Projects starting from October 2008 and ending October 2011
Grant Holder: Dr Matthew Fuchter
Institution: University of London, England
Grant Award: £106,079 for 3 years
Project Title: What can sea sponges teach us about cancer drugs?
Every cell in our body contains thousands of genes that carry the information essential for life, packaged up into what is known as the genome. Our genomes are therefore often compared to an instruction manual or recipe book. While the recipe book (or gene) contains the information needed to make the dishes (the proteins in our cells), how, where, and when this information is used is controlled by the chef (the processing machinery in the cell). Mistakes can happen if there is a typo in the recipe (a mistake in the gene) or if the information is not followed correctly by the chef (the processing machinery) leading to an incorrect final dish (a faulty protein). Faults like these are common in many cancers and some anti-cancer drugs work by blocking the processing machinery in cancer cells which prevents them from growing and dividing. Dr Fuchter is investigating a naturally occurring chemical found in a sea sponge, which is reported to strongly block several components of the processing machinery. The first part of this project is to dissect the naturally-occurring compound to determine what chemical features are necessary for it to work. The second goal is to use this knowledge to develop new anti-cancer drugs.
Grant Holder: Dr Harry Mellor
Institution: University of Bristol, England
Grant Award: £176,220 for 3 years
Project Title: Skin cancer - how is the DBC2 gene involved in?
Every cell in our body contains thousands of genes that are essential for the cells to function. To make a cell do something, the gene or genes that control that particular activity have to be turned on. One gene called DBC2 has been found to be turned off in many cases of breast, lung, bladder and stomach cancer but exactly how DBC2 is involved in causing cancer is yet unknown. Dr Mellor recently discovered that DBC2 controls whether or not cells produce a hormone-like substance called CXCL14. CXLCL14 activates the immune system to fight infections in our body such as viruses, bacteria and even some cancer cells. Many skin cancers lose the ability to produce CXCL14 which makes the tumours grow larger, probably because the immune system is not stimulated to attack the cancer cells. With his AICR grant Dr Mellow is investigating how the DBC2 gene controls the production of CXCL14 in normal skin cells and how this process is lost in skin cancers.
Grant Holder: Dr Catrin Pritchard
Institution: University of Leicester, England
Grant Award: £173,195 for 3 years
Project Title: Location, Location, Location - why is it so important?
Proteins carry out most functions within cells and they control processes such as how the cells grow and divide. Many cancers have been found to have an altered version of the B-RAF protein and this plays a crucial role in making the cells become cancerous. A number of drugs are being developed to block the activity of the altered B-RAF but its exact role in the cell is still unclear. Dr Pritchard has therefore been studying what B-RAF does in cells and where it is located. Surprisingly, she found that B-RAF gets into a part of the cell called the nucleus - the control centre where the genes are stored. Our current understanding of how B-RAF works is based on it staying in other parts of the cell. The fact that it goes into the nucleus suggests that it may have some other important, unknown activities. Until now, no-one suspected that B-RAF might have an effect on genes. With this grant from AICR, Dr Pritchard is investigating what happens to cell control systems when normal and altered B-RAF get into the nucleus and whether this is involved in causing cancer and if so, how?
Grant Holder: Dr John Maher
Institution: Kings College London, England
Grant Award: £182,802 for 3 years
Project Title: The enemy within – how our immune system can fight oral and lip cancer
Our immune system includes T cells, which have the ability to recognise foreign molecules – such as those on bacteria, viruses and even some cancer cells. Once a foreign body has been detected the immune system is able to attack and kill it. But cancer cells have a wide range of ways to prevent the immune system from recognising or attacking them. Dr Maher is developing a new way of using the immune system to attack cancer cells lining the mouth and throat. In the laboratory he will make T cells that recognise a group of molecules called ErbB receptors, which are found on the majority of cells lining the mouth and throat. He will then inject a large number of these T cells directly into the tumours where they can attack the cancer cells. However, if these T cells attacked healthy cells with the ErbB receptors it could cause side-effects for the patients. To prevent this from happening Dr Maher will build a suicide gene into the T cells, so they can be killed rapidly before they harm any healthy cells.
Grant Holder: Dr Rina Rosin-Arbesfeld
Institution: Tel-Aviv University, Israel
Grant Award: £172,300 for 3 years
Project Title: How to treat bowel cancer caused by faults in the APC gene
The way that cells grow, divide and die is normally tightly controlled by certain genes. Cancer is caused by changes to these genes which cause the cells to grow and divide in an uncontrolled manner, forming a tumour. In most cases of bowel cancer, a gene called APC is altered. Recently, it has been shown that drugs known as aminoglycosides can be used to treat some cases of muscular dystrophy and cystic fibrosis, two diseases also caused by different altered genes. These genes have similar changes to those found in the APC gene of colorectal cancer patients. Dr Rosin-Arbesfeld is studying the effect of these aminoglycoside drugs on bowel cancer cells grown in the lab and on mice with colon cancers caused by alterationsin the APC gene. Dr Rosin-Arbesfeld hopes to find out if these drugs could be used to prevent the effect of the altered APC gene and treat human bowel cancer patients.
Grant Holder: Professor Neil Perkins
Institution: University of Bristol, England
Grant Award: £112,992 for 2 years
Project Title: How is NF-kappaB involved in cancer?
When a cell grows and divides to form two new cells, it goes through a series of very carefully controlled steps. Changes to some of these steps can cause the cell to grow and divide more rapidly, making them more likely to develop into a tumour. To understand how this happens, Professor Perkins is carrying out a detailed analysis of the many different molecules involved in controlling how cells divide and investigating how they interact with each other. He is particularly interested in a molecule called NF-kappaB which is known to be involved in cancer.
Grant Holder: Dr Alison Woollard
Institution: University of Oxford, England
Grant Award: £173,787 for 3 years
Project Title: Using tiny worms to study leukaemia
Cancer is caused by changes to either the structure or activity of certain genes which control how cells grow, divide and survive. These changes cause the cells to multiply in an uncontrolled manner and form a tumour. The Runx and CBFbeta genes are known to be involved in causing certain leukaemias and lymphomas. Dr Woollard is going to study these genes in a very simple animal – a tiny worm called C. elegans. If the activity of these genes is increased in the worms, a certain type of cell starts growing rapidly and out of control – just as it does in cancer. Having established this as a model system to study cancer in humans, Dr Woollard is now investigating how these two genes are activated and how they control they way cells grow and divide.
You can watch a lab tour with Dr Woolard here.
Grant Holder: Dr Peter De Wulf
Institution: European Institute of Oncology, Milan, Italy
Grant Award: £82,044 for 3 years
Project Title: What can stop cancer cells dividing?
Healthy cells grow and divide in a highly organised and tightly controlled stepwise process called the cell cycle. Cancer occurs when the cells become able to multiply in an uncontrolled manner, leading to the development of tumours. Many anti-cancer drugs work by blocking specific cell cycle steps. Dr De Wulf is studying one main regulator of the cell cycle, which is called the kinetochore. He is searching for chemicals that block certain activities of the kinetochore, which should result in stopping cell division. Once these chemicals have been identified, he will check to ensure that they do indeed stop the cell cycle. Dr De Wulf will then test the effect of these chemicals on a variety of human cancer cells to see whether they can potentially be used as an anti-cancer drug in the future.
Grant Holder: Dr Karen Blyth
Institution: University of Glasgow, Scotland
Grant Award: £243,566 for 3 years
Project Title: The role of RUNX in breast cancer
Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. These changes allow the cells to multiply in an uncontrolled manner and form a tumour. The Runx2 gene is known to be involved in causing lymphomas. However, more recently, increased levels of Runx2 activity have been found in advanced breast cancer cells, which have the ability to spread to other parts of the body. It is not known if Runx2 is involved with the early cause of these cancers or the later spread of them. Dr Blyth is therefore using her AICR grant to analyse the role of the Runx2 gene in mice to find out if it is involved in the normal development of breast tissue and what role it plays in the cause and spread of breast cancer.
Grant Holder: Dr Valerie Wilson
Institution: University of Edinburgh, Scotland
Grant Award: £168,512 for 3 years
Project Title: Investigating the role of germ cells in cancer
Cancer can arise from almost any type of cell in the body. There are germ cells in the ovaries and testes, which produce the ova and sperm, which can give rise to germ cell tumours. This type of tumour occurs both in very young children and in people in their 20s and 30s. Germ cells are only normally found in the ova or testes but, for reasons that we do not fully understand, about half of all tumours classed as ‘germ cell tumours’ start in distant tissues, such as the brain or spinal cord. One theory is that these tumours develop not from germ cells, but from a type of ‘starter cell’ in the brain or spinal cord known as a stem cell, which have one or more alterations that allow it to grow as a germ cell tumour. To test this out, Dr Wilson and Dr Scotting are making specific, defined alterations in stem cells of the brain and spinal cord to discover whether germ cell tumours develop. Not only will this tell us a lot about where these tumours start but it will allow them to study the genes involved in causing them. The work may also provide a mouse model for this type of cancer, which could be used to investigate germ cell tumours further and to test out possible new treatments.
Grant Holder: Dr Nick Leslie
Institution: University of Dundee, Scotland
Grant Award: £161,494 for 3 years
Project Title: Analysing the more unknown activities of PTEN in cancer
Proteins carry out most of the activities within cells and they control processes such as how the cells grow and divide. Many proteins are either altered, absent or found at increased levels in cancer cells. This causes the cells to grow and divide in an uncontrolled manner, leading to a tumour. The PTEN protein can prevent a number of different cell types from becoming cancerous and losing PTEN was found to be one of the most frequent changes in all human cancers. But, we do not fully understand how it has this effect. PTEN is known to have several roles in cells, some of which may be responsible for its cancer-protective effect. Dr Leslie is carefully analysing the more unknown activities of PTEN to determine which cell types they happen in, where in the cells they occur and how these activities stop the cell from becoming cancerous. It is also hoped that this work may help us understand why cancers that have lost PTEN usually have cells that have lost their normal shape and organised connections with other cells.
Grant Holder: Dr Vincenzo Bronte
Institution: University of Padova, Italy
Grant Award: £138,000 for 3 years
Project Title: What role does Arginase play in cancer?
Proteins carry out most functions within cells and they control processes such as how the cells grow and divide. Many proteins are either altered, absent or found at increased levels in cancer cells. This causes the cells to grow and divide in an uncontrolled manner, leading to a tumour. Scientists have discovered that a protein called Arginase is found in most tumours. It is either produced by the tumour cells themselves or by a type of white blood cell found in the tumour but the role Arginase plays in the tumour is unclear. To investigate its role in tumours, Dr Bronte is breeding a new strain of mice which either produce too much Arginase or non at all. By studying the way tumours develop in these mice he will be able to determine the role of Arginase in cancer.
Grant Holder: Dr Jonathan Pines
Institution: University of Cambridge, England
Grant Award: £157,233 for 3 years
Project Title: Investigating the ‘traffic lights’ that exist within our cells
Cancer is a disease in which cells divide rapidly and out of control. Healthy cells have very complex mechanisms to control the process of cell division. There are several points at which the process is checked to ensure it is working properly but these can become altered in cancer cells. Since cancer is a disease of uncontrolled cell division, we need to know as much as possible about how this process is monitored in healthy cells so we can understand what goes wrong in cancer. Dr Pines is therefore analysing the role of a protein called Cdc20 which is known to play an important part in the cell division process.
Grant Holder: Dr George Zachos
Institution: University of Crete, Greece
Grant Award: £118,000 for 3 years
Project Title: How do our cells implement control checkpoints as they grow and divide?
Cancer is a disease in which cells grow and divide rapidly and out of control, forming a tumour. Healthy cells have very complex mechanisms to control the process of cell division. There are several points at which the process is checked to ensure it is working properly. Without these checks, or if the checks are carried out incorrectly, the process of cell division does not work properly. In this situation the cells can either multiply out of control or become very damaged and die. Dr Zachos is investigating a protein called Chk1, known to be involved in the checking mechanism. Chk1 was found to be important in the final stages of the division process and therefore plays a greater role in protecting the cell against cancer than originally thought.
Grant Holder: Dr Charlotte Proby
Institution: University of Dundee, Scotland
Grant Award: £165,752 for 3 years
Project Title: Skin cancer and the role of the PTPRD gene
Cancer is caused by changes to, or the loss of, certain genes that control how cells grow, divide and survive. These changes cause the cells to multiply in an uncontrolled manner and form a tumour. There is growing evidence that the PTPRD gene is absent or inactivate in a number of aggressive skin cancers. This suggests that its presence and activity in normal skin cells may prevent or protect them from becoming cancerous. Dr Proby is using her AICR grant to analyse the role of the PTPRD gene in skin cancer to find out what role it plays.
You can watch a lab tour with Dr Proby here.
Grant Holder: Professor Tracy Bryan
Institution: Children’s Medical Research Institute, Sydney, Australia
Grant Award: £131,955 for 3 years
Project Title: Why don’t cancers cells grow old and die?
The information our cells need to make proteins is encoded by our genes. The genes themselves are packaged into long, sausage-shaped structures called chromosomes. At the ends of the chromosomes are repeating sections called telomeres. As a cell divides to make new cells, the telomeres get shorter, eventually preventing the cells from dividing further. This is the basic cause of cellular aging and can be responsible for the death of old cells. Cancer cells however do not age as they have increased levels of a group of proteins which together are called telomerase. Telomerase continuously repairs the telomeres as the cells divide, so they do not get shorter. Professor Bryan is analysing one of the components of telomerase, called dyskerin. She hopes that understanding more about this protein will enable scientists to develop new cancer drugs to block its function in the future.
Grant Holder: Dr Giuliana Pelicci
Institution: European Institute of Oncology, Milan, Italy
Grant Award: £110,412 for 3 years
Project Title: The Rai gene and brain tumours
All normal tissues within our bodies have a tiny population of stem cells. Stem cells are a kind of ‘starter cell’ which can multiply and change into a wide variety of other cells depending on where they are located in the body. For example they can become heart cells, liver cells, brain cells and so on. Dr Giuliana Pellici has discovered that a gene called Rai is active in brain stem cells and also in a type of brain tumour called glioblastoma, where it plays a role in causing these cells to multiply. With her AICR grant Dr Giuliana Pellici is investigating what role the Rai gene plays in these two cell types and the relationship between brain stem cells and this type of brain cancer.
Grant Holder: Dr Mark Cragg
Institution: University of Southampton, England
Grant Award: £101,528 for 3 years
Project Title: How are skin cancer cells resistant to treatment?
Melanoma is the most dangerous type of skin cancer and it is very resistant to most cancer drugs. Many cancer drugs work by damaging cells severely enough to trigger the process of cell suicide. But melanoma cancer cells have increased levels of proteins that block this cell suicide mechanism, allowing the cells to survive treatment. Dr Cragg has discovered that one of these proteins which is involved in blocking cell suicide, called A1, is present at very high levels in melanoma but not other cancer types. He is now studying the role of A1 in melanoma, how it makes the cells resistant to treatment and investigating how it to make these cells more sensitive to treatment.
Grant Holder: Dr Giuesppe (Joe) Tiralongo
Institution: Griffin University, Australia
Grant Award: £184,646 for 3 years
Project Title: Stopping cancer cells from spreading
One of the molecules found on the surface of cells is a type of sugar called sialic acid. Scientists have found that cancer cells which spread around the body tend to have more sialic acid on their surface then non-spreading cancer cells. Scientists therefore think that this molecule plays an important role in allowing the cells to spread. Dr Tiralongo is making a range of chemicals designed to prevent cells from putting sialic acid on their surface and then testing whether this can stop cancer cells spreading. He is aiming to find chemicals which could become useful drugs to treat advanced cancers. This is extremely important as cancer that has spread becomes much more difficult to treat, therefore ways to prevent cancer spreading will lead to more people having successful cancer treatment.
Grant Holder: Professor Louise Jones
Institution: Queen Mary University of London, England
Grant Award: £183,890 for 3 years
Project Title: How does breast cancer develop?
A first step in breast cancer is when a tiny tumour has grown inside one of the milk ducts in the breast, but has not spread anywhere else. Professor Jones is investigating what causes these early growths to develop into more advanced breast tumours. She has discovered a change in one of the normal breast cells that forms the wall of the duct which allows them to start producing a protein called avb6 integrin on their surface. These breast cells usually slow down the growth of tumours, but after this change they appear to lose this ability. Professor Jones is investigating how these normal breast cells prevent the growth of these early tumours and the role the altered cells play in encouraging the development into full-blown tumours. She will also determine whether avb6 integrin can be used to help diagnose the more serious breast tumours and whether blocking its activity might be a way to treat these breast cancers.
Grant Holder: Dr Mark Smyth
Institution: Peter McCallum Cancer Centre, Victoria, Australia
Grant Award: £183,182 for 3 years
Project Title: How does cancer beat our immune system?
It has long been suspected that our immune system has the potential to attack and kill cancer cells but, at least in some cases, it appears not to actually prevent tumours from growing. There is now evidence to suggest a more complex relationship between tumours and the immune system in which the two can be in equilibrium for a long time – i.e. the ability of the tumour to grow is matched by the ability of the immune system to destroy it. According to this theory, in the early stages, a tumour will be kept at a small, harmless size by the immune system, perhaps for months or years, until some change allows the tumour to escape from the equilibrium and start growing. Dr Smyth is investigating the immune system and tumours to find out if this theory is correct.
Grant Holder: Dr Jukka Westermarck
Institution: University of Turku, Finland
Grant Award: £113,880 for 3 years
Project Title: How is the CIP2A gene involved in cancer?
Every cell in our body contains thousands of genes which help produce proteins that are essential for the cells to function. For example how cells grow, divide and die is controlled by our genes. Cancer is caused by changes to either the structure or activity of certain genes that control how the cells grow, divide and die. Dr Westermarck recently discovered a gene called CIP2A which, when activated, can make cells cancerous. With a grant from AICR he is now investigating how CIP2A becomes activated in cells and how it causes them to turn into cancer cells.
Grant Holder: Dr Cristina Munoz-Pinedo
Institution: Institut d’Investigacio Biomedica, Barcelona, Spain
Grant Award: £157,149 for 3 years
Project Title: How have genes changed through evolution?
Cancer is a disease where cells divide rapidly in an uncontrolled manner. Healthy cells have complex mechanisms to control the process of cell division. There are several points at which the process is checked to ensure it is working properly and if damage is detected it can make the cell kill itself. Many of the components of the checking mechanism are known, but not all of them. To attempt to identify the remaining ones, Dr Munoz-Pinedo and Dr. Gabaldón are studying the structure of the genes that code for these components. As animals evolve and diverge into fishes, reptiles and mammals, including humans, the genes for many processes in the cell also change in a similar manner. Dr Munoz-Pinedo and Dr. Gabaldón are using this knowledge to study known components of the checking system and how they have changed through evolution. They will then look for other genes that have changed in the same ways and predict that these may well be the genes for the unidentified components of the cell checking system involved in cancer.
Grant Holder: Dr Letizia Lanzetti
Institution: Institute for Cancer Research and Treatment, Turin, Italy
Grant Award: £59,000 for 2 years
Project Title: Doing the splits – what happens when things go wrong?
The information that our cells need to make proteins is coded in our genes. The genes themselves are packaged into long, sausage-shaped 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 daughter cell. This process is very carefully controlled because giving an incomplete set or too large a set of chromosomes can make a daughter cell malfunction – and in some cases it can lead to the cell becoming cancerous. Dr Lanzetti is studying how the cell controls this process by investigating the role of a protein called Rab5 in controlling how chromosomes are passed to each daughter cell.
Grant Holder: Associate Professor Brendan Jenkins
Institution: Monash University, Australia
Grant Award: £162,950 for 3 years
Project Title: Stomach cancer and bacterial infections
A strong link has been found between some stomach cancer and stomach infections, with the bacteria Helicobacter pylori. Helicobacter pylori causes inflammation but the mechanisms by which this bacterial infection causes prolonged inflammation and cancer are unknown. Dr Jenkins has recently found a change in a gene called gp130 which leads to chronic stomach infections, inflammation and also stomach cancer. Using special strains of mice with altered genes which work together with the gp130 gene, he is now trying to understand exactly how the gene alteration causes inflammation and how this leads to stomach cancer.
Grant Award: Dr Justin Sturge
Institution: Imperial College London, England
Grant Award: £186,298 for 3 years
Project Title: Predicting whether prostate cancer will spread
Advanced prostate cancer often spreads to the skeleton where it causes severe pain and the weakening of bones, leading to fractures and other problems. Dr Sturge has found increased levels of a protein, called Endo180, in the type of cancer that can move from the prostate gland to the bone. This suggests that it could be used for predicting if prostate cancer might spread. Endo180 could also be involved in the spreading process itself, so blocking its activity may help prevent prostate cancer moving to the bone. With his AICR grant Dr Sturge is studying how targeting Endo180 may help prevent the spreading process.
Grant Holder: Dr Joanne Edwards
Institution: University of Glasgow, Scotland
Grant Award: £71,415 for 2 years
Project Title: How to treat prostate cancer which has become resistant to current therapies
Prostate cancer cells normally only grow and divide in the presence of the male sex hormone androgen, which activates a protein called the androgen receptor. The main drug treatments for prostate cancer work by blocking the effect of androgens on the androgen receptor. However, in advanced prostate cancer the cells become able to multiply without androgens, meaning the drugs no longer work. Dr Edwards has found that the androgen receptor in these cancer cells is modified, meaning it can become active without the need for androgen. There are ten different places on the androgen receptor that can be modified so Dr Edwards is creating the tools necessary to study each of these sites. She will then determine what modifications the androgen receptor has in early and advanced prostate cancer, to find out if any of these modifications are specifically associated with advanced prostate cancer. This information will be useful for developing new drugs for advanced prostate cancer.
Grant Holder: Professor Claudio Sette
Institution: University of Rome, Italy
Grant Award: £86,358 for 3 years
Project Title: Prostate cancer and the Sam68 gene – what is the link?
Several different types of cancer have increased levels of the protein Sam68 in their cells. Professor Sette and other researchers have discovered that Sam68 controls the activity of three genes known to be important in prostate cancer. Normally, one gene produces only one type of protein. Sam68 however works by allowing the genes to produce several similar proteins, which may have different roles in allowing cancer to develop. Exactly how Sam68 does this is influenced by other proteins which chemically modify it. Since Sam68 may be involved in prostate cancer, Professor Sette is investigating how its activity is controlled inside these cells and how this influences the behaviour of prostate cancer cells. He will also investigate what happens to the prostate cancer cells when Sam68 is blocked from working.