WIMM PI
Curriculum Vitae
Personal Data
Name Richard Cornall
Nationality
Email
UK richard.cornall@ndm.ox.ac.uk
Present Position
2007-present Professor of Immunology, (University of Oxford), University Lecturer in Renal Medicine (University of Oxford) and Honorary Consultant in
Renal and Transplant Medicine (OUH NHS Trust)
Previous Positions
1986 House Surgeon, York District Hospital, York
1987 House Physician, Nuffield Department of Medicine, Oxford
1987 SHO Cardiology, Brompton Hospital, London
1988 SHO Neurology, National Hospital for Nervous Diseases, London
1988 SHO Renal Medicine, Guy's Hospital, London
1989 MRC Training Fellowship, Nuffield Department of Surgery, Oxford.
DPhil supervised by Professor John Todd
1992 Registrar in General Medicine, Ealing District General Hospital, London
1993 Registrar in Renal Medicine, Royal Postgraduate Medical School, London
1994 Wellcome Trust Career Development Fellow, Stanford University, Palo
Alto, California, USA
1998 Renal Specialist Registrar and Wellcome Trust Clinician Scientist,
Churchill Hospital and Nuffield Dept of Medicine, Oxford University and Oxford
Radcliffe Hospitals NHS Trust, Oxford
2000 Wellcome Trust Senior Clinical Fellow and Honorary Consultant
Physician, Nuffield Department of Medicine, Oxford University and
Oxford Radcliffe Hospitals NHS Trust, Oxford

Research Achievements
Describe main research achievements to date (1989-2013) (max 300 words)
Over my career I have been interested in using tools from genetics and immunology to study the development and selection of lymphocytes and the causes of autoimmune disease. As a graduate student I generated the first random library of mouse microsatellites markers and I played a central role in the first genome-wide linkage analysis of a complex trait, insulin dependent diabetes. Later I showed how the interaction of dominant alleles regulating B cell signalling could encode autoimmune susceptibility by altering the threshold for activation.
This has provided a model for how genetic risk is encoded in an outbred human population.
In the last ten years my laboratory has developed models of immunological tolerance and I have helped to pioneer the use of genome-wide ENU mutagenesis to discover new mechanisms in immune regulation, working with my longstanding collaborator Chris
Goodnow. I have played key roles in the discovery of novel genes relevant to human disease, including the autoimmune regulator Roquin, the role of DNA Ligase IV in human SCID, the novel Themis superfamily and the involvement of DOCK8 in maturation of the antibody response and immunological memory. These findings have increased our understanding of pathways involved in B-cell development, selection, autoimmunity and how humans develop long-lasting immunity to infections. They have also brought understanding to human immunodeficiency syndromes, caused by mutations in DNA Ligase IV and DOCK8.
Information from these studies has been used to develop anti-inflammatory drugs that target the inhibitory and activating receptors on human lymphocytes.
What are the Future Aims of Your Current Group?
The aims of our group are to understand lymphocyte development, immune regulation and the generation of immunological memory in the B cell compartment. We want to know how these biological processes could be manipulated for the treatment and prevention of human disease and how their disturbance to immunodeficiency, inflammation or autoimmune disease. (1) To identify novel mutations affecting immune function, the lab will continue to pursue forward genetics in humans and mice. We will then use animal models and cell- based in vitro assays to establish causation and mechanism. To support this activity we want to establish a virtual clinic to access and process human samples, which would be in collaboration with the
WTCHG and the Kennedy Institute, and an alliance between the MRC HIU, WTCHG with the
MRC MGU at Harwell to screen ENU mutant mice. We want to refine the methods for screening pathways and design experiments that will tell us more about how genetic variation encodes phenotypic variation in simple and complex traits. (2) To address specific hypotheses and characterize candidate genes, the lab is supporting a Wellcome Trust
Strategic Award (2013-2017, RJC Deputy Director) to screen gene-targeted mice at the
Wellcome Trust Sanger Centre for immunological phenotypes. The aim is to provide a national resource. (3) To advance our understanding of B cell development and provide a better conceptual framework for the genetics, we are starting to study the epigenetics of B cells during the steps of positive and negative selection by self and foreign antigens, using our antigen-specific transgenic mouse models (in collaboration with Tatjana Sauka-
Spengler). (4) To develop better treatments for autoimmune disease, we are working to develop a range of agonistic antibodies against lymphocyte inhibitory receptors and the IL10 receptor (in collaboration with Simon Davis).
How do These Aims Contribute to the Understanding and/or Management of
Human Disease
Understanding the processes that determine normal and abnormal immune function is important because of the potential to predict, prevent or treat human disease. For example, understanding the processes leading to immunological memory may lead to better

vaccination and strategies to boost immunity in conditions such as malaria, where memory is poor; likewise, knowledge of the processes that underlie autoimmune disease may enable us to tailor treatment to specific pathways and design better treatment for individual patients.
Developing the laboratory-clinical interface in the WIMM will accelerate this process. In this way we will be able to process patient samples and provide the experimental and laboratory support to our collaborating physicians and scientists. We are pursuing this in collaboration with Georg Hollander, Vincenzo Cerundolo and Julian Knight.
Lay Summary of Research
Our immune system is made up of billions of immune cells called lymphocytes. These cells are continuously being produced in the bone marrow (B lymphocytes) and thymus (T lymphocytes) and circulate through our bodies until most commonly they die from neglect or ageing. Each lymphocyte expresses a unique receptor that enables it to detect a specific set of molecules termed antigens. By chance some lymphocytes have receptors for foreign antigens that are unique parts of the molecular makeup of infectious organisms. When these rare lymphocytes bind a foreign antigen during an infection, they receive a signal to multiply and then destroy the infectious agent; and when some of the antigen specific cells persist they provide an "immunological memory", which is what happens when we are immunised.
The generation of lymphocyte receptors is done at random because otherwise the infectious agents would find a way to develop resistance, just as they do in response to antibiotics.
However, because the process is random, it is inevitable that sometimes lymphocytes will carry receptors for self-antigens - in other words, they will react with molecules in our own bodies. Our aim is to understand how this process is normally controlled to prevent "friendly fire" and what happens when control breaks down in autoimmune diseases, such as insulin dependent diabetes mellitus (caused by lymphocytes attacking the insulin producing cells of the pancreas) or rheumatoid arthritis (caused by lymphocytes attacking the cartilage of the joints). We want to understand why some people inherit susceptibility to these diseases and we want to use our knowledge to design new treatments.

All Publications Over the Past 5 Years
Ferry H, Potter PK, Crockford TL, Nijnik A, Ehrenstein MR, Walport MJ, Botto M, Cornall RJ.
Increased positive selection of B1 cells and reduced B cell tolerance to intracellular antigens in c1q-deficient mice. J Immunol 2007 Mar 1;178(5):2916-22.
Lambe T, Leung JC, Ferry H, Bouriez-Jones T, Makinen K, Crockford TL, Jiang HR,
Nickerson JM, Peltonen L, Forrester JV, Cornall RJ. Limited peripheral T cell anergy predisposes to retinal autoimmunity. J Immunol 2007 Apr 1;178(7):4276-83.
Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C, Rodrigues NP, Crockford
TL, Cabuy E, Vindigni A, Enver T, Bell JI, Slijepcevic P, Goodnow CC, Jeggo PA,
Cornall RJ. DNA repair is limiting for haematopoietic stem cells during ageing. Nature
2007 Jun 7;447(7145):686-90.
Silver KL, Crockford TL, Bouriez-Jones T, Milling S, Lambe T, Cornall RJ. MyD88dependent autoimmune disease in Lyn-deficient mice. Eur J Immunol 2007
Oct;37(10):2734-43
Cornall RJ. HO-1 extends to stem cells. Blood2008 Dec 1;112(12):4363-4.
Forrester JV, Xu H, Lambe T, Cornall RJ. Immune privilege or privileged immunity?
Mucosal Immunol 2008 Sep;1(5):372-81.
Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, Taupin D, Thornton DJ, Png CW,
Crockford TL, Cornall RJ, Adams R, Kato M, Nelms KA, Hong NA, Florin TH, Goodnow
CC, McGuckin MA. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med 2008 Mar
4;5(3):e54.
Lau AW, Biester S, Cornall RJ, Forrester JV. Lipopolysaccharide-activated IL-10-secreting dendritic cells suppress experimental autoimmune uveoretinitis by MHCII-dependent activation of CD62L-expressing regulatory T cells. J Immunol 2008 Mar 15;180(6):3889-
99.
Schallreuter KU, Bahadoran P, Picardo M, Slominski A, Elassiuty YE, Kemp EH, Giachino
C, Liu JB, Luiten RM, Lambe T, Le Poole IC, Dammak I, Onay H, Zmijewski MA,
Dell'Anna ML, Zeegers MP, Cornall RJ, Paus R, Ortonne JP, Westerhof W. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp Dermatol 2008 Feb;17(2):139-40; discussion 41-
60.
Lambe T, Simpson RJ, Dawson S, Bouriez-Jones T, Crockford TL, Lepherd M, Latunde-
Dada GO, Robinson H, Raja KB, Campagna DR, Villarreal G, Jr., Ellory JC, Goodnow
CC, Fleming MD, McKie AT, Cornall RJ. Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism. Blood 2009 Feb 19;113(8):1805-8.
Nijnik A, Dawson S, Crockford TL, Woodbine L, Visetnoi S, Bennett S, Jones M, Turner
GD, Jeggo PA, Goodnow CC, Cornall RJ. Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndrome. J Clin Invest 2009 Jun;119(6):1696-705.
Johnson AL, Aravind L, Shulzhenko N, Morgun A, Choi SY, Crockford TL, Lambe T,
Domaschenz H, Kucharska EM, Zheng L, Vinuesa CG, Lenardo MJ, Goodnow CC,
Cornall RJ*, Schwartz RH . (*equal last authors) Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection.
Nat Immunol 2009 Aug;10(8):831-9.
Randall KL, Lambe T, Johnson AL, Treanor B, Kucharska E, Domaschenz H, Whittle B,
Tze LE, Enders A, Crockford TL, Bouriez-Jones T, Alston D, Cyster JG, Lenardo MJ,
Mackay F, Deenick EK, Tangye SG, Chan TD, Camidge T, Brink R, Vinuesa CG, Batista
FD, Cornall RJ*, Goodnow CC*. (*equal last authors) Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Nat
Immunol 2009 Dec;10(12):1283-91.

Morteau O, Blundell S, Chakera A, Bennett S, Christou C, Mason PD, Cornall RJ*,
O'Callaghan CA* (*equal last authors). Renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo. PLoS One 2010. in press
Randall KL, Lambe T, Goodnow CC, Cornall RJ. The essential role of DOCK8 in humoral immunity. Disease Markers 2010;29.: 141-150.
Chakera A, Bennett S, Lawrence S, Morteau O, Mason PD, O'Callaghan CA and Cornall
RJ. Antigen-specific T cell responses to BK Polyomavirus antigens identify functional anti-viral immunity and may help to guide immunosuppression following renal transplantation. Clin Exp Immunol 2011 165(3):401-9
Chakera A, Bennett SC and Cornall RJ. A whole blood monokine-based reporter assay provides a sensitive and robust measurement of the antigen-specific T cell response. J
Transl Med 2011 9 (1):143-6
Randall KL, Chan S S-Y, Ma CS, Fung I, Mei Y, Yabas M, Tan A, Arkwright PD, Suwairi WA,
Reyes SOL, Yamazaki-Nakashimada MA, Garcia-Cruz M, Smart JM, Picard SJM, Okada S,
Jouanguy E, Casanova J-L, Lambe T, Cornall RJ, Russell S, Oliaro J, Tangye SG, Bertram
EM and Goodnow CC. DOCK8 deficiency cripples CD8 T cells in humans and mice. J Exp
Med. 2011 208: 2305-20.
Lambe T, Crawford G, Johnson AL, Crockford TL, Bouriez-Jones T, Smyth AM, Pham THM,
Zhang Q, Freeman AF, Cyster JG, Su H and Cornall RJ. DOCK8 is essential for T cell survival and limits the maintenance of CDT cell memory. Eur J Immunol. 2011, 41: 3423-
3520
Chakera A, Bennett S, Morteau O, Bowness P, Luqmani A and Cornall RJ. The phenotype of circulating follicular-helper T cells in patients with rheumatoid arthritis defines CD200 as a potential therapeutic target. Clin Dev Immunol 2012:948218. Epub 2012 Oct 4.
Bergmann H, Yabas M, Short A, Misoge L, Barthel N, Teh CE, Bull K, Jeelall Y, Horikawa K,
Whittle B, Balakishnan B, Sjollema G, Bertram EM, Mackay F, Rimmer A, Cornall RJ, Filed
MA, Andrews TD, Goodnow CC and Enders A. B cell survival, surface BCR and BAFF-R expression, CD74 metabolism and CD8- DCs require the intramembrane endopeptidase
SPPL2A. J Exp Med 2012, in press
Ten Key Publications Throughout your Career
Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Todd JA, Aitman TJ,
Cornall RJ, Ghosh S, Hall JR, Hearne CM, Knight AM, Love JM, McAleer MA, Prins
JB, and et al. Nature Article 351:542-547, 1991. (News and Views: Genetics. Sweet mice, sugar daddies. Avner P. Nature. 351:519-20.1991)
Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1. Cornall RJ, Prins JB, Todd JA, Pressey A, DeLarato NH, Wicker LS and
Peterson LB. Nature Letter 353:262-265, 1991.
Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Cornall RJ, Cyster JG,
Hibbs ML, Dunn AR, Otipoby KL, Clark EA and Goodnow CC. Immunity 8:497-508,
1998.
The cellular location of self-antigen determines the positive and negative selection of autoreactive B cells. Ferry H, Jones M, Vaux DJ, Roberts IS and Cornall RJ.
Journal of Experimental Medicine 198:1415-1425, 2003.
A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L, Hill
KM, Yu D, Domaschenz H, Whittle B, Lambe T, Roberts IS, Copley RR, Bell JI,
Cornall RJ and Goodnow CC. Nature Article 435:452-458, 2005.

DNA repair is limiting for haematopoietic stem cells during ageing. Nijnik A, Woodbine L,
Marchetti C, Dawson S, Lambe T, Liu C, Rodrigues NP, Crockford TL, Cabuy E,
Vindigni A, Enver T, Bell JI, Slijepcevic P, Goodnow CC*, Jeggo PA* and Cornall RJ*
(joint-senior and corresponding authors*). Nature Article 447:686-90, 2007. (News and Views: Ageing: from stem to stern. Brunet A, Rando TA. Nature. 449:288-91,
2007)
Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndrome. Nijnik A, Dawson S,
Crockford TL, Woodbine L, Visetnoi S, Bennett S, Jones M, Turner GD, Jeggo PA,
Goodnow CC and Cornall RJ. J Clin Invest 119:1696-705. 2009.
Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Johnson AL, Aravind L, Shulzhenko N, Morgun A, Choi SY,
Crockford TL, Lambe T, Domaschenz H, Kucharska EM, Zheng L, Vinuesa CG,
Lenardo MJ, Goodnow CC, Cornall RJ* and Schwartz RH*, (joint-senior and corresponding authors*). Nat Immunol. 10:831-9, 2009. (News and Views: Themis imposes new law and order on positive selection. Allen PM. Nat Immunol. 10:805-6,
2009 and Research Highlights: Themis in the thymus. Nature 460: 309, 2009.)
Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Randall KL, Lambe T, Johnson A, Treanor B,
Kucharska E, Domaschenz H, Whittle B, Tze LE, Enders A, Crockford TL,
Bouriez-Jones T, Alston D, Cyster JG, Lenardo MJ, Mackay F, Deenick EK, Tangye
SG, Chan TD, Camidge T, Brink R, Vinuesa CG, Batista FD, Cornall RJ* and Goodnow
CC* (joint-senior and corresponding authors*). Nat Immunol. 10:1283-91, 2009.
(News and Views: B cell memory: how to start and when to end. Pelletier N, McHeyzer-
Williams MG. Nat Immunol. 10:1233-5., 2009)
Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations. Bull KR, Rimmer AJ, Siggs OM, Miosge LA,
Roots CM, Enders A, Bertram EM, Crockford TL, Whittle B, Potter PK, Simon MM, Mallon
AM, Brown SD, Beutler B, Goodnow CC, Lunter G, Cornall RJ. PLoS Genet.
2013;9(1):e1003219. doi: 10.1371/journal.pgen.1003219. Epub 2013 Jan 31.
Markers of Esteem
1980 Entrance Exhibitioner, Trinity College, Cambridge University.
1982 Senior Scholar, Trinity College, Cambridge University.
1983 Nuffield Foundation Research Assistant, Marine Biological Laboratory, Woods
Hole.
1985 President of Osler House Club, Oxford University
1989 MRCP, Royal College of Physicians.
1989 MRC Training Fellowship, Nuffield Dept of Surgery, Oxford University.
1992 Young Investigator Gold Medal (Medical Research Society)
1994 Wellcome Trust Career Development Award (till 2000)
2000 Wellcome Trust Senior Clinical Fellow (till 2007)
2002 Research Fellow, Corpus Christi College, Oxford Univ ersity
2004 Reader in Immunology, Oxford University
2005 FRCP, Royal College of Physicians
2006 Professor of Immunology, Oxford University
2006 Chairman of Oxford Medical School Animal Ethics Committee.
2007 University Lecturer in Renal Medicine
2007 Full Fellow, Corpus Christi College, Oxford University
2007 Director of Graduate Studies, Nuffield Dept of Medicine
2008 Director of the Oxford NIH Graduate School Programme (till 2012)
2009 Chairman, Kidney Research UK Grants Committee (till 2013)
2010 Member, Arthritis Research UK Project Grants Committee
2011 Coordinator, REF 2013, Medical Sciences Division, Oxford.
Current Grant Support

1. Oxford BioMedical Centre Renal Immunity Project. NIHR 2012-2017 ~£50,000 pa.
2. MRC Human Immunology Unit Core Programme Grant 2012-2017.
3. 3I [Infection and Immunity Immunophenotyping) Consortium. Wellcome Trust Strategic
Award, Co-PI 2013-2018 ~£4,000,000