Projects starting from April 2009 and ending April 2012
Grant Holder: Professor David MacEwan
Institution: University of East Anglia, England
Grant Award: £186,942 for 3 years
Project Title: Why do leukaemia cells refuse to die?
In some types of leukaemia, the cancer cells produce a protein call NFkappaB which is known to block the suicide mechanism normally found in cells. The suicide mechanism is important to allow damaged cells to die and this process is often defective in cancer cells, allowing a tumour to form. New cancer drugs were developed to switch off the activity of NFkappaB, which should allow the suicide mechanism to work and therefore kill the leukaemia cells. However, these drugs were not very effective. Professor MacEwan discovered that switching off NFkappaB caused the cells to produce HO-1, a different protein that also blocked the cell suicide mechanism. With the grant from AICR he will investigate if the HO-1 is the reason that the leukaemia cells are resistant to dying when they are treated with these new drugs. He will then look how HO-1 may be involved in other types of cancer.
Grant Holder: Professor Penny Jeggo
Institution: University of Sussex, England
Grant Award: £169,127 for 3 years
Project Title: Investigating a new mechanism of repairing DNA
Cancer can be caused by damage to the DNA which makes up our genes. All cells have mechanisms to repair this damage, to prevent them becoming cancerous. These repair mechanisms can sometimes become faulty which allows the DNA damage to remain causing the cells to become cancer cells and tumours to develop. Professor Jeggo is investigating how cells repair a type of gene damage called double-strand breaks. She has discovered a new subtype of repair mechanism in cells. With the grant from AICR she is going to investigate how this new gene repair mechanism works.
Grant Holder: Professor Lena Claesson-Welsh,
Institution: Uppsala University, Sweden
Grant Award: £152,745 for 3 years
Project Title: What makes blood vessels leak?
In order for tumours to grow larger than about 1 millimetre across they must have their own blood supply to enable enough oxygen and nutrients to reach the cells. Tumour cells produce a hormone-like molecule called VEGF which encourages new blood vessels to grow towards them. VEGF also causes blood vessels to become more porous and leaky, allowing tumour cells to get into the bloodstream and spread around the body. In addition, the leakiness causes fluid (mainly water) to build up around the tumor and cause swelling and discomfort for the patient. With her AICR grant Professor Claessson-Welsh is going to investigate the effect that VEGF has on cells and how is causes them to make blood vessels more leaky.
Grant Holder: Professor Stephano Biffo,
Institution: University of San Raffaele, Milan, Italy
Grant Award: £124,875 for 3 years
Project Title: How is the molecule eIF6 involved in cancer?
There is growing evidence that some of the molecules involved in making proteins in cells also have an important role in cancer. Professor Biffo is studying one of these molecules, called eIF6. He recently bred a strain of mice that have half the normal levels of eIF6 and discovered that they are much less likely to develop tumours. With a grant from AICR he is further investigating the role of eIF6 in cancer with a long term goal of designing drugs to block eIF6.
Grant Holder: Professor Aart Jochemsen
Institution: Leiden University, Netherlands
Grant Award: £198,223 for 3 years
Project Title: Communication pathways in cancer cells – too much chit chat?
Cells have a complex internal system of genes and proteins which control everything they do. These 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 down the pathway. These pathways are very complex, with many cross-overs and branches. Several of these signalling pathways are involved in controlling how cells grow and divide and can become significantly altered in cancer cells. Dr Jochemsen is investigating how two of the main pathways that change in cancer – the p53 and TGF-beta pathways, influence each other or work together in cancer cells.
Grant Holder: Professor Lorenzo Montanaro
Institution: University of Bologna, Italy
Grant Award: £91,662 for 3 years
Project Title: Why are people with dyskeratosis congenital more prone to cancer?
The inherited blood and skin disorder dyskeratosis congenita is caused by damage to the dyskerin gene. Patients with this condition are more prone to cancer then normal. Studies carried out in mice that lack dyskerin suggest that the normal role of this gene may help prevent the development of various types of tumours, including breast cancer. By studying the activity of dyskerin in human cancer samples from the breast and other tissues, Professor Montanaro is investigating if and how this gene prevents breast cells and possibly other cell types from becoming cancerous.
Grant Holder: Dr Bernard Callus
Institution: La Trobe University, Victoria, Australia
Grant Award: £214,926 for 3 years
Project Title: YAP YAP YAP – why too much can cause tumours to develop
Proteins carry out most functions within cells and they control processes such as how the cells grow and divide. Dr Callus has been studying the YAP protein, which is found at high levels in several types of cancer. He has discovered that YAP can cause tumours to develop in two different ways: not only does it encourage cells to grow and divide more rapidly but it also prevents them from dying. With his grant from AICR he is studying how YAP causes these two effects and identify what other proteins YAP binds to.
Grant Holder: Dr Zoi Lygerou
Institution: University of Patras, Greece
Grant Award: £101,100 for 3 years
Project Title: Cross talk inside cells, what goes wrong in cancer cells?
Cancer can be caused by damage to the DNA which makes up our genes. This damage can be caused by many things such as UV from sunlight or the DNA can become altered or damaged when it is being copied when the cells are growing and dividing. To overcome this problem all cells have two complex systems. One controls how and when the cell can copy their DNA and the other controls how the cell repair the DNA when it gets damaged. These two systems appear to work together because, when the copying system comes across damaged DNA, it stops, activates the repair system, then re-starts copying when it has been repaired. Dr Lygerou is examining how these systems work together in healthy cells and how this co-operation may differ in cancer cells.
Grant Holder: Dr Paolo Dellabona
Institution: University of San Raffaele, Milan, Italy
Grant Award: £204,167 for 3 years
Project Title: Can fat molecules help kill 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. But cancer cells have a wide range of ways to prevent the immune system from recognising or attacking them. Dr Dellabona is examining a recently discovered type of immune system cell that recognises new fat molecules. Since leukaemia cells often have new fats on their surface it may be possible to manipulate these newly discovered immune system cells into attacking and destroying leukaemia cells.
Grant Holder: Professor Chris Moody
Institution: University of Nottingham, England
Grant Award: £92,277 for 3 years
Project Title: Designing cancer drugs based on naturally occurring molecules
Our immune system is able to detect and destroy foreign bodies such as bacteria, viruses and even some cancer cells. The activity of the immune system is influenced by many internal control mechanisms. One of these is the molecule or enzyme called IDO which can decrease the activity of the immune system and is found to be active in a number of cancers. There is now evidence that blocking the activity of IDO results in the immune system attacking and killing cancer cells. Some natural products have been found to block IDO activity but they are not suitable to use as drugs. Professor Moody and his team are therefore using their AICR grant to make a range of potential drugs which are similar to these natural products. They will then test them for their ability to block IDO, test them in cancer cells, and make sure they are effective and safe as potential cancer medicines.
Grant Holder: Dr Pieter Voorhoeve
Institution: Duke-NUS Graduate Medical School, Singapore
Grant Award: £197,055 for 3 years
Project Title: How are microRNAs involved in cancer?
Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. Scientists have recently discovered a new way that cells control the activity of their genes called microRNAs. Several hundred microRNAs have been identified and each one appears to be able to influence the activity of numerous genes in lab experiments. Some of these microRNAs appear to play a role in cancer, by decreasing the activity of cancer-preventing genes but the exact genes the microRNAs act on is not yet clear. Therefore, Dr Voorhoeve is carefully analysing the microRNAs best known to be involved in cancer and try to identify which are the major genes they control in cancer cells.
Project Title: Dr Guiseppe Testa
Institution: European Institute of Oncology, Milan, Italy
Grant Award: £109,281 for 3 years
Project Title: Investigating the role of the histone H3 protein in brain cancer
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. Therefore how cells operate, 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 operate, divide and die. One way that cells control the activity of genes is to add specific chemical groups or ‘tags’ on to the proteins which act as scaffolding for the genetic material to ensure it is held in the correct shape and can work correctly. The addition of tags to these proteins associated with genes can lead to an increase or decrease in gene activity. This often happens incorrectly in cancers and the increase or decrease in gene activity drives the cell to grow and divide in an uncontrolled manner. Dr Testa investigating how tagging of a protein called histone H3 is involved with the development of one of the main types of brain cancer, called a glioma.
Grant Award: Professor Kevin Ryan
Institution: Beatson Institute, Glasgow, Scotland
Grant Award: £176,773 for 3 years
Project Title: Why and how does adenosine cause cell suicide?
Adenosine is a small molecule which plays an important role in many chemical reactions that take place in cells. Scientists have found that in tumours there is an unusually high level of adenosine in between the cells. Professor Ryan has discovered that cells have a mechanism to detect these high levels of adenosine which then somehow activates a mechanism that results in the cell killing itself. With the AICR grant, Professor Ryan is examining the role of adenosine in causing cell death and preventing tumours from developing.
Grant Holder: Dr Paul Shore
Institution: University of Manchester, England
Grant Award: £175,113 for 3 years
Project Title: What is the link between cell movement and cancer?
Cells have many complex internal mechanisms which control all of their activities including how they grow, divide and move. Dr Shore is investigating one component – called filamin A - which is known to be involved in cell movement. He has recently discovered that filamin A has another role where it works with a gene called runx2 which is known to be involved in several types of cancer. With support from AICR Dr Shore is investigating how filamin A and runx2 work together and what connection there is between the control of cell movement and cancer.
Grant Holder: Dr Owen Sansom
Institution: Beatson Institute, Glasgow, Scotland
Grant Award: £223,840 for 3 years
Project Title: How can we stop skin cancers from spreading?
Melanoma is an aggressive form of skin cancer, which tends to spread quite early. Once cancer has spread to other parts of the body it makes successful treatment more difficult. Understanding and preventing cancer spread is therefore one of the biggest challenges for cancer researchers. Previous research discovered that changes to two key genes involved in cancer, called B-RAF and NRAS, play a major role in causing skin melanomas, but other known genes are also known to be involved. Dr Ozanne is using mice with altered B-RAF and NRAS genes to investigate the role of another gene called P-REX1 which is also thought to play a role in the spread of melanoma.
Grant Award: Dr Ingvar Ferby
Institution: University College London, England
Grant Award: £147,562 for 3 years
Project Title: What causes breast cancer and allows it to spread?
Every cell in our body contains thousands of genes which act as blueprints to produce proteins that are essential for the cells to function. Erb B2 is a protein found at high levels in the more aggressive breast tumours. Dr Ferby has discovered that a gene called Mig6 normally limits the amount and activity of Erb B2. Mig6 activity is low in many breast cancers meaning Erb B2 levels are high and it is more active. With a grant from AICR Dr Ferby is investigating whether the complete loss of the Mig6 gene plays a role in causing breast cancer and allowing it to spread. He will also study whether Mig6 has a role in enabling tumours to become resistant to cancer drugs.
Grant Holder: Professor Lars French
Institution: Zurich University Hospital, Switzerland
Grant Award: £122,917 for 3 years
Project Title: What is the link between inflammation and skin cancer?
Long-term inflammation is involved in causing several types of cancers. It has recently been discovered that there is a group of proteins inside the cells, called the inflammosome, are able to encourage inflammation and may therefore contribute to cancer. Professor French is studying the role of the active inflammosome in the development of human skin cancer (melanoma) using human skin samples and laboratory mice models.
Grant Holder: Professor John Hayes
Institution: University of Dundee, Scotland
Grant Award: £198,373 for 3 years
Project Title: How do healthy cells survive exposure to cancer causing chemicals?
Every cell in our body contains thousands of genes that act as blueprints to produce proteins which are essential for the cells to function. Professor John Hayes and Professor Ron Hay are working together to study a gene called Nrf2, which helps protect normal, healthy cells from becoming cancerous. When normal cells are exposed to cancer-causing chemicals Nrf2 becomes activated. Active Nrf2 can switch on genes for defence mechanisms that destroy the cancer-causing chemicals which can get into the cell. Active Nrf2 can also repair or destroy damaged proteins in the cell as a kind of ‘housekeeping’ role. However, in some cancer cells, Nrf2 is corrupted in some way, causing it to be permanently active. In this situation, instead of being helpful the active Nrf2 protein allows cancer cells to efficiently get rid of or destroy anti-cancer drugs, making the cells resistant to treatment. Specifically, one in five lung cancers have active Nrf2 which makes the cancer cells able to survive cancer drug treatment. With the grant from AICR Professor Hayes and Professor Hay are studying a specific mechanism which could make the Nrf2 protein unstable in cancer cells and therefore enable the cancer drugs to take effect.
Grant Holder: Dr Simon Cook
Institution: Babraham Institute, Cambridge, England
Grant Award: £177,728 for 3 years
Project Title: Incorrect communication pathways in cancer cells – how very ERKsome
Every cell contains thousands of genes that act as blueprints to produce proteins which are essential for the cells to function. Many of these genes and proteins are altered in cancer cells and therefore operate quite differently, causing the cells to grow and divide rapidly. The genes and proteins are divided into a series of different pathways, each controlling a group of activities. One of these, called the ERK1/2 pathway, is known to be altered in cancer cells. However, there is a similar pathways known as the ERK5 pathway, which little is known about. Dr Cook is therefore analysing the activity of the ERK5 pathway in normal and cancer cells, to find out what role it plays in cancer.
Grant Holder: Dr Lazlo Tora
Institution: IGBMC, France
Grant Award: £162,300 for 3 years
Project Title: How hybrid genes can cause cancer
Every cell in our body contains thousands of genes that act as blueprints to make the proteins which carry out most of the activities in the cell. Cancer is caused by changes to either the structure or activity of certain genes that control key activities within a cell. In some cancers, one gene can become fused or ‘glued’ to the end of another one, creating a hybrid gene. A type of cancer called extraskeletal myxoid chondrosarcoma (EMC) is caused by the fusion of two genes called TAF15 and TEC. With a grant from AICR Dr Tora is investigating the normal role of TAF15 in healthy cells and the role of the fused TAF15-TEC in causing cancer.
Grant Holder: Dr Tizania Bonaldi
Institution: European Institute of Oncology, Milan, Italy
Grant Award: £109,281 for 3 years
Project Title: What causes Non-Hodgkin’s lymphoma?
Every cell in our body contains thousands of genes that act as blueprints to produce the proteins essential for the cells to function. Cancer is caused by changes to either the structure or activity of certain genes that control how cells grow, divide and survive. Scientists have recently discovered a new way that cells can alter the activity of their genes using microRNAs. microRNAs seem to play wide-spread roles in how cells grow and divide and if microRNAs are working incorrectly this can often lead to the formation of tumours. There is evidence that a microRNA called miR(17-92) plays a role in causing a type of blood cancer known as lymphoma but how it does this is unclear. Dr Bonaldi is going to determine exactly what role miR(17-92) plays in the cause and progression of lymphoma by identifying which genes it acts on. She is using a new technique to monitor the level of thousands of proteins in the cell, which is an indicator of the activity of the genes. She will increase or decrease the levels of miRNA(17-92) in blood cells and then measure the changes in the protein levels in order to identify the effects of the miR(17-92).
Grant Holder: Dr Franklyn Howe
Institution: St Georges Hospital London, England
Grant Award: £213,835 for 3 years
Project Title: Developing MRI scanning techniques for imaging cancer
Almost as soon as a tumour starts growing it needs to get a new blood supply to ensure that the cancer cells receive enough oxygen and nutrients. Over the last decade or so, several new cancer drugs have been developed which block the growth of a new blood supply to tumours. However, they do not work for all cancers, so it is important to find out if they are working or not quickly after the drugs have been given, so that an alternative treatment can be used if necessary. MRI scanning can detect how well the blood vessels are working and areas of low oxygen in the body tissues. Dr Howe is developing this technique further as a way to find out if these treatments are being effective at blocking the development of a new blood supply to brain tumours.
Grant Holder: Professor Margaret Frame
Institution: University of Edinburgh, Scotland
Grant Award: £222,754 for 3 years
Project Title: What is the role of Cofilin in skin cancer?
Every cell contains thousands of proteins which are essential for the cells to function. Many of these proteins are altered in cancer cells and therefore operate quite differently. This can cause the cells to grow and divide more rapidly, and/or be able to move when they normally should not. Once cells can move they can invade surrounding tissue and travel to distant sites in the body in the blood stream or lymphatic system. A protein called cofilin is known to be involved in the normal control of cells in the skin, but we do not understand the role that it plays in skin cancer. Professor Frame is examining its role by breeding a new strain of mice which lacks all forms of the cofilin protein family. She will then study whether, and if so how, skin cancers start and develops in the absence of cofilin. This will allow her team to understand more about skin cancer biology and the role of cofilin and could potentially lead to new ways of treating this cancer.