Matching Items (2)
Description
Aberrant signaling through the canonical RAS/RAF/MEK/ERK (ERK/MAPK) pathway leads to the pathology of a group of neurodevelopmental disorders called RASopathies. RASopathies are caused by germline mutations in the ERK/MAPK pathway and have an incidence of approximately 1:2000 births. The majority of RASopathies stem from mutations that cause gain-of-function in the ERK/MAPK pathway. In this study, we have begun to unravel the roles that GABAergic interneurons play in the pathology of RASopathies. Our data demonstrate that gain-of-function ERK/MAPK signaling expressed in a GABAergic interneuron-specific fashion leads to forebrain hyperexcitability in mutant mice. Further, some GABAergic interneurons experience activated-caspase 3 mediated apoptosis in the embryonic subpallium, leading to a loss of PV-expressing interneurons in the somatosensory cortex. We found that pharmaceutical intervention during embryogenesis using a MEK1 inhibitor may be effective in preventing apoptosis of these neurons. Future work is still needed to understand the mechanism of the death of GABAergic interneurons and to further pursue therapeutic approaches. Taken together, this study suggests potential roles of cortical GABAergic interneurons in ERK/MAPK-linked pathologies and indicates possible approaches to provide therapy for these conditions.
ContributorsShah, Shiv (Author) / Newbern, Jason (Thesis director) / Gipson-Reichardt, Cassandra (Committee member) / School of Life Sciences (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Medical Humanities captures the broad interdisciplinary study of medicine in literature and art. This field of study, that was once in the margins of academic research, has recently appeared at the vanguard of literary studies. Grey Matter is an original journal conceived by medical students at the University of Arizona: College of Medicine in Phoenix and engaged the local Phoenix community to share medically related experiences through poetry. I am currently serving as the Managing Editor of the journal and oversee all of the operations including editorial duties, marketing promotion, and event management. My project will involve curating a collection of poems from the local Phoenix community and organize events to allow for selected poets to share their stories
ContributorsShah, Shiv (Author) / Dombrowski, Rosemarie (Thesis director) / Harkmark-Hill, Jennifer (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of English (Contributor)
Created2022-12