My research interests focus on the molecular mechanisms underlying neurodegenerative diseases, with a focus on Alzheimer Disease and HIV-Associated Neurocognitive Disorders (HAND). Accumulating evidence point to several pathways that are shared among distinct neurodegenerative conditions including oxidative stress, unfolded protein response (UPR), and neuroinflammation. HAND and AD exhibit different pathologic features; however, emerging evidence suggest that neuroinflammation stemming from soluble factors such as cytokines, TNF alpha, and glutamate released from infected/activated macrophages/microglia as well as astrocytes to the extracellular milieu culminate in axonal damage, dendritic simplification, and synaptic loss in both conditions. We have, in the past few years, shown UPR activation in HAND mid-frontal cortex and an in vitro model of HIV-induced neurodegeneration. We have also demonstrated that certain antiretroviral compounds that are prescribed to HIV-infected patients, including several protease inhibitors and integrase inhibitors, lead to synaptic and neuronal damage and death in vitro and in animal models in vivo via oxidative stress- or UPR-mediated mechanisms. My aim is to continue the evaluation of the potential unintended consequences of these life-saving compounds in the central nervous system, with a focus on neurons and astrocytes. A second aspect of my research interest is the role of the ATF6 arm of the UPR in primary HIV infection of macrophages. Our studies suggest that, among the three key regulators of the UPR, ATF6 is a cellular transcription factor contributing to the establishment of long-term HIV infection in macrophages, with a potential role in latency of HIV in these longer-lived tissue reservoirs. Overall, I hope identify the critical players within the UPR pathway that contribute to the dynamic cellular interplay between the glial cells (microglia and astrocytes) and the interpretation of these complex signals by the neurons, with the aim to identify genetic and biological biomarkers for personalized medicine and to develop novel therapeutics that can be utilized in neurodegenerative conditions with shared underlying mechanisms.