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Clinical And Therapeutic Significance Of Obesity In Melanoma, Jennifer L. Mcquade
Clinical And Therapeutic Significance Of Obesity In Melanoma, Jennifer L. Mcquade
Dissertations & Theses (Open Access)
While the FDA approval of targeted and immune therapies in metastatic melanoma (MM) have dramatically improved outcomes in this disease, de novo and/or acquired resistance can limit the clinical benefit of these agents. The IGF-1/PI3K/AKT pathway has been implicated in resistance to both targeted and immune therapy. The IGF-1/PI3K/AKT pathway has also been shown to play a key role in the pathogenesis of obesity in other malignancies. To date, the impact of energy balance on clinical outcomes and therapeutic response in MM has not been studied. I hypothesized that energy balance would impact the molecular biology, behavior, and drug sensitivity …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Electronic Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …