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BioE PhD Proposal
Alyssa F. Pybus
January 22nd, 2021, 1:00 PM
Link: https://bluejeans.com/762484317
Advisor:
Levi B. Wood, Ph.D.
ME, Georgia Institute of Technology
Committee Members:
Erin M. Buckley, Ph.D.
BME, Georgia Institute of Technology and Emory University
Michelle C. LaPlaca, Ph.D.
BME, Georgia Institute of Technology and Emory University
Manu O. Platt, Ph.D.
BME, Georgia Institute of Technology and Emory University
Srikant Rangaraju, M.D. M.S.
Department of Neurology, Emory University
Systems Analysis of Neuroinflammation in Repetitive Mild Traumatic Brain Injury
Repetitive mild traumatic brain injury (rmTBI) has been linked to devastating long-term neurological pathologies including chronic traumatic encephalopathy, which disproportionately affects athletes, military service members, and victims of domestic abuse. Despite the grave public health concern that rmTBI presents, current therapeutic strategies are limited. It is necessary to illuminate the molecular mechanisms underlying neurodegeneration after injury to identify candidate therapies.
Neuroinflammation is implicated in severe traumatic brain injury and represents a likely culprit for driving pathology after rmTBI. The objective of this study is to understand the mechanisms driving neuroinflammation after rmTBI. My hypothesis is that neuroinflammation after rmTBI is driven by specific intracellular signaling pathways first activated in neurons, and that these pathways can be inhibited to improve outcome after rmTBI. The proposed work will identify cell type specific acute phospho-protein signaling pathways and cytokines associated with poor cognitive outcome after rmTBI, investigate neuroinflammatory signaling and its relationship to pathological progression after rmTBI in an Alzheimer’s disease mouse model, and determine whether small molecule inhibition of inflammatory signaling pathways can improve outcome after rmTBI. Uncovering signaling mechanisms driving neuroinflammation after rmTBI will identify possible therapeutic targets for pharmaceutical intervention to improve clinical outcomes of patients recovering from brain injury.
