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.

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 INTEGRITYWhilst 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.

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 TRANSCRIPTIONThe 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 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 SIGNALLINGProfessor 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.

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 polymorphismsThere 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.

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 

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.

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 

Dr Patrick Pollard tells us about his research on cancer metabolism. Cancer cells produce energy predominately through a high rate of glycolysis; it has been suggested that this change in metabolism is the fundamental cause of cancer. Dr Patrick Pollard aims to elucidate the alternative metabolic strategies used by cancer cells with high concentrations of glucose to proliferate, even under conditions of stress. These mechanisms could then become targets for more effective cancer therapies.

Cancer Metabolism 

Dr Opher Gileadi tells us how cells maintain genome integrity and how we can use it in our fight against cancer. While cigarette smoke and sun exposure can lead to DNA damage, which causes cancer, there are a number of natural processes within the body that can also lead to cell mutations. Dr Opher Gileadi studies the structure and chemical biology of the proteins involved in DNA repair and in recovery from DNA damage. Since DNA damage can be both a cause of cancer and a tool in fighting cancer, Dr Gileadi aims to uncover ways to better target and destroy cancer cells.

Genome Integrity 

Professor Chris Pugh tells us about the links between genetics, renal disease and oxygen sensing. The kidney plays a central role in our metabolism, by controlling various physiological balances. Genetics is central to these mechanisms, since gene defects lead to all sorts of malfunctions. Oxygen sensing mechanisms were first discovered as a result of studies on the production of the kidney hormone erythropoietin. We now know that the underlying system controls about 1000 genes. Professor Chris Pugh is working on the oxygen sensing functions of the body to assist in designing better therapies for disorders that involve oxygenation problems, such as angina and cancer.

Renal Disease 

Dr Bee Wee tells us about Palliative Care in Oxford and her research on end of life care and fatigue. Due to advances in medicine prolonging the lives of those with progressive, life limiting diseases, the need for long-term palliative care has increased. Dr Bee Wee is currently researching end of life care for people with incurable cancer and advanced non-malignant disease, symptom management and rehabilitation, to improve quality of life for patients. Dr Wee is the Head of Palliative Care Research and Development, based at Sir Michael Sobell House in Oxford.

Palliative Care 

Professor Yvonne Jones talks about cell-cell communication and how this can help us develop new drugs. Cells communicate through receptors on their surface; however, when these finely tuned systems don't work correctly, diseases can be triggered. Professor Yvonne Jones has been working to identify the structural biology of cell surface recognition and signalling complexes. Receptors embedded in the surface are potential targets for therapeutic intervention in many diseases including cancer. Professor Jones is director of the Cancer Research UK Receptor Structure Research Group.

Cancer and Protein Crystallography 

Cancer

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