Li Gan, PhD

Title(s)Professor, Neurology
SchoolSchool of Medicine
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    Yale University School of MedicinePh.D1996Department of Cellular and Molecular Physiology

    Collapse Overview 
    Collapse Overview
    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.

    Collapse Research 
    Collapse Research Activities and Funding
    Functional characterization of Alzheimer's disease associated genetic variants
    NIH/NIA R01AG057497Sep 30, 2017 - May 31, 2022
    Role: Co-Principal Investigator
    Tau acetylation in Alzheimer's disease
    NIH/NIA R01AG054214May 15, 2017 - Apr 30, 2022
    Role: Principal Investigator
    Linking tau proteostasis with neuronal activity in FTD
    NIH/NINDS U54NS100717Sep 30, 2016 - Aug 31, 2021
    Role: Principal Investigator
    Molecular mechanisms in progranulin deficient frontotemporal dementia
    NIH/NIA R01AG051390Sep 1, 2015 - Apr 30, 2020
    Role: Principal Investigator
    Screening for inhibitors of p300-mediated tau acetylation for Alzheimer's Disease
    NIH/NIA R21AG046526Jul 1, 2014 - Apr 30, 2016
    Role: Co-Principal Investigator
    SIRT1 Limits Microglial Toxicity in Alzheimer's Disease
    NIH/NIA R01AG036884Aug 1, 2012 - Apr 30, 2017
    Role: Principal Investigator
    The Role of Cathepsin B and Cystatin C in Alzheimer's Disease
    NIH/NIA R01AG030207Mar 15, 2010 - Feb 28, 2015
    Role: Principal Investigator
    Cathepsin B and cystatin C in AD-related neuronal damage
    NIH/NIA R21AG024447Aug 15, 2004 - Jun 30, 2006
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Tracy TE, Gan L. Acetylated tau in Alzheimer's disease: An instigator of synaptic dysfunction underlying memory loss: Increased levels of acetylated tau blocks the postsynaptic signaling required for plasticity and promotes memory deficits associated with tauopathy. Bioessays. 2017 04; 39(4). PMID: 28083916.
      View in: PubMed
    2. Sohn PD, Tracy TE, Son HI, Zhou Y, Leite RE, Miller BL, Seeley WW, Grinberg LT, Gan L. Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment. Mol Neurodegener. 2016 06 29; 11(1):47. PMID: 27356871; PMCID: PMC4928318.
    3. Möller T, Bard F, Bhattacharya A, Biber K, Campbell B, Dale E, Eder C, Gan L, Garden GA, Hughes ZA, Pearse DD, Staal RG, Sayed FA, Wes PD, Boddeke HW. Critical data-based re-evaluation of minocycline as a putative specific microglia inhibitor. Glia. 2016 10; 64(10):1788-94. PMID: 27246804.
      View in: PubMed
    4. Wes PD, Sayed FA, Bard F, Gan L. Targeting microglia for the treatment of Alzheimer's Disease. Glia. 2016 10; 64(10):1710-32. PMID: 27100611.
      View in: PubMed
    5. Tracy TE, Sohn PD, Minami SS, Wang C, Min SW, Li Y, Zhou Y, Le D, Lo I, Ponnusamy R, Cong X, Schilling B, Ellerby LM, Huganir RL, Gan L. Acetylated Tau Obstructs KIBRA-Mediated Signaling in Synaptic Plasticity and Promotes Tauopathy-Related Memory Loss. Neuron. 2016 04 20; 90(2):245-60. PMID: 27041503; PMCID: PMC4859346 [Available on 04/20/17].
    6. Min SW, Chen X, Tracy TE, Li Y, Zhou Y, Wang C, Shirakawa K, Minami SS, Defensor E, Mok SA, Sohn PD, Schilling B, Cong X, Ellerby L, Gibson BW, Johnson J, Krogan N, Shamloo M, Gestwicki J, Masliah E, Verdin E, Gan L. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat Med. 2015 Oct; 21(10):1154-62. PMID: 26390242.
      View in: PubMed
    7. Minami SS, Shen V, Le D, Krabbe G, Asgarov R, Perez-Celajes L, Lee CH, Li J, Donnelly-Roberts D, Gan L. Reducing inflammation and rescuing FTD-related behavioral deficits in progranulin-deficient mice with a7 nicotinic acetylcholine receptor agonists. Biochem Pharmacol. 2015 Oct 15; 97(4):454-462. PMID: 26206194; PMCID: PMC4859338 [Available on 10/15/16].
    8. Cho SH, Chen JA, Sayed F, Ward ME, Gao F, Nguyen TA, Krabbe G, Sohn PD, Lo I, Minami S, Devidze N, Zhou Y, Coppola G, Gan L. SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1ß. J Neurosci. 2015 Jan 14; 35(2):807-18. PMID: 25589773; PMCID: PMC4293425.
    9. Minami SS, Min SW, Krabbe G, Wang C, Zhou Y, Asgarov R, Li Y, Martens LH, Elia LP, Ward ME, Mucke L, Farese RV, Gan L. Progranulin protects against amyloid ß deposition and toxicity in Alzheimer's disease mouse models. Nat Med. 2014 Oct; 20(10):1157-64. PMID: 25261995; PMCID: PMC4196723.
    10. Ward ME, Taubes A, Chen R, Miller BL, Sephton CF, Gelfand JM, Minami S, Boscardin J, Martens LH, Seeley WW, Yu G, Herz J, Filiano AJ, Arrant AE, Roberson ED, Kraft TW, Farese RV, Green A, Gan L. Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD. J Exp Med. 2014 Sep 22; 211(10):1937-45. PMID: 25155018; PMCID: PMC4172214.
    11. Huang L, Gan LS, Law LY. Evaluation of a prototype ration aimed at increasing caloric intake in a field environment. Mil Med. 2014 Feb; 179(2):190-6. PMID: 24491616.
      View in: PubMed
    12. Min SW, Sohn PD, Cho SH, Swanson RA, Gan L. Sirtuins in neurodegenerative diseases: an update on potential mechanisms. Front Aging Neurosci. 2013 Sep 25; 5:53. PMID: 24093018; PMCID: PMC3782645.
    13. Kauppinen TM, Gan L, Swanson RA. Poly(ADP-ribose) polymerase-1-induced NAD(+) depletion promotes nuclear factor-?B transcriptional activity by preventing p65 de-acetylation. Biochim Biophys Acta. 2013 Aug; 1833(8):1985-91. PMID: 23597856; PMCID: PMC4041949.
    14. Grinberg LT, Wang X, Wang C, Sohn PD, Theofilas P, Sidhu M, Arevalo JB, Heinsen H, Huang EJ, Rosen H, Miller BL, Gan L, Seeley WW. Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation. Acta Neuropathol. 2013 Apr; 125(4):581-93. PMID: 23371364; PMCID: PMC3692283.
    15. Martens LH, Zhang J, Barmada SJ, Zhou P, Kamiya S, Sun B, Min SW, Gan L, Finkbeiner S, Huang EJ, Farese RV. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J Clin Invest. 2012 Nov; 122(11):3955-9. PMID: 23041626; PMCID: PMC3484443.
    16. Wang C, Sun B, Zhou Y, Grubb A, Gan L. Cathepsin B degrades amyloid-ß in mice expressing wild-type human amyloid precursor protein. J Biol Chem. 2012 Nov 16; 287(47):39834-41. PMID: 23024364; PMCID: PMC3501032.
    17. Pappas DJ, Gabatto PA, Oksenberg D, Khankhanian P, Baranzini SE, Gan L, Oksenberg JR. Transcriptional expression patterns triggered by chemically distinct neuroprotective molecules. Neuroscience. 2012 Dec 13; 226:10-20. PMID: 22986168; PMCID: PMC3489981.
    18. Minami SS, Sun B, Popat K, Kauppinen T, Pleiss M, Zhou Y, Ward ME, Floreancig P, Mucke L, Desai T, Gan L. Selective targeting of microglia by quantum dots. J Neuroinflammation. 2012 Jan 24; 9:22. PMID: 22272874; PMCID: PMC3292839.
    19. Kauppinen TM, Suh SW, Higashi Y, Berman AE, Escartin C, Won SJ, Wang C, Cho SH, Gan L, Swanson RA. Poly(ADP-ribose)polymerase-1 modulates microglial responses to amyloid ß. J Neuroinflammation. 2011 Nov 03; 8:152. PMID: 22051244; PMCID: PMC3247192.
    20. Zhang F, Wang S, Gan L, Vosler PS, Gao Y, Zigmond MJ, Chen J. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol. 2011 Nov; 95(3):373-95. PMID: 21930182; PMCID: PMC3242010.
    21. Cho SH, Sun B, Zhou Y, Kauppinen TM, Halabisky B, Wes P, Ransohoff RM, Gan L. CX3CR1 protein signaling modulates microglial activation and protects against plaque-independent cognitive deficits in a mouse model of Alzheimer disease. J Biol Chem. 2011 Sep 16; 286(37):32713-22. PMID: 21771791; PMCID: PMC3173153.
    22. Min 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. PMID: 20869593; PMCID: PMC3035103.
    23. Gan LS, Loh JP. Rapid identification of chloroquine and atovaquone drug resistance in Plasmodium falciparum using high-resolution melt polymerase chain reaction. Malar J. 2010 May 21; 9:134. PMID: 20487570; PMCID: PMC2881075.
    24. Sun 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 04; 5(6):624-33. PMID: 19951690; PMCID: PMC2823799.
    25. Sun B, Zhou Y, Halabisky B, Lo I, Cho SH, Mueller-Steiner S, Devidze N, Wang X, Grubb A, Gan L. Cystatin C-cathepsin B axis regulates amyloid beta levels and associated neuronal deficits in an animal model of Alzheimer's disease. Neuron. 2008 Oct 23; 60(2):247-57. PMID: 18957217; PMCID: PMC2755563.
    26. Sanchez-Mejia RO, Newman JW, Toh S, Yu GQ, Zhou Y, Halabisky B, Cissé M, Scearce-Levie K, Cheng IH, Gan L, Palop JJ, Bonventre JV, Mucke L. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nat Neurosci. 2008 Nov; 11(11):1311-8. PMID: 18931664; PMCID: PMC2597064.
    27. Gan L, Mucke L. Paths of convergence: sirtuins in aging and neurodegeneration. Neuron. 2008 Apr 10; 58(1):10-4. PMID: 18400158.
      View in: PubMed
    28. Gan L. Therapeutic potential of sirtuin-activating compounds in Alzheimer's disease. Drug News Perspect. 2007 May; 20(4):233-9. PMID: 17637936.
      View in: PubMed
    29. Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L, Gan L. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron. 2006 Sep 21; 51(6):703-14. PMID: 16982417.
      View in: PubMed
    30. Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L. SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem. 2005 Dec 02; 280(48):40364-74. PMID: 16183991.
      View in: PubMed
    31. Kaczmarek LK, Bhattacharjee A, Desai R, Gan L, Song P, von Hehn CA, Whim MD, Yang B. Regulation of the timing of MNTB neurons by short-term and long-term modulation of potassium channels. Hear Res. 2005 Aug; 206(1-2):133-45. PMID: 16081004.
      View in: PubMed
    32. Esposito L, Gan L, Yu GQ, Essrich C, Mucke L. Intracellularly generated amyloid-beta peptide counteracts the antiapoptotic function of its precursor protein and primes proapoptotic pathways for activation by other insults in neuroblastoma cells. J Neurochem. 2004 Dec; 91(6):1260-74. PMID: 15584903.
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    33. Gresch O, Engel FB, Nesic D, Tran TT, England HM, Hickman ES, Körner I, Gan L, Chen S, Castro-Obregon S, Hammermann R, Wolf J, Müller-Hartmann H, Nix M, Siebenkotten G, Kraus G, Lun K. New non-viral method for gene transfer into primary cells. Methods. 2004 Jun; 33(2):151-63. PMID: 15121170.
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    34. Gan L, Ye S, Chu A, Anton K, Yi S, Vincent VA, von Schack D, Chin D, Murray J, Lohr S, Patthy L, Gonzalez-Zulueta M, Nikolich K, Urfer R. Identification of cathepsin B as a mediator of neuronal death induced by Abeta-activated microglial cells using a functional genomics approach. J Biol Chem. 2004 Feb 13; 279(7):5565-72. PMID: 14612454.
      View in: PubMed
    35. Ford BD, Liu Y, Mann MA, Krauss R, Phillips K, Gan L, Fischbach GD. Neuregulin-1 suppresses muscarinic receptor expression and acetylcholine-activated muscarinic K+ channels in cardiac myocytes. Biochem Biophys Res Commun. 2003 Aug 15; 308(1):23-8. PMID: 12890474.
      View in: PubMed
    36. Bhattacharjee A, Gan L, Kaczmarek LK. Localization of the Slack potassium channel in the rat central nervous system. J Comp Neurol. 2002 Dec 16; 454(3):241-54. PMID: 12442315.
      View in: PubMed
    37. Gan L, Anton KE, Masterson BA, Vincent VA, Ye S, Gonzalez-Zulueta M. Specific interference with gene expression and gene function mediated by long dsRNA in neural cells. J Neurosci Methods. 2002 Dec 15; 121(2):151-7. PMID: 12468005.
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    38. Gan L, Hahn SJ, Kaczmarek LK. Cell type-specific expression of the Kv3.1 gene is mediated by a negative element in the 5' untranslated region of the Kv3.1 promoter. J Neurochem. 1999 Oct; 73(4):1350-62. PMID: 10501178.
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    39. Xu X, Yang D, Wyss-Coray T, Yan J, Gan L, Sun Y, Mucke L. Wild-type but not Alzheimer-mutant amyloid precursor protein confers resistance against p53-mediated apoptosis. Proc Natl Acad Sci U S A. 1999 Jun 22; 96(13):7547-52. PMID: 10377452; PMCID: PMC22123.
    40. Gan L, Kaczmarek LK. When, where, and how much? Expression of the Kv3.1 potassium channel in high-frequency firing neurons. J Neurobiol. 1998 Oct; 37(1):69-79. PMID: 9777733.
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    41. Joiner WJ, Tang MD, Wang LY, Dworetzky SI, Boissard CG, Gan L, Gribkoff VK, Kaczmarek LK. Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci. 1998 Oct; 1(6):462-9. PMID: 10196543.
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    42. Wang LY, Gan L, Forsythe ID, Kaczmarek LK. Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse auditory neurones. J Physiol. 1998 May 15; 509 ( Pt 1):183-94. PMID: 9547392; PMCID: PMC2230948.
    43. Wang LY, Gan L, Perney TM, Schwartz I, Kaczmarek LK. Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion. Proc Natl Acad Sci U S A. 1998 Feb 17; 95(4):1882-7. PMID: 9465111; PMCID: PMC19207.
    44. Gan L, Perney TM, Kaczmarek LK. Cloning and characterization of the promoter for a potassium channel expressed in high frequency firing neurons. J Biol Chem. 1996 Mar 08; 271(10):5859-65. PMID: 8621457.
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    45. Kanemasa T, Gan L, Perney TM, Wang LY, Kaczmarek LK. Electrophysiological and pharmacological characterization of a mammalian Shaw channel expressed in NIH 3T3 fibroblasts. J Neurophysiol. 1995 Jul; 74(1):207-17. PMID: 7472324.
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    46. Vicente J. [Current aspects of drug therapy of cancer]. Rev Clin Esp. 1970 Dec 31; 119(6):501-16. PMID: 4928318.
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