Yadong Huang and his team focus on the causes and progression of Alzheimer’s disease. Specifically, they study a variant of apolipoprotein E, called apolipoprotein E4 (apoE4). Approximately 60–75 percent of Alzheimer’s patients carry the apoE4 variant, making it the most important genetic risk factor for Alzheimer’s disease. The team uses mouse models and induced pluripotent stem (iPS) cells made from skin cells of patients carrying apoE4 or other mutations related to Alzheimer’s to study their effects on the development, survival, and degeneration of neurons and glial cells. In addition, Huang’s lab is working to identify drug targets, develop therapeutic strategies, and repurpose existing drugs for Alzheimer’s disease and other neurodegenerative disorders.

Disease Areas

Alzheimer’s Disease
Dementia
Tauopathies
Neurodegenerative Diseases

Areas of Expertise

Disease Models
Stem Cells and iPS Cells
Drug Discovery and Repurposing
Working in the Huang lab

Lab Focus

Studying neuronal and glial expression of apoE as well as its regulation and roles in Alzheimer’s disease and other neurodegenerative disorders
Identifying the protease responsible for apoE cleavage in neurons and determining the role of apoE proteolysis in Alzheimer’s disease
Developing therapeutic strategies targeting apoE4’s detrimental effects and repurposing existing drugs for Alzheimer’s disease and other neurodegenerative disorders

Research Impact

Huang’s group has made important contributions to understanding how apoE4 causes neuronal deficits and cognitive decline in Alzheimer’s disease. Using genetically engineered mouse models, they showed that human apoE4 is expressed in neurons and causes immune response of glial cells and age-dependent learning and memory impairments, as well as degeneration of GABAergic interneurons in the dentate gyrus, a brain region involved in learning and memory. They also discovered that mice with apoE4 have deficits in hippocampal network activities called sharp-wave ripples, which indicates that a decline of interneuron-enabled slow gamma activity during sharp-wave ripples contributes to apoE4-mediated learning and memory impairments.

The second major effort in Huang’s lab has been to develop better drugs for Alzheimer’s disease. Using human neurons derived from iPS cells, the group demonstrated that those harboring apoE4 have higher levels of tau phosphorylation, increased amyloid beta production, and increased risk of degeneration especially when differentiated into GABAergic interneurons. Huang and his team showed that treating apoE4 neurons with a small-molecule structure corrector ameliorated the detrimental effects, suggesting that correcting the pathogenic conformation of apoE4 is a viable therapeutic approach for apoE4-related Alzheimer’s disease. Huang has also led the Gladstone Center for Translational Advancement on drug repurposing for neurological diseases and identified bumetanide as a potential drug for treating apoE4-related Alzheimer’s disease.

 

Lab Members

Mary Amornkul, MS
Senior Research Associate
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Alice An
Research Associate I
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Adriana Arriola
Lab Associate
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Jason Bant, PhD
Collaborator
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Jessie Blumenfeld
Graduate Student
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Norman Chen
Collaborator
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Tenzing Choenyi
Research Associate I
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Samuel De Leon
Research Associate I
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Claire Ellis
Research Associate III
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Rebecca Fulthorpe
Visiting Researcher
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Brian Grone
Collaborator
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Emily Jones, PhD
Collaborator
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Min Joo Kim
Graduate Student
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Nicole Koutsodendris, MS
Visiting Scientist
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Yaqiao Li
Graduate Student
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Zherui Liang
Graduate Student
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Maxine Nelson
Visiting Scientist
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Jeremy Nguyen
Research Associate I
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Zoe Platow
Graduate Student
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Antara Rao, PhD
Visiting Scientist
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David Shostak
Graduate Student
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Kaylie Suan
Research Associate II
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Dennis Tabuena, PhD
Postdoctoral Scholar
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Yung-Hua Wang
Research Associate III
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Min Xie, PhD
Staff Research Scientist I
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Qin Xu, PhD
Senior Staff Research Scientist
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Luokang Yao, MS
Research Associate II
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Oscar Yip, MS
Graduate Student
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Seo Yeon Yoon
Research Scientist
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Misha Zilberter, PhD
Staff Research Scientist III
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