Graduate Research Prize Winners 2008
I graduated from the University of Oxford Medical School in 1998 with a first class degree in Natural Sciences and remained in Oxford for my medical training. I took time out from my specialist training in Respiratory and General (Internal) Medicine to undertake research in Professor Adrian Hill's group in the NDM and based at the Wellcome Trust Centre for Human Genetics in Oxford. The Centre is one of the largest academic units focussed on identifying susceptibility genes for common disease, and the research facilities are outstanding. Professor Hill's group is interested in major infectious diseases, in particular tuberculosis, malaria and leprosy, and has an excellent reputation for research into both vaccine development and immunogenetics. With Professor Hill's support I was awarded funding in the form of a Wellcome Trust Entry-Level Training Fellowship and subsequently a Wellcome Trust Clinical Research Training Fellowship. During my time in Oxford I have been a member of Trinity College.
Within Professor Hill's group in the NDM I developed an interest in host genetic susceptibility to severe respiratory infectious disease, especially invasive pneumococcal disease and thoracic empyema (a suppurative bacterial infection of the pleural space). This correlates with my clinical interests in acute respiratory infection, sepsis, and chronic suppurative lung disease, and it proved interesting and productive to study lung host defence from both clinical and basic science perspectives. The diverse interests of the group also facilitated the investigation of respiratory infection alongside other major infectious diseases, and this led directly to our identification of a novel functional polymorphism within the gene encoding the innate immune signalling protein Mal/TIRAP. This polymorphism was found to associate with protection against invasive pneumococcal disease, Gram-positive and Gram-negative bacteraemia, malaria and tuberculosis in different human populations. I have had the opportunity to present my research at international conferences, and was selected as an ‘Outstanding Young Investigator' to present at the ‘Scientific Breakthroughs of the Year' Symposium of the American Thoracic Society in 2007. I have also published twelve book chapters and review articles on clinical aspects of respiratory disease in addition to co-authoring the Oxford Handbook of Respiratory Medicine (Oxford University Press).
My research experience provided an excellent foundation for a career in academic medicine. I currently hold the post of Clinical Lecturer in Respiratory Medicine at the University of Oxford and am continuing research whilst simultaneously completing my clinical training. Major ongoing research projects include: a genome-wide association study of susceptibility to bacteraemia in childhood (awarded as part of the Wellcome Trust Case Control Consortium Phase II); the identification of susceptibility genes underlying community-acquired lower respiratory tract infection (as part of the European Commission Network of Excellence GRACE, ‘Genomics to combat resistance against antibiotics in community-acquired lower respiratory tract infection in Europe'); and study of genetic predictors of outcomes from severe sepsis (GenOSept, ‘Genetics of Sepsis in Europe', as part of the European Critical Care Network).
- Khor CC*/Chapman SJ*, Vannberg FO, Dunne A, Murphy C, Ling EY, Frodsham AJ, Walley AJ, Kyrieleis O, Khan A, Aucan C, Segal S, Moore CE, Knox K, Campbell SJ, Lienhardt C, Scott A, Aaby P, Sow OY, Grignani RT, Peshu N, Williams TN, Davies RJO, Kwiatkowski DP, Day NP, Crook DW, Marsh K, Berkley JA, O'Neill LAJ*/Hill AVS* (* these authors contributed equally to this work). A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nature Genetics 2007; 39: 523-528. Also reported as a ‘Research Highlight' in Nature Medicine 2007; 13: 417, Nature Reviews Immunology 2007; 7 : 251, and Nature Reviews Microbiology 2007; 5: 244.
- Khor CC*/Chapman SJ*, Vannberg FO, Hill AVS, O'Neill LAJ Reply to "Analysis of association of the TIRAP(MAL) S180L variant and tuberculosis in three populations. Nature Genetics 2008; 40: 262-263. (* these authors contributed equally to this work)
- Vannberg FO, Chapman SJ, Khor CC, Tosh K, Floyd S, Jackson-Sillah D, Crampin A, Sichali L, Bah B, Gustafson P, Aaby P, McAdam KPW, Bow-Sow O, Lienhardt C, Sirugo G, Fine P, Hill AVS. CD209 genetic polymorphism and tuberculosis disease. PLoS ONE 2008, 3: e1388.
- Chapman SJ, Khor CC, Vannberg FO, Frodsham A, Walley A, Maskell NA, Davies CWH, Segal S, Moore CE, Gillespie SH, Denny P, Day NP, Crook DW, Davies RJO, Hill AVS. IkB genetic polymorphisms and invasive pneumococcal disease. American Journal of Respiratory and Critical Care Medicine 2007; 176: 181-187.
- Chapman SJ, Vannberg FO, Khor CC, Segal S, Moore CE, Knox K, Day NP, Davies RJO, Crook DW, Hill AVS. Functional polymorphisms in the FCN2 gene are not associated with invasive pneumococcal disease. Molecular Immunology 2007; 44: 3267-3270.
- Khor CC, Vannberg FO, Chapman SJ, Walley A, Aucan C , Loke H, White NJ, Peto T, Khor LK, Kwiatkowski D, Day N, Scott A, Berkley JA, Marsh K, Peshu N, Maitland K, Williams TN, Hill AVS. Positive replication and linkage disequilibrium mapping of the chromosome 21q22.1 malaria susceptibility locus. Genes and Immunity 2007; 8: 570-6.
- Chapman SJ, Khor CC, Vannberg FO, Maskell NA, Davies CWH, Hedley EL, Segal S, Moore CE, Knox K, Day NP, Gillespie SH, Crook DW, Davies RJO, Hill AVS. PTPN22 and invasive bacterial disease. Nature Genetics 2006; 38: 499-500.
Molecular models of the wild-type (left) and mutant (right) Mal/TIRAP protein. A single nucleotide change encodes an amino acid substitution at position 180 of the protein, which in turn affects the interaction between Mal/TIRAP and toll-like receptors and influences both signalling via this innate immune pathway and susceptibility to multiple infectious diseases (Nature Genetics 2007; 39: 523-528).