Microglia are the primary immune cells of the central nervous system (CNS) and play a crucial role in maintaining brain health and function. Acting as the first line of defense, microglia continuously monitor the brain environment for signs of infection or injury. When activated, they become highly responsive, capable of modulating inflammatory responses, clearing cellular debris, and maintaining neuronal homeostasis. Microglia also play a significant role in synaptic pruning, which is essential for normal brain development and plasticity. However, when microglial activation becomes dysregulated, often due to factors like substance use, chronic stress, or neurodegenerative diseases, it can lead to neuroinflammation that underlies several neurological disorders. Thus, understanding the role of microglia is critical not only to fundamental neuroscience but also to the development of therapeutic strategies for CNS-related disorders. We study the molecular mechanisms underlying microglia dysregulation caused by substance use.

One of our focus areas is methamphetamine use disorder (MUD), which is a major public health problem associated with neurotoxicity and glial cell dysfunction. In the CNS, neurotoxic pathways are typically counterbalanced by cytoprotective pathways, but this balance is disrupted by substance use. There are currently no FDA-approved pharmacologic treatments for MUD. We are exploring cytoprotective molecules that could restore homeostasis in the CNS. Our long-term goal is to identify novel or repurposed molecules that regulate cellular activation, oxidative stress, and neuroinflammation in the context of substance use disorders (SUD). 

To better understand these challenges, we investigate the molecular mechanisms involved in SUD, particularly through the lens of microglia, the primary resident immune cell type in the CNS. Using cell culture and mouse models, we assess how cytoprotective molecules might mitigate the effects of SUD-induced neuroinflammation and oxidative stress, ultimately aiming to re-balance disrupted pathways and promote CNS health.