Research
The Unit investigates the aetiology,
pathogenesis, diagnosis, treatment and control of childhood infections
and has a number of research projects focusing on the host response to
infection.
Many of these projects are joint ventures with the Immunobiology Unit, the Rheumatology Unit, the Cardiac Unit and the Portex Anaesthesia and Intensive Care Unit at ICH, the MRC Clinical Trials Unit and the Royal Free Hospital, UCL.
Key areas of research:
Host-pathogen interactions and their influence on human disease (Prof Nigel Klein)
Professor
Klein’s group focuses on interactions between microbes and microbial
components and the human host. He is particularly concerned with host
susceptibility to infection and host determinants of disease severity.
Within his group there are projects addressing Hospital acquired
infection, Meningococcal disease, HIV, the role of infection in preterm
labour, sepsis and vascular disease.
Mucosal immunity to gastrointestinal infections (Dr Mona Bajaj-Elliott)
Dr
Bajaj-Elliott and her team are addressing various aspects of
mucosal immunity, particularly in the context of gastro-intestinal
infections. Their current focus is in delineating host-pathogen
cross-talk in response to two enteropathogens i.e. Campylobacter
jejuni
and Clostridium difficile, the former a major cause of
bacterial-induced diarrhoea worldwide with the latter emerging in
recent years as a novel threat in immunologically vulnerable age
groups.
Several arms of investigation are underway to elucidate
how the human host responds to these two pathogens, including defining
innate and adaptive immune signalling events that may contribute to
disease pathogenesis. The research team is strengthened by
collaborations with Professor Brendan Wren and Dr Nick Dorrell (LSHTM),
Professor Peter Mullany and Dr Elaine Allan (Eastman, UCL).
Cardio-vascular biology in systemic inflammatory diseases of the young (Dr Paul Brogan)
This is a translational programme of clinically relevant research.
Current projects are on endothelial injury and repair in vasculitis of
the young; on vasculogenesis in idiopathic pulmonary hypertension
(IPAH) of the young;
and identifying targets for intervention on inflammation and
endothelial injury in childhood arterial ischaemic
stroke. Other projects include: Biologic therapy in systemic
vasculitis
of the young; Fetuin-A and calcinosis in Juvenile dermatomyositis;
Mycophenolate mofetil versus
cyclophosphamide for the treatment of ANCA associated vasculitis; Late
cardiovascular sequelae after Kawasaki disease; Periodic fever
syndromes in children at GOSH; and Detection of vascular injury in
renal
allograft rejection.
Interactions of human dendritic cells (DC) and Vascular endothelial cells with Neisseria meningitidis (Dr Garth Dixon)
Current studies:
- to understand how best to target bacteria for optimal antigen presentation, maturation and cytokine responses in DC’s to influence T-cell function with ultimate aim of designing novel vaccines against this pathogen.
- to explore how the meningococcus is able to inflict vascular damage through its interactions with cell adhesion molecules, specifically E-selectin and how this affects leucocyte behaviour and activation.
Bacteriophages in infectious diseases (Dr James Soothill)
Dr Soothill’s current research is on the investigation of strategies for the control of antibiotic-resistant infection; investigation of the role of bacteriophages in infectious diseases; and on the prevention of Central Venous Catheter Infections.
Natural immunity to infections caused by Streptococcus pneumoniae (Dr Jonathan Cohen)
We are investigating the naturally-induced immunity to infection caused by the bacterium Streptococcus pneumoniae. Through prior nasopharyngeal exposure, these powerful mechanisms prevent otherwise fatal pneumonia and sepsis.
Specific current projects include:
- dissecting the complementary contributions of both antibody-mediated and cell-mediated mechanisms including the role of Th17 cells in protection against pneumonia
- identifying the mechanisms which determine antigen dominance during nasopharyngeal colonisation
Other projects include:
- studies of the functional importance of mannose-binding lectin (MBL) in various disease states, particularly Meningococcal Disease, Cystic Fibrosis and Malignancy;
- the role of MBL as a mediator of inflammation;
- the use of MBL replacement therapy in specific deficiency states;
- endothelial responses to microbial infection;
- inflammatory mechanisms in sepsis, cardiac bypass, and multi-organ failure;
- leukocyte – platelet interactions in inflammatory conditions;
- leukocyte adhesion defects;
- development of molecular techniques for improved diagnosis of bacterial, viral and fungal infection;
- development of molecular microbiological techniques for use in assays to aid management of infectious diseases and transfer of these assays into routine clinical practice;
- detection of rare or unsuspected bacterial and fungal species in undiagnosed infections using broad-range PCR techniques based on 16S and 18S ribosomal genes;
- evaluating the impact of broad-range 16S PCR on the diagnosis of bacterial infections and the clinical management of patients;
- the use of quantitative PCR for monitoring viral infections in immunocompromised patients;
- participation in the HPA - Prospective aetiological study of encephalitis;
- trials of novel antimicrobial therapy in prevention and treatment of immunocompromised patients;
- the Unit is involved in a number of studies investigating the pathogenesis and treatment of children with HIV infection. Some of this work is carried out in collaboration with the MRC clinical trials unit, the Paediatric European Network for Treatment of AIDS, CHIVA and Oxford.
- investigating the efficacy of different anti-retroviral regimes in children with HIV;
- exploring the immunological reconstitution of HIV infected children following anti-retroviral therapy;
- investigating the role of CTL in Long Term Non-Progressors.The Unit is involved in the anonymous neonatal screening programme to monitor the prevalence of HIV1 in pregnant women in the North Thames and SE Thames regions of the UK. This work is carried out in collaboration with the Communicable Disease Surveillance Unit, PHL Colindale and is funded by the Department of Health;
- the use of novel methods for diagnosing and monitoring TB.
Page last modified on 28 sep 12 14:28
