Targeting mitochondrial nucleotide metabolism in cancer

Targeting mitochondrial nucleotide metabolism in cancer

Dr Tom MacVicar

CRUK Beatson Institute 

Mitochondria provide cancer cells with the remarkable metabolic flexibility required to respond to signalling cues, environmental change and therapeutic intervention. My talk will focus on our recent advances in understanding how mitochondria metabolise nucleotides and regulate mitochondrial gene expression. We propose that mitochondrial nucleotide metabolism is an untapped therapeutic target in diseases associated with aberrant mitochondrial gene expression including cancer.

My fascination with the plasticity and dynamic nature of the mitochondrial network started during my PhD studies at the University of Bristol with Prof Jon Lane. I then moved to Prof Thomas Langer’s lab at the Max Planck Institute for Biology of Ageing and University of Cologne, Germany, with the support of EMBO and Alexander von Humboldt Postdoctoral Fellowships. We revealed that mitochondria can acutely rewire their proteome in response to hypoxia or nutrient starvation and highlighted how mitochondrial control of nucleotide metabolism can regulate innate immune signalling. Upon award of a CRUK Career Development Fellowship, I established my research group at the CRUK Beatson Institute in December 2021 with the overarching aim to uncover the metabolic vulnerabilities of cancer by targeting mitochondrial metabolite transporters and mitochondrial nucleotide metabolism. We combine cell biology approaches, including genetic screening and high-content imaging, with 3D tumour models to dissect the mechanisms of mitochondrial reprogramming during cancer progression.

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