From bedside to bench and back again - our research is all about what children with inborn errors of immunity can teach us about the normal immune system, and how that knowledge can help us look after patients better. I am a clinical paediatric immunologist at the Great North Children's Hospital, which is home to a supra-regional service for children with primary immunodeficiencies. My work is aimed at understanding the cellular and molecular basis of novel primary immunodeficiencies, and how this informs our knowledge of the normal immune system.

The human immune system has evolved to protect us from a bewildering array of germs, a job it usually performs unnoticed. We can think of the immune system as a network of armed forces that cooperate to defend us. When one element of these defences is weakened, it can leave us critically exposed to certain threats. Unusual or severe infections in young children can indicate a problem with the genes that determine how our immune system works. If affected children survive, they may suffer ongoing ill-health owing to chronic infection, stunted growth and lung damage. Sometimes this is accompanied by other problems such as the "friendly fire" of autoimmune disease or blood cancers. This type of immunodeficiency tends to run in families and is commoner in children whose parents are related to each other.

At the Great North Children's Hospital (GNCH), we care for hundreds of patients with inherited immunodeficiency, but the faulty gene can't always be pinpointed. Making a genetic diagnosis is important for two main reasons, one medical and one scientific:

(1) An accurate diagnosis can help doctors and families make the right treatment decisions. Many immunodeficiencies can now be cured by replacing the immune system with a bone marrow transplant. Unfortunately, this is an unpleasant and risky procedure. Scientists continue to work on smarter methods to replace or repair just the faulty gene. Where cure is not possible we can take steps to prevent and treat complications if we know what to expect.

(2) Linking the faulty gene to the resulting pattern of disease tells us about its normal function. By studying individuals with inherited immunodeficiency, we can learn a great deal about what is important for human immunity. This knowledge can also help us understand the ways germs get round our immune system to cause disease.

My research addresses both these priorities by searching for the underlying cause of unexplained immunodeficiencies. We characterise the faulty immune system in detail to better describe how it is misbehaving. We use modern DNA sequencing methods to look for genetic changes that may link with disease. We test the strength of that link within the family and the wider population.   We try to find out how the genetic change interferes with normal immune function by experiments in the test tube.

As soon as a linked genetic change is confirmed, this can be fed back to the clinical team and inform patient care. Families can then benefit from genetic counselling and the possibility of early diagnosis for other affected family members. We share our research findings with the medical community at large so that patients with a similar disease pattern can be screened for the same genetic problem. We believe our work will lead to improved scientific understanding of human immunity, which is fundamentally important to health and disease.

Google Scholar: Click here.

Group members:

Angela Grainger

Karin Engelhardt

Jarmila Spegarova

Rui Chen

Helen Griffin

Chris Duncan

Becky Payne

Ben Thompson

Ina Schim van der Loeff

Katie Hatton

Alex Nicols

Matt Drummond

Kate Madden

Zoe Kirkham

Our research

Inborn errors of immunity (IEI) represent a rich resource for hypothesis-generating research on the human immune system. Our aim is to elucidate disease mechanism in novel inherited disorders of cellular immunity. We study well-characterised patients presenting in childhood with otherwise unexplained immune dysregulation and/or susceptibility to intracellular pathogens. A variety of methods are used to identify candidate disease-causing genetic variants, including whole exome sequencing and whole genome sequencing. Selected variants are taken forward for biochemical and functional validation by tailored analyses of biobanked material. In recent years we have identified novel defects of T cells, antigen-presenting cells and innate antiviral immunity that have each contributed important mechanistic insights into human immunobiology.  

By comparison with genetically engineered mouse models, a forward genetic approach to human IEI offers inherent scientific advantages such as (1) increased relevance of findings to human immunity in the natural environment, (2) a definite and clinically important phenotype, (3) freedom from preconceptions as to candidate genes. IEI thus represent critically important human models in which to discover and explore the function of individual genes and pathways. A major advantage of our work is its direct relevance to patient care by extending the possibility of molecular diagnosis, with attendant benefits in terms of timely and tailored treatment and genetic counselling.

Postgraduate Supervision

We welcome postgraduate students who are interested in translational immunology research.

Funding

Wellcome Investigator Award 2018-2022

Sir Jules Thorn Charitable Trust Biomedical award 2013-2017

MRC clinician scientist award 2008-2012

Undergraduate Teaching

Extensive experience of mentoring, teaching and assessing students of medicine and biomedical sciences.

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 Immunobiology to MRes students and supervise research projects at all levels.  I participate in various clinical postgraduate courses including the ESID summer school and the Oxford Paediatric Infectious Diseases Diploma.  I lead the Immune Disorders domain of the Genomics England Clinical Interpretation Partnership.

• Schim van der Loeff I, Sprenkeler EGG, Tool ATJ, Abinun M, Grainger A, Engelhardt KR, van Houdt M, Janssen H, Kuijpers TW, Hambleton S. Defective neutrophil development and specific granule deficiency caused by a homozygous splice-site mutation in SMARCD2. Journal of Allergy and Clinical Immunology 2021, 147(6), 2381-2385.e2.
• Duncan CJA, Randall RE, Hambleton S. Genetic Lesions of Type I Interferon Signalling in Human Antiviral Immunity. Trends in Genetics 2021, 37(1), 46-58.
• Krishna MT, Beck S, Gribbin N, Nasser S, Turner PJ, Hambleton S, Sargur R, Whyte A, Bethune C. The Impact of COVID-19 Pandemic on Adult and Pediatric Allergy & Immunology Services in the UK National Health Service. Journal of Allergy and Clinical Immunology: In Practice 2021, 9(2), 709-722.e2.
• Cytlak U, Resteu A, Pagan S, Green K, Milne P, Maisuria S, McDonald D, Hulme G, Filby A, Carpenter B, Queen R, Hambleton S, Hague R, Lango Allen H, Thaventhiran JED, Doody G, Collin M, Bigley V. Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans. Immunity 2020, 53(2), 353-370.
• Spegarova JS, Lawless D, Mohamad SMB, Engelhardt KR, Doody G, Shrimpton J, Rensing-Ehl A, Ehl S, Rieux-Laucat F, Cargo C, Griffin H, Mikulasova A, Acres M, Morgan NV, Poulter JA, Sheridan EG, Chetcuti P, O'Riordan S, Anwar R, Carter C, Przyborski S, Windebank K, Cant AJ, Lako M, Bacon CM, Savic S, Hambleton S. Germline TET2 loss-of-function causes childhood immunodeficiency and lymphoma. Blood 2020, 136(9), 1055-1066.
• Martin E, Minet N, Boschat A-C, Sanquer S, Sobrino S, Lenoir C, de Villartay JP, Leite-De-Moraes M, Picard C, Soudais C, Bourne T, Hambleton S, Hughes SM, Wynn RF, Briggs TA, Patel S, Lawrence MG, Fischer A, Arkwright PD, Latour S. Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation. JCI Insight 2020, 5(5), e133880.
• Lum SH, Anderson C, McNaughton P, Engelhardt K, MacKenzie B, Watson H, Al-Mousa H, Al-Herz W, Al-Saud B, Mohammed R, ALZahrani D, Alghamdi HA, Goronfolah L, Nademi Z, Habibolla S, Flinn AM, Shillitoe B, Owens S, Williams E, Emonts M, Hambleton S, Abinun M, Flood T, Cant A, Gennery AR, Slatter M. Improved transplant survival and long-term disease outcome in children with MHC class II deficiency. Blood 2020, 135(12), 954-973.
• Lum SH, Selvarajah S, Deya-Martinez A, McNaughton P, Sobh A, Waugh S, Burton-Fanning S, Newton L, Gandy J, Nademi Z, Owens S, Williams E, Emonts M, Flood T, Cant A, Abinun M, Hambleton S, Gennery AR, Slatter M. Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency. Journal of Allergy and Clinical Immunology 2020, 146(2), 406-416.
• Anzilotti C, Swan DJ, Boisson B, Deobagkar-Lele M, Oliveira C, Chabosseau P, Engelhardt KR, Xu X, Chen R, Alvarez L, Berlinguer-Palmini R, Bull KR, Cawthorne E, Cribbs AP, Crockford TL, Dang TS, Fearn A, Fenech EJ, de Jong SJ, Lagerholm C, Ma CS, Sims D, Van Den Berg B, Xu Y, Cant AJ, Kleiner G, Leahy TR, de laMorena MT, Puck JM, Shapiro RS, van der Burg M, Chapman JR, Christianson JC, Davies B, McGrath JA, Przyborski S, Santibanez Koref M, Tangye SG, Werner A, Rutter GA, Padilla-Parra S, Casanova JL, Cornall RJ, Conley ME, Hambleton S. An essential role for the Zn²⁺ transporter ZIP7 in B cell development. Nature Immunology 2019, 20, 350-361.
• Boyadzhiev M, Marinov L, Boyadzhiev V, Iotova V, Aksentijevich I, Hambleton S. Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome. Pediatric Rheumatology 2019, 17(1), 19.
• Abolhassani H, El-Sherbiny YM, Arumugakani G, Carter C, Richards S, Lawless D, Wood P, Buckland M, Heydarzadeh M, Aghamohammadi A, Hambleton S, Hammarstrom L, Burns SO, Doffinger R, Savic S. Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency. Journal of Clinical Immunology 2020, 40, 277-288.
• Nademi Z, Wynn RF, Slatter M, Hughes SM, Bonney D, Qasim W, Latour S, Truck J, Patel S, Abinun M, Flood T, Hambleton S, Cant AJ, Gennery AR, Arkwright PD. Hematopoietic stem cell transplantation for cytidine triphosphate synthase 1 (CTPS1) deficiency. Bone Marrow Transplantation 2019, 54(1), 130-133.
• Zhang Z, Gothe F, Pennamen P, James JR, McDonald D, Mata CP, Modis Y, Alazami AM, Acres M, Haller W, Bowen C, Doffinger R, Sinclair J, Brothers S, Zhang Y, Matthews H, Naudion S, Pelluard F, Alajlan H, Yamazaki Y, Notarangelo LD, Thaventhiran JED, Engelhardt KR, Al-Mousa H, Hambleton S, Rooryck C, Smith KGC, Lenardo MJ. Human interleukin-2 receptor β mutations associated with defects in immunity and peripheral tolerance. Journal of Experimental Medicine 2019, 216(6), 1311-1327.
• Dorjbal B, Stinson JR, Ma CA, Weinreich MA, Miraghazadeh B, Hartberger JM, Frey-Jakobs S, Weidinger S, Moebus L, Franke A, Schaffer AA, Bulashevska A, Fuchs S, Ehl S, Limaye S, Arkwright PD, Briggs TA, Langley C, Bethune C, Whyte AF, Alachkar H, Nejentsev S, DiMaggio T, Nelson CG, Stone KD, Nason M, Brittain EH, Oler AJ, Veltri DP, Leahy TR, Conlon N, Poli MC, Borzutzky A, Cohen JI, Davis J, Lambert MP, Romberg N, Sullivan KE, Paris K, Freeman AF, Lucas L, Chandrakasan S, Savic S, Hambleton S, Patel SY, Jordan MB, Theos A, Lebensburger J, Atkinson TP, Torgerson TR, Chinn IK, Milner JD, Grimbacher B, Cook MC, Snow AL. Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease. Journal of Allergy and Clinical Immunology 2019, 143(4), 1482-1495.
• Swan DJ, Aschenbrenner D, Lamb CA, Chakraborty K, Clark J, Pandey S, Engelhardt KR, Chen R, Cavounidis A, Ding Y, Krasnogor N, Carey CD, Acres M, Needham S, Cant AJ, Arkwright PD, Chandra A, Okkenhaug K, Uhlig HH, Hambleton S. Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ. Haematologica 2019, 104(10), e483-e486.
• Al Farsi T, Hughes SM, Wynn RF, Cheesman E, Rieux-Laucat F, Latour S, Picard C, Hambleton S, Arkwright PD. Life-threatening pulmonary interstitial lung disease complicating pediatric nonhumoral immunodeficiencies. Journal of Allergy and Clinical Immunology: In Practice 2019, 7(7), 2456-2458.e4.
• Al Shehri T, Gilmour K, Gothe F, Loughlin S, Bibi S, Rowan AD, Grainger A, Mohanadas T, Cant AJ, Slatter MA, Hambleton S, Lilic D, Leahy TR. Novel Gain-of-Function Mutation in Stat1 Sumoylation Site Leads to CMC/CID Phenotype Responsive to Ruxolitinib. Journal of Clinical Immunology 2019, 39, 776-785.
• Chiesa R, Standing JF, Winter R, Nademi Z, Chu J, Pinner D, Kloprogge F, McLellen S, Amrolia PJ, Rao K, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Gennery AR, Doncheva B, Cant AJ, Hambleton S, Flood T, Rogerson E, Devine K, Prunty H, Heales S, Veys P, Slatter M. Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial. Clinical Pharmacology and Therapeutics 2019, 108(2), 264-273.
• Duncan CJA, Thompson BJ, Chen R, Rice GI, Gothe F, Young DF, Lovell SC, Shuttleworth VG, Brocklebank V, Corner B, Skelton AJ, Bondet V, Coxhead J, Duffy D, Fourrage C, Livingston JH, Pavaine J, Cheesman E, Bitetti S, Grainger A, Acres M, Innes BA, Mikulasova A, Sun R, Hussain H, Wright R, Wynn R, Zarhrate M, Zeef LAH, Wood K, Hughes SM, Harris CL, Engelhardt KE, Crow YJ, Randall RE, Kavanagh D, Hambleton S, Briggs TA. Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2. Science Immunology 2019, 4(42), eaav7501.
• Lum SH, Flood T, Hambleton S, McNaughton P, Watson H, Abinun M, Owens S, Cigrovski N, Cant A, Gennery AR, Slatter M. Two decades of excellent transplant survival for chronic granulomatous disease: A supraregional immunology transplant center report. Blood 2019, 133(23), 2546-2549.
• Tholouli E, Sturgess K, Dickinson RE, Gennery A, Cant AJ, Jackson G, Lordan J, Hambleton S, Slatter MA, Bigley V, Collin M. In vivo T-depleted reduced intensity transplantation for GATA2-related immune dysfunction. Blood 2018, 131(12), 1383-1387.
• Bigley V, Maisuria S, Cytlak U, Jardine L, Care MA, Green K, Gunawan M, Milne P, Dickinson R, Wiscombe S, Parry D, Doffinger R, Laurence A, Fonseca C, Stoevesandt O, Gennery A, Cant A, Tooze R, Simpson AJ, Hambleton S, Savic S, Doody G, Collin M. Biallelic interferon regulatory factor 8 mutation: A complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation. Journal of Allergy and Clinical Immunology 2018, 141(6), 2234-2248.
• Kong X-F, Martinez-Barricarte R, Kennedy J, Mele F, Lazarov T, Deenick EK, Ma CS, Breton G, Lucero KB, Langlais D, Bousfiha A, Aytekin C, Markle J, Trouillet C, Jabot-Hanin F, Arlehamn CSL, Rao G, Picard C, Lasseau T, Latorre D, Hambleton S, Deswarte C, Itan Y, Abarca K, Moraes-Vasconcelos D, Ailal F, Ikinciogullari A, Dogu F, Benhsaien I, Sette A, Abel L, Boisson-Dupuis S, Schroder B, Nussenzweig MC, Liu K, Geissmann F, Tangye SG, Gros P, Sallusto F, Bustamante J, Casanova J-L. Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency. Nature Immunology 2018, 19(9), 973-985.
• Duncan CJA, Dinnigan E, Theobald R, Grainger A, Skelton AJ, Hussain R, Willet JDP, Swan DJ, Coxhead J, Thomas MF, Thomas J, Zamvar V, Slatter MA, Cant AJ, Engelhardt KR, Hambleton S. Early-onset autoimmune disease due to a heterozygous loss-of-function mutation in TNFAIP3 (A20). Annals of the Rheumatic Diseases 2018, 77(5), 783-786.
• Prader S, Felber M, Volkmer B, Truck J, Schwieger-Briel A, Theiler M, Weibel L, Hambleton S, Seipel K, Vavassori S, Pachlopnik Schmid J. Life-Threatening Primary Varicella Zoster Virus Infection With Hemophagocytic Lymphohistiocytosis-Like Disease in GATA2 Haploinsufficiency Accompanied by Expansion of Double Negative T-Lymphocytes. Frontiers in Immunology 2018, 9, 2766.
• Unni MNM, Elfeky R, Rao K, Nademi Z, Chiesa R, Amrolia P, Skinner R, Slater O, Worth A, Flood T, Abinun M, Hambleton S, Qasim W, Gaspar HB, Cant AJ, Gennery AR, Veys P, Slatter MA. Non-posttransplant lymphoproliferative disorder malignancy after hematopoietic stem cell transplantation in patients with primary immunodeficiency: UK experience. Journal of Allergy and Clinical Immunology 2018, 141(6), 2319-2321.e1.
• Bate J, Baker S, Breuer J, Chisholm JC, Gray J, Hambleton S, Houlton A, Jit M, Lowis S, Makin G, O'Sullivan C, Patel SR, Phillips R, Ransinghe N, Ramsay ME, Skinner R, Wheatley K, Heath PT. PEPtalk2: Results of a pilot randomised controlled trial to compare VZIG and aciclovir as postexposure prophylaxis (PEP) against chickenpox in children with cancer. Archives of Disease in Childhood 2018, 104(1), 25-29.
• Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, Hoshino A, Kobayashi M, Imai K, Takagi M, Dybedal I, Haddock JA, Sansom D, Lucena JM, Seidl M, SchmittGräff A, Reiser V, Emmerich F, Frede N, Bulashevska A, Salzer U, Schubert D, Hayakawa S, Okada S, Kanariou M, Kucuk ZY, Chapdelaine H, Petruzelkova L, Sumnik Z, Sediva A, Slatter M, Arkwright PD, Cant A, Lorenz H-M, Giese T, Lougaris V, Plebani A, Price C, Sullivan KE, Moutschen M, Litzman J, Freiberger T, vandeVeerdonk FL, Recher M, Albert MH, Hauck F, Seneviratne S, Schmid JP, Kolios A, Unglik G, Klemann C, Speckmann C, Ehl S, Leichtner A, Blumberg R, Franke A, Snapper S, Zeissig S, Cunningham-Rundles C, Giulino-Roth L, Elemento O, Dückers G, Niehues T, Fronkova E, Kanderová V, Platt CD, Chou J, Chatila T, Geha R, McDermott E, Bunn S, Kurzai M, Schulz A, Alsina L, Casals F, Deyà-Martinez A, Hambleton S, Kanegane H, Taskén K, Neth O, Grimbacher B. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4–insufficient subjects. Journal of Allergy and Clinical Immunology 2018, 142(6), 1932-1946.
• Acres MJ, Gothe F, Grainger A, Skelton AJ, Swan DJ, Willet JDP, Leech S, Galcheva S, Iotova V, Hambleton S, Engelhardt KR. STAT5B deficiency due to a novel missense mutation in the coiled-coil domain. Journal of Allergy and Clinical Immunology 2018, 143(1), 413-416.e4.
• Shah RM, Elfeky R, Nademi Z, Qasim W, Amrolia P, Chiesa R, Rao K, Lucchini G, Silva JMF, Worth A, Barge D, Ryan D, Conn J, Cant AJ, Skinner R, Abd Hamid IJ, Flood T, Abinun M, Hambleton S, Gennery AR, Veys P, Slatter M. T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. Journal of Allergy and Clinical Immunology 2018, 141(4), 1417-1426.e1.
• Slatter MA, Rao K, Abd Hamid IJ, Nademi Z, Chiesa R, Elfeky R, Pearce MS, Amrolia P, Worth A, Flood T, Abinun M, Hambleton S, Qasim W, Gaspar HB, Cant AJ, Gennery AR, Veys P. Treosulfan and Fludarabine Conditioning for Hematopoietic Stem Cell Transplantation in Children with Primary Immunodeficiency: UK Experience. Biology of Blood and Marrow Transplantation 2018, 24(3), 529-536.
• Schepp J, Chou J, Skrabl-Baumgartner A, Arkwright PD, Engelhardt KR, Hambleton S, Morio T, Rother E, Warnatz K, Geha R, Grimbacher B. 14 Years after Discovery: Clinical Follow-up on 15 Patients with Inducible Co-Stimulator Deficiency. Frontiers in Immunology 2017, 8.
• Tangye SG, Pillay B, Randall KL, Avery DT, Phan TG, Gray P, Ziegler JB, Smart JM, Peake J, Arkwright PD, Hambleton S, Orange J, Goodnow CC, Uzel G, Casanova J-L, Lugo Reyes SO, Freeman AF, Su HC, Ma CS. Dedicator of cytokinesis 8-deficient CD4+ T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells. Journal of Allergy and Clinical Immunology 2017, 139(3), 933–949.
• Engelhardt KR, Xu Y, Grainger A, Germani Batacchi MGC, Swan DJ, Willet JDP, Abd Hamid IJ, Agyeman P, Barge D, Bibi S, Jenkins L, Flood TJ, Abinun M, Slatter MA, Gennery AR, Cant AJ, Santibanez Koref M, Gilmour K, Hambleton S. Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing. Journal of Clinical Immunology 2017, 37(1), 42-50.
• Hou TZ, Verma N, Wanders J, Kennedy A, Soskic B, Janman D, Halliday N, Rowshanravan B, Worth A, Qasim W, Baxendale H, Stauss H, Seneviratne S, Neth O, Olbrich P, Hambleton S, Arkwright PD, Burns SO, Walker LSK, Sansom DM. Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations. Blood 2017, 129(11), 1458-1468.
• Ma CA, Xi L, Cauff B, DeZure A, Freeman AF, Hambleton S, Kleiner G, Leahy TR, O'Sullivan M, Makiya M, O'Regan G, Pittaluga S, Niemela J, Stoddard J, Rosenzweig SD, Raffeld M, Klion AD, Milner JD. Somatic STAT5b gain-of-function mutations in early onset nonclonal eosinophilia, urticaria, dermatitis, and diarrhea. Blood 2017, 129(5), 650-653.
• Brent J, Guzman D, Bangs C, Grimbacher B, Fayolle C, Huissoon A, Bethune C, Thomas M, Patel S, Jolles S, Alachkar H, Kumaratne D, Baxendale H, Edgar JD, Helbert M, Hambleton S, Arkwright PD. Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia. Clinical & Experimental Immunology 2016, 184(1), 73-82.
• Singh Dang T, Willet JDP, Griffin HR, Morgan NV, O'Boyle G, Arkwright PD, Hughes SM, Abinun M, Tee LJ, Barge D, Engelhardt KR, Jackson M, Cant AJ, Maher ER, Santibanez Koref M, Reynard LN, Ali S, Hambleton S. Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency. Journal of Clinical Immunology 2016, 36(2), 117-122.
• Slatter M, Nademi Z, Leahy TR, Morillo-Gutierrez B, Dunn J, Barge D, Skinner R, Ryan C, Hambleton S, Abinun M, Flood T, Cant A, Gennery A. Haploidentical CD3 TCRαβ and CD19-depleted second stem cell transplant for steroid-resistant acute skin graft versus host disease. Journal of Allergy and Clinical Immunology 2016, 138(2), 603-605.
• Nademi Z, Slatter MA, Dvorak CC, Neven B, Fischer A, Suarez F, Booth C, Rao K, Laberko A, Rodina J, Bertrand Y, Koltan S, Debski R, Flood T, Abinun M, Gennery AR, Hambleton S, Ehl S, Cant AJ. Hematopoietic stem cell transplant in patients with activated PI3K delta syndrome. Journal of Allergy and Clinical Immunology 2016, 139(6), 1046-1049.
• Slatter MA, Engelhardt KR, Burroughs LM, Arkwright PD, Nademi Z, Skoda-Smith S, Hagin D, Kennedy A, Barge D, Flood T, Abinun M, Wynn RF, Gennery AR, Cant AJ, Sansom D, Hambleton S, Torgerson TR. Hematopoietic stem cell transplantation for CTLA4 deficiency. Journal of ALlergy and Clinical Immunology 2016, 138(2), 615-619.
• Ma CS, Wong N, Rao G, Nguyen A, Avery DT, Payne K, Torpy J, O'Young P, Deenick E, Bustamante J, Puel A, Okada S, Kobayashi M, Martinez-Barricarte R, Elliott M, Kilic SS, El Baghdadi J, Minegishi Y, Bousfiha A, Robertson N, Hambleton S, Arkwright PD, French M, Blincoe AK, Hsu P, Campbell DE, Stormon MO, Wong M, Adelstein S, Fulcher DA, Cook MC, Stepensky P, Boztug K, Beier R, Ikinciogullari A, Ziegler JB, Gray P, Picard C, Boisson-Dupuis S, Phan TG, Grimbacher B, Warnatz K, Holland SM, Uzel G, Casanova JL, Tangye SG. Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4⁺ T cells into distinct effector subsets. Journal of Experimental Medicine 2016, 213(8), 1589-1608.
• Hambleton S. When the STATs are against you. Blood 2016, 127(25), 3109-3110.
• Savic S, Parry D, Carter C, Johnson C, Logan C, Gutierrez BM, Thomas JE, Bacon CM, Cant A, Hambleton S. A new case of Fas-associated death domain protein deficiency and update on treatment outcomes. Journal of Allergy and Clinical Immunology 2015, 136(2), 502-505.
• Speckmann C, Doerken S, Aiuti A, Albert MH, Al-Herz W, Allende LM, Scarselli A, Avcin T, Perez-Becker R, Cancrini C, Cant A, Di Cesare S, Finocchi A, Fischer A, Gaspar HB, Ghosh S, Gennery A, Gilmour K, Gonzalez-Granado LI, Martinez-Gallo M, Hambleton S, Hauck F, Hoenig M, Moshous D, Neven B, Niehues T, Notarangelo L, Picard C, Rieber N, Schulz A, Schwarz K, Seidel MG, Soler-Palacin P, Stepensky P, Strahm B, Vraetz T, Warnatz K, Winterhalter C, Worth A, Fuchs S, Uhlmann A, Ehl S. A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis. Journal of Allergy and Clinical Immunology 2015, 139(4), 1302-1310.e4.
• Robertson N, Engelhardt KR, Morgan NV, Barge D, Cant AJ, Hughes SM, Abinun M, Xu YB, Koref MS, Arkwright PD, Hambleton S. Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis. Journal of Clinical Immunology 2015, 35(7), 598-603.
• Milner JD, Vogel TP, Forbes L, Ma CA, Stray-Pedersen A, Niemela JE, Lyons JJ, Engelhardt KR, Zhang Y, Topcagic N, Roberson EDO, Matthews H, Verbsky JW, Dasu T, Vargas-Hernandez A, Varghese N, McClain KL, Karam LB, Nahmod K, Makedonas G, Mace EM, Sorte HS, Perminow G, Rao VK, O'Connell MP, Price S, Su HC, Butrick M, McElwee J, Hughes JD, Willet J, Swan D, Xu Y, Santibanez-Koref M, Slowik V, Dinwiddie DL, Ciaccio CE, Saunders CJ, Septer S, Kingsmore SF, White AJ, Cant AJ, Hambleton S, Cooper MA. Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood 2015, 125(4), 591-599.
• Duncan CJA, Mohamad SMB, Young DF, Skelton AJ, Leahy TR, Munday DC, Butler KM, Morfopoulou S, Brown JR, Hubank M, Connell J, Gavin PJ, McMahon C, Dempsey E, Lynch NE, Jacques TS, Valappil M, Cant AJ, Breuer J, Engelhardt KR, Randall RE, Hambleton S. Human IFNAR2 deficiency: lessons for antiviral immunity. Science Translational Medicine 2015, 7(307), 307ra154.
• Okada S, Markle JG, Deenick EK, Mele F, Averbuch D, Lagos M, Alzahrani M, Al-Muhsen S, Halwani R, Ma CS, Wong N, Soudais C, Henderson LA, Marzouqa H, Shamma J, Gonzalez M, Martinez-Barricarte R, Okada C, Avery DT, Latorre D, Deswarte C, Jabot-Hanin F, Torrado E, Fountain J, Belkadi A, Itan Y, Boisson B, Migaud M, Arlehamn CSL, Sette A, Breton S, McCluskey J, Rossjohn J, de Villartay JP, Moshous D, Hambleton S, Latour S, Arkwright PD, Picard C, Lantz O, Engelhard D, Kobayashi M, Abel L, Cooper AM, Notarangelo LD, Boisson-Dupuis S, Puel A, Sallusto F, Bustamante J, Tangye SG, Casanova JL. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 2015, 349(6248), 606-613.
• Turley AJ, Gathmann B, Bangs C, Bradbury M, Seneviratne S, Gonzalez-Granado LI, Hackett S, Kutukculer N, Alachkar H, Hambleton S, Ritterbusch H, Kralickova P, Marodi L, Seidel MG, Dueckers G, Roesler J, Huissoon A, Baxendale H, Litzman J, Arkwright PD. Spectrum and Management of Complement Immunodeficiencies (Excluding Hereditary Angioedema) Across Europe. Journal of Clinical Immunology 2015, 35(2), 199-205.
• Abinun M, Lilic D, Devlin L, Christie S, Edgar D, Depner M, Fuchs S, Grimbacher B, Cant A, Flood T, Hambleton S, Gennery A, Nademi Z, Slatter M. Successful Allogeneic Haematopoietic Stem Cell Transplantation In A Child With Severe Immunodeficiency 31-C (OMIM # 614162) Due To STAT1-GOF Mutation. In: UKPIN 2015. 2015, Wiley-Blackwell.
• Reynolds B, Hambleton S, Dammann D, Lambert H, Emonts M. Troublesome Thai travels. Archives of Disease in Childhood Education and Practice Edition 2015, 100(3), 166-167.
• Duncan CJA, Hambleton S. Varicella zoster virus immunity: A primer. Journal of Infection 2015, 71(Suppl. 1), S47-S53.
• Rensing-Ehl A, Volkl S, Speckmann C, Lorenz MR, Ritter J, Janda A, Abinun M, Pircher H, Bengsch B, Thimme R, Fuchs I, Ammann S, Allgauer A, Kentouche K, Cant A, Hambleton S, da Cunha CB, Huetker S, Kuhnle I, Pekrun A, Seidel MG, Hummel M, Mackensen A, Schwarz K, Ehl S. Abnormally differentiated CD4⁺ or CD8⁺ T cells with phenotypic and genetic features of double negative T cells in human Fas deficiency. Blood 2014, 124(6), 851-860.
• Kharya G, Nademi Z, Leahy T, Brigham K, Barge D, Hambleton S, Abinun M, Flood T, Cant A, Slatter M, Gennery A. Common Gamma chain- and JAK3-deficient SCID, conditioned versus unconditioned transplant: a single centre experience. In: 40th Annual Meeting of the European Group for Blood and Marrow Transplantation. 2014, Milan, Italy: Nature Publishing Group.
• Lu W, Zhang Y, McDonald DO, Jing HE, Carroll B, Robertson N, Zhang Q, Griffin H, Sanderson S, Lakey JH, Morgan NV, Reynard LN, Zheng L, Murdock HM, Turvey SE, Hackett SJ, Prestidge T, Hall JM, Cant AJ, Matthews HF, Koref MFS, Simon AK, Korolchuk VI, Lenardo MJ, Hambleton S, Su HC. Dual Proteolytic Pathways Govern Glycolysis and Immune Competence. Cell 2014, 159(7), 1578-1590.
• Zhou Q, Yang D, Ombrello AK, Zavialov AV, Toro C, Zavialov AV, Stone DL, Chae JJ, Rosenzweig SD, Bishop K, Barron KS, Kuehn HS, Hoffmann P, Negro A, Tsai WXL, Cowen EW, Pei W, Milner JD, Silvin C, Heller T, Chin DT, Patronas NJ, Barber JS, Lee CCR, Wood GM, Ling A, Kelly SJ, Kleiner DE, Mullikin JC, Ganson NJ, Kong HH, Hambleton S, Candotti F, Quezado MM, Calvo KR, Alao H, Barham BK, Jones A, Meschia JF, Worrall BB, Kasner SE, Rich SS, Goldbach-Mansky R, Abinun M, Chalom E, Gotte AC, Punaro M, Pascual V, Verbsky JW, Torgerson TR, Singer NG, Gershon TR, Ozen S, Karadag O, Fleisher TA, Remmers EF, Burgess SM, Moir SL, Gadina M, Sood R, Hershfield MS, Boehm M, Kastner DL, Aksentijevich I. Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2. New England Journal of Medicine 2014, 370(10), 911-920.
• Salem S, Langlais D, Lefebvre F, Bourque G, Bigley V, Haniffa M, Casanova JL, Burk D, Berghuis A, Butler KM, Leahy TR, Hambleton S, Gros P. Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8^K108E mutation. Blood 2014, 124(12), 1894-1904.
• Elfeky R, Nademi Z, Brigham K, Barge D, Hambleton S, Abinun M, Flood T, Cant A, Slatter M, Gennery A. Haematopoietic stem cell transplantation for RAG1/2 severe combined immunodeficiency or Omenn syndrome: a single centre experience. In: 40th Annual Meeting of the European Group for Blood and Marrow Transplantation. 2014, Milan, Italy: Nature Publishing Group.
• Duncan CJA, Hambleton S. Host genetic factors in susceptibility to mycobacterial disease. Clinical Medicine 2014, 14(Suppl. 6), s17-s21.
• Lane JR, Evans PTG, Nademi Z, Barge D, Jackson A, Hambleton S, Flood TJ, Cant AJ, Abinun M, Slatter MA, Gennery AR. Low-Dose Serotherapy Improves Early Immune Reconstitution after Cord Blood Transplantation for Primary Immunodeficiencies. Biology of Blood and Marrow Transplantation 2014, 20(2), 243-249.
• O'Reilly S, Cant R, Ciechomska M, Finnegan J, Oakley F, Hambleton S, van Laar JM. Serum Amyloid A (SAA) induces IL-6 in dermal fibroblasts via TLR2, IRAK4 and NF-κB. Immunology 2014, Accepted article.
• O'Reilly S, Cant R, Ciechomska M, Finnigan J, Oakley F, Hambleton S, van Laar JM. Serum amyloid A induces interleukin-6 in dermal fibroblasts via Toll-like receptor 2, interleukin-1 receptor-associated kinase 4 and nuclear factor-kappa B. Immunology 2014, 143(3), 331-340.
• Nademi Z, Slatter M, Gambineri E, Mannurita SC, Barge D, Hodges S, Bunn S, Thomas J, Haugk B, Hambleton S, Flood T, Cant A, Abinun M, Gennery A. Single centre experience of haematopoietic SCT for patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Bone Marrow Transplantation 2014, 49(2), 310-312.
• Hambleton S. STAT2. In: Stiehm's Immune Deficiencies. Amsterdam: Academic Press, 2014, pp.721-725.
• Dickinson RE, Milne P, Jardine L, Zandi S, Swierczek SI, McGovern N, Cookson S, Ferozepurwalla Z, Langridge A, Pagan S, Gennery A, Heiskanen-Kosma T, Hamalainen S, Seppanen M, Helbert M, Tholouli E, Gambineri E, Reykdal S, Gottfreosson M, Thaventhiran JE, Morris E, Hirschfield G, Richter AG, Jolles S, Bacon CM, Hambleton S, Haniffa M, Bryceson Y, Allen C, Prchal JT, Dick JE, Bigley V, Collin M. The evolution of cellular deficiency in GATA2 mutation. Blood 2014, 123(6), 863-874.
• Slatter M, Nademi Z, Patel S, Barge D, Valappil M, Brigham K, Hambleton S, Clark J, Flood T, Cant A, Abinun M, Gennery A. Haploidentical hematopoietic stem cell transplantation can lead to viral clearance in severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 2013, 131(6), 1705-1708.e1.
• Rensing-Ehl A, Janda A, Lorenz MR, Gladstone BP, Fuchs I, Abinun M, Albert M, Butler K, Cant A, Cseh AM, Ebinger M, Goldacker S, Hambleton S, Hebart H, Houet L, Kentouche K, Kuhnle I, Lehmberg K, Mejstrikova E, Niemeyer C, Minkov M, Neth O, Duckers G, Owens S, Rosler J, Schilling FH, Schuster V, Seidel MG, Smisek P, Sukova M, Svec P, Wiesel T, Gathmann B, Schwarz K, Vach W, Ehl S, Speckmann C. Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia. Haematologica 2013, 98(12), 1948-1955.
• Hambleton S, Goodbourn S, Young DF, Dickinson P, Mohamad SMB, Valappil M, McGovern N, Cant AJ, Hackett SJ, Ghazal P, Morgan NV, Randall RE. STAT2 deficiency and susceptibility to viral illness in humans. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(8), 3053-3058.
• Ciechomska M, Huigens CA, Hugle T, Stanly T, Gessner A, Griffits B, Radstake TR, Hambleton S, O'Reilly S, van Laar JM. Toll-like receptor-mediated, enhanced production of profibrotic TIMP-1 in monocytes from patients with systemic sclerosis: role of serum factors. Annals of Rheumatic Disease 2013, 72(8), 1382-1389.
• Plagnol V, Curtis J, Epstein M, Mok KY, Stebbings E, Grigoriadou S, Wood NW, Hambleton S, Burns SO, Thrasher AJ, Kumararatne D, Doffinger R, Nejentsev S. A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics 2012, 28(21), 2747-2754.
• Bate J, Chisholm J, Skinner R, Breuer J, Ramsay M, Wheatley K, Hambleton S, Heath PT. Varicella post-exposure prophylaxis in children with cancer: urgent need for a randomised controlled trial. Archives of Disease in Childhood 2012, 97(9), 853-854.
• 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.
• Hambleton S. A Better Grip: T Cells Strengthen Our Hand against Influenza. Clinical Infectious Diseases 2011, 52(1), 8-9.
• 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 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.
• 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.
• 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 TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ⁺ T cells. 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, 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, 127(2), 533-535.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.