Research/Rotation Opportunities for Graduate Students
Within the framework of each of the ongoing research projects in the lab there are numerous opportunities for rotation projects. In the context of tau and Alzheimer disease project rotation projects could include: identifying the interactors in the complex that targets tau for autophagic degradation, delineating how different protein complexes orchestrate the maturation of the autophagic vacuoles or determining if certain differentially modified forms of tau are preferentially cleared by autophagy, using C.elegans to delineate if pathological tau species negative impact mitochondrial biology. In the context of the role of TG2 in differentially mediating cell survival processes in neurons and astrocytes rotation projects could include: determining how TG2 is mediating transcriptional repression in neurons and what signaling pathways are being predominantly affected and determining how and whyTG2 mediates differential gene expression in astrocytes that contribute to detrimental responses to ischemia
Research Opportunities for Residents
The Basic Science Division within the Department of Anesthesia wishes to invite faculty or residents to participate in a research project examining potential mechanisms for post-operative cognitive dysfunction after anesthesia. Postoperative cognitive dysfunction in the elderly is a common occurrence. Patients with Alzheimer disease (AD) are particularly at risk for the development of postoperative cognitive dysfunction. There are also studies suggesting that exposure to anesthesia may increase the risk of AD.
Intraneuronal neurofibrillary tangles composed of cleaved and hyperphosphorylated tau are a pathological hallmark of the Alzheimer disease (AD)brain. The abnormal cleavage and hyperphosphorylation of tau is a pivotal event in the neurodegenerative process in AD. However, it is not clear how these pathological forms of tau facilitate neuronal cell dysfunction and death. Recent studies have shown in mouse models that exposure to anesthetics results in persistent increases in tau phosphorylation, however the mechanisms involved remain unclear, and have been suggested to be due to the hypothermia rather than the anesthesia per se.
In this project a cellular model approach will be used to determine whether anesthesia alone, hypothermia alone or the combination of the two effect tau phosphorylation and function. Analyses will involve immunocytochemistry, immunoblotting, cell viability measures and fractionation assays
AG067617 -Tau Post-Translational Modifications and Mitochondrial Quality Control
NS098769 – The degradation of tau by selective autophagy
DOH01-C34458GG-3450000 Transglutaminase 2 as a therapeutic target to facilitate recovery after spinal cord injury
PubMed Publication List