DESCRIPTION
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.\r\n
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.
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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.
Associated research programmes
Associated staff research interests
Interests:
My research focus is the development and application of statistical methods in human genetics, to identify and characterise genes contributing to common, complex disorders. Current research includes genome-wide association studies and disease risk prediction using genetic and environmental factors.
Fax:
020 7188 2585
Email:
Website:
Interests:
- Investigation of the genetic basis of susceptibility to common, complex disorders, including the inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and cancer.
- The role of genetic instability in susceptibility to acute myeloid leukaemia.
Tel:
020 7188 3713
Fax:
020 7188 2585
Email:
Website:
Interests:
I am interested in the molecular mechanisms underlying the pathogenesis of acute promyelocytic leukaemia (APL), which is one of the commonest forms of acute myeloid leukaemia (AML). APL is characterised by the t(15;17)(q22;q21) chromosomal translocation which fuses the genes encoding PML and Retinoic Acid Receptor Alpha (RARA). APL is of particular interest, being the first form of leukaemia in which therapies (ie all trans retinoic acid (ATRA) and arsenic trioxide) that specifically target the underlying molecular lesion, and which have led to dramatic improvements in outcome of this disease, were introduced into clinical practice.
My research focuses particularly upon characterizing the mechanisms underlying formation of the t(15;17) chromosomal translocation which represents a critical step in leukaemogenesis, defining the progenitors in which this occurs, and the role of deregulation of the PML protein in leukaemic transformation. The laboratory also acts as the National Reference Centre for Molecular Diagnosis of APL, providing a minimal residual disease (MRD) monitoring service to direct patient treatment.
Tel:
020 7188 2579
Fax:
020 7188 2585
Email:
Website:
Interests:
Much of my work centres on the genetics of breast cancer (especially where this is of an early onset, familial nature), and adopts several approaches:
A molecular analysis of the BRCA1 gene, which confers susceptibility to breast cancer in a proportion of women. This involves the investigation of the structure and expression of the gene product (including its role in sporadic breast and ovarian cancer), its regulation, and its behaviour as a tumour suppressor, and studies of transgenic mice with altered BRCA1 genes. Collaborative investigations of the structure of the RING finger domain of BRCA1 are also under way.
The analysis of further genes implicated in the genesis of breast cancer, which exist in close proximity to BRCA1. Molecular analysis of the function, expression and regulation of these genes is gradually disentangling their complex relationship with BRCA1.
A sib-pair genome search, which aims to identify regions of the genome containing further genes predisposing to breast cancer, is being undertaken with Professor Cathryn Lewis.
I also have an interest in the PML/RARA translocation underlying Acute Promyelocytic Leukaemia, and with Professor David Grimwade am investigating the regulation of PML, and the structure of its RING finger domain.
Tel:
020 7188 3713
Fax:
020 7188 2585
Email:
Website:
Interests:
I have a long-standing interest in the genetics of psoriasis, a common inflammatory skin disorder that is inherited as a multifactorial trait. My research is aimed at characterizing genes that confer susceptibility to the disease, using both genetic (e.g. association studies) and functional tools (e.g. cell -based assays).
Tel:
020 7188 8079
Fax:
020 7188 2585
Email:
Website:
Interests:
The use of mouse models to understand the molecular basis of Huntington's disease and to develop therapeutic approaches. Specific interests: molecular chaperones; heat shock factor 1; proteolysis of huntingtin; histone deacetylase inhibitors; HDAC4; stem cell models.
Tel:
020 7188 3722
Fax:
020 7188 2585
Email:
Website:
Interests:
Tissue-specific and ubiquitious genetic control elements with a long-range chromatin remodelling capability and their use in gene therapy especially lentiviral vectors, generation of animal models of human disease and other biotechnology applications.
Tel:
020 7188 3708
Fax:
020 7188 2585
Email:
Website:
Interests:
My interests lie in the development of new methods for the analysis of genetic data, with various fields of application ranging from medicine to forensics to genetic history. Of particular interest to me is the analysis of large-scale association data, either via genomewide SNP chips or via Next Generation Sequencing. I also work on population genetic questions arising from these genomewide data, such as the ability to query one's biogeographic origins based on one's DNA alone. Other research include data integration, gene-gene and genome-genome interaction, forensics, expression QTLs and selection.
Tel:
020 7188 2601
Fax:
020 7188 2585
Email:
Website:
Interests:
DNA carries heritable information and genes guide development to adulthood. The discovery of epigenetics, changes in gene expression not encoded for by DNA sequence, has added another layer of complexity to our understanding of inheritance. One class of genes under epigenetic control includes imprinted genes. Mammals inherit two copies of most genes, one from their mother and one from their father and they are normally both active. However, for a small number of imprinted genes in mammals, only one is active, either the maternal or the paternal copy. Imprinted genes are typically involved in embryonic growth and development and in post-natal growth, viability and behavior. The aims of this group include learning about transcriptional control mechanisms and the roles of imprinted genes in mammalian development and human disease. This group has developed bioinformatics tools for the analysis of genomic sequence and epigenetic features of imprinting in mammals and plants. We are interested particularly in a group of imprinted retrogenes derived from the X chromosome, both the mode of gene regulation and evolution in the genome. While a wealth of data demonstrate epigenetic mechanisms can regulate transcription initiation, we have shown for the first time that epigenetic modifications can influence the choice of alternative polyadenylation sites used in the process of transcriptional termination. This has implications for transcriptome diversity and tissue specific gene regulation and is likely to be a widespread mechanism.
Disease related work in the laboratory focuses on identifying DNA methylation defects in a series of growth-related diseases using microarrays and deep sequecing approaches and a gene imprinted specificlly in the developing heart is under molecular and developmental analysis.
Tel:
020 7188 3714
Fax:
020 7188 2585
Email:
Website:
Interests:
Investigation into the molecular mechanisms underlying pulmonary arterial disease; functional characterization of TGF-beta; cell signaling in vascular cells; identification of candidate susceptibility genes in the common skin disease psoriasis; genome-wide linkage analysis in familial cluster headache; functional characterization of human developmental disease genes, identified through homozygosity mapping in a range of autosomal recessive disorders; management of the National Autozygosity Mapping Resource (NAMR). Identification of major and minor susceptibility genes for psoriasis, using genome-wide linkage analysis, SNP-based approaches, construction and refinement of susceptibility haplotypes (with ProfessorJonathan Barker); functional role of psoriasis susceptibility genes (with ProfessorAdrian Hayday/Professor Frank Nestle); candidate gene approach to susceptibility gene identification in atopic dermatitis (with Professor Jonathan Barker). Identification of susceptibility loci in psoriasis.
Tel:
020 7188 7993
Fax:
020 7188 2585
Email:
Website:
