Cancer genetics and cancer biology

Birmingham Centre for Genome BiologyWe 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.

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.

We are working on the following research themes:

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 hydroxlases.

Key researchers

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
Carmel McConville Gene expression in neuronal cancer
Claire Palles Gastrointestinal cancer genetics and epigenetics

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

Constanze Bonifer Epigenetics and gene regulation in blood cells
Peter Cockerill Epigenetics and gene regulation in blood cells
Charles Craddock Myeloid malignancies and stem cell transplantation
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

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

 
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

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

 
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

The metabolomics of cancer cells

We use Nuclear Magnetic Resonance spectroscopy (NMR) to study metabolism and cancer. This includes standard metabolomics and tracer based approaches to study metabolic fluxes in human cells and cell lines. We recently developed a protocol for studying real-time metabolism in leukaemia patient cells. We also use NMR to investigate protein-ligand interactions and to characterise binding modes of proteins for small molecules.

Key researcher

 
Ulrich Günther NMR and metabolomics

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

 
Andrew Bell The role of EBV in lymphoma
Roger Grand Adenovirus biology and cellular transformation
Hisham Mehanna Head and neck cancer
Joanna Parish HPV gene expression and replication
Sally Roberts HPV biology and carcinogenesis
Andy Turnell Adenovirus biology and cellular transformation

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

 
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

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

 
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