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
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)
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)
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
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
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).
Systemic autoinflammatory and vasculitic diseases of the young (Dr Paul Brogan)
This is a translational programme of clinically relevant research studying the pathogenesis of and biomarker discovery for systemic vasculitides; gene discovery for novel autoinflammatory diseases; clinical trials of new therapies; and methodology for conducting clinical trials in rare paediatric diseases. Current projects also include endothelial injury and repair in vasculitis of the young; long-term cardiovascular outcomes in Kawasaki disease; and identifying targets for intervention on inflammation and endothelial injury in childhood arterial ischaemic stroke. Active clinical trials include the use of canakinumab in cryopyrin associated periodic fever syndromes; the use of rituximab in ANCA vasculitis in children; and the MYPAN trial, a Bayesian clinical trial examining mycophenolate mofetil vs cyclophosphamide for the treatment of childhood polyarteritis nodosa.
Interactions of human dendritic cells (DC) and Vascular endothelial cells with Neisseria meningitidis (Dr Garth Dixon)
- 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.
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 26 sep 13 14:47