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We are interested in how the cells and other factors surrounding a tumour (the ‘tumour microenvironment’) affect cancer development and spread. In particular we examine how molecules termed non-coding RNA influence this communication, and what roles extracellular vesicles may play in this. We are using this information to find new drug targets to improve survival. We are also interested in how non-coding RNA influence the ways in which human cells respond to bacteria, with the aim of understanding how this may be involved in the development of disease.

The cells and extracellular matrix that surround tumours, collectively termed the tumour microenvironment, are critically important in regulating metastatic spread to other parts of the body. We are pursuing a number of research avenues which aim to identify diagnostic markers and prognostic indicators within the tumour microenvironment and to elucidate novel therapeutic targets to halt disease progression:

The role of non-coding RNA in the tumour microenvironment

Non-coding RNA (which do not encode proteins) make up a significant proportion of the RNA in a cell, but their functions are still enigmatic. MicroRNA, perhaps the best understood non-coding RNA, are small RNA which regulate the expression of target genes by binding to complementary sequences in their transcripts. Changes in the levels of a number of microRNA have been detected in a variety of cancers, and understanding is growing of their role in the tumour microenvironment. We study how miRNA in both cancer cells and cells of the tumour microenvironment change during the development and spread of cancer, how they influence disease progression, and how they may be used clinically. We are also studying whether other non-coding RNA, such as long non-coding RNA (lncRNA) play a role in regulating tumour:microenvironmental interactions. We are exploring the importance of extracellular vesicles as vehicles by which non-coding RNA and other cargo may transfer between cells in the tumour microenvironment.

The role of peptides in the tumour microenvironment

The tumour microenvironment is host to a wealth of small peptides and proteins, generated locally or elsewhere in the body and introduced from the circulation. These peptides may be further modified by proteolytic enzymes in the microenvironment and often bind to receptors on the surface of a variety of cell types, influencing tumour growth and spread. We are investigating these interactions with the aim of developing novel targets for drug treatments.

Host-microbe interactions in disease

Chronic periodontitis, an inflammatory disease leading to tooth loss, affects over 300 million people worldwide and is a significant healthcare burden particularly in the older population. Although not a classical infectious disease, the role of bacteria in causing periodontitis is unequivocal with several bacterial species such as Porphyromonas gingivalis and Tannerella forsythia being implicated as causative agents. The virulence of periodontal pathogens is attributed not only to bacterial factors that directly damage tissue but also to their ability to dysregulate the host immune response. We are currently investigating the ability of periodontal pathogens to modulate the immune response by altering the expression of specific microRNA and other non-coding RNA, which in turn influence the expression of components of the innate immune response.