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dc.contributor.authorVanegas, Camilo
dc.date.accessioned2024-02-02T16:39:34Z
dc.date.available2024-02-02T16:39:34Z
dc.date.issued2023
dc.identifier.urihttp://hdl.handle.net/10713/21349
dc.descriptionUniversity of Maryland, Baltimore, School of Medicine, Ph.D., 2023en_US
dc.description.abstractMicrotubules (MT) are dynamic polymers of tubulin protein whose post-translational modifications regulate MT interactions with other proteins, including intermediate filaments and actin. This integrated cytoskeletal network performs a vast array of cellular functions, including cell movement, transport of cellular cargo, defining cell shape and stiffness, and transmitting mechanical information to proteins that generate biological signals (mechanotransduction). My work is in Duchenne muscular dystrophy, where the absence of dystrophin leads to the proliferation of microtubules marked by an increase in posttranslational (PTM) modifications to their tubulin including detyrosination (deTyr-tubulin) and acetylation (acetyl-tubulin). The consequences of this change are increased cytoskeletal mechanics (i.e., stiffness) of the muscle fiber and increased mechanotransduction through NADPH Oxidase 2 (Nox2) dependent reactive oxygen species (ROS) and calcium signals during contraction that together have been implicated in the contraction injury that drives the pathology. My work addressed two open questions related to the pathobiology of these microtubule changes independent of dystrophic disease (Aim 1; Chapter 2) and the potential for targeting their reduction as a therapeutic option for halting or slowing disease progression (Aim 2; Chapter 3).en_US
dc.language.isoen_USen_US
dc.subjectX-ROSen_US
dc.subject.meshColchicineen_US
dc.subject.meshProtein Processing, Post-Translationalen_US
dc.subject.meshMuscular Dystrophy, Duchenneen_US
dc.subject.meshMicrotubulesen_US
dc.titleMicrotubules as a therapeutic target in Duchenne muscular dystrophyen_US
dc.typedissertationen_US
dc.date.updated2024-02-01T02:06:02Z
dc.language.rfc3066en
dc.contributor.advisorWard, Christopher, Ph.D.


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