
Cancer genetics and cancer biology

We are investigating many different model systems to identify the mechanisms by which cancer mutations deregulate the normal processes of cellular growth, maintenance and differentiation. We are screening different classes of cancer, such as leukaemia, for a wide range of potential mutations and then performing a range of genomic analyses to determine how individual mutations deregulate the normal functions of cells to cause cancer.
About our research group
We use genome-wide epigenetic and transcriptional profiling as tools to decipher gene regulatory networks in normal cells and in cancer cells where these processes are deregulated. We study stem cell growth and differentiation to determine how cancer cells evade the normal regulation of cellular development. Our research also reveals how some specific mutations promote DNA damage and thereby increase the mutation rate in cancer cells.
Our research themes
Cancer genetics and epigenetics
Cancer genetics and epigenetics
We are using genomic-based approaches to identify DNA mutations and epigenetic modifications associated with different types of cancers. We are performing genome and epigenome analyses in tumours, and are using epigenetic biomarkers to stratify cancer diagnostics. We study the roles of specific regulatory pathways in cancer, including genes encoding hydroxylases.
Key researchers
| Researcher | Group |
|---|---|
| Andrew Beggs | Colorectal cancer genetics and biology |
| Constanze Bonifer | Epigenetics and gene regulation in blood cells |
| Peter Cockerill | Epigenetics and gene regulation in blood cells |
| Mathew Coleman | Protein hydroxylation in cancer |
| Michael Griffiths | Cancer genetics and mutation screening |
| Claire Palles | Gastrointestinal cancer genetics and epigenetics |
Deregulation of transcriptional networks in leukaemia
Deregulation of transcriptional networks in leukaemia
We are using genome wide approaches to study the deregulation of epigenetic and gene regulation networks in acute myeloid leukaemia as compared to normal blood progenitor cells. We are performing intensive analyses of the mechanisms utilised by specific mutations in such commonly mutated genes as RUNX1, FLT3 and LMO2. We are also investigating how leukaemia is maintained by over-expression of factors such as MYB.
Key researchers
| Researcher | Group |
|---|---|
| Constanze Bonifer | Epigenetics and gene regulation in blood cells |
| Peter Cockerill | Epigenetics and gene regulation in blood cells |
| Jonathon Frampton | Blood stem cells and leukaemia |
| Paloma Garcia | The role of MYB proteins in blood cells |
| Maarten Hoogenkamp | Epigenetics and gene regulation in blood cells |
| Manoj Raghavan | Myeloid malignancies |
The regulation of DNA damage and repair
The regulation of DNA damage and repair
Defects in the replication and repair of DNA are major contributors to the development of cancer. These processes are also major targets of chemotherapy in cancer. We have an extensive programme of research where several different research teams work closely on the regulation of DNA replication and repair. Our research interests include the role of post translational modifications in the regulation of DNA replication and repair and the role it plays in maintaining genome stability. We are also investigating the role of tumour suppressors and oncogenes, and the influence of ongoing transcription, in replication stress.
Key researchers
| Researcher | Group |
|---|---|
| Agnieszka Gambus | Mechanisms of DNA replication |
| Paloma Garcia | The role of MYB proteins in blood cells |
| Martin Higgs | Lysine Methylation and DNA Damage |
| Jo Morris | Breast cancer genetics and DNA repair |
| Eva Petermann | DNA replication and repair |
| Marco Saponaro | Transcription-mediated genome instability |
| Steve Smerdon | Genome stability and DNA repair |
| Grant Stewart | The role of DNA damage response genes in disease |
| Richard Tuxworth | Lysosomal storage diseases |
The roles of mutations that promote DNA damage in cancer
The roles of mutations that promote DNA damage in cancer
Specific mutations in genes that control DNA replication and repair can lead to error prone replication and the accumulation of errors. We are investigating the roles of mutations of these genes which include ATM, BRCA1, BRCA2 and PALB2. Processes that protect genome integrity are also central to the actions of many DNA damaging anti-cancer therapeutics and we are exploring these pathways for potential therapeutic targets. We are also investigating how some genes such as MYBL2 are essential for the maintenance of genome stability.
Key researchers
| Researcher | Group |
|---|---|
| Charles Craddock | Myeloid malignancies and stem cell transplantation |
| Paloma Garcia | The role of MYB proteins in blood cells |
| Tatjana Stankovic | Genetics and biology of B cell malignancies |
| Malcolm Taylor | Role of ATM in DNA repair and cancer |
Viral oncology
Viral oncology
The aim of our Viral Oncology research programme is to elucidate the molecular and cellular mechanisms by which tumour viruses cause malignant and non-malignant disease. Viruses underlie several types of cancer. These include Epstein Barr virus in B cell tumours and human papilloma virus in cervical cancer and head and neck cancers. We are also studying the mechanisms used by adenovirus oncoproteins to transform cells.
Key researchers
| Researcher | Group |
|---|---|
| Andrew Bell | The role of EBV in lymphoma |
| Roger Grand | Adenovirus biology and cellular transformation |
| Hisham Mehanna | Head and neck cancer |
| Jo Parish | HPV gene expression and replication |
| Andy Turnell | Adenovirus biology and cellular transformation |
Breast cancer cell and molecular biology
Breast cancer cell and molecular biology
We are investigating the cellular and molecular basis of breast cancer from many different angles. We are identifying mechanisms whereby DNA mutations deregulate transcription signalling, or generate additional mutations by promoting DNA damage. We are also working in the clinic to improve the treatment of breast cancer, as well as studying how breast cancer cells break away from tumours to form metastases.
Key researchers
| Researcher | Group |
|---|---|
| Fedor Berditchevski | Breast cancer tissue microenvironment |
| Clare Davies | Protein methylation in breast cancer |
| Padma-Sheela Jayaraman | The role of PRH in stem cells and cancer |
| Jo Morris | Breast cancer genetics and DNA repair |
| Elena Odintsova | Breast cancer tissue microenvironment |
| Daniel Rea | Breast cancer treatment |
Cancer diagnosis, analysis and therapy
Cancer diagnosis, analysis and therapy
We cooperate across the hospital/university campus to deliver comprehensive research programmes that span the full range of cancer diagnosis, molecular investigations of cancer cells, and delivery of cancer treatments. The Cancer Research UK Clinical Trials Unit is a world leader in the development and assessment of new cancer therapies.
Our aims are to develop new tools for diagnosing and treating cancer. We are developing new screening tools, and evaluating different therapies. These aims are supported by our laboratory studies that identify biomarkers and molecular defects in cancer cells. We have made significant advances in many areas which include colorectal cancer, bladder cancer and leukaemia.
Key researchers
| Researcher | Group |
|---|---|
| Simon Bach | Colorectal cancer and pre-cancer |
| Rik Bryan | Bladder cancer biology and treatment |
| Charles Craddock | Myeloid malignancies and stem cell transplantation |
| Nicholas James | Treatment of prostrate cancer |
| Pam Kearns | Paediatric oncology/Clinical Trials |
| Sean Kehoe | Gynaecological Cancer |
| Hisham Mehanna | Head and neck cancer |
| Dion Morton | Colorectal cancer and pre-cancer |
| Prashant Patel | Urology |
| Andrew Peet | Imaging in Paediatric oncology |
| Thomas Pinkney | Colorectal cancer and pre-cancer |
| Sudha Sundar | Ovarian cancer treatment |
| Douglas Ward | Biomarker discovery by mass spectrometry |
| Colin Watts | Glioma genetics and treatment |