I am a Newcastle University Research Fellow working within the Wellcome Centre for Mitochondrial Research. My group is focussed on investigating the role of mitochondrial DNA mutations in ageing stem cells and cancer. I am interested in elucidating the mechanisms by which mitochondrial DNA mutations occur and clonally expand within individual cells with age, and the functional consequences of these mutations on cellular homeostasis and tumour development.
I first became interested in mitochondrial genetics in 2002 when I began my PhD studies looking at the presence of mitochondrial DNA mutations in ageing human colonic epithelium. Upon discovering the high frequency of these mutations I wanted to pursue this area further to investigate their functional consequences at the cellular and tissue level, and to determine how they contribute to human ageing and disease.
Investigating the role of mitochondrial DNA mutations in ageing and cancer
1.Investigating the link between age-related accumulation of mitochondrial dysfunction and cancer development: We have shown that there is an accumulation of mitochondrial DNA mutations in a number of tissues as we get older. These mutations cause changes in the molecular mechanisms of cellular energy metabolism and are also prevalent in human cancers. We are using model systems to induce cancer in cells with mitochondrial dysfunction to see if there is any advantage to a tumour having alterations in their metabolic pathways due to age-related mitochondrial dysfunction. We are focussing on the colon and the prostate in particular, as age is the biggest risk factor for developing cancer in these tissues. We hope to develop targeted therapies to slow cancer growth based on our findings.
2.What is the effect of age-related mitochondrial DNA mutations on stem cell function? We know that there are changes in cellular metabolism due to age-related mitochondrial DNA mutations but we do not know what effect this has on the function of the cell as a whole, and in particular on stem cell regeneration. In this project we are testing the regenerative capacity of stem cells with mtDNA mutations and seeing whether we can modulate the regenerative response.
3.Why are inherited mtDNA mutations lost from stem cell populations with age? In contrast to ageing cells, some stem cell populations in patients with inherited mitochondrial DNA diseases are able to selectively deplete the levels of mutated mitochondrial DNA over time. We are investigating the underlying cellular and molecular mechanisms in the hope of harnessing these mechanisms to modulate the accumulation of age-related mitochondrial DNA mutations.
4.What are the mechanisms underlying intestinal pathogenesis in patients with mitochondrial DNA disease. We know that bowel problems are common in patients with mitochondrial DNA disease. We are investigating the effects of mitochondrial DNA mutations on intestinal motility, the gut microbiome and gut inflammation with aim of modulating these features to reduce symptoms.
Sponsor/Funder: Newcastle University Research Fellowship, LLHW Newcastle University Centre for Ageing and Vitality