Projects starting from January 2013 to January 2016
Grant Holder: Dr Vincenzo Costanzo
Institution: IFOM The FIRC Institute of Molecular Oncology Foundation, Italy
Grant Award: £148,634 for 3 years
Project Title: Controlling how DNA is copied when cells divide
DNA replication happens when all the information in one cell is copied before it divides to make two new cells. DNA replication starts from something called the replication origin, and cancer cells have many more of these than healthy cells, meaning they can divide much more quickly. Dr Costanzo is using frog eggs, which have many replication origins, and where replication happens often, to study how the formation of replication origins.
Grant Holder: Professor Andrew Fry
Institution: University of Leicester, England
Grant Award: £226,358 for 3 years
Project Title: EML, microtubules, and chemotherapy
Many chemotherapy drugs work by interfering with microtubules, which are one of the main components of a cell’s internal structure, but resistance to these drugs can develop quickly. Professor Fry is studying EML proteins to see if they play a role in how cancer cells respond to chemotherapy drugs that affect microtubules.
Grant Holder: Professor Stefano Biffo
Institution: Fondazione Centro San Raffaele del Monte Tabor, Italy
Grant Award: £144,138 for 3 years
Project Title: The role of the eIF6 protein in cancer
Proteins are produced through a process called translation; some steps that control translation appear to be changed in cancer cells. Professor Biffo’s lab has been studying a protein called eIF6, which is involved in controlling translation. More eIF6 is found in cancer cells than in normal cells, and the protein plays a central role in tumour development and growth. Using their new grant, they aim to find changes that affect other molecules through eIF6’s activity, and to see if these molecules could be used to develop new treatments.
Grant Holder: Dr Anna Bigas
Institution: Fundacio IMIM, Barcelona, Spain
Grant Award: £199,867 for 3 years
Project Title: The Notch pathway in T-Acute Lymphoblastic Leukemia
Functions within our cells are controlled by molecules, which are in turn controlled by other molecules. This is called a molecular pathway, and Dr Bigas will be using her AICR grant to study several pathways that work together to cause T-acute Lymphoblastic Leukemia This is a rare type of leukemia affecting older children and teenagers; the scientist hope to find new way of treating the disease.
Grant Holder: Professor John Trowsdale
Institution: University of Cambridge, England
Grant Award: £175,694 for 3 years
Project Title: Macrophages and Dendritic cells in cancer
Epithelial cells are a layer of cells that cover the surfaces of most of the organs and tissues inside the body. Most cancer types are formed from epithelial cells. Professor Trowsdale and his team have found a molecule, which is found on the surface of epithelial tumour cells. This molecule reacts with a protein called LILRB3, which is found on immune system cells called macrophages and dendritic cells, and it stops these immune cells from recognising tumour cells. They are planning on using their AICR grant to learn more about how these molecules interact.
Grant Holder: Dr Sonia Lain
Institution: Karolinska Institute, Stockholm, Sweden
Grant Award: £149,512 for 2 years
Project Title: Using sirtuins to treat cancer
While many chemotherapy drugs already exist to treat different cancer types, tumour cells often become resistant to these drugs. Dr Laín and her team previously discovered a small anti-tumour molecule called tenovin-6. They recently identified new molecules that are similar to tenovin-6 and that act in the same way. They are using their AICR grant to carry out further tests on these molecules, as well as other tenovin molecules, to understand how they work.
Grant Holder: Dr Sandra Peiró
Institution: Fundacio IMIM, Barcelona, Spain
Grant Award: £167,495 for 3 years
Project Title: The Snail1 gene and EMT
A phenomenon called EMT (epithelial-mesenchymal transition), is believed to help cancer cells spread throughout the body. Snail1 is one of the genes involved in EMT. Dr Peiró will use mice that have been genetically engineered to no longer have the Snail1 protein, in order to study how EMT is controlled in these mice compared to normal mice. By understanding more about how tumour cells become mobile, we might be able to develop ways to block the spread of cancer.
Grant Holder: Dr Andrew Hislop
Institution: University of Birmingham, England
Grant Award: £125,278 for 3 years
Project Title: How do T cells control Kaposi’s sarcoma associated herpes virus infection in cells?
Kaposi’s sarcoma-associated herpes virus causes a cancer called Kaposi’s sarcoma. The virus produces a group of proteins which should allow a type of immune cell called a T cell to recognise the virus as a foreign body to be eliminated. Some of these proteins use methods that may prevent them from being recognised by T cells, thereby avoiding attack by the immune system. Dr Hislop and his team are studying how T cells interact with these proteins to better understand how they avoid being detected by T cells, and if it is possible to make the T cells recognise these proteins.
Grant Holder: Dr Sharon Rossiter
Institution: University of Hertfordshire, England
Grant Award: £98,754 for 3 years
Project Title: Designing a new drug against pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that very few people survive from. No effective treatment has been found to treat people with this disease. A protein, called S100P, is found at high levels in PDAC. Dr Rossiter will be using the AICR grant to design new chemotherapy drugs, using computer based drug design, which are specifically aimed at stopping S100P.
Grant Holder: Dr Gary Parkinson
Institution: University of London, England
Grant Award: £110,358 for 3 years
Project Title: Protein interactions in tumour development
STAT3 proteins are involved in controlling how our proteins are produced. When cells are under stress, STAT3 proteins can be activated very quickly, and when this happens more than normal, or at the wrong times, it can lead to diseases such as cancer. Dr Parkinson and his team want to study small molecules that change important interactions between proteins. They carried out a pilot study, which showed how small molecules that attack tumours were attached to STAT3, at the atomic level. They will design new variations of STAT3 proteins to understand key areas of interaction between proteins.
Grant Holder: Professor Julian Downward
Institution: London Research Institute, England
Grant Award: £173,461 for 2.6 years
Project Title: Finding ways to block the Ras pathway in lung cancer
Nearly half of patients with non-small cell lung cancer (more than 80% of all lung cancers) have mutations in a group of molecules called the Ras pathway. Professor Downward and his team have found that cancer cells that develop with Ras mutations are dependent on a protein called GATA2. They developed a mouse model which showed that when GATA2 was removed, lung tumours became dramatically smaller. They are now exploring the relationship between GATA2 and lung cancer, how the absence of GATA2 affects the tumour and the surrounding area, and whether tumours can evolve to survive without it.
Grant Holder: Dr Heiko Wurdak
Institution: University of Leeds, England
Grant Award: £211,220 for 3 years
Project Title: Testing TRRAP as a treatment for malignant brain tumours
Stem cells are a type of ‘starter cell’ that can multiply and change into a wide variety of different cells, and brain tumour stem cells (BTSCs) are thought to be the most dangerous type of cell within brain tumours. They are able to ‘renew’ themselves and can avoid being killed by anti-tumour treatments. Dr Wurdak previously found that a protein called TTRAP was directly involved in making BTSCs grow. They are now investigating how TRRAP works and makes BTSCs grow, as well as looking at whether removing TRRAP at a critical time can stop the spread of the disease.
Grant Holder: Dr Renata Basto
Institution: Institut Curie, Paris, France
Grant Award: £212,382 for 2 years
Project Title: Studying the role of aneuploidy in cancer
The centrosome is a small unit within our cells that helps to control the equal separation of chromosomes to the daughter cells during cell division. The presence of more than two centrosomes during cell division can cause aneuploidy, and this can happen in cancer. Dr Basto and her team have created a mouse model where it is possible to cause aneuploidy by increasing the number of centrosomes. Using this mouse model, they are studying what happens within cells when extra centrosomes are present, as well as whether aneuploidy later on in the development of the embryo can lead to tumour development.
Grant Holder: Dr Fredrik Swartling
Institution: Uppsala University, Sweden
Grant Award: £146,965 for 2 years
Project Title: The MYCN protein and its involvement in brain tumours
The MYCN protein is needed for the brain to develop normally, but too much of the protein can be found in medulloblastoma, one of the most common malignant brain tumours in children. Dr Swartling and his team have discovered that one of the ways that MYCN can accumulate in brain tumours is because it is not being broken down the way it should be. They are studying the importance of MYCN in the development and growth of brain tumours. They hope to find what causes MYCN-driven brain cancer as well as new ways to keep the protein stable.
Grant Holder: Dr Amir Eden
Institution: The Hebrew University of Jerusalem, Israel
Grant Award: £143,100 for 3 years
Project Title: The role of histone H3 methylation in cancer
Genes can sometimes be controlled by adding specific chemical groups, or ‘tags’ onto the genes, or to proteins that act as their scaffolding. This can alter the activity of the genes. One such form of tagging involves addition of a small molecule called a methyl group, and addition of too many methyl groups is linked with tumour development. Dr Eden and his team will study methylation of a protein called histone H3, and what role this plays in changes that are associated with cancer.
Grant Holder: Dr Giuseppe Testa
Institution: European Institute of Oncology, Milan, Italy
Grant Award: £136,500 for 3 years
Project Title: Dr Testa is continuing research from a previous AICR grant, where he was researching how addition of small molecules, called methyl groups, to a gene scaffolding protein called histone H3, is involved in the development of gliomas. Gliomas are the most common type of brain tumour. With his group, they will be studying how addition of these methyl groups are involved in gliomas recurring.
Grant Holder: Dr Erwin Wagner
Institution: CNIO, Madrid, Spain
Grant Award: £151,364 for 3 years
Project Title: Fra-1 and Fra-2 are proteins that can be found in a large number of cancers. When cancer cells are studied in the lab, Fra proteins can cause the cells to change into a different cell type, which is sometimes associated with cancer development. Dr Wagner has previously shown that 3 proteins, including Fra-2, were present at high levels in samples from lung cancer patients, as well as mice with the disease. He is now studying the role of Fra-2 proteins in lung cancer, by changing the amounts of Fra-2 protein produced in mice during lung tumour development.
Grant Holder: Dr Diego Arango
Institution: Vall d’Hebron Research Institute, Barcelona, Spain
Grant Award: £165,311 for 3 years
Project Title: The brush-like border on the cells that line our intestines disappears as tumours grow in the bowel. MYO5B is a protein that helps to shape this brush-like border, and when the protein is no longer present in cells, this border is damaged. Dr Arango and his team will investigate how MYO5B affects cancer progression, by studying the genetic changes that delete the protein from bowel cancer cells, and looking at how the presence of the protein might stop tumours from growing.
Grant Holder: Dr Richard Jenner
Institution: University College London, England
Grant Award: £199,175 for 3 years
Project Title: How DNA is packaged in the cell: changes in cancer of the womb
Dr Jenner and his team have found that a mutated protein, called polycomb protein, is unable to function properly in womb cancer, and may play a role in causing tumours to develop. They will be using their AICR grant to look at the changes this causes to chromatin, which is a tightly packaged form of DNA, and how this may cause tumours to develop.
Grant Holder: Professor Alain Trautmann
Institution: Institut Cochin, Paris, France
Grant Award: £156,200 for 2 years
Project Title: Studying the role of the immune system in tumour regression
images taken from growing tumours have shown that a type of immune cell called lymphocytes play an important role in preventing tumour cells from spreading to other parts of the body, but other immune cells have been found to help tumours grow. Dr Trautmann and his team will use tumours in mice to look at the different immune cell types that are driven to the tumours and the surrounding areas, and the molecules they produce. They will try to visualise in 3D where the different immune cells go to within the tumour and surrounding tissue.
Grant Holder: Professor Graham Packham
Institution: University of Southampton, England
Grant Award: £199,563 for 3 years
Project Title: Studying the role of B-cell receptors in human lymphomas
B-cells are immune cells that have a key molecule on their surface, called the B-cell receptor (BCR), which allows them to recognise specific structures, called antigens. B cells get switched on when they recognise an antigen. Many cancers that affect B-cells are thought to depend on the BCR to grow and survive. If the BCR is switched on without antigen, it may allow these cancer cells to gain supporting signals from cells within the surrounding area, and Professor Packham will be studying whether these signals cause the growth or survival of lymphomas, a type of cancer that affects B cells.
Grant Holder: Dr Jacco van Rheenen
Institution: University Medical Center, Utrecht, The Netherlands
Grant Award: £192,823 for 3 years
Project Title: Watching (cancer) stem cell behaviour in genetic mouse models
Dr van Rheenen and his team developed state-of-the-art microscope technology, to study live stem cells, in real time to, watch what they are doing as tumours develop and grow. They will use mice in which the stem cells, from healthy and cancerous bowel and breast tissues, have been genetically modified to be fluorescent. They will be able to watch what happens to these stem cells, as it happens within the mice, over a period of several weeks. They want to find out whether specific changes occur to the stem cells, and where these changes take place.
Grant Holder: Dr Johan De Rooij
Institution: Hubrecht Institute, Utrecht, The Netherlands
Grant Award: £200,822 for 3 years
Project Title: The role of E-cadherin and HGF in bowel cancer
Cells are able to respond to both chemical and mechanical signals. A hormone called HGF is known to increase the likelihood of tumours spreading, and Dr De Rooij and his team think this may happen, because it increases mechanical force on tumour cells. They have developed a 3D cell model from bowel cancer samples, which react to a hormone, called HGF, by changing shape. They will use this model to investigate how bowel cancer responds to HGF, and also study a molecule called E-cadherin, which they think may be involved in sending the mechanical signals.
Grant Holder: Professor Alan Clarke
Institution: Cardiff University, Wales
Grant Award: £228,353 for 3 years
Project Title: PTEN, stem cells, and cancer
Deletion or mutation of a protein called PTEN is often linked with the development of some cancer types. Professor Clarke and his team recently showed that, in bowel cancer, the PTEN mutations can happen in the surrounding cells (stromal cells), rather than the cancer cells themselves. They will use their AICR grant to study exactly how the deletion of PTEN from stromal cells can cause other cells in the bowel to become cancerous.
Grant Holder: Dr Sergio Quezada
Institution: University College London, England
Grant Award: £225,479 for 3 years
Project Title: Understanding how CD4+ T cells react to tumours
A type of immune cell called CD4+ T cell has been shown to play a part in the immune response to cancer; they are able to produce a strong killer response, which leads to impressive rejection of large, fully established tumours. Killer CD4+ T cells have been found in patients with different diseases that are related to inflammation, or swelling, but we know nearly nothing about the possible role of these cells in helping or stopping tumour development. Dr Quezada and his team will study what systems control these cells, and the signals that are involved in making them form an immune response against tumours.
Grant Holder: Professor Michael Seckl
Institution: Imperial College London, UK
Grant Award: £156,217 for 3 years
Project Title: Studying drug resistance in lung cancer
Non-small cell lung cancer accounts for more than 80% of lung cancer and about 10% of these patients have a mutation in the gene that controls a protein called EGFR. Some drugs work on this mutation and they are initially very effective, but the cancer quickly becomes resistant to the drugs. Professor Seckl and his team previously found that low levels of a protein called glutathione inside cells is linked to drug resistance, they will now study molecules that control glutathione levels in the cancer cells and determine how they relate to resistance in drugs that are aimed at EGFR mutations.