Department of Internal Medicine
Rheumatology Faculty
Graduate School:
Biochemistry and Molecular Biology, Harvard University
Fellowship:
University of California,
San Francisco
Gloria Lee, Ph.D.
Associate Professor
Our laboratory studies tau protein, a microtubule associated protein that is critical to axonal development. We are currently investigating newly discovered interactions of tau that suggest a role for tau in signal transduction. We have found that tau interacts with non-receptor src family tyrosine kinases and is tyrosine phosphorylated. We hypothesize that the phosphorylation of tau controls its ability to stabilize microtubules and to associate with other components in the growth cone, including the plasma membrane and the non-receptor tyrosine kinases, src and fyn. We are investigating tau's role in signal transduction in 1) the growth cone, where microtubules are involved in growth cone motility in response to extracellular signals and in 2) cultured neuronal cell systems where tau is required for neurite outgrowth in response to growth factors.
Tau is also the primary component of the neurofibrillary tangles of Alzheimer's disease. We are investigating the role of tyrosine phosphorylation of tau in tangle formation in neurodegenerative disease. Additionally, recently, other inherited neurodegenerative diseases have been shown to be due to missense mutations in tau and to mutations that alter tau alternative splicing, leading to the overproduction of certain tau isoforms. We are investigating the function of these mutant forms of tau and the consequences of overproduction of the disease related tau isoforms.
Honors, Awards, and Organizations
- American Society for Cell Biologists
- Society for Neuroscience
- American Cancer Society Post-doctoral Fellow 1982-83
- Phi Beta Kappa
Recent Publications
- Lee, G., Thangavel, R., Sharma, V., Litersky, J., Bhaskar, K., Fang, S., Do, L., Andreadis, A., Van Hoesen, G., Ksiezak-Reding, H. Phosphorylation of tau by fyn: implications for Alzheimer's disease. J. Neurosci 24:2304-12, 2004.
- Victor M. Miller, Haibin Xia, Ginger L. Marrs, Cynthia M. Gouvion, Gloria Lee, Beverly L.Davidson, and Henry L. Paulson Allele-specific silencing of dominant disease genes. Proc. Natl. Acad. Sci. 100: 7197-200, 2003.
- Zamora-Leon, S.P., Lee, G., Davies, P., and Shafit-Zagardo, B. Binding of fyn to MAP-2c through an SH3 binding domain: regulation of the interaction by ERK2. J. Biol. Chem. 276:39950-8, 2001.
- Hall, G.F., Chu, B., Lee, G., and Yao, J. Human tau filaments induce microtubule and synapse loss in vertebrate central neurons. J. Cell Science, 113:1373-1387, 2000.
- Lee, G., Newman, S.T., Gard, D.L., Band, H., and Panchamoorthy, G. Tau interacts with src-family non-receptor tyrosine kinases. J. Cell Sci., 111:3167-3177, 1998.
Links of Interest