The research in Zou’s lab focuses on understanding the molecular mechanisms underlying pathogenic events of neurodegenerative diseases and developing corresponding treatment strategies in cell-type specific manner. We are mainly focusing on exploring molecular regulators of cell death and neuroinflammation in different types of central nervous system cells and peripheral immune cells.

We have uncovered a novel state of inflammatory microglia in amyotrophic lateral sclerosis, the prevalence of which could be prevented by inhibiting RIPK1 and thus termed as RIPK1-Regulated Inflammatory microglia (RRIMs). The finding of RRIMs helps to elucidate a mechanism by which inhibiting RIPK1 provides therapeutic benefits in ALS.

We have previously shown the selective vulnerability of venular and capillary cerebral endothelial cells to necroptosis in Alzheimer’s disease and identified reduced cerebral endothelial expression of murine N-acetyltransferase 1 that could promote endothelial necroptosis and cause blood brain barrier damage. Our study suggests that targeting peripherally facing cerebral endothelial cells that do not require BBB penetrant therapeutics may provide a strategic target for AD therapies.

One of the keys to successfully treat AD is to identify pathophysiological events in its preclinical stages. We have previously observed impaired dendric spine structural plasticity in preclinical AD and identified multiple underlying molecular mechanisms, including elevated neuroinflammatory cytokines, disturbed extracellular D-serine homeostasis and increased intraneuronal amyloid precursor protein. These studies have provided valuable insights into the biology of dendritic spines and may open avenues for discovery of novel therapeutic targets for AD.