缅北禁地

Introduction:

I am a MRC Senior Clinical Fellow based in the Translational and Clinical Research Institute, with research interests spanning haematology and immunology. I also practice as an honorary consultant haematologist at Freeman Hospital, specialising in bone marrow transplantation, with a particular interest in adult primary inborn errors of immunity (IEI).

Research: As one of two Principle Investigators in the Haematopoiesis and Immunogenomics Laboratory, I lead a small group working to map the cellular pathways and genetic control of myeloid cell haematopoiesis, the genetic causes of dendritic cell (DC) primary immunodeficiency and the immunological consequences of these disorders. The group has also pioneered methods to probe the phenotype and function of human monocytes and DCs in clinical samples.

Clinical Practice: This immunological approach to haematology is reflected in my clinical practice, leading the bone marrow transplant service for adults with inborn errors of immunity in 缅北禁地 upon Tyne. As one of two National Centres, we work in close collaboration with 缅北禁地 paediatric immunology at the Great North Children's Hospital, Great Ormond Street Hospital and The Royal Free Hospital, London.

Funding has recently been agreed by NHS England to provide bone marrow transplantation for those adult patients with IEI who would benefit from the procedure.

NanoString Facility: I lead the 缅北禁地 NanoString facility and welcome enquiries about this gene expression technology.

Qualifications:

BA (Natural Sciences), Cambridge University

BM, BChir, Cambridge University

MRCP, Royal College of Physicians (UK)

FRCPath, Royal College of Pathologists (UK)

Ph.D., 缅北禁地

Membership of Learned Societies:

European Society for Immunodeficiencies

British Society of Immunology

British Society of Blood and Marrow Transplantation

British Society of Haematology

Esteem Indicators:

Editorial Board Membership:

Frontiers in Immunology

Professional responsibilities:

Reviewer for Science, Nature Immunology, Blood, Nature Reviews Immunology, Journal of Clinical Immunology, Journal of Immunology, Molecular Immunology, Cellular Immunology

Expert reviewer for MRC Infection and Immunity Board

Frontiers in Immunology Editorial Board Member

Member of Genomics England Clinical Interpretation Partnership (GeCIP)

Member of Working Party for NHS England Policy Proposal ‘All ages bone marrow transplantation for primary immunodeficiencies’

Member of the National adult primary immunodeficiency bone marrow transplant multidisciplinary team

缅北禁地 Athena Swan Self Assessment Team member

Selected Lectures at Recent National and International Meetings:

European Bone Marrow Transplant Annual Meeting (EBMT2020), Virtual (2020)

UK Primary immunodeficiency Network Annual Meeting, Liverpool, UK (2019)

Paediatric Immunodeficiency Annual Meeting, London, UK (2019)

BSHI Annual meeting, Leeds (2019)

Dean's Celebratory Lecture, 缅北禁地 (2018)

15th International Symposium on Dendritic Cells, Aachen, Germany (2018)

28th Nikolas Symposium, Athens, Greece (2018)

Keystone Myeloid Cells, Brechenridge, USA (2018)

Northern Immunology and Allergy Meeting, 缅北禁地 (2018)

European Society of Immunodeficiencies Annual Meeting, Edinburgh (2017)

Clinical Immunology Society (USA) Annual Meeting, Seattle, USA (2017)

Infections, Immunity, Inflammation Seminar Series, UCL, GOS Institute of Child Health, London UK (2017)

Peter Gorer Department of Immunobiology Seminar, King's College London (2016)

European Haematology Association 21st Congress, Copenhagen, Denmark (2016)

UK Primary Immunodeficiency Network, Belfast (2015)

Research Interests:

1. Dendritic Cell Haematopoiesis. 

Dendritic Cells are professional antigen presenting cells which initiate and control immune responses. They act as innate effector cells, able to recognise and respond to danger signals and influence the innate immune response. However, they are best know for their role in antigen-specific priming and activation of naive T cells to drive adaptive immune responses. On the other hand, in the absence of danger signals, DCs critically maintain tolerance to non-pathogenic and self antigen. Despite the pivotal role these cells play in infection, cancer biology, vaccine medicine and autoimmunity, the cellular pathways of their development, and the genes which control their differentiation were unknown in human. Through in vitro culture of prospective progenitors, single cell transcriptomics and the study of patients with DC deficiencies, the group has mapped the pathways and defined genes important in DC development and function, including GATA2, IRF8 and IKZF1.

2. Dendritic Cell Immunodeficiency

During my PhD work we identified an immunodeficiency syndrome associated with heterozygous GATA2 mutation, encompassing dendritic cell, monocyte and lymphoid (DCML) deficiency. We successfully treated the index case with bone marrow transplantation. In collaboration with Sophie Hambleton, we defined the clinical and cellular characteristics of a patient with bi-allelic IRF8 mutations leading to complete loss of dendritic cells and monocytes. More recently, in collaboration with Sinisia Savic and Gina Doody in Leeds, we further refined the complex immunological phenotype of bi-allelic IRF8 mutations through the study of a patient with compound heterozygous mutations. A recent international collaboration allowed us to dissect the role of IKZF1 in human DC development, based on analysis of a cohort of patients with IKZF1 haploinsufficiency and myeloma patients with pharmacological IKZF1 deficiency induced by lenalidomide treatment. These studies have highlighted the importance of DCs in human health and disease and opened avenues for therapeutic manipulation.

3. Dendritic Cell Therapy

Despite the therapeutic potential of DCs, the application of monocyte-derived DCs as vaccines has proven underwhelming. One reason for this may be that these in vitro generated cells do not sufficiently resemble in vivo DCs which develop through independent haematopoietic pathways and share their specialised roles between subsets. One prime therapeutic candidate subset, cDC1, specialised for antigen cross-presentation and critical for immune responses to tumour, virus and intracellular pathogens, is very rare in human blood. We have developed a culture system to derive clinically-relevant numbers of cDC1 from primary progenitors, leading the way for further studies to develop their translational potential.

Future work will investigate the molecular mechanisms of genes important in human DC haematopoiesis, the role of these genes in health and disease and explore options for therapeutic manipulation of in vivo cells or in vitro-generated DCs for therapy.

Future work will investigate the molecular mechanisms of genes important in human DC haematopoiesis, the role of these genes in health and disease and explore options for therapeutic manipulation of in vivo cells or in vitro-generated DCs for therapy.

Grant Funding:

MRC Senior Clinical Fellowship, 2022-2027

缅北禁地 Joint Research Executive Scientific Committee award, 2019

Wellcome Intermediate Clinical Fellowship, 2013-2019

Bright Red PhD Fellowship 2014-2016

缅北禁地 Joint Research Executive Scientific Committee award, 2014

George Walker Fellowship 2011-2013

British Society of Haematology Start up Award 2011-2013

MRC Clinical Training Fellowship 2009-2011

Tyneside Leukaemia Research Association 2008

缅北禁地 Healthcare Charity 2008

Undergraduate Teaching:

Medical Sciences BSc project supervisor

Postgradulate Teaching

Medical Sciences MRes and MSc project supervisor

PhD students:

3 students completed

1 current student

The lab welcomes clinicians and scientists keen to pursue doctoral and post-doctoral studies in human immunology, haematopoiesis or cellular therapy. 

• Gothe F, Hatton CF, Truong L, Klimova Z, Kanderova V, Fejtkova M, Grainger A, Bigley V, Perthen J, Mitra D, Janda A, Fronkova E, Maravicikova D, Hambleton S, Duncan CJA. . Clinical Infectious Diseases 2022, 74(1), 136-139.
• Albert MH, Sirait T, Eikema DJ, Bakunina K, Wehr C, Suarez F, Fox ML, Mahlaoui N, Gennery AR, Lankester AJ, Beier R, Bernardo ME, Bigley V, Lindemans CA, OBurns S, Carpenter B, Dybko J, Gungor T, Hauck F, Lum SH, Balashov D, Meisel R, Moshous D, Schulz A, Speckmann C, Slatter MA, Strahm B, Uckan-Cetinkaya D, Meyts I, Vallee TC, Wynn R, Neven B, Morris EC, EBMT IEWP, ESID. . Blood 2022, 140(14), 1635-1649.
• Cox F, Bigley V, Irvine A, Leahy R, Conlon N. . Journal of Clinical Immunology 2022, 42, 955–958.
• Singh P, Heer M, Resteu A, Mikulasova A, Reza M, Largeaud L, Dufrechou S, Prade N, Dickinson RE, Bustamante J, Neven B, Bigley V, Delabesse E, Rico D, Pasquet M, Collin M. . Blood Advances 2021, 5(24), 5631-5635.
• Collin M, Bigley V. . Immunity 2021, 54(10), 2188-2190.
• 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. . Immunity 2020, 53(2), 353-370.
• Jardine L, Cytlak U, Gunawan M, Reynolds G, Green K, Wang XN, Pagan S, Paramitha M, Lamb CA, Long A, Hurst E, Nair S, Jackson GH, Publicover A, Bigley V, Haniffa M, Simpson AJ, Collin M. . The Journal of Clinical Investigation 2020, 130(9), 4574-4586.
• Bigley V, Collin M. . Molecular Immunology 2020, 122, 116-123.
• Heger L, Hofer TP, Bigley V, de Vries IJM, Dalod M, Dudziak D, Ziegler-Heitbrock L. . Frontiers in Immunology 2020, 11, 559166.
• Günther P, Cirovic B, Bassler K, Händler K, Becker M, Dutertre CA, Bigley V, Newell E, Collin M, Ginhoux F, Schlitzer A, Schultze JL. . bioRxiv 2019, 1-59.
• Bigley V, Cytlak U, Collin M. . Seminars in Cell & Developmental Biology 2019, 86, 50-61.
• Milne P, Wilhelm-Benartzi C, Grunwald MR, Bigley V, Dillon R, Freeman SD, Gallagher K, Publicover A, Pagan S, Marr H, Jones GL, Dickinson AM, Grech A, Burnett AK, Russell NH, Levis M, Knapper S, Collin M. . Blood Advances 2019, 3(20), 3052-3061.
• Tholouli E, Sturgess K, Dickinson RE, Gennery A, Cant AJ, Jackson G, Lordan J, Hambleton S, Slatter MA, Bigley V, Collin M. . Blood 2018, 131(12), 1383-1387.
• Bogaert DJ, Kuehn HS, Bonroy C, Calvo KR, Dehoorne J, Vanlander AV, De Bruyne M, Cytlak U, Bigley V, De Baets F, De Baere E, Rosenzweig SD, Haerynck F, Dullaers M. . Journal of Allergy and Clinical Immunology 2018, 141(1), 432-435.e7.
• 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. . Journal of Allergy and Clinical Immunology 2018, 141(6), 2234-2248.
• Collin M, Bigley V. . Immunology 2018, 154(1), 3-20.
• Cytlak U, Resteu A, Bogaert D, Kuehn HS, Altmann T, Gennery A, Jackson G, Kumanovics A, Voelkerding KV, Prader S, Dullaers M, Reichenbach J, Hill H, Haerynck F, Rosenzweig SD, Collin M, Bigley V. . Nature Communications 2018, 9, 1239.
• Kirkling ME, Cytlak U, Lau CM, Lewis KL, Resteu A, Khodadadi-Jamayran A, Siebel CW, Salmon H, Merad M, Tsirigos A, Collin M, Bigley V, Reizis B. . Cell Reports 2018, 23(12), 3658-3672.e6.
• Fox TA, Chakraverty R, Burns S, Carpenter B, Thomson K, Lowe D, Fielding A, Peggs K, Kottaridis P, Uttenthal B, Bigley V, Buckland M, Grandage V, Denovan S, Grace S, Dahlstrom J, Workman S, Symes A, Mackinnon S, Hough R, Morris E. . Blood 2018, 131, 917-931.
• Schlums H, Jung M, Han H, Theorell J, Bigley V, Chiang SCC, Allan DSJ, Davidson-Moncada JK, Dickinson RE, Holmes TD, Hsu AP, Townsley D, Winkler T, Wang W, Aukrust P, Nordøy I, Calvo KR, Holland SM, Collin M, Dunbar CE, Bryceson YT. . Blood 2017, 129(14), 1927-1939.
• Mace EM, Bigley V, Gunesch JT, Chinn IK, Angelo LS, Care MA, Maisuria S, Keller MD, Togi S, Watkin LB, LaRosa DF, Jhangiani SN, Muzny DM, Stray-Pedersen A, Akdemir ZC, Smith JB, Hernandez-Sanabria M, Le DT, Hogg GD, Cao TN, Freud AG, Szymanski EP, Savic S, Collin M, Cant AJ, Gibbs RA, Holland SM, Caligiuri MA, Ozato K, Paust S, Doody GM, Lupski JR, Orange JS. . Journal of Clinical Investigation 2017, 127(1), 306-320.
• Milne P, Bigley V, Bacon CM, Néel A, McGovern N, Bomken S, Haniffa M, Diamond EL, Durham BH, Visser J, Hunt D, Gunawardena H, Macheta M, McClain KL, Allen C, Abdel-Wahab O, Collin M. . Blood 2017, 130(2), 167-175.
• McGovern N, Shin A, Low G, Low D, Duan K, Yao LJ, Msallam R, Low I, Shadan NB, Sumatoh HR, Soon E, Lum J, Mok E, Hubert S, See P, Kunxiang EH, Lee YH, Janela B, Choolani M, Mattar CNZ, Fan Y, Lim TKH, Hong DK, Tan KK, Tam JKC, Schuster C, Elbe-Bürger A, Wang XN, Bigley V, Collin M, Haniffa M, Schlitzer A, Poidinger M, Albani S, Larbi A, Newell EW, Chan JKY, Ginhoux F. . Nature 2017, 546, 662-666.
• Green K, Pearce K, Sellar RS, Jardine L, Nicolson PL, Nagra S, Bigley V, Jackson G, Dickinson AM, Thomson K, Mackinnon S, Craddock C, Peggs KS, Collin M. . Biology of Blood and Marrow Transplantation 2017, 23(5), 805-812.
• Hunt D, Milne P, Fernandes P, Bigley V, Collin M. . Neurology: Neuroimmunology & Neuroinflammation 2017, 4(1), e299.
• Patel AA, Zhang Y, Fullerton JN, Boelen L, Rongvaux A, Maini AA, Bigley V, Flavell RA, Gilroy DW, Asquith B, Macallan D, Yona S. . Journal of Experimental Medicine 2017, 214(7), 1913-1923.
• Bigley V, Barge D, Collin M. . Current Opinion in Allergy & Clinical Immunology 2016, 16(6), 530-540.
• Hardie C, Green K, Jopson L, Millar B, Innes B, Pagan S, Tiniakos D, Dyson J, Haniffa M, Bigley V, Jones DE, Brain J, Walker LJ. . EBioMedicine 2016, 14, 65-73.
• Collin M, Bigley V. . Microbiology Spectrum 2016, 4(5).
• Webb G, Chen YY, Li KK, Neil D, Oo YH, Richter A, Bigley V, Collin M, Adams DH, Hirschfield GM. . Journal of Hepatology 2016, 64(5), 1190-1193.
• Mannurita SC, Vignoli M, Colarusso G, Tucci F, Veltroni M, Frenos S, Tintori V, Arico M, Bigley V, Collin M, Favre C, Gambineri E. . Journal of Allergy and Clinical Immunology 2016, 138(5), 1480-1483.
• Jardine L, Publicover A, Bigley V, Hale G, Pearce K, Dickinson A, Jackson G, Collin M. . British Journal of Haematology 2015, 168(6), 874-881.
• Salotti J, Collin M, Wood K, Bigley V, Windebank K. A survey of adults with histiocytic disorders in Northeast England. 2015. In Preparation.
• Milne P, Bigley V, Gunawan M, Haniffa M, Collin M. . Blood 2015, 125(3), 470-473.
• Collin M, Bigley V, McClain KL, Allen CE. . Hematology/Oncology Clinics of North America 2015, 29(5), 825-838.
• Collin M, Dickinson R, Bigley V. . British Journal Of Haematology 2015, 169(2), 173-187.
• Haniffa M, Bigley V, Collin M. . Seminars in Cell & Developmental Biology 2015, 41, 59-69.
• Bigley V, McGovern N, Milne P, Dickinson R, Pagan S, Cookson S, Haniffa M, Collin M. . Journal of Leukocyte Biology 2015, 97(4), 627-634.
• Holzinger D, Fassl SK, de Jager W, Lohse P, Rohrig UF, Gattorno M, Omenetti A, Chiesa S, Schena F, Austermann J, Vogl T, Kuhns DB, Holland SM, Rodriguez-Gallego C, Lopez-Almaraz R, Arostegui JI, Colino E, Roldan R, Fessatou S, Isidor B, Poignant S, Ito K, Epple HJ, Bernstein JA, Jeng M, Frankovich J, Lionetti G, Church JA, Ong PY, LaPlant M, Abinun M, Skinner R, Bigley V, Sachs UJ, Hinze C, Hoppenreijs E, Ehrchen J, Foell D, Chae JJ, Ombrello A, Aksentijevich I, Sunderkoetter C, Roth J. . Journal of Allergy and Clinical Immunology 2015, 136(5), 1337-1345.
• Berres ML, Lim KPH, Peters T, Price J, Takizawa H, Salmon H, Idoyaga J, Ruzo A, Lupo PJ, Hicks MJ, Shih A, Simko SJ, Abhyankar H, Chakraborty R, Leboeuf M, Beltrao M, Lira SA, Heym KM, Bigley V, Collin M, Manz MG, McClain K, Merad M, Allen CE. . Journal of Experimental Medicine 2014, 211(4), 669-683.
• 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. . Blood 2014, 124(12), 1894-1904.
• McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A, Poyner E, Green K, Dickinson R, Wang XN, Low D, Best K, Covins S, Milne P, Pagan S, Aljefri K, Windebank M, Saavedra DM, Larbi A, Wasan PS, Duan K, Poidinger M, Bigley V, Ginhoux F, Collin M, Haniffa M. . Immunity 2014, 41(3), 465-477.
• Sturgess K, Thoulouli E, Jackson G, Bigley V, Collin M. . In: 40th Annual Meeting of the European Group for Blood and Marrow Transplantation. 2014, Milan, Italy: Nature Publishing Group.
• 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. . Blood 2014, 123(6), 863-874.
• Jardine L, Barge D, Ames-Draycott A, Pagan S, Cookson S, Spickett G, Haniffa M, Collin M, Bigley V. . Frontiers in Immunology 2013, 4(4), 495.
• Jardine L, Hambleton S, Bigley V, Pagan S, Wang X-N, Collin M. . Leukemia and Lymphoma 2013, 54(1), 167-173.
• Hugle T, O'Reilly S, Simpson R, Kraaij MD, Bigley V, Collin M, Krippner-Heidenreich A, van Laar JM. . Arthritis & Rheumatism 2013, 65(2), 481-491.
• Haniffa M, Shin A, Bigley V, McGovern N, Teo P, See P, Wasan PS, Wang XN, Malinarich F, Malleret B, Larbi A, Tan P, Zhao H, Poidinger M, Pagan S, Cookson S, Dickinson R, Dimmick I, Jarrett RF, Renia L, Tam J, Song C, Connolly J, Chan JK, Gehring A, Bertoletti A, Collin M, Ginhoux F. . Immunity 2012, 37(1), 60-73.
• Haniffa M, Shin A, Bigley V, McGovern N, Wang X, Wasan P, Gehring A, Bertoletti A, Collin M, Ginhoux F. . In: European Congress of Immunology. 2012, Glasgow: Wiley-Blackwell.
• 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. . New England Journal of Medicine 2011, 365(2), 127-138.
• Bigley V, Collin M. . Haematologica 2011, 96(8), 1081-1083.
• 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. . Blood 2011, 118(10), 2656-2658.
• Collin M, Bigley V, Haniffa M, Hambleton S. . Nature Reviews Immunology 2011, 11(9), 575-583.
• 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. . Journal of Experimental Medicine 2011, 208(2), 227-234.
• Haniffa M, Ginhoux F, Wang XN, Bigley V, Abel M, Dimmick I, Bullock S, Grisotto M, Booth T, Taub P, Hilkens C, Merad M, Collin M. . Journal of Experimental Medicine 2009, 206(2), 371-385.
• Bigley VH, Duarte RF, Gosling RD, Kibbler CC, Seaton S, Potter M. Fusarium dimerum infection in a stem cell transplant recipient treated successfully with voriconazole. BONE MARROW TRANSPLANTATION 2004, 34(9), 815-817.