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Current PhD student projects

We're really proud of our research students. We're also really proud that we've helped and trained nearly 200 of them through our PhD studentship funding programme.

To see recently completed lab projects, click here.

Currently supported projects

The researchers we've supported have already done so much to help cancer patients. Below are the projects that Tenovus Cancer Care is currently supporting to continue helping those affected by cancer.   

The role of STEAP2 in prostate cancer invasion and metastasis

Stephanie B Pic

Student: Stephanie Burnell

Supervisor: Dr Shareen Doak

Co-Supervisor: Prof Howard Kynaston (Cardiff and Vale University Health Board)

Institute of Life Science, College of Medicine, Swansea University

Early prostate cancer confined to the gland is not always life threatening and many patients do not require immediate treatment such as major surgery or radiotherapy. However, the question of when to start therapy and determining the best treatment plan can be problematic because diagnostic tools to accurately distinguish between aggressive (invasive) or dormant tumours are lacking. Recent studies have identified the gene STEAP2 as over-expressed in prostate cancer but its importance is poorly understood.

Our initial studies have shown STEAP2 over-expression is specifically associated with aggressive prostate cancer, so this project is aimed at determining the role that STEAP2 plays in driving the development of this cancer. This will be achieved by depleting STEAP2 in cancerous prostate cells and enhancing its expression in normal prostate cells. We will then perform a series of experiments to assess if and how characteristic invasive cancer properties are altered.

Additionally, the predictive value of STEAP2 as a marker for aggressive prostate cancer will be assessed. In the future this will enable targeted treatment by aiding identification of those patients most in need, and improving therapeutic strategies by highlighting potential drug targets for development of new therapies.


The role of nucleotide excision repair in providing resistance to the nucleoside analogues Gemcitabine and Cytarabine

Helena Pic

Student: Helena Robinson

Supervisor: Dr Edgar Hartsuiker

School of Biological Sciences, Bangor University

The majority of cancer drugs used in the clinic kill cancer cells by damaging their DNA. Unfortunately, the therapeutic efficiency of these drugs is often limited. Novel approaches to improve the therapeutic efficiency of existing DNA damaging cancer drugs rely on a detailed understanding of DNA repair mechanisms that repair treatment-induced DNA lesions.

One group of cancer drugs frequently used in the clinic are nucleoside analogues. These drugs resemble naturally occurring nucleosides, which are the building blocks of DNA. Nucleoside analogues are modified to interfere with DNA replication, thus preventing division of (cancer) cells. We have obtained evidence that a DNA repair pathway, which has previously been associated with the repair of DNA damage caused by ultraviolet light, is also involved in the removal of nucleoside analogues from DNA. The aim of this project is to study the mechanistic role of this repair pathway in providing resistance to treatment with nucleoside analogues in human cells.

In the long term, the project might lead to the identification of novel molecular markers that help inform cancer therapeutic decisions and novel targets for drugs that specifically increase the sensitivity of cancer cells to nucleoside analogues.


Testing the efficacy of iFLIP/TRAIL mediated cytotoxicity in breast tumour tissues ex vivo

Andreia SilvaStudent: Andreia Silva

Supervisor: Dr Richard Clarkson

Co-Supervisor: Dr Luke Piggott

School of Biosciences, Cardiff University

We have discovered a method to selectively eliminate the tumour-forming potential of breast cancers by destroying the so-called cancer stem cells, thought to be responsible for the spread of the disease in breast cancer patients.  These experiments were performed in a laboratory setting using cancer cells that had been propagated for long periods outside of the body.  Thus despite the striking anti-cancer effects observed, there remains the key question of whether these findings have direct clinical relevance for patients.  We aim to address this by testing our putative therapeutic strategy directly on breast tumour tissues. 

We have recently obtained ethical consent to acquire fresh tumour tissues from patients.  These tissues will be used to test the experimental therapy over a shorter time frame in the laboratory, in order to maintain the clinical relevance of the human tissues. The approach involves suppression of the gene for cFLIP combined with the addition of the anti-cancer agent TRAIL.  We will use two existing experimental anti-cancer agents that are known to suppress cFLIP (in addition to other effects) and will compare these outcomes to conditions in which we use a genetic approach to specifically suppress cFLIP. 

We will assess the effects on both cancer stem cells and the tumour as a whole, and will correlate any responses to the particular subtypes of breast cancer.  This study represents a key translational step towards testing this therapeutic strategy in clinical trials.


The role of Reactive Oxygen Species (ROS) and glycolytic metabolism in leukaemogenesis

Andy Pic

Student: Andrew Robinson

Supervisor: Dr Alex Tonks

Co-Supervisor: Dr Richard Darley

Department of Haematology, Cardiff University

Leukemia arises from disruption of normal blood cell development. This occurs because the  molecules which control development are disturbed. The production of reactive oxygen species (ROS) are usually thought to play a role in bacterial killing but have more recently been identified as regulatory molecules of growth and development.

Although we know the importance of ROS in immunity, leukaemia and cancer development, we do not know how their production is disrupted in acute myeloid leukaemia (AML) and what the consequence to the tumour cell is. This study will determine how ROS can promote leukaemia and whether it involves pathways perturbing glucose metabolism.


Treating Metastatic Disease by Manipulation of Regulatory T Cells

Ellyn Hughes

Student: Ellyn Hughes

Supervisor: Dr Awen Gallimore

Co-Supervisor: Dr Ann Ager

Dept of Infection and Immunity, Cardiff University

The main role of our immune systems is to fight infection. The results of many studies show that the immune system can also recognise and kill cancer cells. However, while these studies show the potential of the immune system to attack cancer cells, ways of harnessing this activity for the purpose of cancer therapy is not well understood.

It is known that a small population of white cells known as Tregs, which form part of the immune system, act to suppress immune responses that are perceived as detrimental. These include immune responses to normal tissues and organs and those that cause longlived inflammation. As cancer originates from our own cells, the immune system does not necessarily recognise the danger posed by the cancer. Indeed, we have found that Tregs actively prevent the development of immune responses to cancer.

Using model systems we have found that removing Tregs can boost anti-cancer immune responses and that these responses subsequently act to kill cancer cells. However, whether disabling the activity of Tregs is effective for limiting metastatic disease, when the cancer has spread to other parts of the body, is not yet known. This is important, as cancer often remains undiagnosed until it has spread in this way. The main goal of this study is to determine whether manipulation of Tregs is beneficial for treatment of metastatic disease. This information will be used to improve current methods of cancer treatment.


Molecular and functional characterisation of the nutri-epigenetic effects of chemopreventative polyphenols in intestinal cancer

Steph May

Student: Stephanie May

Supervisor: Prof Alan Clarke

Co-Supervisor: Dr Kirsty Greenow

School of Biosciences, Cardiff University

Bowel cancer is the second most prevalent cancer worldwide and while the mortality rates have declined over the past two decades the five year survival rate from this disease is still only 54%. Risk factors for developing bowel cancer include hereditary predisposition, obesity, smoking, alcohol consumption, and poor nutrition. While there has been a great advancement in drug treatments for this disease, toxicity and drug resistance has emphasised the importance of prevention in the treatment of this disease.

Chemoprevention refers to the agents that block, reverse, or delay the process of cancer development. In this study we will investigate the chemopreventative properties of dietary polyphenols, such as those found in berry fruits and turmeric. Previous work has shown that both edible berries and turmeric reduce tumour incidence in bowel cancer patients and in mouse models of the disease, although the precise mechanism is still unclear. We will investigate the effect of dietary polyphenols on a key signalling pathway that is deregulated in cancer and characterise the molecular effect of these active dietary constituents on tumour incidence. We will also analyse the expression of protective genes (tumour suppressors) to identify the mechanism of chemoprevention.

We will investigate the hypothesis that dietary polyphenols alter the epigenetic signature (molecular marks that modify gene activity that don’t involve alterations to the genetic code) on key tumour suppressor genes which will results in reduced tumorigenesis in the intestine. 



Decoding the Genetics of Brain Tumour Development

Student - Karolina-Janina Jaworek

Supervisor - Dr Claudia Barros

School of Biological Sciences, Bangor University

A devastating event during cancer treatment is the relapse of a tumour even after a severe reduction in tumour mass. Recent studies indicate that a possible reason for this occurrence is the existence of particular cells within a tumour, called stem cells, which are often not efficiently destroyed by current therapies. Surviving stem cells are able to generate all cell types of a particular cancer, and can therefore recreate the whole tumour mass. We need to increase our knowledge about stem cells and their conversion into tumour-initiating cells. Thus, we propose to identify changes at the gene level in neural stem cells during brain tumour formation in a living organism. Analysis of identified factors will be done both in a model animal system allowing genetic manipulation and in a human brain tumour cell line. Understanding the changes occurring in stem cells and their role in tumour initiation will bring novel insights essential for the development of more effective drug cancer therapies.


Characterising exosome uptake for elucidating their role in cancer progression and as potential drug delivery vectors Alex Cocks

Student: Alex Cocks

Supervisor: Dr Aled Clayton
Co-Supervisors: Professor Arwyn T Jones and Dr Pete Watson, Institute of Cancer & Genetics, Cardiff University Start Date: Oct 2015

Cancer cells produce and release tiny bubbles of fat called exosomes. These accumulate in fluid around the cells and act in several ways to promote disease: they inhibit the immune system, encourage blood vessel formation (supporting cancer growth), and also activate surrounding cells (called stroma) making the cancer more aggressive. These fat bubbles are analogous to miniature biological parcels, packed with important cargomolecules that are taken inside neighbouring cells to control their behaviour. This cellular uptake is thought to be critical in how exosomes work, however the mechanism of exosome uptake, and where in the cell the cargo is delivered to is not well understood. Importantly, however, we may utilise this natural cargo-delivery mechanism to our advantage by loading exosomes with therapeutic molecules. This would be an exciting new way of delivering active drugs through cell membranes to the insides of target cells to elicit a therapeutic response. Fundamental to identifying their role in cancer and also drug delivery is an understanding of their interaction with cells and their fate inside cells. The study will investigate the details of exosome uptake by cells, and utilise this as a means of delivering therapeutics to cancer cells. It will bring together established expertise in exosome-biology (AC), drug delivery (ATJ) and state of the art microscopy (PW). Together, this expertise will address some very poorly understood questions in the field of cancer exosomes, providing fundamental new insights about how cancers grow and spread and how they could be manipulated to deliver drugs.

Development of novel Antibody Drug Conjugates for oncology applications David Howard

Student: David Howard

Supervisor: Professor Steve Conlan
Co-Supervisors: Professor Christopher McGuigan, Dr Deyarina Gonzalez and Dr Lewis Francis Institute of Life Science, Swansea University Start Date: Oct 2015

Despite recent breakthroughs in oncology, many cancers are still incurable and cancer remains the leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Most anticancer drugs, including nucleoside analogues, currently in use are dosed at suboptimal concentrations, are highly toxic and nonspecific attacking both cancer and normal cells. In addition, nucleoside analogues require nucleoside transporters to enter the cells and exert their toxic action. Deficit of nucleoside transporters expression by cancer cells contributes to cancer resistance to nucleoside treatment. Novel nucleoside analogues named ProTides with a high cytotoxic activity can enter the cells freely without the aid of transporters. However, a need remains for the delivery of these drugs directly into the cancer cells without targeting healthy cells. Antibody Drug Conjugates (ADC) are novel drugs that can kill cancer cells while sparing normal cells. ADC molecules consist of an antibody and a drug married together through a linker. Chemical bonding of the drug to the antibody inactivates the drug so that it is not toxic while in circulation. The antibody then delivers the drug to the antigen-expressing cancer cell, where internalization of the ADC occurs, releasing the drug in its active form to kill the targeted cancer cells. This project will profit from the specifity of the antibody part of the ADC and the cytotoxic activity of nucleoside analogues and ProTide derivatives to create novel ADC molecules for oncology applications. The anti-tumour activity of these newly synthesised ADC drugs will be also characterised in cancer cell lines.

Development of immune-modulators for preventing immune suppression by cancer-associated LAG3+CD4+ T-cells Georgie Mason

Student: Georgina Mason

Supervisor: Professor Andrew Godkin

Co-Supervisors: Dr David Cole and Professor Awen Gallimore, Institute of Infection and Immunity, Cardiff University Start Date: TBC This PhD studentship is funded in partnership with Sêr Cymru.

CD4+ T-cells play an important role in natural immunity to pathogens and cancer, facilitating the B-cell and cytotoxic T-cell response. Depletion of CD4+ T-cells during HIV infection is a major factor in the development of AIDS, underscoring their importance during adaptive immunity. The receptors on the surface of these cells including the T-cell Receptor (TCR); the glycoprotein CD4, and its homologue lymphocyte activation gene-3 (LAG3), govern the nature of CD4+ T-cell antigen recognition. LAG3 has been implicated as a major regulator of CD4+ T-cell activation. However the actual structure and function of LAG3 is not defined. We have recently identified a novel population (20%) of colorectal-infiltrating CD4+ T cells expressing LAG3 that renders these cells strikingly immunosuppressive (Scurr M et al. Mucosal Immunology 2013). Thus, LAG3 seems to play a role in protecting tumours from immune attack. Understanding the molecular rules that determine LAG3+CD4+ T-cell immune suppression will enable the development of new therapies to block this effect thereby promoting cancer immunity.

Human gdT-APCs: Processing of Tumour Antigens and Induction of Anti-Tumour Immunity

Student: Teja Rus

Supervisor: Professor Bernhard Moser Co-Supervisors: Dr Matthias Eberl and Professor Awen Gallimore Institute of Infection and Immunity, Cardiff University Start Date: Oct 2015

This PhD studentship is fully funded thanks to the generous support of the Masonic Samaritan Fund

Recent progress in cancer treatment with new drugs targeting so‐called “immune checkpoints” clearly established the critical importance of the immune system in fighting cancer. Under healthy conditions immune surveillance cells keep an eye out for spontaneously emerging tumour cells and kill them before they can establish cancer. If this system fails, for instance in elderly or transplant patients on immune suppressing drug, then tumour cells can grow into cancer that become blind against the patient’s own immune system. It is, therefore, logical to consider new strategies to reengage the patients’ own immune system in order to tilt the balance in favour of effective anti-tumour immunity. One such strategy is based on our discovery of γδT‐APCs, a subset of peripheral blood‐derived T lymphocytes (γδ T cells) able to interact with and trigger responses in αβ T cells. αβ T cells form the majority fraction of lymphocytes that also include those able to kill tumour cells. We have studied this new function of γδT‐APCs with many types of αβ T cells, including those specific for bacterial and viral proteins. We now need to examine whether γδT‐APCs can also engage tumour‐specific αβ T cells. This PhD project addresses this important question and, in addition, aims to study the vaccine function of γδT‐APCs in a preclinical model involving humanized mice. The PhD student will be supported throughout his/her studies by three supervisors whose labs will provide all hands‐on and intellectual expertise necessary for the successful completion of the proposed studies.

Development of a novel adenovirus serotype for cancer virotherapy applications Alex Baker

Student: Alex Baker

Supervisor: Dr Alan Parker
Co-supervisors: Professor Gavin Wilkinson and Professor John Chester Institute of Infection and Immunity, Cardiff University Start Date: Oct 2015

A significant limitation of existing drug based cancer therapies is that a significant proportion of patients develop resistance, resulting in aggressive tumour relapse. The use of viruses to kill tumour cells, but not normal cells, represents an appealing avenue as a cancer therapy that is unlikely to be susceptible to cross-resistance in tumours. Tumour killing (oncolytic) adenoviruses have been studied for over a decade, with multiple studies focussing on an adenovirus known as Ad5, which has been modified to be tumour selective. One of these viruses, ONYX-015, has shown promise as an adjunctive therapy in combination with chemotherapy and was has gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer. However, there is significant evidence that viruses based on Ad5 are sub-optimal for cancer virotherapy, and that less well studied types of adenoviruses might be better suited.

Our research has pinpointed a virus called Ad49 as ~ 100x better at infecting cancer cells than Ad5. This proposal will evaluate Ad49 for its potential to kill cancer cells and enable us to better understand how this virus interacts with and infects cancer cells. By better understanding how these viruses interact, infect and kill tumour cells, we will “tailor” them to make them more “selective” for tumour cells. By increasing the tumour selectivity such that the virus only kills tumour cells, we hope to translate our laboratory findings into real clinical benefits in treating patients with advanced, chemotherapy-resistant cancers.

Functions of MIF in glioblastoma tumour progression Ana Jimenez

Student: Ana Jimenez-Pascual

Supervisor: Dr Florian Siebzehnrubl European Cancer Stem Cell Research Institute, Cardiff University Start Date: Oct 2015

Glioblastoma is the most common and lethal of the brain cancers, and the re-appearance, or recurrence, of these cancers after treatment is a particular problem contributing to patient demise. Recent advances in the study of cancer have identified cancer stem cells as important drivers of tumour growth and recurrence. Our understanding of why and how cancer stem cells cause recurrence is fairly limited, and new approaches are required to curb the capacity of brain cancer stem cells to regrow tumours after therapy. This proposal aims directly at identifying mechanisms that allow cancer stem cells to regrow into new tumours after therapy, and may lead to new treatment regimens to prevent glioblastoma recurrence. In particular, a protein present in the tumour environment will be scrutinized for its abilities to cause tumour cells to become more aggressive and to increase their dispersion throughout the healthy brain. We will further assess whether this protein is preferentially produced in more aggressive cancer stem cells and whether this contributes to the ability of glioblastoma to escape immune surveillance. Studying whether blocking the functions of this protein can reduce glioblastoma aggressiveness will reveal if this approach is useful as a new strategy for cancer treatment. These studies are an essential step towards a better understanding of the biology of highly aggressive brain cancers and will set the stage for future development of new anti-cancer therapies.

Are prostate cancer stem-cells susceptible to T cell-mediated killing? Amy Codd

Student: Amy Codd Supervisor: Dr Zsuzsanna Tabi

Co-supervisor: Dr Stephen Man Velindre Cancer Centre Start Date: Oct 2015

Conventional cancer treatments, such as radio- or chemotherapy, may eliminate the bulk of tumours but spare highly aggressive cancer cells that have an exceptional capacity to survive and multiply, leading to tumour recurrence. These residual cells are called cancer stem cells and their resistance and persistence is thought to be responsible for the failure of conventional cancer treatments. A different treatment approach, called immunotherapy, is gaining importance for the treatment of various cancers, including prostate cancer. It utilizes the patients’ own immune cells to specifically attack the tumour. Early prostate cancer can be treated successfully with radiotherapy in many patients but local recurrence is common. One possible reason behind it is the re-growth of the tumour from cancer stem cells. We hypothesise that cancer stem cells that are resistant to radiotherapy are still susceptible to attack by immune cells. There is relatively little known about the susceptibility of stem cells to immune attack. We are proposing to study, for the first time, whether immune cells in prostate cancer can target radiation-resistant cancer stem cells effectively. The results will provide important information for the design of new treatment approaches that eliminate not only the bulk of the tumour but also the highly aggressive and resistant cancer stem cells.

Targeting zinc signalling to prevent cell division in cancer Silvia

Student: Silvia Ziliotto

Supervisor: Dr Kathryn Taylor School of Pharmacy and Pharmaceutical Sciences, Cardiff University Start Date: Oct 2015

Cancer cells divide and grow much quicker than ordinary cells thus making targeting cell division to reduce cancer growth a viable clinical prospect. Zinc is an essential dietary nutrient, known to be essential for cell division for over 50 years but the exact mechanism of zinc function is still undiscovered. Zinc transporters are molecules that control the zinc level cells and our recent discovery of a new mechanism of how they work has led to our breakthrough that they are not only involved in cell division but are actually required for the initiation of cell division. We have recently discovered that two of these zinc transporters, called ZIP6 and ZIP10, are required to be on the outside of cells before cell division can start. We did this by blocking the function of these two zinc transporters using specific antibodies to each one which completely abolished the onset of cell division. This is an extremely exciting and important result that now needs further investigation to allow us to decipher the exact molecular mechanism involved. This information provides useful information that will allow new targets to be designed to inhibit the activation of these zinc transporters, and thus prevent cell division and reduce cancer growth. Additionally, since these zinc transporters are only involved in cell division when on the cell surface, any drugs that target them may have potentially few side effects. Furthermore, because these agents are essential for cell division, any new drugs should be relevant to many different cancer types.

Genetic instability upon loss of the tumour suppressor Folliculin Rachel Russell

Student: Rachel Russell

Supervisor: Dr Andy Tee
Co-supervisor: Professor Duncan Baird Institute of Cancer and Genetics, Cardiff University Start Date: Oct 2015

Genetic material within the human body is constantly being damaged by environmental factors that over time can lead to cancer. Examples of DNA damaging factors include: ultraviolet irradiation, a component of sunlight, and carcinogens, such as those found in cigarette smoke. Luckily, we have numerous methods to repair DNA-damage, termed the DNA-damage response. However, when genetic information is not properly maintained, damaging changes to our DNA occur and will accumulate over time, leading to life threatening cancer. A faulty copy of the FLCN gene causes the genetic disease, Birt-Hogg- Dubé (BHD) syndrome, and patients with this condition have increased risk of developing kidney cancer. We recently discovered that human cells lacking FLCN exhibit increasing DNA damage over time (referred to as genetic instability), which would help explain why BHD syndrome patients are prone to cancer. Genetic conditions, such as BHD syndrome that predispose individuals to cancer, provide valuable insight into tumour development within the general population. Using BHD syndrome as a model of genetic instability, this project will investigate how FLCN maintains our genetic code to prevent cancer. We will look at changes to DNA structures called telomeres which function to protect our DNA from damaging alterations. Additionally, we will examine how FLCN interacts with other DNA binding proteins that are instrumental in keeping our genetic material healthy. Overall, the project will address fundamental and important scientific gaps in our knowledge of human disease and cancer biology through understanding how FLCN prevents the formation of tumours.

T-cell correlates of successful immunotherapy

Sarah GStudent: Sarah Galloway

Supervisor: Professor Andrew Sewell Co-Supervisors: Dr Meriem Attaff, Dr Garry Dolton, Dr Tomas Connork  Institute of Infection and Immunity, Cardiff University Start Date: Oct 2016

‘Rapid TIL’ immunotherapy for end-stage metastatic melanoma involves removing the immune cells from a melanoma lesion, expanding these cells in the laboratory and then putting them back into the patient’s blood (Figure 2). Remarkably, this process is currently resulting in a cure rate of ~35% with disease steadying in a further 3rd of patients. We believe that this cure will be lifelong in much the same way as we are protected against an infection once our immune system has successfully cleared it. We have privileged access to patients that have been cured using rapid TIL therapy by the leading centre pioneering this new therapy in Europe. We have identified that the main cells that recognize the cancer within these immune cells are killer T-cells. These anti-cancer killer T-cells appear to attack the cancer in more than a hundred different ways within an individual patient. Killer T-cells ‘seek and destroy’ the cancer cells using a molecule on their surface called the T-cell receptor (TCR). We aim to determine which TCRs are used by the patients that successfully clear their cancer. This will allow us to better understand why this therapy succeeds and then aim to replicate this success in other patients and with other types of cancer. Our initial studies have shown that the killer T-cells from these patients can often kill other types of cancer. We aim to provide the first ever in depth dissection of how and why such therapy succeeds.