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.
Lab Members —
|Xin Zhang||Graduate Student||Postdoctoral Research Fellow, Dana-Farber Cancer Institute (DFCI), Harvard Medical School (HMS), Boston, MA|
|Sarah Bohl||Assistant Researcher||D.O. Program, Kansas City University of Medicine, Kansas City, MO|
|Nadine Alshakhshir||Graduate Student||Ph.D. Program, University of Florida, Gainesville, FL|
|Anindit Chhibber||Graduate Student||Ph.D. Program, University of Utah, Salt Lake City, UT|
|Lucy He||Graduate Student||Assistant Specialist, UCSF, San Francisco, CA|
|Shaher Ibrahimi||Assistant Researcher||M.S. Program, Kansas City University, Kansas City, MO|
|Shreya Indulkar, M.S.||Graduate Student||Research Technician, Albany Medical College, Albany, NY|
|Jeriel Keeney, Ph.D.||Postdoctoral Researcher||Postdoctoral Researcher, Michigan State University, East Lansing, MI|
|Kenneth McFarlin||Graduate Student||Research Associate, Vium Inc, San Mateo, CA|
|Sarah Woody||Graduate Student||Scientist, Citoxlab, Stillwell, Kansas|
|Long Wu||Graduate Student||Postdoctoral Researcher, UCSF, San Francisco, CA|
Selected Publications —
Current Projects —
Recently Funded Projects
- NIH: Reprogramming Circulating Lipidome by rhApoE2
- NIH: Reshaping ApoE4 and Alzheimer’s Brains with ApoE2
- NIH: Sporadic Alzheimer’s Disease: A Bioenergetic Etiology?
- NIH: ApoE, Energy, and Synaptic V-ATPase
- NIH: Role of Clusterin in Brain Mitochondria
- J.R. and Inez Jay Fund: ApoE2 as a Therapeutic Shield Against Alzheimer’s Disease: A Proof-of-Concept Study