Transcription-based Therapies for Stroke
Brain injury after cardiac arrest is a common condition with devastating consequences ranging in severity from memory loss to coma and death. Ischemia-induced gene expression controlled by the oxygen-dependent transcription factor HIF-1α and multiple factors associated with endoplasmic reticulum stress play important roles in the survival of brain cells following ischemic insults. These studies seek to identify new therapeutic nodes in oxygen-dependent signaling pathways that could serve as rational drug targets for global ischemic brain injury.
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Anti-inflammatory Strategies for Post Cardiac Arrest Syndrome (PCAS)
Neurologic recovery after cardiac arrest is complicated by systemic injury, which augments the peripheral immune response and increases the trafficking of leukocytes to the brain during reperfusion. After return of spontaneous circulation, reperfusion of the brain is accompanied by the migration of “primed,” neurotoxic neutrophils (PMNs) that cause blood-brain-barrier dysfunction and damage to local tissue with the release of degradative enzymes, cytokines, and reactive oxygen species. This project focuses on mediators of systemic inflammation, specifically the processes of PMN “priming” and “de-priming,” and how activation status affects PMN migration to the central nervous system and their cytotoxic potential once they encounter ischemic tissue.
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Phosphatase Regulation of HIF-1α Activity in Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (GBM) is the most common primary brain malignancy in the United States and represents a range phenotypes displaying extreme heterogeneity and aggressiveness. Hypoxic gradients within the tumor microenvironment activate transcription by the master regulator hypoxia-inducible factor 1α (HIF-1α) with profound effects on tumor metabolism among other cardinal features of the disorder. The current project tests the hypothesis that the mitogen-activated protein kinase phosphatase MKP-1 plays an important role in tumorigenesis through its ability to suppress HIF-1α activity.
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Medical Crowdsourcing / Mobile Health Technology Development
We developed and piloted the use of a mobile application for physicians called DocCHIRP (Crowdsourcing Health Information Retrieval Protocol), which uses a system of point-to-multipoint push notifications designed to help health care providers problem solve by crowdsourcing from their peers. Results from our use trial and post-trial surveys suggest that crowdsourcing could have significant value by assisting providers solve unusual cases, communicate with peers, and coordinate patient care activities between disciplines. Our ongoing work will investigate the benefits of this approach as well as ethical and legal implications of this novel and rapidly evolving information-sharing tool.
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