Yadong Huang, MD, PhD

Associate Investigator

Phone: (415) 734-2511
Fax: (415) 355-0824
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Other Professional Titles

Investigator, Roddenberry Center for Stem Cell Biology and Medicine at Gladstone

Associate Professor, Pathology and Neurology, University of California, San Francisco

Administrative Assistant

Linda Turney
(415) 734-2513
lturney@gladstone.ucsf.edu

More about Dr. Huang

Dr. Huang studies the origination and development of Alzheimer’s disease, focusing on the pathological role of apolipoprotein E4 (apoE4)—the major genetic risk factor for Alzheimer’s. By using mice modified to replicate the disease, Dr. Huang showed that apoE4 is broken down into fragments that contribute to the development of Alzheimer’s disease. He is also interested in identifying strategies to treat or prevent Alzheimer’s. Recently, his lab used induced pluripotent stem (iPS) cells—adult cells made to act like embryonic stem cells—made from skin cells of patients carrying apoE4, or other mutations related to Alzheimer’s, to study the effect of iPS cells on the development, survival and degeneration of human neurons. These patient- and disease-specific human iPS cells are being used in different drug-discovery and development projects for Alzheimer’s. Dr. Huang has published more than 70 scientific papers in the field of apoE and Alzheimer’s disease research and drug discovery.

In 1995, Dr. Huang joined the Gladstone Institute of Neurological Disease as a postdoctoral fellow and in 1999 became a Staff Research Investigator. In 2005, after a nationwide search, Dr. Huang was promoted to Assistant Investigator. In 2009, he became an Associate Investigator.

Dr. Huang also has an appointment in UCSF’s Biomedical Sciences Graduate Program and is a member of several scientific and professional societies, including the Society for Neuroscience and the Alzheimer’s Association. He has served as referee for several government and private grant agencies, including the National Institutes of Health and the American Federation for Aging Research. He also serves as a reviewer for numerous scientific journals.

Dr. Huang earned an MD from Qingdao Medical University in China in 1985 and a PhD in biochemistry and pathology from Peking Union Medical College and Chinese Academy of Medical Sciences in Beijing in 1991. He then trained as a postdoctoral fellow at the Arteriosclerosis Research Institute at the University of Muenster, Germany.

 

More scientific details, please

Other Professional Titles

Investigator, Roddenberry Center for Stem Cell Biology and Medicine at Gladstone

Associate Professor, Pathology and Neurology, University of California, San Francisco

Administrative Assistant

Linda Turney
(415) 734-2513
lturney@gladstone.ucsf.edu

Areas of Investigation

Research in our laboratory focuses on the biological and pathophysiological functions of apolipoprotein (apo) E. Long-term goals of our research are to understand the molecular and cellular mechanisms by which apoE4 increases the risk of Alzheimer’s disease (AD) and related neurodegeneratative disorders and to develop therapeutic strategies to treat or prevent AD.

Human apoE has three isoforms, apoE2, apoE3 and apoE4. ApoE4 is a major gene, with semi-dominant inheritance, for late-onset AD; however, its roles in the pathogenesis of AD are unclear.

We use neuronal cultures, induced pluripotent stem (iPS) cells and transgenic and gene-targeted mouse models to study the differential effects of apoE3 and apoE4 on cell signaling pathways and cytoskelatal structure and function at molecular, cellular and behavioral levels. We also use these approaches to develop and evaluate novel treatment strategies for AD and other apoE4-related neurodegenerative disorders.

Current Lab Focus

Our laboratory is currently working to:

  • Validate the apoE proteolysis hypothesis of AD in animal models and humans.
  • Identify the protease responsible for apoE cleavage in neurons.
  • Determine how apoE4 fragments cause cytoskeletal disruption and mitochondrial dysfunction.
  • Develop therapeutic strategies targeting apoE4’s detrimental effects.
  • Determine the mechanisms controlling apoE expression in neurons.
  • Establish human iPS cell models of neurodegeneration.

Joined Gladstone

1995

Why Gladstone?

I came to Gladstone because I appreciate its core values: excellence, integrity and teamwork.

Key Achievements

  • Established the apoE proteolysis hypothesis of AD. This hypothesis suggests that, in response to stresses or injuries, neuronal apoE expression is triggered to facilitate neuronal repair. However, neuronal apoE undergoes proteolytic cleavage, with apoE4 being more susceptible to the cleavage than apoE3, resulting in the formation of neurotoxic fragments. The apoE4 fragments enter the cytosol and cause tau pathology and mitochondrial impairment, leading to neurodegeneration and learning and memory deficits.
  • Demonstrated that hilar GABAergic interneurons in the hippocampus are particularly vulnerable to apoE4 fragment toxicity and the resulting impairments contribute to learning and memory deficits.
  • Established human iPS cell models of AD and frontotemporal dementia.

Education

Qingdao Medical University, Qingdao, China (MD) (1985)
Peking Union Medical College, Chinese Academy of Medical Sciences (MSc), Cell Biology (1988)
Peking Union Medical College, Chinese Academy of Medical Sciences (PhD), Biochemistry/Pathology (1991)

Affiliations

American Heart Association
Society for Neuroscience
American Society for Biochemistry and Molecular Biology
Alzheimer’s Association
International Society to Advance Alzheimer’s Research and Treatment

Awards

  • W.H. Hauss Award on Atherosclerosis Research, German Arteriosclerosis Research Society (1995)
  • Young Investigator Award, XII International Symposium on Drugs Affecting Lipid Metabolism (1996)
  • Young Investigator Award for Scientific Excellence, International Society for Aterosclerosis Research (2000)
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Featured Publications

Yadong Huang, MD, PhDRing KL, Tong LM, Balestra ME, Javier R, Andrews-Zwilling Y, Li G, Walker D, Zhang WR, Kreitzer AC, Huang Y. Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor. Cell Stem Cell. 2012 Jul 6; 11(1):100-109. View in: PubMed
Yadong Huang, MD, PhDAndrews-Zwilling Y, Gillespie AK, Kravitz AV, Nelson AB, Devidze N, Lo I, Yoon SY, Bien-Ly N, Ring K, Zwilling D, Potter GB, Rubenstein JL, Kreitzer AC, Huang Y. Hilar GABAergic interneuron activity controls spatial learning and memory retrieval. PLoS One. 2012;7(7):e40555. View in: PubMed