Pilot research projects

Disease Type: Oral cancer
Research Target: Underpinning biology; Treatment targets; Biological markers
Lead Researcher: Karolin Hijazi
Location: University of Aberdeen
Funding: £14,973

Oral cancer, including tongue, cheek, palate and lip, is a significant health problem in Scotland, where rates are almost double those seen in England. Despite some advances in treatment, the prognosis of this cancer remains poor, mainly because of late diagnosis. Whilst a wealth of knowledge is emerging in relation to the role of human bacteria, diet and the immune system in a range of cancers, there remains little knowledge of the importance of these factors in oral cancer.

Three groups of patients attending NHS clinics will be asked to take part in the study: oral cancer patients, those with oral pre-cancer, and a comparator group of patients who have neither oral cancer or pre-cancer. The researchers will use cutting-edge technologies to compare patterns in the diets of the people within the study, as well as mouth and gut bacteria, inflammation factors and microscopic changes within their cells and tissues. By examining the results and the relationships between these factors, the group aims to provide initial knowledge that can then be taken to the next level

This early seed project, along with its subsequent large study, have the potential to define the role of oral and gut bacteria, in order to improve early diagnosis of oral cancer and pre-cancer. Given the focus on diet within this study, the project could also identify dietary factors that can be exploited for prevention of oral cancer and pre-cancer progression. These two outcomes would ultimately contribute to the development of technologies that will alleviate the suffering and the mortality rates of oral cancer patients in Scotland and beyond.

Disease Type: Colon cancer
Research Target: Underpinning biology, Biological markers, New technology
Lead Researcher: Mr George Ramsay
Location: University of Aberdeen
Funding: £13,679

The large intestine is the last part of the digestive tract, and absorbs water and dietary substances. However, it is also where most of our bacteria are resident. These bacteria are important for our health and influence many different diseases, including colon cancer, ulcerative colitis and Crohn’s disease. The interactions between these bacteria and the rest of our cells are only now becoming understood. Whilst the large intestine is only one organ, it is more than a metre long and is situated in our abdomen as well as our pelvis. It is known that the genes and structure of the large intestine change along its length but what is not as well understood is if the bacteria change as well.

This study will work in direct conjuction with patients, as the research group will identify patients with right sided bowel cancer who require an operation to remove their cancer. The research team will ask for samples of the patient’s last poo before their operation and compare this with the gut contents taken from the colon section removed during their operation. By doing so, they will be able to compare the profile of right sided bugs with those in the rectum, thereby increasing our understanding of the colonic bacteria.

To do this, scientists will process the poo specimens to remove the bacterial genetic material (DNA) and process it on a machine to read the genetic code. They can then make a direct comparison between different samples of the relative numbers of different bacteria present.

We have some evidence from research recently published from our region that having had some antibiotics previously might increase the risk of right sided bowel cancer. We wish to work out if this can occur, and the work in this study would be the first step in undertaking a larger study to explore any connection between antibiotics, bacteria and bowel cancer. By understanding these interactions further, we might be able to influence the potential cause of these cancers and therefore potentially reduce their frequency or improve the treatment options available to future patients.

Disease Type: Blood disorders - sickle cell disease
Research Target: Underpinning biology; Treatment targets; New technology
Lead Researcher: Dr Nicola Mutch
Location: University of Aberdeen
Funding: £15,000

Sickle cell disease (SCD) is a group of rare inherited red blood cell disorders. Healthy red blood cells are round, but in individuals with SCD they become hard and sticky and look like a C-shaped farm tool called a “sickle”. Sickle cells die early and express aberrant signals on their surface, which causes a constant shortage of red blood cells (anaemia) and alters their interaction with other cells and molecules. Blockages of blood vessels, both temporary and permanent, cause many of the problems that SCD patients suffer from, including clots in both veins and arteries. Very little is currently known about how sickle cells impact on blood clotting.

Our work has previously shown that, in other diseases, a reduced number of red blood cells can enhance blood clot formation and alter the body’s ability to remove blood clots from the circulation. We also know that a chronic inflammatory state can promote blood clotting.

In this study we will analyse whether the blood clotting complications in SCD arise from the specific shape change in the red blood cells, the number of red blood cells present, changes on the surface of the red blood cells or an increase in inflammatory markers. To do this we will use several specialised techniques to monitor blood clot formation, strength and stability using blood from SCD patients compared to normal healthy controls.

There is a strong need for studies to identify key mechanisms and pathways that play a significant role in Sickle Cell Disease (SCD). Affected individuals and their families are extremely aware of the cruel and relentless nature of this condition and how it affects their ethnic group. New treatments for sickle cell disease are desperately needed and these will only be developed by understanding how the underlying mutation causes its clinical manifestations. Our studies could lead to the identification of therapeutic targets to improve the health outcomes and quality of life for affected individuals and their families.

Disease Type: Oncology
Research Target: Underpinning biology; Treatment targets; Imaging markers
Lead Researcher: Dr Sergio Dall'Angelo
Location: University of Aberdeen
Funding: £9,770

The use of natural toxins to treat cancer is not a novel idea and some toxin-derived drugs like Paclitaxel are well established in the clinic and more drugs are in development. All these treatments are effective in controlling tumour cell growth, unfortunately they have a significant toxicity toward healthy cells. To reduce this toxicity and to target these treatments specifically to cancer cells there are efforts in finding the “magic bullet” that can discriminate between cancerous and healthy cells.

All cells have on their surface proteins with sugar molecules attached to them and recently it has been found that cancer cells have different ways to attach these sugars. These differences have been already used in cancer diagnosis and prognosis, but they can also be used to specifically direct drugs toward cancer. Intriguingly, one powerful toxin produced by some strains of a Salmonella enterica uses some of the sugars that are more abundant on the cancer cells to attach and penetrate the cells suggesting that its toxicity could be increased toward cancer cells.

The inflammatory response protects the body against infection by activating an initial “pro-inflammatory stage”, involving the recruitment of white blood cells to the site of injury, culminating in the characteristic signs of inflammation such as swelling, redness and pain. The second anti-inflammatory stage serves to resolve and switch off this process to return the system to its previous, uninflamed condition. Failure to successfully regulate this leads to chronic inflammatory diseases such as sepsis. The formyl peptide receptor 2 (FPR2) has been proposed as a potential candidate for the development of novel therapeutics in this area. This receptor is a protein residing in the membrane of cells that, once activated, initiates a cascade of downstream signalling molecules. Recent research has shown that FPR2 is essential in controlling the switch from pro-inflammation to pro-resolution signalling to enable tissue healing and a return to ‘normal’ physiology. However, further investigation into the mechanism of this response is needed before new treatments can be developed.

We researchers aim to generate a tumour-specific delivery system that exploits the difference in the sugars between transformed and non-transformed cells. Such platform will benefit patients in different ways. We could potentially develop a new treatment for cancer. A targeted drug delivery system that will minimise or remove the chemotherapy side effects on healthy cells. Moreover, finding a better system to direct the toxicity toward cancer cells, will allow the use of already known drugs that are highly effective currently, to be used as treatment because of the serious toxicity on normal cells.

Disease Type: Breast cancer
Research Target: New technology; imaging markers
Lead Researcher: Dr Jiabao He
Location: University of Aberdeen
Funding: £14,663

We aim to investigate if UTE can show a difference between malignant and benign calcium deposits, and the link with dead tissue and speed of tumour growth. We will conduct a 2-arm study in 32 patients, one arm with confirmed calcium deposits on mammography and the other arm without calcium deposits. Each patient will undergo a single UTE imaging scan on a clinical research 3T MRI scanner (Ingenia dStream Conversion, Philips Healthcare, Best, Netherlands) at Aberdeen Biomedical Imaging Centre. The results from UTE imaging will be checked against the results from pathology, to assess the ability of UTE imaging for accurate early detection of malignant calcium deposits even before surgery.

Using specialist MRI methods, the team will compare premenopausal genetic mutation carriers against premenopausal controls, with an aim to improve early and accurate cancer detection in women at high risk of breast cancer through a better understanding of the role of fat composition in breast cancer development. This project represents the very first attempt in the investigation of prevention and initiation of breast cancer using novel imaging methods. The team is uniquely positioned to conduct this research in Aberdeen, thanks to the specialist MR imaging capabilities within the University of Aberdeen.

This project will develop a novel imaging method to sort malignant and benign lesions non-invasively (without the use of needle), allowing a more accurate early diagnosis of breast cancer. Since the optimal clinical treatment for benign and malignant lesions are significantly different, the developed method will facilitate precision medicine for personalise care.