Projects starting from June 2011 to June 2014
Grant Holder: Dr Christos Tsatsanis
Institution: University of Crete, Greece
Grant Award: £131,385 for 3 years
Project Title: How can tumours hijack the immune system?
The cancer microenvironment consists of the space between the cancer cells in a tumour. Amongst other things, the microenvironment contains cells of the immune system which usually help the body attack the tumour to try to destroy it. However, there are some types of immune cells that can be “convinced" by the tumour to work in its favour. For example, to help build new blood vessels to bring nutrients and oxygen to the tumour, in order to help it grow and spread. This is one of the main things that makes cancer so dangerous, its ability to grow and spread away from the original tumour and into surrounding tissues and organs. Dr Tsatanis is using his AICR grant to investigate how these immune system cells switch to work in favour of the tumour instead of against it and how we can switch them back to attack the tumour. In particular he is focusing on two molecules called AKT1 and AKT2 which he thinks may play a key role in this switch.
Grant Holder: Dr Julian Sale
Institution: MRC Laboratory of Molecular Biology, Cambridge, England
Grant Award: £144,710 for 3 years
Project Title: How do cells copy themselves correctly?
Every cell in our body contains thousands of genes. Genes are like our blueprint - they determine everything that our cells do. Cancer is caused by changes to either the structure or activity of key genes that regulate how cells operate, divide and die. While every cell has a copy of every gene, any given type of cell needs only some of the genes to be active. So, when a cell divides to produce two new cells, it not only has to copy all of its genetic information and then give one complete and properly functioning set of genes to each of the two new cells, the new cells also have to remember which genes were turned on and which were turned off. With a grant from AICR Dr Sale is investigating a gene called REV1 which, if missing or damaged, alters how cells copy their DNA in such a way that cells forget, as they divide, which genes were on and which were off. This type of cellular memory loss is seen in many cancers and understanding how it happens is important for understanding how cancer develops and how it can be treated.
Grant Holder: Professor Christian Münz
Institution: University of Zurich, Switzerland
Grant Award: £207,842 for 3 years
Project Title: Improving vaccines against lymphoma
Vaccinations are widely used to protect us from serious diseases such a polio or diphtheria. They work by introducing an inactive version or small part of a foreign body such as a virus or bacteria. Once inside us the foreign body often triggers the production of antibodies and immune system cells which can kill or neutralise the potentially harmful invader. A type of immune system cell called a T cell are thought to be primarily required for protection against tumors. In order to develop vaccines that trigger this type of immune responses, research has to be done in animals like mice, as the experiments cannot be done on humans. However, although genetically mice and humans are quite similar, the immune systems are quite different, which is why some vaccines that look promising in mouse studies, fail to invoke an immune response in humans. Professor Münz is exploring a new strain of mouse which has components of a human immune system. He will be using his AICR grant to study this new animal model to try to find a way to get a better immune response, mainly from the T cells, against the cancer-causing Epstein Barr virus which can cause several human lymphomas and carcinomas.
Grant Holder: Dr Angelo De Milito
Institution: Karolinska Institute, Stockholm, Sweden
Grant Award: £205,779 for 3 years
Project Title: Optimising the way we test cancer drugs
The physical cancer microenvironment consists of the space surrounding cancer cells within the tumour mass. Recent research has shown this microenvironment is often very acidic (low pH) and hypoxic (low oxygen) which can allow cancer cells to become more malignant and to develop resistance to drug treatments. With his AICR grant Dr De Milito is analysing how this acidic microenvironment is established and what survival mechanisms the cancer cells develop in order to grow and to avoid death when treated with cancer drugs. Usually, cancer drugs are tested at neutral pH conditions in presence of normal oxygen pressure, therefore Dr De Milito also plans to test a large number of drugs, known as drug-libraries, to see if any new drug works well in acidic and hypoxic conditions, which more closely resemble the environment they would be working in inside a patient's tumour.
Grant Holder: Professor Ian Alexander
Institution: Children’s Medical Research Institute, Sydney, Australia
Grant Award: £76,403 for 1 year
Project Title: How to improve gene therapy as a potential way to treat cancer patients
Gene therapy is a technique used for correcting defective genes responsible for diseases like cancer. A normal gene is inserted to replace the defective gene or sometimes the defective gene can be turned off. Although the idea of gene therapy holds great promise and has been successfully used to cure some diseases, it is still under research to make sure it will be safe and effective. The technique itself can introduce dangerous gene alterations or there is a chance that each time the treated cells divide, new alterations can occur. Professor Alexander is investigating the relationship between how often a cell divides and the number of genetic alterations that occur. He hopes that his research could help improve the safety of gene therapy for use in the future.
Grant Holder: Professor James Varani
Institution: The Regents of the University of Michigan, USA
Grant Award: £157,973 for 2 years
Project Title: Does calcium play a role in bowel cancer prevention?
A high fat diet, particularly high in saturated fat, can increase a person’s risk of developing bowel cancer. In addition to the high content of saturated fat, the ‘typical’ Western diet contains only low levels of calcium and other minerals. Previous studies have suggested that an increased intake of calcium can reduce the growth of precancerous lesions in the bowel. Professor Varani is expanding on these findings and investigating whether increasing the levels of calcium in conjunction with other important minerals can help prevent the development of bowel cancer, compared to treating with calcium alone.
Grant Holder: Dr Mario Colombo
Institution: Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy
Grant Award: £205,136
Project Title: Investigating the role of SPARC in blood system cancers
Dr Colombo has been studying a protein called SPARC which is normally only produced by cells as part of the process of growing and healing to repair a wound. It is part of the ‘extra-cellular matrix’ – the glue between cells which holds them together. The bone marrow, where all new blood cells come from, normally has almost no SPARC protein. However, Dr Colombo has discovered that, in leukaemia and pre-leukaemia blood disorders, there are high levels of SPARC in the bone marrow. Along with other research findings, this suggests that SPARC may be involved in the cause of some types of blood system cancers. With his grant from AICR he will investigate the role of SPARC in the normal and leukaemic bone marrow.
Grant Holder: Dr Claudia Ghigna
Institution: Institute of Molecular Genetic - Italian National Research Council (IGM-CNR), Pavia, Italy
Grant Award: £102,666 for 3 years
Project Title: Do cancer cells rearrange the information stored in our genes?
Dr Claudia Ghigna is using her AICR grant to investigate how alternative splicing is involved in angiogenesis, the process through which a tumour can grow its own blood supply to enable enough oxygen and nutrients to reach the cells and allow tumours to grow. Alternative splicing is a mechanism that rearranges information as it is being read from the blueprints stored in the DNA inside our cells. The DNA is coded instructions to make proteins that then carry out activities within the cell. Through alternative splicing cells can make different versions of proteins. With her grant from AICR Dr Ghinga will investigate whether cancer cells use alternative splicing as a way to control angiogenesis.
Grant Holder: Dr Marina Mione
Institution: IFOM, The FIRC Institute of Molecular Oncology Foundation, Milan, Italy
Grant Award: £139,563 for 3 years
Project Title: Investigating the hippo pathway in cancer
Cells control all their activities with an internal network of genes and proteins, which are organised into a series of different pathways, each controlling a group of activities such as cell growth or death. Many of these genes and proteins are altered in cancer cells and therefore operate quite differently, causing the cells to grow and divide rapidly, forming a tumour. A group of genes called the Ras genes are known to be altered in cancer cells and once altered; they can then affect many other pathways. One of these is the hippo pathway, an important regulator of tissue growth, but how Ras affects it is unclear. Using zebrafish as a model system Dr Mione is investigating how altered Ras controls the hippo pathway in cancer cells.
Grant Holder: Professor Karen Vousden
Institution: Beatson Institute for Cancer Research, Glasgow, Scotland
Grant Award: £185,899 for 3 years
Project Title: How do molecules switch from being anti-cancer to being able to encourage it?
Professor Vousden’s research focuses on a protein called p53 which has a key role in the body's defence against cancer. p53 causes cells to stop growing or die in response to damage to their DNA. This built-in control mechanism prevents damaged cells from going on to cause cancer. In some cells however the p53 protein can become altered or turned off.. This is the case in most cancer cells and is at the heart of why many cells become cancerous. With her AICR grant Professor Vousden is investigating altered forms of the p53 protein which have lost their ability to prevent cancer and how, instead, they are able to develop cancer-causing attributes, including helping cells to invade surrounding tissues and spread around the body. Since the altered forms of p53 are only found in cancer cells they could be a potential target for drugs as they would only affect these cells and not the healthy ones.
Grant Holder: Dr Alexander Hergovich
Institution: University College London, England
Grant Award: AICR grant £207,966 for 3 years
Project Title: Investigating the communication pathways within our cells
Every cell contains thousands of genes. These act as blueprints to produce proteins which carry out all the functions within the cells. The genes and proteins are divided into a series of different pathways, each controlling a group of activities such as cell growth or death. Many of these genes and proteins, and therefore pathways, are altered in cancer cells. These alterations make the pathways operate differently, causing the cells to grow and divide rapidly and forming a tumour. One protein often altered in cancer is the hMOB2 protein which forms part of the hippo pathway. Its exact role in cancer formation is unclear and this is the focus of Dr Hergovich’s AICR grant.
Grant Holder: Dr Karin de Visser
Institution: Netherlands Cancer Institute, The Netherlands
Grant Award: AICR grant £205,680 for 3 years
Project Title: Can our own immune system actually work to encourage the spread of breast cancer?
As with all cancers, the earlier breast cancer is diagnosed the better chance of successful treatment. One of the things that make cancer so dangerous is its ability to grow and spread away from the original tumour and into surrounding tissues and organs. It is now known that the cancer microenvironment plays a large role in how the tumour develops and becomes able to spread. The cancer microenvironment consists of the space in between the cancer cells within the tumour mass. Among other things, it contains cells of the immune system which, instead of attacking the tumour and trying to destroy it, can instead be manipulated by the tumour to help the cancer cells spread. Indeed, high levels of immune system cells in the tumour microenvironment indicate a lower chance of successful treatment for the patient. The main focus of Dr de Visser’s AICR grant it to better understand how these immune system cells are involved in causing breast cancers to spread and if they affect how a patient responds to chemotherapy.
Grant Holder: Dr Pei-Yun Jenny Wu
Institution: CNRS National Centre for Scientific Research, Rennes University, Rennes, France
Grant Award: AICR grant £180,573 for 3 years
Project Title: Understanding the control systems inside our cells
Cancers can result from accumulation of damaging changes to our DNA. These alterations may be caused by many things, including damage from the environment such as UV from sunlight and mistakes that are made when the DNA is copied before a cell divides. Although cells have mechanisms to prevent or repair such damage, these safeguards can sometimes become faulty. In this case, changes to the DNA can accumulate and be passed on from one cell generation to the next. This may then cause cells to become cancerous, forming a tumour by growing and dividing in an uncontrolled manner. Dr Wu is investigating how cells acquire the multiple alterations to the DNA that can contribute to the development of cancer and how they are able to limit the copying of their DNA when it is at high risk of being damaged. This work is being conducted in yeast, which is an excellent system for studying such questions as yeast cells are fundamentally similar to human cells but much easier to manipulate. In addition, since yeast are less complicated than human cells and they provide an opportunity to understand difficult biological problems that can then be directly tested in humans.
Grant Holder: Professor Maurice van Steensel
Institution: Maastricht University Medical Centre, Maastricht, The Netherlands
Grant Award: AICR grant £153,409 for 2 years
Project Title: How does Birt-Hogg-Dubé syndrome develop into cancer?
Birt-Hogg-Dubé (BHD) syndrome is a rare disorder where people develop non-cancerous growths on their faces and are at risk of developing kidney cancer. Patients are also at risk of developing cysts in their kidneys, liver and lungs. It is known that BHD is caused by alterations in a gene called FLCN but it is unclear how this alteration can cause cysts and cancer. Dr van Steensel believes that formation of the cysts precedes the cancer and he is using his AICR grant to investigate how lack of FLCN causes cysts to develop.
Grant Holder: Professor Martin Eilers
Institution: University of Würzburg, Würzburg, Germany
Grant Award: £249,824 for 3 years
Project Title: How can we stop certain genes causing cancer?
Every cell in our body contains thousands of genes which carry all of the information the cell needs. Some key genes control how the cells grow, divide and die. It is when these important genes get altered that the cells become able to multiply rapidly in an uncontrolled manner and fail to die which can lead to cancer. These cancer-causing genes are known as oncogenes. One such oncogene is Myc and there is evidence that interfering with Myc, using a molecule called OmoMyc, could potentially be a way to treat cancers. However, it is still not clear exactly how OmoMyc achieves its therapeutic effects and this is the focus of Professor Eilers’ AICR grant.
Grant Holder: Professor Eamonn Maher
Institution: University of Birmingham, England
Grant Award: AICR grant £156,226 for 2 years
Project Title: Understanding how some people inherit a higher risk of developing kidney cancer
Kidney cancer can run in some families and some people may inherit a gene causing a higher risk of developing kidney cancer from their parents. In some cases the altered gene (e.g. the VHL gene) can be detected and by testing the family doctors can determine who will benefit from cancer screening. However, in most families it is not clear how the risk is passed on and this is the focus of Professor Maher's AICR grant. By studying patients with inherited kidney cancer Professor Maher hopes to identify new genes that are responsible and to find out if these are also involved in non-inherited kidney cancers. His findings could be important for identifying those who may be at risk of developing inherited kidney cancer. These people and their close relatives could then be monitored and any cancer caught early when treatment has a much better chance of being successful.
Grant Holder: Dr David Bernard
Institution: INSERM The Cancer Research centre of Lyon, Lyon, France
Grant Award: AICR grant £122,067 for 3 years
Project Title: How do cells stop and have a rest?
Healthy cells grow and divide in a highly organised and tightly controlled manner in a process called the cell cycle. Cancer occurs when the DNA gets damaged and the cells become able to multiply in an uncontrolled manner, leading to the development of tumours. One way cells are able to protect themselves if their DNA becomes damaged is by stopping dividing and entering a ‘rest’ phase. Dr Bernard has found that a molecule called PLA2R1 is involved in enabling cells to enter this rest phase and has other anti-cancer roles. Dr Bernard is using his AICR grant to further investigate these roles and to understand the mechanism behind them.
Grant Holder: Professor Claus
Institution: University of Edinburgh, Scotland
Grant Award: AICR grant £212,400
Project Title: Investigating genes involved in acute myeloid leukaemia
For some time it has been known that leukaemia goes through several early stages, first as non-cancerous pre-stem cells, then leukaemia stem cells and finally becoming leukaemia cells. Professor Nerlov is using his AICR grant to investigate the stem cells of a specific type of leukaemia called acute myeloid leukaemia (AML). Professor Nerlov has previously identified genes that are turned off in AML leukaemia stem cells. He is now trying to pinpoint which of these genes has anti-cancer properties and therefore allows the development of AML when it is turned off. In the future this information could be helpful when developing new treatments against this type of cancer.
Grant Holder: Professor Eric So
Institution: Kings College London, England
Grant Award: AICR grant £230,006 for 3 years
Project Title: Improving models for the study of mixed lineage leukaemia
Despite the difference in appearance, when we are looking at the DNA level we are quite similar to animals such as mice. Before any treatments can ever be trialled in humans, the early research and development is done in animals first. Researchers use animals to discover how the cancer begins in the first place, how it is able to grow and how and where it spreads to. It is therefore important to have animal models that closely mimic human cancers so that any research carried out is accurate and relevant for human cancers. Professor So, who has been funded by AICR for the past 6 years through one of our prestigious Research Fellowships, is using his new AICR grant to develop a mouse model that mimics human mixed lineage leukaemia (MLL) leukaemia. He will be using cutting edge techniques and hopes that the resulting mouse model will prove a ‘proof of principal’ and help with the development of other cancer models in the future that are cheaper and quicker than the current techniques.
Grant Holder: Dr Valeria Cavaliere
Institution: University of Bologna, Bologna, Italy
Grant Award: AICR grant £124,935 for 3 years
Project Title: Using fruit flies to study human cancer
Dr Cavaliere is studying the role of a gene called Nm23 which has anti-cancer abilities. She is looking at how and when Nm23 is made in the cell and what other molecules it interacts with. To do this Dr Cavaliere is using fruit flies and bowel cancer models. Scientists use fruit flies for their research as these tiny creatures are extremely useful for lab studies focusing on how cells behave. Importantly, the genes that control the growth and death of cells in flies are almost identical to those found in human cells, making their findings highly relevant to what goes on in the human body.
Grant Holder: Professor David Bowtell
Institution: Peter MacCallum Cancer Centre, Melbourne, Australia
Grant Award: £210,003 for 3 years
Project Title: Understanding why chemotherapy drugs stop working in ovarian cancer patients
Worldwide, there are more than 204,000 new cases of ovarian cancer diagnosed each year. The most common treatment for ovarian cancer is surgery followed by chemotherapy using drugs that contain the metal platinum. There are several different types of ovarian cancer and one of the most common is called serous. About three quarters of patients with serous ovarian cancer normally respond well to their first chemotherapy treatments but many women with advanced forms of the disease find the cancer returns after months or even years. When the cancer recurs women are then given the chemotherapy again but in many cases the drugs no longer work as the cancer has become resistant and so develops further. Sadly many women with serous cancer will die several years from the date they were initially diagnosed. The reasons why the cancers become resistant to treatment are poorly understood and they are the focus of Professor Bowtell’s AICR grant. Using samples from ovarian cancer patients collected before and after treatment he has found a gene which he believes could play a role in this resistance to the drugs and he is now working to understand how it may do this.
Grant Holder: Dr Vincenzo Russo
Institution: Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy
Grant Award: £144,783 for 3 years
Project Title: Can inflammation near tumours encourage it to grow?
Recent findings indicate that inflammation in the area a tumour is forming may actually help the tumour develop. Indeed, in mice where inflammation is prevented, tumours stop growing and some even disappear. Inflammatory cells are found in the tumour microenvironment - the space in between the cancer cells within the tumour mass. However, it is not yet clear how the tumours persuade these inflammatory cells to promote the growth of the tumour and this is the focus of Dr Russo’s AICR grant. In particular he is focussing on the pro-tumour role of a group of molecules called LXR agonists as he already has some convincing evidence that they play a role in tumour growth.
Grant Holder: Dr Jonathan Higgins
Institution: Brigham and Womens Hospital, Harvard, Boston, USA
Grant Award: £169,911 for 3 years
Project Title: Doing the splits - how do cells divide correctly?
Vital information that our cells require is coded for by our genes. The genes themselves are packaged into string-like structures called chromosomes. When a cell divides to produce two new cells, it firstly has to copy all of its chromosomes and then give one complete set to each of the two new cells. To do this, all of the identical pairs of chromosomes are compacted into sausage-shaped structures and are lined up down the middle of the cell. Traction fibres then pull the pairs apart, moving each set towards the opposite ends of the cell. The other ends of the traction fibres are attached to tiny bodies called the spindle poles, which lie at each end of the dividing cell. This process is very carefully controlled because having an altered, incomplete or too large a set of chromosomes can make a cell malfunction - and in some cases it can lead to the cell becoming cancerous. When this process goes wrong it is often because, instead of one spindle pole at each end of the cell, there are several spindle poles. Dr Higgins is using his AICR grant to understand how this occurs and what consequences it has for the resulting cells which can cause them to become cancerous. The more we know about the mechanism of cell division, the greater the opportunities for developing new and improved drugs.
Grant Holder: Dr Gareth Inman
Institution: University of Dundee, Scotland
Grant Award: £202,807 for 3 years
Project Title: Researching the mechanisms that allow cancer to occur
Healthy cells grow and divide in a tightly controlled manner. Cancer occurs when the cells become able to multiply in an uncontrolled manner, leading to the development of tumours. Dr Inman is using his AICR grant to study a protein called TGF-beta which he has previously shown to have anti-tumour properties and helps ensure cells divide correctly. However, during the growth of some tumours they are able to switch TGF-beta from being anti-cancer to pro-cancer but how, when and where this occurs is still unclear. Dr Inman is now investigating this important switch further to try to understand the mechanisms behind it.
Grant Holder: Professor Anne Ridley
Institution: Kings College London, England
Grant Award: £212,082 for 3 years
Project Title: How can prostate cancer spread to other organs?
One of the main factors that make tumours so dangerous is their ability to invade into surrounding tissues and organs and spread throughout the body. Individual cancer cells squeeze between the normal cells nearby and push their way through the tissue. They are then carried in the blood stream and can form new tumours in other parts of the body. The ability of prostate cancer cells to move and spread is controlled by many different proteins, including one called Met and a group called Rho GTPases. These proteins are usually tightly controlled but can become unregulated in cancer. With her AICR grant Professor Ridley is analysing how the Rho GTPases interact with the Met protein to allow the cancer cells to spread. She also hopes to identify other proteins that may be involved. This could lead to the design of new treatments in the future.