Professor Skirmantas Kriaucionis aims to to elucidate the molecular function of DNA modifications in normal cells and cancer. Although all cells in our body have the same genome, they look different and perform different functions. Epigenetic modifications such as methylations ensure which sets of genes are expressed in specific cells and how this specificity is inherited. Cancer cells show particular epigenetic abnormalities which can be targeted for cancer therapies.

Cancer

Epigenetic modifications and cancer

Dr Ross Chapman studies the molecular events triggered by DNA damage detection, and why defects in these events lead to immune deficiency and cancer in humans. GENOME INTEGRITY Whilst controlled DNA breaks allow for our vast repertoire of antibodies, DNA damage happening out of context can lead to cancer or predisposition to cancer. Recent developments in personalised medicine exploit the DNA repair weaknesses of cancer cells to selectively kill them. A better understanding of the underlying mechanisms can help develop innovative and targeted therapies.

Repairing DNA damage

Misfolded proteins can either create the loss of a cellular function, or escape degradation, causing aggregation diseases. Dr John Christianson's research focusses on ER-associated degradation, which is responsible for clearing non-functional and orphan translation products. These processes play a central role in inherited diseases such a cystic fibrosis and various forms of cancer. Dr Christianson's long term goal is to identify novel points of interventions for cancer therapies.

Cleaning up misfolded proteins

Professor Robert Gilbert's research focuses on the molecular mechanisms underlying membrane pore formation and cell adhesion. Switching mechanisms within our cells are in part responsible for their development. MicroRNAs control a whole set of proteins associated with stem cell biology, particularly cancer stem cells. Targeting these components raises the potential for new anti-cancer therapeutics, which work by switching off protein production rather than inhibiting them later.

Targeting cancer mechanisms

Melanoma or skin cancer is one of the fastest rising cancer types. When identified early, melanoma is relatively easy to cure, but once it starts to metastasise, it becomes very difficult to treat. DEREGULATION OF TRANSCRIPTION The interface between signal transduction and transcription regulation coordinates gene expression. Deregulation of transcription is a key factor in cancer. Professor Colin Goding studies how a precise programme of transcription regulation is achieved, particularly in the transition between normal and cancer stem cells, and the parallels with normal stem cell populations.

Melanoma

Transcription is a tightly regulated process, where chemical modifications initiate the duplication of genetic material. This epigenetic process is often dysregulated in cancer, but it can be targeted with small molecule inhibitors. EPIGENETIC SIGNALLING Professor Panagis Filippakopoulos is interested in the molecular mechanisms of transcription, where the formation of non-covalent protein complexes is mediated by post-translational modifications. Dysfunction in this epigenetic signalling process is linked to disease, particularly cancer.

Targeting epigenetics to treat cancer

Dr Gareth Bond, Associate Member of the Ludwig Institute for Cancer Research, studies the influence of genetic variants on the origins, progression and treatment of human cancer. SNP - single nucleotide polymorphisms There is great heterogeneity between individuals in their risk of developing cancer, disease progression and responses to therapy. Specific single nucleotide polymorphisms (SNPs) are associated with human cancers. They have the potential to help us identify individuals more at risk of developing cancer, and better target preventative or therapeutic strategies.

Human Cancer Genetics

Dr Jenny Taylor is the Programme Director for the Genomic Medicine Theme, Wellcome Trust Centre for Human Genetics. Her research bridges the gap between genetics research and the use of its discoveries in diagnosis or treatment of medical conditions. Clinical diagnoses can be broad descriptions, but today's test results can help better understand the condition as well as target treatment. Cancer is a good example in which personalised medicine can help decide which molecular targeted therapy is most appropriate.

Personalised Medicine

Identifying genes that increase the risk of bowel or other cancers allows us to offer preventative measures, such as removing tumours at an early stage. A better understanding of how and why cancers grow also helps develop improved treatments. Ian Tomlinson, Professor of Molecular and Population Genetics at the Wellcome Trust for Human Genetics, works on the identification of genes that predispose to colorectal and other cancers. His research focuses on the relative importance of selection and genomic instability.

Cancer predisposition and evolution

Cancer research now generates huge amounts of data, and sophisticated computational tools are needed to answer biological questions. Making sense of this variability at molecular level will help us better tailor treatments to individual cancer patients. Dr Benjamin Schuster-Böckler heads the computational group at the Ludwig Institute for Cancer Research. His work has demonstrated that epigenetic modifications influence the mutational landscape in cancer cells. He studies the effects of DNA-binding proteins on transcription factors, with the aim to understand the regulation (and mis-regulation) of the transcription of important oncogenes and tumour suppressors.

Cancer Informatics

Inflammatory signalling Dr Mads Gyrd-Hansen aims to elucidate fundamental mechanisms governing pro-inflammatory signalling during innate immune responses, and through this, to better understand how aberrant inflammatory signalling contributes to tumour development and cancer progression.

Cancer and innate immunity

Adult gastrointestinal stem cells The gastrointestinal tract is lined with a single sheet of epithelium that is replaced every 4-5 days. The base of a flask-shaped structured called the crypt is where the gastrointestinal stem cells are found. These divide to form daughter cells that travel up the crypt to replace these cells. Dr Simon Leedham's current research focuses on the cell-signaling pathways that control intestinal stem cells and the dysregulation of these pathways in cancer.

Stem cells and cancer

Professor Vincenzo Cerundolo tells us how research in immunology leads to the development of new cancer treatments. Immunotherapy stimulates the body's immune system, and can be a powerful treatment for cancer. The most efficient prophylactic cancer vaccine today is the vaccine against papilloma virus, whereas the development of therapeutic vaccines is more challenging. With the aim of developing better treatment strategies for cancer patients, Professor Vincenzo Cerundolo is working to gain a better understanding of the cell-to-cell interplay required for optimal expansion and activation of tumour-specific T cell populations.

Cancer Immunlogy

Professor Xin Lu talks about the links between cancer and regenerative medicine. Identifying the switches that turn cell growth off and on would have profound implications for cancer medicine. If the right mechanisms can be found, cancer cells could be targeted specifically, resulting in more efficient treatments. Professor Xin Lu is working to identify the molecular mechanisms that naturally suppress tumour growth. Nuclear reprogramming could also enable cells to be utilized more safely and effectively in regenerative medicine.

Cancer and regenerative medicine

Dr Raghib Ali talks about INDOX, the cancer research network in India. The INDOX Cancer Research Network is a collaboration between Oxford and twelve leading cancer centres in India. As Director of this Network, Dr Raghib Ali aims to improve early detection of cancer and to develop effective and affordable cancer treatments for low and middle-income countries. Dr Ali's main interest is in colorectal (bowel) cancer and other chronic, non-communicable diseases. Incidence of colorectal cancer in India has been relatively low historically; understanding why may help us establish risk factors and also lead to new treatments.

INDOX Cancer Research NetworK

Cancer is studied from several angles at NDM, from its epidemiology and potential causes, to its effect on patient lives and outcomes, as well as the basic science underpinning the unregulated cell growth that is the hallmark of the disease. Our Cancer podcasts illustrate the diversity of this research, and provide snapshots to the work of NDM scientists and clinicians to understand, treat and prevent cancer.

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Cancer

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