There are currently thirteen research teams within the European Cancer Stem Cell Research Institute, each working on a variety of themes, all with a common goal - to bring the aim of creating personalised treatments for cancer patients closer to reality.
Currently, our research includes:
Mechanisms of glioblastoma progression
Glioblastoma is the most common and lethal of the brain cancers in adults. Currently there is no cure, and the average survival is only 15 months.
Dr Florian Siebzehnrubl's research is directed at identifying molecular mechanisms that allow brain cancer cells to regrow into new tumours after therapy. His work has identified a protein called ZEB1 that causes cancer cells to become resistant to chemotherapy, and enables them to move away from the original tumour mass and form new tumours.
Currently, the Siebzehnrubl group is uncovering molecular signals that cause cancer cells to produce ZEB1, and how blocking these signals can stop glioblastoma from growing.
Skin cancer stem cells
Skin cancers have been the fastest growing types of cancer, and numbers are continuing to increase in the UK.
Early diagnosis and surgical management of skin cancer is often curative. Thus skin cancers are also model tumours for the study of cancer stem cell biology since fresh human tumour tissue is readily accessible, their biology is similar to other malignancies, and that DNA mutations that give rise to these cancers can be characterised by a UV signature.
We have developed both in vivo and in vitro assays leading to the identification of cancer stem cell populations in human basal cell carcinoma and human squamous cell carcinoma.
Dr Girish Patel's group are currently exploring the origin and evolution of cancer stem cells in primary and metastatic skin cancers and their role in disease recurrences.
Haematopoietic stem cells and cancer stem cells in leukaemia
Over 9,000 new cases of leukaemia are diagnosed every year in the UK.
Haematopoietic stem and progenitor cells (HSPCs) in the bone marrow produce specific classes of blood and immune cells. Disruption in the functions of HSPCs is considered fundamental in the emergence of blood cancers.
Dr Neil Rodrigues is identifying the molecular mechanisms that regulate HSPCs and how dysregulation can lead to blood disorders such as myelodysplastic syndromes and acute myeloid leukaemia.
The aim of this research is to understand how a subtype of blood cancer cell called a cancer stem cell sustains tumour growth and to identify cellular mechanisms that could be targeted to produce novel therapies against cancer stem cells.
The aim of this research is to understand how blood cancer stem cells sustain tumour growth and identify cellular mechanisms that could be targeted to produce new cancer therapies.
Notch signalling and Acute Myeloid Leukaemia
Targeting specific cell types to form a new generation of therapies.
Dr Fernando Anjos-Afonso research group is concerned with studying acute myeloid leukaemia. Patients with acute myeloid leukaemia cannot produce normal blood cells and cannot fight off infections properly, and patients often present anaemia and severe bleeding, which leads to death.
Currently, the only way to cure acute myeloid leukaemia is via a bone marrow transplant, but this can be a problematic method of treatment. Current drug treatments are extremely toxic and not very specific, and although they can be successful at clearing the disease, the leukaemia often returns in a more aggressive form. Hence, there is therefore an unmet need for more tolerable and specific treatments for acute myeloid leukaemia patients.
In order to achieve this, Dr Afonso’s group is exploring the differences between normal blood stem cells versus in acute myeloid leukaemia cells. By exploiting the potential differences it is possible that the group could find ways to specifically target acute myeloid leukaemia cells while sparing the healthy blood stem cells – thus paving the way for the development of new treatments.
Stem cells and cancer heterogeneity
Understanding the origins of cancers, and the biological basis of the differences between them, could open up new avenues in both treatment and prevention.
Professor Matt Smalley studies how a change in the stem cell of origin of breast cancer can change the appearance and biology of that cancer and its response to treatment. The research in his laboratory range from very basic studies of tumour biology to projects in collaboration with clinicians aiming to translate those findings into patient benefit.
Targeting the causes of metastatic disease
The spread of malignant tumours around the body is the principal cause of death in patients with solid tumours.
Dr Richard Clarkson’s lab focuses on identifying new ways to prevent tumours from spreading around the body, a process termed metastasis. Their work involves understanding the changes that occur within tumour cells that cause them to metastasise and the development of new therapeutic strategies to either prevent this from taking place, or to eliminate the cells altogether.
Stem cell gene expression in mammary glands
Dr Geraint Parfitt’s research aims to identify cancer stem cells in a variety of cancers – including breast cancer.
By marking these cancer stem cells in models of breast cancer, based on their slow cycle rate and their gene expression, Dr Parfitt’s group hope to better understand the behaviour of the different types of tumours. Through this work, they hope to make tumours more predictable and therefore develop more effective treatments.
Genetic alterations and prostate cancer
Exploring the molecular mechanisms that underpin prostate cancer growth and therapeutic resistance.
Prostate cancer is a second most common cause of cancer-related deaths in men worldwide, reflecting the limitations of current treatment approaches. To increase patient survival, we need to improve our understanding of the cellular mechanisms that facilitate prostate cancer growth and therapeutic resistance.
Dr Helen Pearson’s research integrates basic prostate cancer biology, biomarker discovery and the preclinical assessment of novel therapeutic approaches with the ultimate goal to improve upon the current standard of care for men with prostate cancer.
Her lab’s research employs novel model systems to investigate how different genetic drivers of prostate cancer can initiate tumour formation and/or contribute to malignant progression, explore how prostate tumours become resistant to current therapies, and to identify new therapeutic strategies for the treatment of prostate cancer.
New treatments for metastatic prostate cancer
Understanding the genetic drivers of the spread of prostate cancer cells could help us develop new treatments for advanced disease.
Professor Matt Smalley’s interest in the clinical differences between tumours primarily focuses on breast cancer, but also extends to prostate cancer.
His team of researchers has been working with models of prostate cancer to both understand the molecular drivers of the spread of cancer and also to test novel therapeutic approaches. In particular, they are working with collaborators on blocking the Wnt signalling pathway and the role of a cell surface molecule called PlexinB1 as a driver of metastasis.
Preventing the reoccurrence of prostate cancer
Prostate cancer returns in one in three men who have surgery or radiotherapy treatment.
Prostate cancer can often reoccur, even if the cancer was diagnosed and treated before spreading outside the prostate. As well as focusing on breast cancer, Dr Richard Clarkson’s laboratory is looking at targeting cells that cause the cancer to return. They aim to create therapies that will be used alongside existing cancer therapies to help patients remain cancer free.
Stem cell gene expression in prostate cancer
Dr Geraint Parfitt is focused on revealing gene expression patterns in slow-cycling cancer stem cells. His lab aims to label these tumour cells in a variety of cancers, including prostate cancer, to better understand the behavior of the different types of tumours and their level of stem cell gene expression.
The research will help to create more efficient cancer therapies, by enabling us to understand the behaviours of different types of cancers in greater detail.
Understanding the interactions that link diet to cancer
Of the 41,000 new cases of bowel cancer diagnosed each year in the UK it is estimated that 50% were preventable by lifestyle and diet changes.
Bowel cancer leads to approximately 600,000 deaths globally each year and is one of the major causes of death in the western world. However the exact reasons why some diets are associated with bowel cancer protection, and some with promotion, are not fully understood.
To gain a better understanding, we study the intestinal stem cells that are responsible for maintaining a healthy bowel, as damage to these cells can cause cancer.
Dr Lee Parry’s group works closely with the clinicians at the University Hospital of Wales to obtain human samples, helping them to understand how diet influences stem cells in normal and cancerous bowel tissue. The focus of the research is to improve our understanding of diet and health to provide accurate public advice and develop ways of utilising diet to prevent and treat bowel cancer.
Gastric cancers and cell signalling
Dr Toby Phesse aims to understand the role of Wnt signalling in gastrointestinal cancers.
Dr Phesse’s research interest is in understanding how cell signalling controls maintaining healthy tissue, regeneration, stem cell function and disease, with a focus on Wnt signalling in the gastrointestinal tract.
Many of the cell signalling pathways that are critical for development and regeneration of tissues after damage are deregulated during disease, and in particular cancer. By understanding the molecular events that regulate cell signalling during these biological processes, and the disruptions that result in disease, his research team aim to identify novel therapeutic strategies for cancer.
Cell-cell interactions in tissue health and disease
Epithelial tissues act as protective barrier to our inner organs and to the outside world. Maintaining tissue health and integrity is key to promote health and prevent disease. Healthy tissue is maintained by a number of tightly regulated processes that ensure that unhealthy cells are removed before they develop into disease.
Dr Catherine Hogan’s research investigates how cells carrying mutations in a cancer-causing gene, Ras, expand to initiate tumour formation within the tightly controlled environment of a healthy tissue. Dr Hogan’s research has shown that Ras-expressing mutant cells are detected by healthy neighbours and are actively removed from tissues.
Detection and elimination of mutant cells requires a specific cell-cell communication signal belonging to the Eph-ephrin family. Dr Hogan’s research suggests that in order for a tumour to form, mutant cells must first evade detection by normal cells.
Her research group is exploring the mechanisms underlying how mutant cells bypass the detection system imposed by normal healthy cells and how risk factors may contribute to this evasion process. This work will provide key insights into how sporadic cancer develops at the earliest stages.
Dr Hogan’s team specifically investigate the biology of early pancreatic cancer because Ras mutations are required to initiate the development of pancreatic tumours. Early detection is key to improving survival of pancreatic cancer patients and to prevent escalating numbers of deaths in the future. A better understanding of the biology of early pancreatic cancer will improve our ability to detect and diagnose this deadly disease before it reaches incurable stages.
Neutral competition during intestinal homeostasis and repair
Dr Joaquín de Navascués is interested in how cells make fate decisions.
He wants to understand how cells integrate cues from their environment to make decisions about their fate, both in development and homeostasis, and how these decisions are coordinated in tissues during the life span of an organism.
He approaches this question through an integration of classical genetic approaches, quantitative data analysis and modelling through collaboration with theoreticians. He uses the fruit fly, Drosophila melanogaster, as a model system for in vivo studies, focussing on the regulation of adult intestinal stem cells.
Wnt signalling in liver cancer
Professor Trevor Dale is interested in the consequences of genetic mutations.
The Wnt signalling pathway in cells is abnormally activated in many tumour types, including in liver cancer. Professor Dale’s research group are interested in how genetic mutations lead to changes in protein structure, and how this changes the function of protein machines, cells and tissues.
By understanding how mutations bring about changes in cells, we hope to better understand how cancers develop.