The immune and the nervous system evolved to respond to changes in the environment. Both systems recognize the outer world (by antibodies or sensory organs), learn (pathogens or food sources), and remember them. Back in 1967, Hood, Gray, & Dreyer proposed a genetic learning and memory mechanism for the immune and the nervous systems. Since then, site-specific somatic recombination and hypermutation in T and B cells have been well established as a genetic mechanism for learning and memory in the immune system but how the nervous system achieves learning and memory is still unclear. In the last ten years, revolutionary developments in high-throughput “-omics” measurements allowed us to characterize interactions between immune and nervous systems, which revealed surprising roles of immune mechanisms in shaping the nervous system in health and disease. Our group focuses on identifying shared mechanisms regulating nervous and immune systems and how these two systems regulate each other during aging and diseases.

1. Role of white matter and cerebrovascular aging in neurodegeneration 

White matter volume starts to decrease gradually from 50 years of age onwards. Electron microscopy studies performed in non-human primates have shown that the major changes observed during normal aging are not a loss of neurons, but rather changes in myelinated nerve fiber morphology. Our single-cell RNA-seq work showed that aging results in microglial activation in the white matter. We propose that age-related gliovascular changes induce myelindamage, which in turn affects microglia function in the white matter. Our group focuses on understanding how age-related gliovascular changes form and lead to the development neurodegenerative diseases.

2. Emerging Roles of cytokines in neurological diseases 

The highest expressed chemokine in neurons is macrophage migration inhibitory factor (MIF), which is also a newly identified nuclease. In collaboration with Prof. Bernhagen, we are studying MIF functions in the brain. We are testing if targeting MIF functions is a viable therapeutic strategy for neurodegenerative disorders.