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Full-Text Articles in Molecular Biology

Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar Jan 2016

Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar

Publicly Accessible Penn Dissertations

With breakthroughs in synthetic biology, improved cell culture techniques and advanced genetic engineering, it has now become possible to generate bi-specific primary human T cells with desired specificities. One mode of redirecting specificity is the modification of T cells to express chimeric antigen receptors (CARs). Recent studies indicate that natural T cells have distinct biochemical and metabolic features that endow them with short lived effector or long lived memory fates. The central objective of this thesis was to investigate whether the signaling endodomain of CARs could reprogram T cells with pre-specified effector and memory fates. This thesis describes a novel ...


Nampt-Mediated Nad+ Homeostasis In Skeletal Muscle: Implications For Healthy Aging, David Frederick Jan 2016

Nampt-Mediated Nad+ Homeostasis In Skeletal Muscle: Implications For Healthy Aging, David Frederick

Publicly Accessible Penn Dissertations

Mammalian skeletal muscle is a highly dynamic organ capable of structural and metabolic remodeling in response to exercise demands, nutrient supply, and environmental insults. Muscle also plays a central role in the maintenance of whole-body energy balance, capable of both storing and oxidizing carbohydrate and lipid fuels. The course of natural aging leads to a gradual decline in the mass, strength, and oxidative capacity of skeletal muscle, which increases the susceptibility of the elderly to frailty and metabolic diseases, such as Type II Diabetes. Ectopic muscle lipids can also exacerbate the metabolic complications of obesity, prompting interest in new means ...