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One or more keywords matched the following properties of Macleod, Kay
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overview Understanding the role of mitochondria in tissue homeostasis and cancer. The Macleod Lab investigates how control of mitochondrial mass, mitochondrial function and mitochondrial signaling affects cellular responses to stress, homeostatic control of tissue maintenance and influences tumor growth and progression to malignancy. We use cutting edge approaches in cell and molecular biology, systems biology, novel mouse models and human patient samples to ask some of the most important questions about how mitochondria control tissue homeostasis, and how mitochondrial dysfunction contributes to cancer progression and metastasis. For example, we examine how BNIP3-dependent mitophagy is essential for proper metabolic zonation in the liver across the hypoxic gradient making up the liver lobule and how loss of BNIP3 promotes hepatic steatosis and liver cancer. This tumor suppressive role of BNIP3 involves coordinated turnover of lipid droplets with mitochondria at the autolysosome in a process we have termed “mitolipophagy”. In addition, we address how the BNIP3-related protein, BNIP3L (or NIX) which is also a mitochondrial cargo receptor, shares mitophagy functions with BNIP3 but we are increasingly focused on the divergent properties of BNIP3 and NIX in cellular growth control, both in the liver and in the pancreas. Our work indicates that while BNIP3 and NIX share functions in mitophagy in various tissues, they also possess unique growth control properties that explain how BNIP3 functions to suppress tumor growth while NIX acts as a tumor promoter. Ongoing work is addressing these functions in hepatocellular carcinoma, pancreatic ductal adenocarcinoma and in muscle atrophy linked to cancer cachexia. In other areas, we are examining how defects in mitophagy can promote tumor responses to chemotherapy and radiotherapy. Finally, we are examining how mitochondrial stress affects other signaling pathways in the cell.
One or more keywords matched the following items that are connected to Macleod, Kay
Item TypeName
Concept Adaptor Proteins, Signal Transducing
Concept Intracellular Signaling Peptides and Proteins
Concept Signal Transduction
Concept Signal-To-Noise Ratio
Academic Article Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system.
Academic Article Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
Academic Article The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system.
Academic Article Autophagy: cellular and molecular mechanisms.
Academic Article High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.
Academic Article p62/SQSTM1 accumulation in squamous cell carcinoma of head and neck predicts sensitivity to phosphatidylinositol 3-kinase pathway inhibitors.
Academic Article Measuring autophagy in stressed cells.
Academic Article Novel insights into how autophagy regulates tumor cell motility.
Academic Article In Brief: Mitophagy: mechanisms and role in human disease.
Academic Article Autophagy in cancer metastasis.
Academic Article Expanding perspectives on the significance of mitophagy in cancer.
Academic Article Dia1-dependent adhesions are required by epithelial tissues to initiate invasion.
Academic Article mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors.
Academic Article Autophagy in major human diseases.
Academic Article ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3.
Grant Functions of pRb in Stress Erythropoiesis
Grant Multi-Disciplinary Training grant in Cancer Research
Grant (PQ5) Consequences of imbalanced mitophagy and mitochondrial biogenesis in cancer
Grant BNIP3 and BNIP3L (NIX) in lipid homeostasis and growth control in the liver
Search Criteria
  • Signaling
  • Pathways