Our group studies changes in metabolism and metabolic stresses that are caused by oncogene activation and how these stresses lead to tumour suppressive responses.
Dr Andy Finch will be joining the BCI in January 2020.
PhD position available in this lab.
Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence. Aging Cell (2019) 18(4): e12981 PMID: 31148378
AssayR: A Simple Mass Spectrometry Software Tool for Targeted Metabolic and Stable Isotope Tracer Analyses. Anal Chem (2017) 89(18):9616-9619. PMID: 28850215
Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev (2011) 25(9):917-929. PMID: 21536732
Bcl-xL gain of function and p19 ARF loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms. Cancer Cell (2006) 10(2):113-20. PMID: 16904610
Cells take up nutrients to meet their energetic and biosynthetic requirements and the balance between nutrient uptake and usage is a carefully controlled process. Thus when individual nutrients are in short supply, cells alter their metabolism to reduce consumption of that nutrient. This is a good example of cellular homeostasis - ‘the tendency towards a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes.'
Cancer cells usually have biosynthetic demands that are elevated and altered compared to those in normal cells. The proto-oncogenes Myc and Ras are strong drivers of growth and proliferation through activation of target genes and signalling pathways that activate processes such as ribosome and mitochondrial biogenesis, lipid synthesis and the cell cycle. However, when they are deregulated/activated they promote uncontrolled demand for nutrients and energy that may not always be met by supply, giving rise to metabolic stresses.
Our lab primarily studies metabolic stresses that accompany oncogene activation and how the cell responds to those stresses. We hope that by understanding these processes, we will reveal nodes of metabolic regulation that can be targeted to develop new cancer therapies.
I did my PhD with Jerry Saklatvala at the Babraham Institute and then the Kennedy Institute of Rheumatology in Hammersmith, studying protein kinases activated by interleukin 1. After my PhD, I went to work with Gerard Evan at the UCSF Cancer Center (in San Francisco) on mechanisms of oncogene-induced tumour suppression. During this period, I developed my interests in apoptosis, tumour suppression and homeostasis and I realised that cellular metabolism was a likely key contributor to these processes. I returned to the UK to work with Alan Warren at the MRC Laboratory of Molecular Biology (LMB) in Cambridge where I studied a disorder of ribosome biogenesis called Shwachmann Diamond Syndrome.
Since setting up my lab in 2013 at the Cancer Research UK Edinburgh Centre (part of the Institute of Genetics and Molecular Medicine, IGMM), I have focused upon metabolic stresses elicited by oncogene activation and how they lead to tumour suppressive outcomes (including apoptosis and senescence). I set up the mass spectrometry capability at the IGMM and developed my metabolic/metabolomic and lipidomic expertise there.
I joined Barts Cancer Institute in Jan 2020.