Projects starting April 2010 and ending April 2013
Grant Holder: Professor Ofer Mandelboim
Institution: The Hebrew University of Jerusalem, Israel
Grant Award: £63,111 for 3 years
Project Title: What controls how our immune system fights cancer cells?
Our immune system is made up of cells that have the ability to recognise foreign bodies – such as 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. With his grant from AICR Professor Mandelboim is identifying molecules called microRNAs which can affect how the immune system fights cancer. Once the microRNAs are found he will then go on to investgate how the microRNAs are able to do this.
Grant Holder: Dr Duncan Baird
Institution: Cardiff University, Wales
Grant Award: £176,473 for 3 years
Project Title: How do bowel and prostate cancer progress?
The information our cells need to survive 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. When 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. However, cancer cells often have dysfunctional telomeres which can be unstable. This can lead to the loss of anti-cancer activities within the cells meaning they do not get old and die. In some cancers, one telomere can become glued or ‘fused’ to the end of another one. Dr Baird has developed a sophisticated technique to study the mechanism of telomere instability and fusion. He is using this technique to improve our understanding of how both bowel and prostate cancer progress.
You can watch a lab tour with Dr Baird here.
Grant Holder: Dr Bo Porse
Institution: Biotech Research and Innovation Centre Copenhagen University (BRIC-KU), Denmark
Grant Award: £241,508 for 3 years
Project Title: Understanding acute myeloid leukaemia
Cancer is caused by changes to either the structure or activity of key genes that control how cells mature, grow, divide and survive. Scientists have recently discovered a new way that cells control the activity of their genes involving molecules called microRNAs. Several hundred microRNAs have been identified, in lab experiments, and each one appears able to influence the activity of numerous genes. Some of these microRNAs play a role in cancer but the exact genes the microRNAs act on is unclear in most instances. With a grant from AICR Dr Porse is using a mouse model for acute myeloid leukaemia (AML) which mimics the symptoms of the human disease due to an alteration in the gene called C/EBPalpha. He will be using this model to identify microRNAs that either encourage or prevent the development of leukaemia. Dr Porse hopes that his results will uncover genes that could potentially be important in preventing the disease in the future.
Grant Holder: Professor Michael Hay
Institution: The University of Auckland, New Zealand
Grant Award: £137,596 for 3 years
Project Title: Designing drugs for kidney cancer
Cancer is caused by changes to either the structure or activity of key genes that regulate how the cells operate, divide and die. These changes cause the cells to multiply in a rapid and uncontrolled manner, forming a tumour. In many kidney cancers, the von Hippel landau (VHL) gene is switched off and this is involved in causing these tumours. Associate Professor Hay and colleagues have identified two ways to make these kidney cancer cells die, either by causing them to 'eat' themselves or by preventing them from getting enough 'food' to survive. However the exact mechanism by which these two processes work to ensure the cancer cells die is not yet clear. With his AICR grant he is using sophisticated computer programmes to design improved chemicals with better shapes that “fit” into the targets more effectively. This cutting edge technique allows potential new drugs to be assessed much more quickly than if they were hand made in a lab. The chemicals with the best fit will be made and tested for their ability to kill kidney cancer cells. He will also try to determine the actual targets in cells which these potential anti-cancer drugs act on. He hopes that in the future his results may help develop potential new treatments for kidney cancer and other cancers with altered VHL genes.
Grant Holder: Dr Sonia Laín
Institution: Karolinska Institute, Stockholm, Sweden
Grant Award: £148,572 for 2 years
Project Title: Are Tenovins safe and effective as anti-cancer treatments?
Every cell in our body contains thousands of genes that act as blueprints to produce proteins. Cancer is caused by changes to either the structure or activity of key genes that control how the cells operate, divide and die. This causes altered proteins to be made or some proteins are absent entirely. Normally a protein called p53, helps prevent cells from becoming cancerous but it has been found to be inactive or absent in half of all human cancers. Many potential new drugs are therefore being designed to reactivate p53 in cells where it has been inactivated. Dr Laín is working on one of these types of drug called Tenovins. However, although Tenovins are successful in lab experiments, it not yet known if Tenovins are safe and effective as potential anti-cancer treatments, which is what Dr Laín aims to find out with her current AICR grant.
Grant Holder: Dr Salvador Benitah
Institution: Fundació Privada Centre de Regulació Genòmica, Barcelona, Spain
Grant Award: £59,612 for 3 years
Project Title: Understanding skin cancer stem cells
All tissues within our bodies have a specialized population of stem cells. Stem cells are a kind of 'starter cell' which can multiply and change into a wide variety of cells depending on where they are located in the body such as the skin, liver, brain and so on. Dr Benitah is using his AICR grant to study skin stem cells. The way these cells grow and divide is influenced by their genes and the environment surrounding the cell. Dr Benitah believes that skin stem cells may contain 'molecular clock machinery' which times and synchronizes their roles, but when altered or perturbed, can predetermine their proneness to become cancerous. He is trying to understand this process further by studying cells in different stages of skin and mouth cancer.
You can watch a lab tour with Dr Benitah here.
Grant Holder: Professor Wayne Phillips
Institution: Peter MacCallum Cancer Centre, Melborne, Australia
Grant Award: £144,635 for 3 years
Project Title: How is the PI3K/Akt pathway involved in breast cancer?
Cells have a complex internal system of genes and proteins which control everything they do. The genes and proteins are organised into pathways in which the first activates the second and that activates the third, and so on, passing the activation signal onwards. These pathways are very complex, with many cross-overs and branches and several are involved in controlling how cells grow and divide. One of these, called the PI3K/Akt pathway, is known to be unregulated in cancer cells due to alterations in the PI3K genes. With a grant from AICR Professor Phillips is using a mouse model to study how a common alteration in a PI3K gene is involved in breast cancer development.
Grant Holder: Dr Ugo Cavallaro
Institution: IFOM the FIRC Institute of Molecular Oncology Foundation, Milan, Italy
Grant Award: £139,037 for 3 years
Project Title: How does the microenvironment help pancreatic cancer spread?
The cancer microenvironment consists of the area in between the cancer cells within the tumour mass. Among other components, the microenvironment contains cells of the immune system which attack the tumour trying to destroy it. However, there are some types of cancer, such as pancreatic cancer, that "convince" immune cells to work for its own benefit, thus favouring tumour spreading. One of the things that makes cancer so dangerous is its ability to grow and spread away from the original tumour and into surrounding tissues and organs. Another component of the pancreatic cancer microenvironment the helps tumour spread is the net of blood vessels that provide cancer cells with oxygen and "food". Dr Cavallaro is using his AICR grant to investigate how all these factors in the microenvironment help pancreatic cancer cells to acquire the ability to spread.
Grant Holder: Dr Stefano Casola
Institution: IFOM the FIRC Institute of Molecular Oncology Foundation, Milan, Italy
Grant Award: £193,395 for 3 years
Project Title: What causes Non-Hodgkin’s lymphoma?
Dr Casola is using his AICR grant to study lymphomas, and in particular Non-Hodgkin's lymphomas. Lymphomas are cancers involving cells of the immune system, in particular of lymphocytes which play a crucial role in our daily battle against infectious agents such bacteria and viruses. Lymphomas occur when key genes in the lymphocytes become damaged or altered, allowing them to grow and divide in an uncontrolled manner and unable to fight infection. These damaged lymphocytes accumulate in lymph nodes (glands throughout the body - particularly in the armpits, neck and groins) and grow into tumours. Currently only a small number of alterations in specific genes are known to cause Non-Hodgkins Lymphoma. Dr Casola hopes to identify many more of these gene alterations in order to improve our understanding of the disease and possibly find new ways to predict or potentially treat it.
Grant Holder: Professor Michael Threadgill
Institution: University of Bath, England
Grant Award: £262,801 for 3 years
Project Title: Finding new anti-cancer drugs
Professor Threadgill is using his AICR grant to make potential new anti-cancer drugs that will act on a protein called Tankyrase-1 and stop it from working. He hopes that the drugs will kill cancer cells through two different mechanisms of action to increase their chance of success. Designing, making and testing drugs is an extremely long process but Professor Threadgill is using several ways in which he can reduce this time. Firstly, he already has a catalogue of potential drugs which act on a similar protein called PARP-1 and stop it from working. He is therefore testing these drugs to see if they also work on Tankyrase-1. Secondly, the specific shape of the Tankyrase-1 protein is already known and Professor Threadgill is using computer software to make and test potential new drugs in virtual reality, reducing costs and cutting out time-consuming laboratory work on those chemicals which turn out to be ineffective. Potential drugs which appear successful in killing cancer cells on screen will be made in the lab and tested further. Professor Threadgill hopes the completion of this project will provide one or more potential anti-cancer drugs which work by a new mechanism of action. These would then need to be developed further and tested for their safety and effectiveness before being tested in patients.
Grant Holder: Dr Cathy Tournier
Institution: University of Manchester, England
Grant Award: £207,720 for 3 years
Project Title: Altered communication pathways in cancer cells
Cells in every organism have the ability to respond to signals from their environment. External stimuli trigger a cascade of events inside the cell which leads to a change in the cells behaviour. These internal systems are known as cell signalling pathways and one of them, the ERK5 pathway, is the focus of Dr Tournier’s group. In particular, they are researching how alterations in ERK5 signalling causes cells to grow and divide in an uncontrolled manner, forming a tumour. Their research uses a novel, genetically modified mouse model which has had ERK5 removed from the skin cells. In human cancers high levels of ERK5 are linked to shorter disease-free intervals, an increased risk of cancer spread (metastasis) and resistance to chemotherapy. Consequently, one potential important outcome of this study funded by AICR is the validation of ERK5 as a drug target which will provide scientists with a new and exciting opportunity to intervene at specific stages of tumour formation in humans. A number of similar drugs known as ‘protein kinase inhibitors’ are already successfully used for cancer treatment.
Grant Holder: Dr Lesley Stark
Institution: University of Edinburgh, Scotland
Grant Award: £158,439 for 3 years
Project Title: How do painkillers like aspirin prevent bowel cancer?
There is now substantial evidence that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDS) are able to help prevent bowel cancer but the mechanisms behind this are not yet fully understood. Dr Stark is using her AICR grant to determine, at a molecular level, how these drugs work to prevent bowel cancer. Her findings could have a major impact on cancer prevention, for example in the future it may be possible to design new agents to prevent common cancers.
Grant Holder: Dr Luciano Di Croce
Institution: Fundació Centre de Regulació Genòmica, Barcelona, Spain
Grant Award: £121,752 for 3 years
Project Title: How does ‘tagging’ of genes contribute to cancer?
Every cell in our body contains thousands of genes. Cancer is caused by changes to either the structure or activity of key genes that regulate how the cells operate, divide and die. One way that cells control the activity of genes is to add specific chemical groups or 'tags' on to them or on to the proteins which act as scaffolding to ensure they are held in the right shape and can work correctly. The addition of tags can lead to an increase or decrease in gene activity. This often happens incorrectly in cancer and the change in gene activity drives the cell to grow and divide in an uncontrolled manner, forming a tumour. Dr Di Croce is investigating what effect the addition of a tag called ubiquitin, onto a specific site on the protein H2A has, and its role in gene regulation. The levels of ubiquitin on H2A are altered in several types of cancer and so Dr Di Croce aims to find out what interacts with ubiquitinated H2A in both healthy and cancer cells.
Grant Holder: Dr Kaisa Lehti
Institution: University of Helsinki, Finland (female)
Grant Award: £135,352 for 2 years
Project Title: How is FGFR4 involved in allowing cancer to spread?
One of the things that makes cancer so dangerous is its ability to spread away from the original tumour and into surrounding tissue and organs. Some treatments are being developed to stop this, but cancers often find new ways to spread, making the treatments ineffective. Dr Lehti is therefore exploring alternative ways to stop cancers spreading. She believes a protein called FGFR4 may be involved because it is found at high levels in aggressive cancers which spread rapidly. With a grant from AICR Dr Lehti is now investigating if blocking the activity of FGFR4 can stop cancers spreading and if so, what mechanism does it use?
Grant Holder: Dr David Neuhaus
Institution: MRC Laboratory of Molecular Biology, Cambridge, England
Grant Award: £105,245 for 2 years
Project Title: Investigating how PARP-1 proteins repair damaged DNA
DNA, or more specifically genes, control how cells grow, divide and survive. Cancer is caused by alterations or damage to the DNA. If this damage is very severe the cells may die, but otherwise cells have mechanisms to repair this DNA damage. However, these repair mechanisms can sometimes become faulty, allowing the damage to remain and causing the cells to become cancerous. One protein that is involved in detecting and repairing damaged DNA is PARP-1 but it is still relatively unknown how PARP-1 recognises damaged DNA and how it becomes activated to allow the DNA to be repaired. With a grant from AICR Dr Neuhaus is using a technique called NMR spectroscopy to visualise how PARP-1 finds and attaches itself to damaged DNA. He will then try to determine the mechanism by which PARP-1 is activated. This information is particularly important as many anti-cancer drugs are being developed to stop PARP-1 from working and thereby kill cancer cells so any new information about PARP-1 will be very beneficial.
Project Title: Professor Henning Walczak
Institution: Imperial College London, England
Grant Award: £188,679 for 3 years
Project Title: What is the link between cancer cells failing to die and their ability to spread around the body?
Cancer occurs when cells become able to grow and divide in an uncontrolled manner, forming a tumour. One of the things that makes cancer so dangerous is its ability to spread away from the original tumour and into surrounding tissue and organs, making the disease harder to treat. Cancer cells also fail to die and one way they do this is by stopping a cell suicide mechanism known as apoptosis. Professor Walczak is using his AICR grant to investigate why the cancer cells fail to die and how this may also be linked with their ability to spread around the body.
Grant Holder: Dr Grant Dewson
Institution: Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Grant Award: £170,228 for 3 years
Project Title: Investigating cell suicide mechanisms
Cancer occurs when cells become able to grow and divide in an uncontrolled manner, forming a tumour. Unlike normal cells, cancer cells also fail to die. One way they do this is by stopping a cell suicide mechanism known as apoptosis. Two key proteins which encourage apoptosis are Bak and Bax but scientists are still uncertain as to how they are regulated and activated. Dr Dewson is using a grant from AICR to study how Bak and Bax become activated and what are the first steps involved in cell death. He hopes that in the future his findings could allow Bak and Bax to be activated artificially to cause cell death as a potential new way to kill cancer cells which are not affected by current chemotherapeutic agents.
Grant Holder: Dr Francesco Colucci
Institution: Babraham Institute, Cambridge, England
Grant Award: £173, 711 for 2 years
Project Title: How does the immune system detect skin cancer cells?
Our immune system is made up of cells that have the ability to recognise foreign molecules – such as those found 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. Healthy cells are not usually destroyed by the immune system, therefore Dr Colucci is using his AICR funding to understand a very important step in this anti-cancer mechanism: at what point does a cell get altered enough to become recognised by the immune system as a cancer cell? Dr Colucci is working on skin cancer cells but if he is able to pinpoint the changes that occur to allow recognition of this cancer by the immune system, the same may also be true for many other types of cancer.
Grant Holder: Dr Bruno Amati
Institution: Instituto Europeo di Oncologia, Milan, Italy
Grant Award: £248,100 for 3 years
Project Title: Understanding cancer-causing and anti-cancer responses in cells
Every cell in our body contains thousands of genes that control the processes occurring within cells. Some genes can be cancer-causing or oncogenic and are therefore called oncogenes, for example Myc. These oncogenes are involved in driving the cells to grow and divide more rapidly, forming a tumour. However, oncogenes also activate cancer suppressing responses, which can include triggering the cell to kill itself or making it enter a ‘coma-like’ state called ‘cellular senescence’. Blocking anti-cancer responses like these are one way that cancer becomes able to develop, while re-activating these responses in cancer cells has therapeutic potential. Dr Amati is using his AICR grant to study a protein called Cdk2 which seems to block anti-cancer responses after the cells have started to become cancerous due to the Myc oncogene. Therefore stopping Cdk2 could potentially be a new way to target cancer cells in the future.
Grant Holder: Dr John Diffley
Institution: Cancer Research UK London Research Institute, England
Grant Award: £185,862 for 3 years
Project Title: Investigating the internal ‘checkpoints’ inside our cells
Cancer is a disease in which cells divide rapidly and out of control, forming a tumour. Healthy cells have complex mechanisms to control this process of cell growth and division for example there are several ‘checkpoints’ at which the DNA is monitored to ensure the cells remain healthy. These checkpoints often become altered or turned off in cancer cells and without them, the process of cell division does not work correctly, and the cells can multiply out of control. Dr Diffley is studying a protein called Exo1 which may have a role in allowing cancer cells to become resistant to anti-cancer drugs.
Grant Holder: Dr Antonio García de Herreros
Institution: Fundació IMIM, Barcelona, Spain
Grant Award: £100,254 for 3 years
Project Title: How do cancer cells move?
Cancer occurs when cells grow and divide in an uncontrolled manner, forming a tumour. Healthy cells are usually fairly fixed in their position which they do by forming contacts with neighbouring cells. However cancer cells lose their connections with other cells and become able to move into surrounding tissue and around the body. This is one of the main things that makes cancer so dangerous, its ability to spread away from the original tumour. This makes the disease harder to treat and can cause vital organs to fail. The molecular mechanisms that allow cancer cells to become mobile is still relatively unknown and is the focus of an AICR funded project awarded to Dr García de Herreros.
Grant Holder: Dr Johanne Murray
Institution: University of Sussex, England
Grant Award: £94,900 for 3 years
Project Title: How does cancer begin?
All of the information that our cells need is encoded by 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 of the new cells. This process is very carefully controlled because giving an altered, incomplete or too large a set of chromosomes can make a cell malfunction – and it can become cancerous. In some cancers, chromosomes can break and one can become fused or ‘glued’ to the end of another one, a process known as chromosome rearrangements. Dr Murray is studying a type of chromosomal rearrangement involving palindromes – where the chromosome sequence is the same when read both ways. Her findings will be important to further our understanding of how some cancers begin.
Grant Holder: Dr John Rouse
Institution: University of Dundee, Scotland
Grant Award: £167,027 for 3 years
Project Title: Detecting and repairing damaged DNA to prevent cancer
DNA can be damaged by external factors in the environment, such as UV in sunlight, and by internal processes arising inside the cell. Since DNA encodes the instructions for the proper working of cells, damage to DNA can cause the cell to lose control and this leads to cancer. In fact, most cancers are caused by DNA damage. Dr Rouse will use his AICR grant to study a "molecular toolkit called the SLX complex of proteins’ that is required for the repair of damaged DNA and were recently identified in his lab.
Grant Holder: Dr Nicolas Thoma
Institution: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Grant Award: £197,787 for 3 years
Project Title: Determining the shape of cancer causing proteins
Every cell in our body contains thousands of genes that act as blueprints to produce proteins, which carry out most of the processes occurring within cells. Cancer is caused by changes to either the structure or activity of key genes that regulate how the cells operate, divide and die. Some of these key genes can be cancer-causing or oncogenic and are therefore called oncogenes. These oncogenes and the oncoproteins they encode for are involved in driving the cells to grow and divide more rapidly, forming a tumour. Dr Thoma is studying a group of oncoproteins called the polycomb repressive complex 2 (PRC2) which is found at high levels in aggressive prostate and breast cancer and correlates with cancer spread and a poor prognosis for the patient. Lowering the levels of PRC2 is therefore an attractive mechanism for new cancer therapies. In order to design potential drugs to block PRC2 scientists first need to know its shape. As PRC2 is a very large and complicated collection of different proteins it is impossible to determine the shape of the entire assembly, therefore Dr Thoma intends to use his AICR grant to determine the shape of the active centre of PRC2 using a technique called crystallography. This will lay the foundations for future research into designing and testing new anti-cancer therapies.