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Macleod, Kay

One or more keywords matched the following properties of Macleod, Kay

Property	Value
keywords	Mitochondria
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.

Property

Value

keywords

Mitochondria

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 Type	Name
Concept	Mitochondria, Liver
Academic Article	Regulation of mitochondrial integrity, autophagy and cell survival by BNIP3.
Academic Article	Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
Academic Article	BNip3 regulates mitochondrial function and lipid metabolism in the liver.
Academic Article	Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors.
Academic Article	Tumor suppressor functions of BNIP3 and mitophagy.
Academic Article	In Brief: Mitophagy: mechanisms and role in human disease.
Academic Article	Expanding perspectives on the significance of mitophagy in cancer.
Academic Article	Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes.
Academic Article	Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer.
Academic Article	BNIP3-dependent mitophagy promotes cytosolic localization of LC3B and metabolic homeostasis in the liver.
Academic Article	Mitophagy in tumorigenesis and metastasis.
Grant	(PQ5) Consequences of imbalanced mitophagy and mitochondrial biogenesis in cancer
Grant	Functions of BNIP3 in Mammary Tumorigenesis
Grant	BNIP3 and BNIP3L (NIX) in lipid homeostasis and growth control in the liver

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Mitochondria