BSc (Hons) in Molecular Biology, The University of Edinburgh, Scotland; PhD, The Beatson Institute for Cancer Research, The University of Glasgow, Scotland; Post-doctoral fellow, The Pasteur Institute, France; Post-doctoral fellow, MIT, Cambridge, MA
Autophagy is a well-conserved survival mechanism that plays a cellular house keeping function in promoting the catabolic degradation of non-functional protein aggregates, organelles or pathogens by autolysosomes - â??garbage disposalâ? â?? and thus plays a key role in maintaining cellular integrity and promoting efficient cellular function. Autophagy is also ramped up in response to energy deficits when it becomes critical for generating ATP and metabolites for survival. Thus, not only is AUTOPHAGY the â??garbage collectorâ? â?? autophagy also promotes â??re-cyclingâ?.
The role of AUTOPHAGY in cancer is complex with evidence indicating it can act both as an anti-tumorigenic mechanism by inducing a growth arrest and cellular senescence, limiting genomic instability and maintaining organelle integrity while yet other data suggests that it can also be pro-tumorigenic by promoting tumor cell survival under hypoxia, allowing tumor cell dormancy at second sites that can lead to metastasis and limiting the therapeutic efficacy of anticancer treatments.
Work in the Macleod laboratory makes use of mouse models of cancer, in vivo imaging and clinical collaborations to explore the consequences of defective mitochondrial function and autophagy for tumor growth, progression to metastasis and cancer treatment.
Our work is specifically focused on the following goals:
(a) how defects in mitophagy contribute to tumor progression to metastasis, including through altered responses to hypoxia, levels of reactive oxygen species, and tumor cell invasion;
(b) how defects in mitophagy influence cellular metabolism and lipid catabolism in particular;
(c) use switchable mouse models of cancer to ask whether the role of autophagy in cancer varies depending on the stage of tumorigenesis, the driving oncogene or the tissue type;
(d) examine the effect of inhibiting autophagy for tumor cell invasion and metastasis in vivo;
(e) assess the effect of inhibiting or promoting autophagy for cancer therapy.