Li Gan, PhD

Associate Investigator

Phone: (415) 734-2524
Fax: (415) 355-0824
Fewer scientific details, please
Download a Printable PDF

Other Professional Titles

Associate Professor, Neurology, University of California, San Francisco

Administrative Assistant

Latrice Goss
(415) 734-2516
latrice.goss@gladstone.ucsf.edu

More about Dr. Gan

Dr. Gan studies the molecular mechanisms behind the loss of functional neurons in neurodegenerative diseases, including Alzheimer’s disease and Frontotemporal Dementia. Her lab explores the relationship between the aging of neural circuits, the accumulation of toxic proteins and the subsequent activation of a chronic inflammatory response. Understanding how these processes become dysfunctional in neurodegeneration could lead to new therapeutic strategies to tackle Alzheimer’s disease and Frontotemporal dementia.

One aspect of Dr. Gan’s research focuses on why toxic proteins accumulate in the brains of Alzheimer patients. Dr. Gan and her team discovered new cellular mechanisms that could lead to novel approaches to get rid of the toxic proteins from aging neurons. Dr. Gan’s research also explores stem cell-based regenerative approaches 
in Alzheimer’s disease—a promising yet highly challenging therapeutic direction. Her study showed that neural stem cells in the hippocampus of mice genetically modified to mimic Alzheimer’s symptoms develop abnormally and integrate poorly into the network of neural circuits. More importantly, Dr. Gan and her colleagues find that they can offset these deficits by manipulating electrical signals via pharmacological approaches. Their research provides important clues to encourage the development of new brain cells in those with Alzheimer’s disease.

At UCSF, Dr. Gan is active in graduate training and has joint appointments in the Neuroscience Graduate Program and the Biomedical Sciences Graduate Program. She is also a member of several scientific and professional societies, including the Society for Neuroscience. Dr. Gan has served as a referee
 for several government and private grant agencies, including the National Institutes of Health, the Alzheimer’s Association and the California Department of Health Services. She is also an ad hoc reviewer for numerous professional journals including Neuron, Nature Medicine, Journal of Neuroscience, and Journal of Cell Biology.

Dr. Gan received a bachelor’s degree in physiology from China’s Peking University and a PhD in cellular and molecular physiology from Yale University School of Medicine. Later, she did postdoctoral training at Yale University School of Medicine, Harvard Medical School and the Gladstone Institutes.  

 

More scientific details, please

Other Professional Titles

Associate Professor, Neurology, University of California, San Francisco

Administrative Assistant

Latrice Goss
(415) 734-2516
latrice.goss@gladstone.ucsf.edu

Areas of Investigation

Our laboratory focuses on dissecting the molecular pathways in Alzheimer’s disease (AD) and frontotemporal dementia (FTD), two of the most common dementia in the elderly population. We are intrigued by two interconnected mechanisms that are common to neurodegenerative processes: the accumulation of protein aggregates and miscommunications between neurons and glia, especially microglia. Accumulation of protein aggregates could activate microglia, exacerbating neurodegeneration. On the other hand, microglia could be activated to remove abnormal protein aggregates. We are particularly interested in how aging-related pathways, such as sirtuins, modulate the processes underlying the abnormal accumulation and microglial activation. Our long-term goal is to develop new small-molecule or cell-based approaches to delay or prevent the progression of these devastating aging-associated diseases.

Current Lab Focus

  • Do aging-related pathways affect the stability and clearance of protein aggregates in AD and FTD?
  • How does aging affect inflammatory and protective function of microglia?
  • Can we generate patients-specific microglia to remove abnormal protein aggregates?
  • What are the roles of aging-associated epigenetic modification in neuronal injury and inflammatory responses?

Joined Gladstone

1998

Why Gladstone?

Gladstone offers the best research environment that combines innovative and rigorous scientific inquiry with a deep passion to tackle the most devastating diseases facing us today.  It is truly an exciting and rewarding place to work.

Key Achievements

  • Found that cathepsin B (CatB) degrades the protein amyloid β (Aβ) via a unique catabolic mechanism. Accumulation of Aβ, the key pathogen in AD, results from an imbalance of production and clearance/degradation.
  • Showed that reducing cystatin C (CysC), the endogenous inhibitor of CatB, lowers Aβ levels in a CatB-dependent manner, establishing a critical role of CysC-CatB axis in regulating Aβ degradation and clearance.
  • Discovered that the activation of sirtuins—class III histone deacetylases strongly associated with longevity—protects neurons by block NF-κB activation in microglia through deacetylation.
  • Found that the neural stem cells in the hippocampus of AD mice exhibit abnormal development and impaired functional integration. By combining in vivo labeling, confocal microscopy and electrophysiological recordings, we identified an Aβ-induced aberrant neuronal network as the primary mechanism.
  • Discovered a new mechanism that contributes to the accumulation of tau, a key pathogen in AD and FTD. We found that tau is acetylated and acetylation blocks the degradation and tau. Moreover, reducing tau acetylation with a small molecule inhibitor leads to depletion of pathogenic phosphorylated-tau in neurons. These findings offer a novel therapeutic direction in AD and related neurodegenerative diseases.

Education

Peking University (BS), Physiology, Summa Cum Laude (1990)
Yale University School of Medicine (PhD), Cellular and Molecular Physiology (1996)

Affiliations

Society for Neuroscience
New York Academy of Sciences, Women in Science

Awards

  • Hellman Family Award, University of California, San Francisco (2007)
  • Glenn Award for Biological Mechanisms of Aging (2010)
Syndicate publications

Featured Publications

Li Gan, PhDMin SW, Cho SH, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, Huang EJ, Shen Y, Masliah E, Mukherjee C, Meyers D, Cole PA, Ott M, Gan L. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron. 2010 Sep 23; 67(6):953-66. View in: PubMed
Li Gan, PhDSun B, Halabisky B, Zhou Y, Palop JJ, Yu G, Mucke L, Gan L. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell. 2009 Dec 4; 5(6):624-33. View in: PubMed