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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at the University of Cambridge

Studying at Cambridge

 

Professor Ken Smith

Professor Ken Smith

Basic immunological mechanisms, and how defects in regulatory control of the immune system can lead to autoimmunity and alter defence against infection.


Departments and Institutes

Medicine:

Research Interests

Ken Smith established the Cambridge Immunology Strategic Research Network, which unifies both basic and translational immunological research across the broader Cambridge area.  He also runs the Immunity, Infection & Inflammation Theme of the NIHR Biomedical Research Centre, which has an annual budget of £850,000, and is designated as a Federation of Clinical Immunological Societies International Centre of Excellence.
 

The Smith laboratory has two main components.  The first studies basic immunological mechanisms, and how defects in regulatory control of the immune system can lead to autoimmunity and alter defence against infection. The second component is a translational programme in autoimmune disease (particularly SLE and vasculitis) and has led to the discovery of a novel prognosis-predicting biomarker now entering clinical trials, and the identification of important genes involved in disease pathogenesis.

Ken Smith’s research focussed initially on basic B cell biology, in which he was involved in defining mechanisms of selection within the germinal centre, particularly exploring the role of apoptosis in driving selection of high affinity B cells.  Subsequent work defined the mechanisms of action of inhibitory receptors in a B cell immune response, and in particular the role of FcγRIIb variation, in both mice and humans, in driving autoimmune disease. This work explored the evolutionary pressures driving autoimmune disease susceptibility in different ethnic groups, and demonstrated that a Lupus-associated variant in FcγRIIb which is very common in sub-Saharan Africa and South East Asia may well be under evolutionary selection pressure because it is associated with a substantially reduced risk of severe malaria, to about the same extent as that conferred by heterozygous thalassaemia.  This work was performed in collaboration with the KEMRI/ Wellcome Trust Unit in Kilifi. 

 Fc gamma RIIb

More recently, Smith and his colleagues have established a translational research programme aimed at performing detailed genetic and post-genomic studies on patients with autoimmune disease.  This has led to the development of new cell-specific biomarkers which are now entering clinical trials, which promise to predict prognosis and allow personalised therapy. These studies have also led to insights into disease pathogenesis, and in particular one prognosis-associated genetic variant in an important transcription factor has been found to control TNF production, associated not only with mild Crohn’s Disease, but also a reduction in TNF production that is associated with an increase in the incidence of severe malaria (in collaboration with Tom Williams in Kilifi, and Sarah Dunstan in Ho Chi Minh City).  More recently, the first Genome Wide Association Study of ANCA-Associated Vasculitis has demonstrated that this condition is actually made up of two genetically distinct subsets, which may have practical implications in the clinic.