Projects starting from January 2011 until January 2014
Grant Holder: Associate Professor Brendan Jenkins
Institute: Monash University, Australia
Grant Award: £196,447 for 3 years
Project Title: Investigating stomach cancer
Despite the progress being made in cancer research, stomach cancer is still one of the cancers with a low survival rate. In 2008 almost 990,000 people around the world were diagnosed with stomach cancer and 738,000 people died from the disease. Stomach cancer is strongly linked to prolonged inflammation of the lining of the stomach and changes in the bacteria found there. But why these changes happen and how the inflammation occurs is unknown. Using stomach cells grown in the lab and samples taken from stomach cancer patients Dr Jenkins is investigating the mechanisms behind this inflammation and stomach cancer. In particular he is looking at the role of a gene called STAT3 which is over-active in stomach cancer and how that affects molecules called miRNAs, which have been found to play a role in cancer.
Grant Holder: Dr Davide Robbiani
Institution: Rockefeller University, USA
Grant Award: £158,105 for 3 years
Project Title: What causes lymphoma?
Every cell in our body contains thousands of genes that act as blueprints to make the proteins which carry out activities in the cell. Cancer is caused by changes to either the structure or function of certain genes that control key activities including how the cell grows, divides and dies. In some cancers, particularly lymphomas and leukaemias, one gene can become fused or ‘glued’ to the end of another one, creating a hybrid gene. Dr Robbiani has previously shown that a molecule called AID is responsible for producing breaks in many genes. These breaks predispose genes to fusion together and initiate cancer. Using his AICR grant Dr Robbiani is investigating how AID is causing lymphomas. Lymphomas are cancers of lymphocytes (white blood cells of the immune system which defend us against viruses, bacteria and parasites). Using animal models he will also look at how an immune response can lead to lymphomas, in particular chronic infection with the malaria parasite which can cause Burkitt’s lymphoma in humans.
Grant Holder: Dr Simona Polo
Institution: IFOM The FIRC Institute of Molecular Oncology Foundation, Italy
Grant Award: £131,118 for 3 years
Project Title: Investigating cancer spread
Dr Simona Polo is investigating how cancer cells can move around the body in a process called metastasis. Cells are normally limited in their movement, and this is tightly regulated but cancer cells can lose this control and begin to move into surrounding tissue. The cancer cells can then travel in the blood stream to other sites around the body to form secondary tumours. The focus of this AICR funded project is a protein called myosin VI, which has been implicated in cancer spread and has two unique places where a molecule called ubiquitin can attach. Ubiquitin is a special molecule which, when attached to another protein, can signal to the cell that it is to be destroyed. Dr Polo therefore is investigating the involvement of ubiquitin signalling in the control system of myosin VI.
Grant Holder: Dr George Zachos
Institution: University of Crete, Greece
Grant Award: £128,500 for 3 years
Project Title: How do cells grow and divide correctly?
Healthy cells grow and divide in a highly organised and tightly controlled manner in a process called the cell cycle. Cancer occurs when the cells become able to multiply in an uncontrolled manner, leading to the development of tumours. Dr Zachos is using his AICR grant to study a protein called Chk1 which he has previously shown to have anti-tumour properties and helps ensure cells divide correctly. He now wants to investigate this important role further and try to understand the mechanism behind it.
Grant Holder: Professor Stephen M Jane
Institution: Melbourne Health, Australia
Grant Award: £198,139 for 3 years
Project Title: Investigating skin cancer
Skin cancers are the commonest of all human cancers. Their incidence is increasing dramatically, with the depletion of the ozone layer leading to overexposure to UV radiation from sunlight which damages the DNA inside skin cells. This damage can allow the cells to grow and divide in an uncontrolled manner, forming a tumour. Professor Jane has previously identified a molecule called Grainy head-like 3 which appears to have properties that can protect skin cells from becoming cancerous. With his AICR grant Professor Jane is now hoping to better understand the mechanisms behind Grainy head-like 3's ability to protect against cancer. He will do this by investigating what happens when it is removed from cells or when drugs are used to disrupt its usual effects. Professor Jane is carrying out the research in Australia which, along with New Zealand, has the highest rates of skin cancer in the world.
Grant Holder: Dr Laura Cerchia
Institution: CNR, Italy
Grant Award: £107,500 for 3 years
Project Title: Designing new ways to deliver drugs to brain and lung cancer tumours
One of the difficulties when designing new cancer therapies is getting them to go to the site of the tumour and inside the cancer cells where they can do their work, without affecting nearby healthy cells. One new method of delivering cancer drugs involves using aptamers - small pieces of DNA or RNA that are highly selective and can stick to the surface of cancer cells without any unwanted toxic side effects. Dr Cerchia has made two types of aptamers, one which selectively goes to lung cancer cells and the other to brain tumour cells. She is now using her AICR grant to validate these aptamers and is testing attaching new anti-cancer drugs to these aptamers to see if they do indeed go to the correct site and once there, if the drug will enter the cell. She hopes her findings will reveal a potential new tool for innovative and selective cancer therapies that can be further developed and one day, hopefully used for cancer patients.
Grant Holder: Dr Cynthia K. Miranti
Institution: Van Andel Research Institute, USA
Grant Award: £179,532 for 3 years
Project TItle: Studying the origins of prostate cancer
The prostate gland is composed of two layers, the lower layer is made of basal cells and the upper layer of secretory cells. Dr Cindy Miranti recently discovered that a hormone-like molecule called KGF could make the basal cells develop into secretory cells. This suggests that, in the healthy prostate gland, as the secretory cells wear out and die, they are replaced by cells from the basal layer undergoing this change. This discovery also suggests a possible new explanation for how prostate cancer arises. Prostate cancer cells have some of the characteristics of basal cells and some of the characteristics of secretory cells. So, if the process of changing from one cell type to another were to go wrong, it could create an early form of a prostate cancer cell. With a new research grant from AICR, Dr Miranti will be investigating the mechanism that controls this basal to secretory change and the possibility that prostate cancer arises because of some form of mistaken change happening to these cells. This sort of ‘mistaken change’ has been found to be the cause of at least one type of leukaemia, which can now be treated with drugs to force the cells to complete the proper change. If Dr Miranti’s theory proves to be correct, it may be possible to design new drugs for prostate cancer, based on the same principle.
Read about more about Cynthia's grant here.
Grant Holder: Dr Raul Méndez
Institution: Centre for Genomic Regulation (CRG), Spain
Grant Award: £112,393 for 3 years
Project Title: How does the wrong ‘tagging’ of genes lead to pancreatic cancer?
Every cell in our body contains thousands of genes. Genes contain the information used to make proteins, in a process known as gene expression. Cancer is caused by changes to either the expression 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 'tags' on to the intermediary molecules that carry their information, to ensure they are localized in the right place and expressed at the right time. Cancer cells often misread these "tags" and the expression of genes at the wrong time drives the cell to grow and divide in an uncontrolled manner, forming a tumour. Dr Mendez is using his AICR grant to investigate how incorrect lecture of these "tags" can lead to the development of pancreatic cancer and its ability to spread around the body.
Grant Holder: Dr Joy Burchell
Institution: Kings College London, England
Grant Award: £220,418 for 3 years
Project Title: Why do some women with breast cancer respond better than others?
Many breast cancers require the female sex hormone oestrogen in order to grow and are known as ‘hormone sensitive’ or ‘hormone receptor positive’. These breast cancers can be treated with drugs that block the effects of oestrogen, such as tamoxifen. Dr Burchell is investigating the function of a protein called JARID1B which plays a role in hormone receptor positive breast cancer cells. Low levels of JARID1B are linked to lower survival levels for patients and so Dr Burchell is also studying whether the JARID1B works together with tamoxifen and if so, how.
Grant Holder: Dr Maria Rescigno
Institution: Istituto Europeo di Oncologia, Italy
Grant Award: £141,972 for 3 years
Project Title: Can our immune system kill skin cancer cells?
Our body has a natural defence mechanism – the immune system – that can attack and kill foreign bodies, such as viruses, bacteria and, in some cases, cancer cells. However, for reasons we do not understand the immune system fails to attack tumours in most cases. Dr Rescigno is following on from her previous AICR grant and investigating the immune system molecules inside and outside skin cells which promote or protect against skin cancer.
Grant Holder: Professor Laura Machesky
Institution: Beatson Institute for Cancer Research, Scotland
Grant Award: £183,266 for 3 years
Project Title: Investigating cancer spread and the role of the N-WASP protein
One of the main factors that makes 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, known as secondary tumours or metastases. This ability to move and spread is controlled by key genes and proteins, but we do not yet know how they allow this spread and many more may be found. Professor Machesky is using her AICR grant to study a protein called N-WASP which has a key role in skin cancer cell invasion and spread.
Grant Holder: Dr Jeanette Leusen
Institution: University Medical Center Utrecht, the Netherlands
Grant Award: £225,316 for 3 years
Project Title: Improving antibody treatments for solid tumours
Our body has a natural defence mechanism - the immune system - that can attack and kill foreign bodies, such as viruses, bacteria and, in some cases, cancer cells. However, for reasons we do not understand the immune system fails to attack tumours in most cases. In recent years several cancer treatments have been developed which use antibodies, part of the immune system, to treat specific cancers. For example, certain lymphomas and leukaemias can be treated with the antibody therapy Rituximab. Dr Leusen is using her AICR grant to develop a new type of antibody treatment. She will then test the treatment using a model system for lung and colon cancer.
Grant Holder: Dr Ronit Satchi-Fainaro
Institution: Tel Aviv University, Israel
Grant Award: £200,000 for 3 years
Project Title: Stopping the blood supply to tumours using nanocarriers
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. One of the key proteins involved in this process is Akt which is very active in cancer cells. Dr Satchi-Fainaro is therefore using her AICR grant to find ways to turn off Akt using a new mechanism called nanocarriers. One of the difficulties for scientists designing new cancer therapies is getting them to go to the site of the tumour and inside the cancer cells where they can do their work, without affecting nearby healthy cells. Dr Satchi-Fainaro will fill the nanocarriers with a molecule called siRNA which is designed to turn off Akt. Using model systems to carry out her investigations she hopes the nanoparticles will go straight to the cancer cells and turn off Akt without affecting other proteins in nearby healthy cells. Starving the tumour by cutting off the blood supply will stop the tumour from growing and spreading and turn it into a more manageable and treatable disease.
Grant Holder: Professor Jeffrey E. Segall
Institution: Albert Einstein College of Medicine, USA
Grant Award: £167,902 for 3 years
Project TItle: Investigating brain cancer spread
One of the main factors that makes 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. Brain cancers are particularly difficult to treat because they are located in the control centre for the entire body. There is also the chance of damaging nearby healthy brain tissue when trying to remove the cancer by surgery or by treating with radiation or chemotherapy to kill the cancer cells. Professor Segall is using his AICR grant to investigate how one type of brain cancer cell, known as glioblastoma cells, can invade the surrounding tissue. So far the team have identified two proteins called CSF1 and EGF which play a role in allowing this spread and are developing a way to watch this microscopic event. They are now building on these findings by investigating how CSF1 and EGF encourage brain cancers to spread, including testing drugs that block the effects of CSF1. They will also continue developing their unique microscope technique to watch the cancer spread in model systems.
Grant Holder: Dr Dirk Pegtel
Institution: VU University Medical Center, the Netherlands
Grant Award: £198,500 for 3 years
Project Title: What goes wrong when a virus infection causes cancer?
Some cancers are caused by viruses, but only after something goes seriously wrong. For example, the Epstein-Barr virus (EBV) infects 90% of the world population apparently causing little harm. In fact EBV is generally known as the herpes virus that causes kissing disease in adolescents. However EBV is associated with cancers such as lymphomas, carcinomas and childhood cancers. Infection with a virus triggers the cell's alarm system to try to fight the infection and defend the body from the virus. However some cancer-associated viruses, including EBV have evolved clever mechanisms to counteract these defences to establish a persistent infection. In some circumstances the disarmament of these defences increases the chance that infection leads to cancer. Dr Pegtel is using his AICR grant to investigate how EBV disarms the host's antiviral defence.
Grant Holder: Dr Peter Siegel
Institution: McGill University, Canada
Grant Award: £187,710 for 3 years
Project Title: Breast cancer spread
The earlier cancer is detected, the greater chance of successful treatment. One of the main factors that makes tumours so dangerous is their ability to invade into surrounding tissues and organs and spread throughout the body, known as metastasis. 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, known as secondary tumours. Dr Siegel is using his AICR grant to study how breast cancer cells invade the surrounding tissues and move around the body. In particular he will focus on two proteins called ShcA and Lpp which have important roles in this process.
Grant Holder: Professor Razqallah R H Hakem
Institution: University Health Network, Canada
Grant Award: £127,886 for 3 years
Project Title: Breast cancer and the role of damaged DNA
Cancer can be caused by damage to the DNA inside our cells. 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. 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. Using an AICR grant Professor Hakem is studying two proteins called RNF8 and RNF168 which have important roles in the DNA repair mechanisms and in supressing cancer. In particular he is investigating the role of these proteins in the development of normal breast tissue and in breast cancer.
Grant Holder: Professor Marja Jäättelä
Institution: Danish Cancer Society, Denmark
Grant Award: £213,851 for 3 years
Project Title: Seeking new ways to kill cancer cells
One of the things that makes cancer cells so hard to kill is their ability to escape natural or drug-induced death. New ways to kill these drug-resistant cancer cells are therefore sought by scientists. Professor Jäättelä is using her AICR grant to investigate a newly-identified way to kill cancer cells - by causing lysosomes (small acid-containing sacs inside the cell) to become ‘leaky’ and release their toxic contents, killing the cell. The group will focus on the protein Hsp70 along with other molecules they identify which stop the lysosomes from becoming leaky and therefore protect the cancer cells from dying. In the long term Professor Jäättelä hopes their findings will lead on to the development of a new type of anti-cancer drug and help clarify if other existing drugs could be beneficial for cancer treatment.
Grant Holder: Dr Nabil Djouder
Institution: CNIO, Spain
Grant Award: £189,374 for 3 years
Project Title: Liver cancer and the role of the URI protein
Cells have a complex internal system of proteins controlling everything they do. These proteins are organized 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 often very complex, with many crosstalks and branches. Several of these signalling circuits are involved in controlling how cells grow and divide and can become significantly altered in cancer cells. One such pathway is the mTOR pathway which has been linked to low survival rates for patients with liver cancer. However the final 'targets' of this pathway are not yet fully understood. Dr Djouder has recently identified one of these “targets” called URI which allows cells to survive when turned on and promotes cell death when turned off. In several human cancer cells however, including liver cancer, URI is present at high levels. This prevents the cells from dying, resulting in aggressive cancer and is therefore associated with lower patient’s survival rates. This indicates that URI may help cancer cells avoid being killed and it may also have cancer-causing abilities. With a grant from AICR Dr Djouder is examining exactly how URI is involved in liver cancer.
Grant Holder: Professor Primo L Schär
Institution: University Basel, Switzerland
Grant Award: £219,112 for 3 years
Project Title: Bowel cancer and the role of ‘tagging’ genes
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 the genes or the proteins which act as scaffolding for the genes 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 cancers and the change in gene activity drives the cell to grow and divide in an uncontrolled manner, forming a tumour. Professor Schär is using his grant from AICR to investigate a type of tagging called methylation and how too much methylation can lead to the cell becoming cancerous.
Grant Holder: Dr Carolyn A Moores
Institution: Birkbeck College, England
Grant Award: £55,611 for 2 years
Project Title: Biological motors and cell division
All of the information that our cells require is coded 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 two new cells. To do this, all of the identical pairs of chromosomes line up down the middle of the cell and then biological machinery pulls them apart to opposite sides of the old cell, one set for each new 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. Dr Moores is using her AICR grant to study one component of this biological machinery called the Kinesin-5 motor to determine how it is able to generate the mechanical force needed to pull apart the chromosomes. Knowing how these motors are developed is important as drugs that block the activity of motor proteins like Kinesin-5 are able to stop cells dividing, so they are being developed as possible cancer therapies.
Grant Holder: Dr Luca Tamagnone
Institution: University of Torino Medical School, Italy
Grant Award: £90,800 for 2 years
Project Title: Understanding how bowel cancer can spread
One of the main factors making tumours so dangerous and hard to treat is their ability to invade into surrounding tissues and spread throughout the body, known as metastasis. Dr Tamagnone is using his AICR grant to study a molecule called Semaphorin 3E which is involved in this process of cancer spread and the growth of new blood vessels to supply tumours with oxygen and nutrients. It is not currently known how Semaphorin 3E carries out these roles so this is what Dr Tamagnone’s project hopes to discover. Ways to stop Semaphorin 3E could potentially help kill cancer cells and this will also be the focus of Dr Tamagnone’s work.
Grant Holder: Dr Ronit Weisman
Institution: The Open University of Israel, Israel
Grant Award: £112,500 for 3 years
Project Title: Studying cell growth and division in yeast
Cells have a complex internal control system of genes and proteins. 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. This allows the cells to divide in an uncontrolled manner and form a tumour. Dr Weisman is investigating how a group of proteins called TORC2 affects these pathways. She is carrying out the research in yeast cells as they also have the TOR proteins but are simpler than human cells making the experiments quicker and easier but still relevant to human cancer. Understanding more about how TORC2 is involved in a variety of cellular processes will help us determine the crucial differences in the way that cancer cells work.
Grant Holder: Professor Kevin Ryan
Institution: Beatson Institute for Cancer Research, Scotland
Grant Award: 182,068 for 3 years
Project Title: Tagging proteins and how things go wrong in cancer
Proteins carry out most roles within our cells. They control processes such as how the cells grow and divide. Cancer is caused by changes to either the structure or activity of key proteins that regulate how the cells operate, divide and die. One way that cells control the activity of proteins is to add on specific chemical groups or ‘tags’. The addition of tags can lead to an increase or decrease in protein activity. This often happens incorrectly in cancers and the change drives the cell to grow and divide in an uncontrolled manner, forming a tumour. Professor Ryan is studying a type of tagging called glycosylation which is important to ensure the proteins are folded up into the right shape and allows them to work in communication pathways within the cell. He aims to understand in more detail how the process is controlled and what goes wrong in cancer.
Grant Holder: Dr Arthur Zelent
Institution: The Institute of Cancer Research, England
Grant Award: £187,143 for 3 years
Project Title: Finding new treatments for Non-Hodgkin’s Lymphoma
Cancer drugs known as histone deacetylase (HDAC) inhibitors, that work by blocking the action of a molecule called histone deacetylase, have recently been approved for the treatment of some lymphomas. Dr Zelent has evidence that they may also be effective treatments for other lymphomas including Non-Hodgkin’s Lymphoma. He is now using his AICR grant to investigate exactly how a specific type of HDAC called HDAC9 is involved in Non-Hodgkin’s Lymphoma and to investigate if HDAC inhibitors could also be given to these patients.