Mike Stratton

Professor Mike Stratton is Director of the Wellcome Trust Sanger Institute. He was appointed in May 2010, when Allan Bradley stepped down as Director after ten years of leadership. From Allan, Mike inherited an Institute that had been transformed from world class sequencing centre to world class research Institute focused on developing biological understanding and potential healthcare benefits for populations worldwide. Prior to taking up the directorship, Mike was Deputy Director of the Institute. He is founder and co-leader of the Institute's Cancer Genome Project.

Colour-enhanced image of a breast cancer cell. Mike led the mapping and subsequent identification of BRCA2, the breast cancer gene. The discoveries have shaped clinical practice, with predictive testing for mutations in the gene now routine.

Colour-enhanced image of a breast cancer cell. Mike led the mapping and subsequent identification of BRCA2, the breast cancer gene. The discoveries have shaped clinical practice, with predictive testing for mutations in the gene now routine. [Anne Weston, Wellcome Images]

zoom

Mike's appointment as Director was made as the Institute was defining new goals and reshaping its research as part of a new five-year research strategy for 2011 to 2016. Mike brings to the Directorship a commitment to international collaboration and a determination to drive research at the Institute to real improvements in our understanding of health and disease and our approaches to clinical practice.

Education and early career

Mike studied medicine at the University of Oxford and Guy's Hospital, qualifying in 1982, and went on to train as a histopathologist at the Hammersmith and Maudsley Hospitals. During his training, Mike became fascinated by the opportunities to understand causes of cancer through molecular biology. Pursuing this interest, Mike earned his PhD in the molecular biology of cancer at the Institute of Cancer Research in 1989.

After completing his PhD, Mike took up a Faculty appointment at the Institute of Cancer Research where he led what remains a seminal development in cancer research - the mapping and subsequent identification of BRCA2, the breast cancer susceptibility gene. Mike located BRCA2 on chromosome 13 in 1994. To build on this success, he assembled a collaborative group of breast cancer geneticists and molecular biologists - including the Sanger Institute - to clone the gene, an aim they achieved in 1995. The discovery ensured that BRCA2 was not subject to complete commercial monopolisation through patenting and has shaped clinical genetics practice, with predictive testing for BRCA2 mutations now routine around the world. In the years following this discovery, Mike went on to uncover further breast cancer genes, broadening understanding of the genetic basis of breast cancer susceptibility. From this foundation, Mike diversified his hunt for cancer predisposition genes to the mapping and positional cloning of genes underlying susceptibility to other types of cancer, including genes for hereditary cylindromatosis, Wilms tumour, testicular cancer, colorectal cancer, thyroid cancer and the Peutz-Jegher syndrome.

Mutation spectra of human cancers by tumour type. The numbers of each of the six classes of base substitution and insertion/ deletions are shown. C:G.T:A substitutions have been divided into those at CpG dinucleotides and those not at CpG dinucleotides. The Cancer Genome Project identified variation in the number and type of somatic mutations in different cancers. [Nature, 2007. DOI: 10.1038/nature05610]

Mutation spectra of human cancers by tumour type. The numbers of each of the six classes of base substitution and insertion/ deletions are shown. C:G.T:A substitutions have been divided into those at CpG dinucleotides and those not at CpG dinucleotides. The Cancer Genome Project identified variation in the number and type of somatic mutations in different cancers. [Nature, 2007. DOI: 10.1038/nature05610]

zoom

In addition to inherited changes which can predispose to the disease, all cancers carry somatically acquired alterations in their genomes. A subset of these somatic mutations occurs in cancer genes where they act as driver mutations, causing cells to behave in the abnormal manner that we recognise as cancer. Towards the end of the 1990s, while Mike was at the Institute of Cancer Research, the Human Genome Project began to deliver the human genome sequence. Mike saw that systematic, genome-wide approaches to detecting mutations based on the imminent reference human genome sequence could ultimately lead to the identification of all somatic mutations in cancer genomes and thus all cancer genes operative in human cancer. Armed with that vision, in 1999 Mike proposed the concept of a Cancer Genome Project - a project that he envisaged would harness the infrastructure and resources of a large genome centre. In 2000, the Wellcome Trust Sanger Institute became home to that project, the first of its kind worldwide, when Mike joined the Institute's Faculty.

The Cancer Genome Project

During his time at the Institute, Mike has led the Cancer Genome Project from its infancy to its position as one of the leading projects of its type in the world - providing data and tools for researchers globally.

The team produced a dramatic result in 2002, with the identification of BRAF mutations in around 60 per cent of malignant melanomas. This finding was a glimpse into the potential for massive screening on the scale of the Cancer Genome Project to unveil genes involved in cancers. Treatments based on this discovery show highly promising responses in malignant melanomas that harbour BRAF mutations, a disease that is essentially resistant to all other forms of therapy.

In 2004 Mike's team announced that genetic mutations in the ERBB2 gene are present in around 4 per cent of non-small-cell lung cancers. The team proposed that a drug already in use - called Herceptin - might be used to treat that 4 per cent of patients. More recently the team have identified several new cancer genes including UTX, SETD2 and JARD1C which operate on DNA associated proteins that influence gene activity.

The Cancer Genome Project established the basic patterns of somatic mutation that are present in cancer genomes. They showed that there is substantial variation in the number and type of somatic mutations in different cancers. Moreover, they demonstrated that most mutations appear to be passengers, although there are many more drivers than can currently be accounted for by well-established cancer genes.

As well as continuing their hunt for cancer genes, the team has established a set of resources, including the Catalogue of Somatic Mutations in Cancer (COSMIC) database, to ensure that the successes emanating from this large scale project would be shared among the research community. Making data from the Cancer Genome Project available has been a primary focus and a major investment for the Mike's team.

New opportunities in cancer research

The catalogue of somatic mutations in a small-cell lung cancer genome (top) and a malignant melanoma genome (bottom). Mike and his colleagues at the Institute were the first to contribute full catalogues of all the mutations in the genomes of two cancers.

The catalogue of somatic mutations in a small-cell lung cancer genome (top) and a malignant melanoma genome (bottom). Mike and his colleagues at the Institute were the first to contribute full catalogues of all the mutations in the genomes of two cancers.

zoom

Technological advances in sequencing meant that, as the Cancer Genome Project grew, the possibilities to study cancer were also widening. As the first decade of the 21st Century drew to a close, a comprehensive catalogue of human cancer mutations - Mike's dream since his days at the Institute of Cancer Research - seemed deliverable.

Mike was one of the primary forces in the creation in 2007 of the first international collaboration to coordinate that search for cancer mutations. One of the most ambitious biomedical research efforts since the Human Genome Project, the International Cancer Genome Consortium - under the leadership of Mike and other international colleagues - set out to coordinate current and future large-scale projects to understand the genomic changes involved in cancer. By making data rapidly available to other investigators and by preventing members from applying for patents on fundamental data, the ICGC promises to maximize the public benefit from the research of its member organisations, generating a resource for the future.

As part of the ICGC, Mike and his colleagues at the Institute were the first to contribute full catalogues of all the mutations in two tumours: one lung cancer, one malignant melanoma. The analyses have opened the door to a new era of whole cancer genome sequencing and are the first of many thousands that will be produced as part of the project.

Leading the Sanger Institute

As well as Mike's new role as Director of the Sanger Institute, he continues to provide leadership and play an active role in his research group and as well as in the Cancer Genome Project and the ICGC.

Mike leads the Institute as it enters a new era of genome research - an era that will be about translating the research efforts of the past decade to develop new treatments for the patients of the future. For Mike, this will involve working with the teams at the Institute to continue to develop and refine a portfolio of research to remain at the very cutting edge in the ever changing landscape of genetic research.

* quick link - http://q.sanger.ac.uk/5l2ri1nv