Seema Singh, PhD

Instructor

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Laboratory of Shilpa Buch, PhD

Research Interests

My research goal is to investigate the biochemical and molecular mechanisms underlying cognitive dysfunction and neurodegeneration associated with glial activation in individuals affected by drug addiction and HIV-related neurocognitive disorders (HAND). My research centers on understanding inflammasome activation, dysregulated autophagy, ER stress in glial cells like astrocytes and microglia, and the release of extracellular vesicles that contribute to neuronal injury in the context of substance abuse as well as HIV. Ultimately, my aim is to acquire profound insights into these molecular pathways to develop therapeutic interventions.

Ongoing Projects

Co-operative effects of substance abuse in NeuroHIV: 

Substance abuse, including cocaine and alcohol, is a significant factor associated with HIV infection, leading to chronic neuroinflammation characterized by the activation of microglia and astrocytes. These glial cells respond to HIV proteins like Transactivator of transcription (Tat) and drugs by initiating inflammasome activation, contributing to neuroinflammation and neurotoxicity. Autophagy, a cellular recycling mechanism, is impaired by HIV Tat and substances like cocaine and alcohol, affecting lysosomal function and leading to cellular stress. This stress triggers the unfolded protein response, which is crucial for maintaining protein homeostasis, but its impairment exacerbates neuroinflammation in HAND pathogenesis. Additionally, autophagy intersects with extracellular vesicle (EV) biogenesis, where dysregulated autophagy and EV release, influenced by HIV Tat exposure, promote the release of detrimental mediators of ferroptosis and inflammasome signaling via EVs, propagating neuroinflammation to astrocytes and neurons and contributing to disease progression.