Dr, Senior Lecturer
My major research interest is the study of human genetic susceptibility to severe bacterial respiratory disease, and this correlates with my clinical interests in acute respiratory infection, sepsis, and chronic suppurative lung disease (cystic fibrosis and bronchiectasis). My initial research utilised a case-control study design with a candidate gene approach, focusing primarily on the role of inflammatory signalling pathway components in susceptibility to invasive pneumococcal disease and thoracic empyema. This research identified a number of gene variants in association with susceptibility to phenotypes of respiratory infection, including the following examples:
- Identification of novel functional polymorphisms in the innate immune signalling protein Mal and the suppressor of cytokine signalling CISH, each of which associates with susceptibility to multiple major infectious diseases (Nature Genetics 2007, New England Journal of Medicine 2010)
- Associations were identified between common polymorphisms in four genes that encode different inhibitors of the transcription factor NF-kB and susceptibility to invasive pneumococcal disease (Am J Resp Crit Care Med 2007, Genes and Immunity 2010, Critical Care 2010).
- The first description of an association between the major autoimmune susceptibility locus PTPN22 and infectious disease (Nature Genetics 2006).
My ongoing research focuses on the use of genome-wide studies to identify major common susceptibility alleles for bacteraemia, and the application of large-scale sequencing technology to identify uncommon intermediate/high penetrance susceptibility variants.
Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4.
Gilchrist JJ. et al, (2018), Nat Commun, 9
Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children
Rautanen A. et al, (2016), The American Journal of Human Genetics, 98, 1092 - 1100
Absence of Atypical Pathogens in Pleural Infection.
Wrightson JM. et al, (2015), Chest, 148, e102 - e103
Variants in the Mannose-binding Lectin Gene MBL2 do not Associate With Sepsis Susceptibility or Survival in a Large European Cohort.
Mills TC. et al, (2015), Clin Infect Dis, 61, 695 - 703
Resistance to cellular HIV infection.
Clomegah AM. and Chapman SJ., (2015), Evol Med Public Health, 2015