Research Overview—

Research conducted in the Zhao Lab is dedicated to understanding the neuroendocrinology, neurometabobiology, and neuroglycobiology of aging that drive or prevent the onset and progression of neurodegeneration leading to the development of sporadic Alzheimer’s disease (sAD). We are particularly interested in understanding the sex and genetic influences (with a focus on ApoE and clusterin/ApoJ) on brain glycometabolism and sialometabolism that contribute to brain resilience or risk for sAD. Our ultimate goal is to translate these mechanistic investigations into novel therapeutic strategies for precision prevention, risk reduction, and early intervention of sAD.

In summary, we are currently studying the following areas:

• Female susceptibility in the etiology of sAD
• ApoE2-mediated mechanisms of brain resilience to sAD
• ApoE2 regulation of blood-brain lipidomic dynamics
• ApoE posttranslational sialylation in sAD pathogenesis
• Regulation of microglial homeostasis by secreted clusterin
• Mitochondria-targeted clusterin expression and function

The research models used in our studies include the following: rodent primary neural cell models (neurons, astrocytes, microglia), human induced pluripotent stem cell (hiPSC)-derived neural cell models, human AD-related gene stably transfected cell lines, and human AD-related gene knock-in or knock-out mouse models.

The research techniques applied in our studies include the following: OMICS data-driven discovery (proteomics, metabolomics, glycomics, lipidomics, steroidomics, RNA-seq, scRNA-seq, snRNA-seq), qRT-PCR arrays, gene cloning, recombinant protein production, synaptic physiology, mitochondrial biochemistry, fluorescent microscopy, behavioral modeling, and many other general methods commonly used in molecular and cellular biological, pharmacological, and drug discovery research.

Selected Publications —

Liqin Zhao Publications (PubMed)