Genetics & Molecular Medicine (Research Division)

St John’s Hospital for Diseases of the Skin was founded in London in 1868, supported by voluntary contributions. St John’s relocated to St Thomas’ Hospital in the mid 1980s. Soon after, St John’s was formally renamed ‘St John’s Institute of Dermatology’ to include both the St John’s Hospital and the Institute. The academic laboratories of St John’s Institute of Dermatology moved into state-of-the-art new facilities at Guy’s Hospital in April 2007, and is fully integrated into the Division of Genetics and Molecular Medicine, part of the School of Medicine.

St John’s Institute of Dermatology is an internationally recognised centre of excellence for the treatment, research and teaching of diseases of the skin. These extend from cancer, through skin inflammation to rare genetic disorders and effects of the environment on the skin. Integrated transitional research programmes exist in each of these sub-specialty areas and are headed by internationally recognised clinicians and scientists. Research spans genetic discovery, through study of disease mechanisms, to clinical research investigating intervention and outcome measures. Research is supported by grants from a range of sources including MRC, Wellcome Trust, EU, British Skin Foundation and commercial sources.

The Department of Medical & Molecular Genetics was founded in 1960 as the Paediatric Research Unit, with an endowment from the Spastics Society (now Scope), in order to undertake developmental biology research relating to the origin of childhood handicaps such as cerebral palsy and spina bifida. The current Head of Department is Professor Christopher Mathew.

The Department aims to identify the genes and genetic modifications which are implicated in a range of human diseases, including inflammatory bowel disease, psoriasis, systemic lupus erythematosus, birth defects, breast cancer and leukaemia. Our progress in this research has been greatly facilitated by the acquisition of several high-throughput second-generation DNA sequencers by the King's College/Guy's and St Thomas' Biomedical Research Centre - these instruments can sequence all 20,000 genes in multiple patients in one week. Gene hunting in the Department is also supported by specialist expertise in mathematics and genetic epidemiology, which is required for studying inherited susceptibility to common, adult-onset diseases. Other work seeks to develop an understanding of epigenetic effects such as imprinting and control of gene expression, and to formulate novel analytical methodologies and methods of studying epistatic interactions between genes. Our research also encompasses Functional Genomics, which involves the application of new technologies in cell biology, molecular biology and biochemistry to study the molecular mechanisms of pathogenesis.

The research strategy of the Department includes a strong commitment to apply the fruits of basic scientific discoveries to improved diagnosis and treatment for patients, in partnership with the adjacent NHS Genetics Centre and our comprehensive Biomedical Research Centre. In the progressive and fatal neurological disorder Huntington's disease, for example, we are screening large collections of chemical compounds for molecules that might delay or prevent the onset of this condition. In an acute form of leukaemia we have developed a molecular test that detects the recurrence of the cancer at a very early stage so that patients can be treated effectively, and we are screening tumours for the genetic changes that cause the cancer to progress. Such studies are likely to have a major impact on the future management of human disease.

The Centre for Stem Cells & Regenerative Medicine will be led by Professor Fiona Watt. It will be based at Guy’s Hospital and will bring together the cutting-edge stem cell research currently taking place across the College and its partner NHS trusts, as part of King’s Health Partners. Through the Centre, King’s aims to drive collaboration between scientists and clinicians to translate the potential of stem cells into clinical reality for patients.

The major research interest of the research group is in establishing how the differentiated state of adult tissues is maintained. Current projects are concerned with self-renewal and lineage selection by human and mouse epidermal stem cells, and the roles of stem cells in tumour formation. The group is particularly interested in the interplay between intrinsic and extrinsic factors in the regulation of the cell fate decisions.

The Twin Research and Genetic Epidemiology Unit (TRU) has been part of the King's Division of Genetics and Molecular Medicine since September 2006 and has a team of over 40 staff. The unit was initially set up at St Thomas' Hospital in 1992 via grants form the Wellcome Trust and Arthritis and Research Campaign. Its initial focus was on the genetic influences on osteoporosis, hip arthritis, asthma and allergy, on twins. This study enabled a range of unique approaches to the understanding of genetic and environmental influences on disease and their interaction. The unit has grown steadily and has now the most detailed phenotypic database in Europe, with records of 10,000 adult MZ and DZ twins from across the UK, as well as extensive data on a range of disease markers. This is the only UK adult wide twin database and it incorporates all active participants form the only previous adult twin registers in the UK - the Aberdeen Twin Registry and the Institute of Psychiatry database.

Research is funded by a number of charitable bodies such as the Wellcome Trust, ARC, BHF NIH, BBSRC and Guide Dogs for the Blind, as well as some commercial funding. The TRU has been actively involved in FP5-, FP6- and FP7-funded EU Projects, both as co-ordinator and participating partner. TRU research today focuses on the genetics of complex diseases, in particular age-related diseases, with a current main focus on the genetics of metabolic syndrome and cardiovascular disease, the musculoskeletal system, and ageing. The unit also carries out research into eyesight and miscellaneous areas such as skin disease, immunology, gastroenterology and behaviour. Over 4,000 phenotypes on our twin dataset are available to collaborators (most phenotypes having been collected on at least 1,000 individuals). In addition novel phenotypes can be incorporated into our research studies, and our questionnaires (sent out annually to 10,000 twins) regularly include questions from collaborators. As part of our Wellcome Trust funded research, lymphocyte cell lines on 370 twins are available for use by approved researchers. We actively encourage collaborations with other national and international researchers interested in using the twin dataset for ethics committee-approved studies.