Pilot research projects

Disease Type: Prostate cancer
Research Target: Prostate cancer, androgen resistance, G protein-coupled receptors
Lead Researcher: Dr Fiona Murray
Location: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen
Funding: £14,967

Prostate cancer is the second most common cause of cancer-related deaths in men, with cases expected to double by 2040.

It can be slowed through androgen deprivation therapy (ADT), a treatment that involves slowing or stopping the body from making testosterone. It can shrink prostate tumours or slow their growth.

However, aggressive forms of the disease develop resistance to ADT.

Discovering novel drug targets for effective treatment and uncovering diagnostic markers to identify aggressive prostate cancer are essential.

The team are looking at a specific G-protein receptor, known as the GPR75, to understand how it contributes to prostate cancer progression.

The lab has uncovered that genetic changes in GPR75 are associated with prostate cancer, so are investigating the regulation and function of it – with the hope it could become a novel biomarker and drug target for the disease.

The study focuses on uncovering the function of GPR75 and its impact in prostate cancer cells. The team will also examine how it can promote resistance to ADT.

By understanding the role of GPR75 in prostate cancer, the team would be able to provide evidence for its use as a drug target. Ultimately this could lead to new treatments to prevent the progression of prostate cancer.

Disease Type: Pelvic cancers
Research Target: Radiotherapy, pelvic cancers, dendritic cells, intestinal barrier, tumour micro-environment, cytotoxic T cells
Lead Researcher: Prof Anne Kiltie
Location: Rowett Institute, University of Aberdeen
Funding: £14,345

Patients receiving curative radiotherapy to their pelvic tumours, including prostate, bladder, gynecological or colorectal cancers, can suffer from intestinal side effects, due to the bowel receiving a dose of irradiation (radiotherapy).

This kills the lining cells of the intestine which allows the bacteria living in the gut to cross this barrier, ultimately causing inflammation which can result in diarrhoea.

Some bacteria cause less inflammation than others, so if the growth of these can be promoted the diarrhoeal side effects may be less severe.

Prof Kiltie’s team has previously discovered that some fibres can protect the intestine from radiation damage in mice, but more needs to be done to understand why. They have also shown that feeding mice these fibres can also slow the growth of tumours situated under the skin away from the intestine. This means something in the intestine related to the fibre intake is affecting the growth of these tumours, and the immune system might be involved.

This pilot project will investigate this further, looking at the chemicals produced by the beneficial bacteria and how they alter the immune cells, including dendritic cells and T-cells.

The team will test two hypotheses.

First, that intestinal dendritic cells contribute to dietary fibre's ability to protect the intestine from injury following ionising radiation.

Second, intestinal dendritic cells promote the anti-tumour effects of dietary fibre in mice.

The team will examine intestinal and tumour tissue from mouse experiments where mice were fed a low-fibre diet or one enriched with pectin, inulin or beta-glucan enriched flour before abdominal or tumour irradiation, staining them as they look for immune-related markers.

It is hoped this pilot project will provide the team with strong preliminary data to open up future funding opportunities to examine the mechanisms in more depth.

Ultimately this study could help reduce the side-effects pelvic cancer patients suffer while going through radiotherapy.

Disease Type:  Breast cancer
Lead Researcher: Dr Nicholas Senn
Location: Aberdeen Biomedical Imaging Centre, Institute of Medical Sciences, University of Aberdeen
Funding: £13,293.34

One in eight women will currently develop breast cancer in their lifetime, and by 2040 the number of women diagnosed is expected to rise by a quarter.

Treatments such as chemotherapy are increasingly being used before surgery to reduce the tumour’s size before it is removed and allow a larger amount of healthy tissue to be conserved.

However, not all patients respond well to these treatments and a more targeted approach is needed to further reduce tumour size and the amount of healthy tissue removed during surgery, while increasing the number of patients who respond best to treatment.

New ways to use this type of chemotherapy are being developed, which aim to tailor the treatment plan based on how well each patient responds to the first doses of chemotherapy.

Imaging is the only way to detect these changes during treatment, but currently available methods are not sensitive enough to detect changes after just one dose.

More tissue could be conserved during surgery if the boundary between tumour and healthy tissue can be more accurately measured.

To solve these problems, new ways of imaging breast cancer are needed.

The overall goal is to create new imaging methods that can measure early patient response to pre-surgery treatments and guide surgery planning.

The team will develop new ways of analysing breast cancer images obtained from field-cycling imaging (FCI), a new whole-body MRI technology pioneered at the University of Aberdeen.

As a first step towards this goal, Dr Senn will create the methods needed to match breast cancer images obtained from FCI directly to ground truth microscope images of tissue. This work will involve imaging breast cancer tissue samples provided by NHS Grampian Biorepository, in collaboration with Dr Ehab Husain and Joan Wilson (pictured).

These methods will then be used in future research projects to develop and test new imaging methods to see how well they can detect early reduction in tumour cells in response to chemotherapy and measure the boundary between tumour and healthy tissues.

This research will help develop and translate emerging MRI technologies towards improved breast cancer treatment outcomes.

Disease Type:  Oral cancer
Research Target: Oral cancer, potentially malignant oral disorders, immune profiling, disease progression
Lead Researcher: Dr Rasha Abu-Eid
Location: Institute of Dentistry, University of Aberdeen
Funding: £15,000

Dr Abu Eid’s project aims to identify markers that can predict disease progression and help clinicians identify patients at a higher risk of developing cancer and ultimately diagnosis patients at the early stages of the disease, where the potential for cure is more likely.

The research team  has identified changes in some immune markers across normal, OPMD and cancer tissues.

By using a platform called  Nanostring GeoMx, the team hope to identify markers associated with disease progression capable of identifying patients who are at higher risk of developing cancer.

They will analyse the immune profile in archival normal, premalignant and malignant oral tissues using advanced techniques combined with artificial intelligence. By doing this, they hope to identify markers for predicting disease progression and discover novel targets for cancer therapy

Ultimately, the study should help improve the ability to detect oral cancer at early stages and identify high risk patients, improving their outcome.

 

Lead Researcher: Dr Gael Morrow
Location:  School of Pharmacy & Life Sciences, Robert Gordon University
Funding: £12,348.72

Traumatic injury accounts for 4.9 million deaths worldwide each year. Approximately 25% of trauma patients die within six hours of injury from uncontrolled bleeding, termed trauma induced coagulopathy (TIC).

TIC describes the overall failure of the blood clotting system to stop bleeding after injury, and is associated with an increased risk need for transfusion therapy and increased risk of death.

Tranexamic acid (TXA) is an anti-fibrinolytic drug given to prevent bleeding. However, there is a short window of time (three hours post-injury) where it can be used safely.

Dr Morrow is investigating how changes in key molecules of the blood clotting process may cause TXA to become harmful after the three-hour therapeutic window.

Due to the difficulty in studying these early time points in humans, Dr Morrow will use a pig polytrauma model from the UK Defence Science and Technology Laboratory.

This will give her access to serial blood samples from the onset of injury, allowing her to study changes in molecules that are important in blood clot formation and degradation that may affect TXA efficiency and safety.

Dr Morrow will compare plasma samples taken at regular time points from the onset of injury to get a better understanding of changes in blood clotting molecules by measuring their concentration and activity levels, and performing microscopic analysis of blood clot structure.

This project will improve understanding of the early stages of TIC, and could help develop more targeted, precise transfusion therapies for trauma patients – potentially reducing trauma deaths.

The research will improve understanding of the cellular and molecular mechanisms of blood clot formation and degradation in health and disease states, which may improve the available treatments all patients with haematology disorders at risk of thrombosis or bleeding.