Michael Lee, PhD
Professor, Department of Neuroscience
Professor, Department of Neuroscience
Co-Director and ITN Scholar, Center for Neurodegenerative Disease, Institute for Translational Neuroscience (ITN)
Professor, Department of Pharmacology
Mechanisms of human neurodegenerative diseases
My group is using transgenic mouse models to study the mechanisms of human neurodegenerative diseases, particularly AD and PD. There are three broad areas of active interest.
- Understanding the pathogenesis/progression of PD using alpha-synuclein and LRRK2 transgenic mouse models.
- Mechanisms of amyloid-dependent neurodegeneration using transgenic mouse models of AD.
- Pathologic interactions between genetic and environmental factors.
While most cases of AD and PD are “sporadic”, the key assumption is that genetic lesions that cause classic forms of the relevant neurodegenerative diseases will cause neural abnormalities that are common between the genetic and sporadic forms of the disease. When used in conjunction with careful analysis of human subjects, invertebrate models, and cell culture models, we will be able to define mechanisms that are directly relevant to the pathogenesis and identify possible targets for therapeutic intervention. The models generated are also essential for cross-platform screening and validation of novel therapeutic approaches. My group has identified several robust biochemical, pathological and behavioral outcome measures in transgenic mouse models of AD and PD. These measures will be essential for in vivo preclinical evaluation of therapeutics.
Clemente V, Hoshino A, Meints J, Shetty M, Starr T, Lee MK, Bazzaro M. UNC-45A is highly expressed in proliferative cells of the mouse genital tract and in the microtubule-rich areas of mouse nervous system. cells. 2021, 10(&):1604. doi: 10.3390/cells10071604. JIF-6.6
Lines J, Baraibar AM, Fang C, Martin ED, Aguilar J, Lee MK, Araque A, Kofuji P. Astrocyteneuronal network interplay is disrupted in Alzheimer's disease mice. Glia. 2021, Nov 2;. Doi: 10.1002/glia.24112. [Epub ahead of print] PubMed PMID: 34726298. JIF-8.59
Portz P and Lee MK. Changes in Drp1 function and mitochondrial morphology are associated with the a-synuclein pathology in transgenic mosue model of Parkinson’s disease. cells. 2021,10(4), 885; https://doi.org/10.3390/cells10040885. JIF-7.66
Stanojlovic, M, Pallais, JP, Lee, MK & Kotz, CM 2019, 'Pharmacological and chemogenetic orexin/hypocretin intervention ameliorates Hipp-dependent memory impairment in the A53T mice model of Parkinson's disease', Molecular brain, vol. 12, no. 1. https://doi.org/10.1186/s13041-019-0514-8
Singh, B, Covelo, A, Martell-Martínez, H, Nanclares, C, Sherman, MA, Okematti, E, Meints, J, Teravskis, PJ, Gallardo, C, Savonenko, AV, Benneyworth, MA, Lesne, SE, Liao, D, Araque, A & Lee, MK 2019, 'Tau is required for progressive synaptic and memory deficits in a transgenic mouse model of ?-synucleinopathy', Acta Neuropathologica, vol. 138, no. 4, pp. 551-574. https://doi.org/10.1007/s00401-019-02032-w
Mooneyham, A, Iizuka, Y, Yang, Q, Coombes, C, McClellan, M, Shridhar, V, Emmings, E, Shetty, M, Chen, L, Ai, T, Meints, J, Lee, MK, Gardner, MK & Bazzaro, M 2019, 'UNC-45A is a novel microtubule-associated protein and regulator of paclitaxel sensitivity in ovarian cancer cells', Molecular Cancer Research, vol. 17, no. 2, pp. 370-383. https://doi.org/10.1158/1541-7786.MCR-18-0670
Teravskis, PJ, Covelo, A, Miller, EC, Singh, B, Martell-Martínez, HA, Benneyworth, MA, Gallardo, C, Oxnard, BR, Araque, A, Lee, MK & Liao, D 2018, 'A53t mutant alpha-synuclein induces tau-dependent postsynaptic impairment independently of neurodegenerative changes', Journal of Neuroscience, vol. 38, no. 45, pp. 9754-9767. https://doi.org/10.1523/JNEUROSCI.0344-18.2018
Khan, SS, LaCroix, M, Boyle, G, Sherman, MA, Brown, JL, Amar, F, Aldaco, J, Lee, MK, Bloom, GS & Lesné, SE 2018, 'Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons', Acta Neuropathologica, vol. 136, no. 4, pp. 589-605. https://doi.org/10.1007/s00401-018-1886-z
Colla, E, Panattoni, G, Ricci, A, Rizzi, C, Rota, L, Carucci, N, Valvano, V, Gobbo, F, Capsoni, S, Lee, MK & Cattaneo, A 2018, 'Toxic properties of microsome-associated alpha-synuclein species in mouse primary neurons', Neurobiology of Disease, vol. 111, pp. 36-47. https://doi.org/10.1016/j.nbd.2017.12.004
Ordonez, DG, Lee, MK & Feany, MB 2018, '?-synuclein Induces Mitochondrial Dysfunction through Spectrin and the Actin Cytoskeleton', Neuron, vol. 97, no. 1, pp. 108-124.e6. https://doi.org/10.1016/j.neuron.2017.11.036
Salazar, SV, Gallardo, C, Kaufman, AC, Herber, CS, Haas, LT, Robinson, S, Manson, JC, Lee, MK & Strittmatter, SM 2017, 'Conditional deletion of Prnp rescues behavioral and synaptic deficits after disease onset in transgenic Alzheimer’s disease', Journal of Neuroscience, vol. 37, no. 38, pp. 9207-9221. https://doi.org/10.1523/JNEUROSCI.0722-17.2017
Larson, ME, Greimel, SJ, Amar, F, LaCroix, M, Boyle, G, Sherman, MA, Schley, H, Miel, C, Schneider, JA, Kayed, R, Benfenati, F, Lee, MK, Bennett, DA & Lesné, SE 2017, 'Selective lowering of synapsins induced by oligomeric ?-synuclein exacerbates memory deficits', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 23, pp. E4648-E4657. https://doi.org/10.1073/pnas.1704698114
Iizuka, Y, Mooneyham, A, Sieben, A, Chen, K, Maile, M, Hellweg, R, Schütz, F, Teckle, K, Starr, T, Thayanithy, V, Vogel, RI, Lou, E, Lee, MK & Bazzaro, M 2017, 'UNC-45A is required for neurite extension via controlling NMII activation', Molecular biology of the cell, vol. 28, no. 10, pp. 1337-1346. https://doi.org/10.1091/mbc.E16-06-0381