Research

Subcellular mitochondrial positioning dictates local metabolite levels:

Signal InputMitochondria, the powerhouse of our cells are dynamic organelles that orchestrate numerous cellular process. Mitochondria change shape, size and position within cells and between cells based on cellular cues including metabolic needs, redox status and varying inter- and intracellular stimuli. The movement of mitochondria is coordinated by a specific set of adapter proteins that connect mitochondria to microtubule motors for transport. The transport of mitochondria to specific subcellular locations influences the local metabolic state and induces cell responses. For example, our work has demonstrated that mitochondrial movement to the leading edge of migrating cells fuels cell migration, a process required for tumor cell metastasis. Projects in the lab focus on determining factors that govern subcellular mitochondrial movement and how local mitochondrial metabolites regulate cell signaling pathways and downstream cell outcomes.

Current Projects with opportunities for Rotation Projects:
  1.  The influence of mitochondrial positioning on subcellular reactive oxygen species levels and protein redox status.
  2. Metabolic control of subcellular mitochondrial movement.
  3. Mitochondrial dynamics dictating lung epithelial response to allergic insults.
Pro-migratory pathways

Model: Mitochondria couple to microtubule motors through the action of adapter proteins Miro1 and Trak1/2. Signal input in the form of metabolic and/or 2nd messenger signals controls mitochondrial movement. Mitochondrial movement promotes localized production of mitochondrial metabolites such as ATP and reactive oxygen species (ROS). 


Mitochondrial redox status as a therapeutic target in cancer:

Tumor cells reorganize mitochondrial metabolism to survive and proliferate. Changes in mitochondrial function in cancer leads to altered redox balance in which tumor cells are under increased mitochondrial oxidative stress. This provides a window for therapeutic intervention exploitable through redox-dependent therapies. We are investigating mitochondrial metabolism in malignant mesothelioma and ovarian cancer and have identified promising new compounds that selectively kill tumor cells through redox-dependent mechanisms. 
Rotation projects related to mitochondrial metabolism in supporting redox-dependent pro-tumorigenic signaling are available.
Mitochondrial Redox Status
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