Brain inflammation (neuroinflammation) has recently garnered significant attention as a novel therapeutic target for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. However, precise mechanisms underlying the initiation and progression of brain inflammation and blood-brain barrier (BBB) disruption still remain unclear. Our goal is to understand how inflammation in the central nervous system (CNS) is initiated under various physiological and pathological conditions, including systemic inflammation, brain disorders, and external stress and to unravel the potential role of neuroinflammation for the pathogenesis of neurological disorders. Within the unique immunological environment of the brain, we explore the pivotal role of brain-resident glial cells and brain-infiltrating myeloid cells in orchestrating immune-neural function in the brain parenchyma. Ultimately, our effort seeks to unveil promising avenues for therapeutic interventions in many neurological disorders.

‘Circadian clock’ controls the daily timing of numerous physiological, metabolic, and biochemical processes. The mammalian molecular clock machinery is present in nearly all cell types, including immune cells. Consequently, the immune system exhibits circadian fluctuation in the levels of chemokines, cytokines, and circulating innate and adaptive immune cells, as well as in the expression of clock-controlled genes that influence immune function. Furthermore, the intensity of immune responses in the inflammatory diseases, such as atopic dermatitis, asthma, and sepsis, vary according to the time of day. We aim to elucidate the molecular mechanisms by which circadian rhythms and circadian clock machinery regulate immune responses in the inflamed tissues mainly using the cell-specific circadian disruption mouse models. Ultimately, we aim to develop more effective chronotherapeutic approaches for these inflammatory diseases.

Inflammation is an immune cell-mediated host defense response that removes potentially dangerous foreign molecules and endogenous metabolites. Upon tissue injury and damage, the inflammatory process initiated by damaged-associated molecular patterns (DAMPs), act as a critical step in activating tissue regenerative programs and aiding the proliferation and differentiation of neighboring stem cells. Among these inflammatory responses, we focus on the role of an immune complex called the inflammasome. The inflammasome is a caspase-1-activating intracellular protein complex that induces the formation of gasdermin D (GSDMD) pores, through which the release of pro-inflammatory cytokine (ex. IL-1β, IL-18) occurs. Our laboratory aims to elucidate how DAMP-mediated activation of inflammasome complex and GSDMD pore formation regulate proliferative capacity of neighboring progenitor/stem cells and the overall regenerative outcome of injured tissue.