
• Morgan NV, Goddard S, Cardno TS, McDonald D, Rahman F, Barge D, Ciupek A, Straatman-Iwanowska A, Pasha S, Guckian M, Anderson G, Huissoon A, Cant A, Tate WP, Hambleton S, Maher ER. Mutation in the TCR alpha subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCR alpha beta(+) T cells. European Journal of Clinical Investigation 2011, 121(2), 695-702.
• Bate J, Chisholm J, Heath P, Breuer J, Skinner R, Manley S, Patel S, Wheatley K, Ramsay M, Kearns P, Hambleton S. PEPtalk: post-exposure prophylaxis against varicella in children with cancer. Archives of Disease in Childhood 2011, 96(9), 841-845.
• Slatter MA, Rao K, Amrolia P, Flood T, Abinun M, Hambleton S, Nademi Z, Goulden N, Davies G, Qasim W, Gaspar HB, Cant A, Gennery AR, Veys P. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood 2011, 117(16), 4367-4375.
• Hambleton S. A Better Grip: T Cells Strengthen Our Hand against Influenza. Clinical Infectious Diseases 2011. Cary, North Carolina, USA: Oxford University Press Inc, 52(1), 8-9.
• Slatter MA, Angus B, Windebank K, Taylor A, Meaney C, Lester T, Norbury G, Hambleton S, Abinun M, Flood TJ, Cant AJ, Gennery AR. Polymorphous lymphoproliferative disorder with Hodgkin-like features in common gamma-chain-deficient severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 2011. 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA: MOSBY-ELSEVIER, 127(2), 533-535.
• Purvis HA, Stoop JN, Mann J, Woods S, Kozijn AE, Hambleton S, Robinson JH, Isaacs JD, Anderson AE, Hilkens CMU. Low-strength T-cell activation promotes Th17 responses. Blood 2010,116 23 4829-4837.
• Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, Puel A, Bacon CM, Rieux-Laucat F, Pang K, Britland A, Abel L, Cant A, Maher ER, Riedl SJ, Hambleton S, Casanova J-L. Whole-exome-sequencing-based discovery of human FADD deficiency. American Journal of Human Genetics 2010,87 6 873-881.
• Rensing-Ehl A, Warnatz K, Fuchs S, Schlesier M, Salzer U, Draeger R, Bondzio I, Joos Y, Janda A, Gomes M, Abinun M, Hambleton S, Cant A, Shackley F, Flood T, Waruiru C, Beutel K, Siepermann K, Dueckers G, Niehues T, Wiesel T, Schuster V, Seidel MG, Minkov M, Sirkia K, Kopp MV, Korhonen M, Schwarz K, Ehl S, Speckmann C. Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency. Clinical Immunology 2010,137 3 357-365.
• Skinner R, Hambleton S. Prevention of varicella in children with cancer: Is it time to reconsider our strategy?. Pediatric Blood & Cancer 2008. John Wiley & Sons, Inc., 51(4), 451-452.
• Hambleton S, Steinberg SP, Gershon MD, Gershon AA. Cholesterol dependence of Varicella-Zoster virion entry into target cells. Journal of Virology 2007, 81(14), 7548-7558.
• Moreira D, Slatter M, Nademi Z, Brigham K, Barge D, Jackson A, Flood T, Cant A, Abinun M, Hambleton S, Gennery A. Immune reconstitution and clinical outcome after HSCT infusion for severe combined immunodeficiency in Newcastle. In: Biology of Blood and Marrow Transplantation: BMT Tandem Meeting. 2012, San Diego, California, USA: Elsevier Inc.
• Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M. Exome sequencing identifies GATA-2 mutation as the cause of the dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 2011, 118(10), 2656-2658.
• Passerini L, Olek S, Di Nunzio S, Barzaghi F, Hambleton S, Abinun M, Tommasini A, Vignola S, Cipolli M, Amendola M, Naldini L, Guidi L, Cecconi M, Roncarolo MG, Bacchetta R. Forkhead box protein 3 (FOXP3) mutations lead to increased T(H)17 cell numbers and regulatory T-cell instability. Journal of Allergy and Clinical Immunology 2011, 128(6), 1376-1379.e1.
• Dickinson RE, Bigley V, Griffin H, Lakey JH, McGovern N, Chua I, Wallis J, Hambleton S, Santibanez-Koref M, Collin M. Human dendritic cell deficiency is caused by GATA-2 mutation. In: Immunology: Annual Congress of the British Society for Immunology. 2011, Liverpool, UK: Wiley-Blackwell Publishing Ltd.
• Collin M, Bigley V, Haniffa M, Hambleton S. Human dendritic cell deficiency: the missing ID?. Nature Reviews Immunology 2011, 11(9), 575-583.
• Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD, Cant AJ, Thrasher AJ, Cowan MJ, Albert MH, Small T, Pai SY, Haddad E, Lisa A, Hambleton S, Slatter M, Cavazzana-Calvo M, Mahlaoui N, Picard C, Torgerson TR, Burroughs L, Koliski A, Zanis-Neto J, Porta F, Qasim W, Veys P, Kavanau K, Hönig M, Schulz A, Friedrich W, Notarangelo LD. Long-term outcome and lineage-specific chimerism in 194 Wiskott-Aldrich Syndrome patients treated by hematopoietic cell transplantation between 1980-2009: an international collaborative study. Blood 2011, 118(6), 1675-1684.
• Fisher JPH, Bate J, Hambleton S. Preventing varicella in children with malignancies: what is the evidence?. Current Opinion in Infectious Diseases 2011, 24(3), 203-211.
• Sturgess K, Slatter M, Bigley V, Haniffa M, Wang XN, Dickinson R, McGovern N, Jardine L, Pagan S, Chua I, Wallis J, Lordan J, Morgan C, Cant A, Gennery A, Edmondson R, Bacon C, Black F, Kirkham N, Jackson GH, Hambleton S, Collin MP. Reduced Intensity Hematopoietic Stem Cell Transplant Rescues Immune Function and Corrects Pulmonary Alveolar Proteinosis in DCML Deficiency/GATA 2 Mutation. In: Blood: 53rd Annual Meeting and Exposition of the American Society of Hematology (ASH). 2011, San Diego, California, USA: American Society of Hematology.
• McDonald D, Morgan N, Griffin H, Dang TS, Grainger A, Reynard L, Loughlin J, Santibanez-Koref M, Hambleton S. Whole-exome deep sequencing identifies a novel causative mutation in primary immunodeficiency. In: Immunology: Annual Congress of the British Society for Immunology. 2011, Liverpool, UK: Wiley-Blackwell Publishing Ltd.