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Gloria Lee, PhD

Portrait
Emeritus Professor of Internal Medicine - Immunology

Contact Information

Primary Office
B191 ML
Iowa City, IA 52242
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Education

AB, University of California, Berkeley, California
PhD, Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts
Postdoctoral Fellow, Dept of Biochemistry & Biophysics, University of Californa, San Francisco

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Molecular Medicine, Interdisciplinary Graduate Program in Neuroscience, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center on Aging, Holden Comprehensive Cancer Center

Research Summary

Our laboratory investigates the structure and function of the neuronal cytoskeleton and its role in neurodegenerative diseases
Tau protein is a microtubule-associated protein that is critical for neuronal development. Our laboratory has been elucidating new functions for tau beyond its ability to promote microtubule assembly and stability. We have found that tau can be a membrane-associated protein with putative roles in signal transduction in neuronal cells. In particular, we have discovered an interaction between tau and src family non-receptor tyrosine kinases. We are currently investigating the functional implications of this interaction in neuronal cells. For example, the interaction may affect the spatial localization of tau, the activity of the tyrosine kinase, the actin cytoskeleton, the cell cycle, or the phosphorylation of tau. We are also investigating other new interactions of tau. In our studies, we use a combination of cell biological, molecular biological, and biochemical tools and assays.
Tau is also a prominent component of the neurofibrillary tangles of Alzheimer's disease. In addition, mutations in the tau gene cause other age-related neurodegenerative diseases such as frontotemporal dementia. The mechanisms underlying the formation of abnormal tau lesions in Alzheimer's disease and other dementias and the mechanisms that cause neuronal cell death in these age-related diseases are unknown. We are testing the hypothesis that tau's interactions with proteins other than microtubules, have a role in the neurodegenerative process.

Publications

Liu, G., Thangavel, R., Rysted, J., Kim, Y., Francis, M. B., Adams, E., Lin, Z., Taugher, R. J., Wemmie, J. A., Usachev, Y. M. & Lee, G. (2019). Loss of tau and Fyn reduces compensatory effects of MAP2 for tau and reveals a Fyn-independent effect of tau on calcium. Journal of neuroscience research, 97(11), 1393-1413. PMID: 31452242.

Kim, Y., Liu, G., Leugers, C. J., Mueller, J. D., Francis, M. B., Hefti, M. M., Schneider, J. A. & Lee, G. (2019). Tau interacts with SHP2 in neuronal systems and in Alzheimer's disease brains. Journal of cell science, 132(14). PMID: 31201283.

Hilderley, A. J., Fehlings, D., Lee, G. W. & Wright, F. V. (2016). Comparison of a robotic-assisted gait training program with a program of functional gait training for children with cerebral palsy: design and methods of a two group randomized controlled cross-over trial. SpringerPlus, 5(1), 1886. PMID: 27843743.

Liu, J., Tanrikut, C., Wright, D. L., Lee, G. Y., Toner, M., Biggers, J. D. & Toth, T. L. (2016). Cryopreservation of human spermatozoa with minimal non-permeable cryoprotectant. Cryobiology, 73(2), 162-7. PMID: 27498216.

Lee, G., Kim, N. H., Martini, K. M., Sherer, N. A., Goldenfeld, N. & Kuhlman, T. E. (2016). Real-time transposable element activity in individual live cells. (Vols. 2016 Jun 28;113(26)). pp. 7278-83. Proc Natl Acad Sci U S A. PMID: 27298350.

Kanmert, D., Cantlon, A., Muratore, C. R., Jin, M., O'Malley, T. T., Lee, G., Young-Pearse, T. L., Selkoe, D. J. & Walsh, D. M. (2015). C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal Fragments, Are Released from Neurons Independently of Cell Death. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35(30), 10851-65. PMID: 26224867.

Leugers, C. J., Koh, J. Y., Hong, W. & Lee, G. (2013). Tau in MAPK activation. Frontiers in neurology, 4, 161. PMID: 24146661.

Lee, G., Leugers, C. J. (2012). Tau and tauopathies. Progress in molecular biology and translational science, 107, 263-93. PMID: 22482453.

Souter, S., Lee, G. (2010). Tubulin-independent tau in Alzheimer's disease and cancer: implications for disease pathogenesis and treatment. Current Alzheimer research, 7(8), 697-707. PMID: 20678073.

Bhaskar, K., Hobbs, G. A., Yen, S. H. & Lee, G. (2010). Tyrosine phosphorylation of tau accompanies disease progression in transgenic mouse models of tauopathy. Neuropathology and applied neurobiology, 36(6), 462-77. PMID: 20609109.

Leugers, C. J., Lee, G. (2010). Tau potentiates nerve growth factor-induced mitogen-activated protein kinase signaling and neurite initiation without a requirement for microtubule binding. The Journal of biological chemistry, 285(25), 19125-34. PMID: 20375017.

Kim, W., Lee, S., Jung, C., Ahmed, A., Lee, G. & Hall, G. F. (2010). Interneuronal transfer of human tau between Lamprey central neurons in situ. Journal of Alzheimer's disease : JAD, 19(2), 647-64. PMID: 20110609.

Souter, S., Lee, G. (2009). Microtubule-associated protein tau in human prostate cancer cells: isoforms, phosphorylation, and interactions. Journal of cellular biochemistry, 108(3), 555-64. PMID: 19681044.

Lee, S., Jung, C., Lee, G. & Hall, G. F. (2009). Exonic point mutations of human tau enhance its toxicity and cause characteristic changes in neuronal morphology, tau distribution and tau phosphorylation in the lamprey cellular model of tauopathy. Journal of Alzheimer's disease : JAD, 16(1), 99-111. PMID: 19158426.

Hernandez, P., Lee, G., Sjoberg, M. & Maccioni, R. B. (2009). Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Abeta (25-35): involvement of lipid rafts. Journal of Alzheimer's disease : JAD, 16(1), 149-56. PMID: 19158430.

Sarkar, M., Kuret, J. & Lee, G. (2008). Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone. Journal of neuroscience research, 86(12), 2763-73. PMID: 18500754.

Sharma, V. M., Litersky, J. M., Bhaskar, K. & Lee, G. (2007). Tau impacts on growth-factor-stimulated actin remodeling. Journal of cell science, 120(Pt 5), 748-57. PMID: 17284520.

Bhaskar, K., Yen, S. H. & Lee, G. (2005). Disease-related modifications in tau affect the interaction between Fyn and Tau. The Journal of biological chemistry, 280(42), 35119-25. PMID: 16115884.

Vega, I. E., Cui, L., Propst, J. A., Hutton, M. L., Lee, G. & Yen, S. H. (2005). Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates. Brain research. Molecular brain research, 138(2), 135-44. PMID: 15913839.

Krylova, S. M., Musheev, M., Nutiu, R., Li, Y., Lee, G. & Krylov, S. N. (2005). Tau protein binds single-stranded DNA sequence specifically--the proof obtained in vitro with non-equilibrium capillary electrophoresis of equilibrium mixtures. FEBS letters, 579(6), 1371-5. PMID: 15733843.

Lee, G. (2005). Tau and src family tyrosine kinases. Biochimica et biophysica acta, 1739(2-3), 323-30. PMID: 15615649.

Lee, G., Thangavel, R., Sharma, V. M., Litersky, J. M., Bhaskar, K., Fang, S. M., Do, L. H., Andreadis, A., Van Hoesen, G. & Ksiezak-Reding, H. (2004). Phosphorylation of tau by fyn: implications for Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience, 24(9), 2304-12. PMID: 14999081.

Miller, V. M., Xia, H., Marrs, G. L., Gouvion, C. M., Lee, G., Davidson, B. L. & Paulson, H. L. (2003). Allele-specific silencing of dominant disease genes. Proceedings of the National Academy of Sciences of the United States of America, 100(12), 7195-200. PMID: 12782788.

Zamora-Leon, S. P., Lee, G., Davies, P. & Shafit-Zagardo, B. (2001). Binding of Fyn to MAP-2c through an SH3 binding domain. Regulation of the interaction by ERK2. The Journal of biological chemistry, 276(43), 39950-8. PMID: 11546790.

Hall, G. F., Lee, V. M., Lee, G. & Yao, J. (2001). Staging of neurofibrillary degeneration caused by human tau overexpression in a unique cellular model of human tauopathy. The American journal of pathology, 158(1), 235-46. PMID: 11141497.

Hall, G. F., Chu, B., Lee, G. & Yao, J. (2000). Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease. Journal of cell science, 113 ( Pt 8), 1373-87. PMID: 10725221.

Sontag, E., Nunbhakdi-Craig, V., Lee, G., Brandt, R., Kamibayashi, C., Kuret, J., White, 3rd, C. L., Mumby, M. C. & Bloom, G. S. (1999). Molecular interactions among protein phosphatase 2A, tau, and microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies. The Journal of biological chemistry, 274(36), 25490-8. PMID: 10464280.

Arawaka, S., Usami, M., Sahara, N., Schellenberg, G. D., Lee, G. & Mori, H. (1999). The tau mutation (val337met) disrupts cytoskeletal networks of microtubules. Neuroreport, 10(5), 993-7. PMID: 10321473.

Lee, G. (1999). Special-interest subgroups at the ASCB: Tau protein in neurodegenerative disease. Trends in cell biology, 9(3), 119. PMID: 10203780.

Liu, C. W., Lee, G. & Jay, D. G. (1999). Tau is required for neurite outgrowth and growth cone motility of chick sensory neurons. Cell motility and the cytoskeleton, 43(3), 232-42. PMID: 10401579.

Lee, G., Newman, S. T., Gard, D. L., Band, H. & Panchamoorthy, G. (1998). Tau interacts with src-family non-receptor tyrosine kinases. Journal of cell science, 111 ( Pt 21), 3167-77. PMID: 9763511.

Hall, G. F., Yao, J. & Lee, G. (1997). Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ. Proceedings of the National Academy of Sciences of the United States of America, 94(9), 4733-8. PMID: 9114060.

Léger, J., Kempf, M., Lee, G. & Brandt, R. (1997). Conversion of serine to aspartate imitates phosphorylation-induced changes in the structure and function of microtubule-associated protein tau. The Journal of biological chemistry, 272(13), 8441-6. PMID: 9079670.

Brandt, R., Kempf, M. & Lee, G. (1997). Expression and Purification of Tau for in vitro studies. In J. Avila , R. Brandt & K. S. Kosik (Eds.) Brain Microtubule-Associated Proteins: Practical Approaches. Amsterdam: Harwood Academic Publishers.

Lee, G. (1997). Expression MAP cDNAs in eukaryotic cells. In J. Avila , R. Brandt , K. S. Kosik (Eds.) Brain Microtubule-Associated Proteins: Practical Approaches. Amsterdam: Harwood Academic Publishers.

Sontag, E., Nunbhakdi-Craig, V., Lee, G., Bloom, G. S. & Mumby, M. C. (1996). Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron, 17(6), 1201-7. PMID: 8982166.

Kempf, M., Clement, A., Faissner, A., Lee, G. & Brandt, R. (1996). Tau binds to the distal axon early in development of polarity in a microtubule- and microfilament-dependent manner. The Journal of neuroscience : the official journal of the Society for Neuroscience, 16(18), 5583-92. PMID: 8795614.

Wu, J. M., Chen, Y., Hsieh, T. C., Brandt, R. & Lee, G. (1996). Phosphorylation of native and truncated isoforms of protein tau by the double-stranded DNA-dependent protein kinase (DNA-PK) shows that the primary phosphorylation sites are localized between amino acid residues 212-231 of the longest tau. Biochemistry and molecular biology international, 40(1), 21-31. PMID: 8886266.

Brandt, R., Léger, J. & Lee, G. (1995). Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain. The Journal of cell biology, 131(5), 1327-40. PMID: 8522593.

Léger, J. G., Brandt, R. & Lee, G. (1994). Identification of tau protein regions required for process formation in PC12 cells. Journal of cell science, 107 ( Pt 12), 3403-12. PMID: 7706394.

Brandt, R., Lee, G., Teplow, D. B., Shalloway, D. & Abdel-Ghany, M. (1994). Differential effect of phosphorylation and substrate modulation on tau's ability to promote microtubule growth and nucleation. The Journal of biological chemistry, 269(16), 11776-82. PMID: 8163474.

Brandt, R., Lee, G. (1994). Orientation, assembly, and stability of microtubule bundles induced by a fragment of tau protein. Cell motility and the cytoskeleton, 28(2), 143-54. PMID: 8087873.

Brandt, R., Lee, G. (1993). The balance between tau protein's microtubule growth and nucleation activities: implications for the formation of axonal microtubules. Journal of neurochemistry, 61(3), 997-1005. PMID: 8360696.

Brandt, R., Lee, G. (1993). Functional organization of microtubule-associated protein tau. Identification of regions which affect microtubule growth, nucleation, and bundle formation in vitro. The Journal of biological chemistry, 268(5), 3414-9. PMID: 8429017.

Lee, G. (1993). Non-motor microtubule-associated proteins. Current opinion in cell biology, 5(1), 88-94. PMID: 8448035.

Vulliet, R., Halloran, S. M., Braun, R. K., Smith, A. J. & Lee, G. (1992). Proline-directed phosphorylation of human Tau protein. The Journal of biological chemistry, 267(31), 22570-4. PMID: 1429606.

Lee, G., Brandt, R. (1992). Microtubule-bundling studies revisited: is there a role for MAPs?. Trends in cell biology, 2(10), 286-9. PMID: 14731912.

Lee, G., Rook, S. L. (1992). Expression of tau protein in non-neuronal cells: microtubule binding and stabilization. Journal of cell science, 102 ( Pt 2), 227-37. PMID: 1400630.

Knops, J., Kosik, K. S., Lee, G., Pardee, J. D., Cohen-Gould, L. & McConlogue, L. (1991). Overexpression of tau in a nonneuronal cell induces long cellular processes. The Journal of cell biology, 114(4), 725-33. PMID: 1678391.

Lee, G. (1990). Tau protein: an update on structure and function. Cell motility and the cytoskeleton, 15(4), 199-203. PMID: 2110865.

Lee, G., Neve, R. L. & Kosik, K. S. (1989). The microtubule binding domain of tau protein. Neuron, 2(6), 1615-24. PMID: 2516729.

Kosik, K. S., Orecchio, L. D., Binder, L., Trojanowski, J. Q., Lee, V. M. & Lee, G. (1988). Epitopes that span the tau molecule are shared with paired helical filaments. Neuron, 1(9), 817-25. PMID: 2483104.

Selkoe, D. J., Podlisny, M. B., Joachim, C. L., Vickers, E. A., Lee, G., Fritz, L. C. & Oltersdorf, T. (1988). Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proceedings of the National Academy of Sciences of the United States of America, 85(19), 7341-5. PMID: 3140239.

Lee, G., Cowan, N. & Kirschner, M. (1988). The primary structure and heterogeneity of tau protein from mouse brain. Science (New York, N.Y.), 239(4837), 285-8. PMID: 3122323.

Podlisny, M. B., Lee, G. & Selkoe, D. J. (1987). Gene dosage of the amyloid beta precursor protein in Alzheimer's disease. Science (New York, N.Y.), 238(4827), 669-71. PMID: 2960019.

Lee, G., Hynes, R. & Kirschner, M. (1984). Temporal and spatial regulation of fibronectin in early Xenopus development. Cell, 36(3), 729-40. PMID: 6697394.

Moran, Jr, C. P., Lang, N., LeGrice, S. F., Lee, G., Stephens, M., Sonenshein, A. L., Pero, J. & Losick, R. (1982). Nucleotide sequences that signal the initiation of transcription and translation in Bacillus subtilis. Molecular & general genetics : MGG, 186(3), 339-46. PMID: 6181373.

Pero, J., Lee, G., Morgan, C. P., Lang, N. & Losik, R. (1982). Promoters controlled by novel sigma factors in Bacillus Subtilis. In R. L. Rodriguez , M. J. Chamberlin (Eds.) Promoters: Structure and Function. New York: Praeger.

Lee, G., Pero, J. (1981). Conserved nucleotide sequences in temporally controlled bacteriophage promoters. Journal of molecular biology, 152(2), 247-65. PMID: 6276567.

LEE, G. (1981). Temporally-Controlled Phage Spoi Promoters. United States – Massachusetts: Harvard University.

Lee, G., Hannett, N. M., Korman, A. & Pero, J. (1980). Transcription of cloned DNA from Bacillus subtilis phage SP01. Requirement for hydroxymethyluracil-containing DNA by phage-modified RNA polymerase. Journal of molecular biology, 139(3), 407-22. PMID: 6449597.

Lee, G., Talkington, C. & Pero, J. (1980). Nucleotide sequence of a promoter recognized by Bacillus subtilis RNA polymerase. Molecular & general genetics : MGG, 180(1), 57-65. PMID: 6777632.