Research Interests:

Biology of tau, synucleins and amyloid beta precursor proteins (APPs) in health and disease.

Research Techniques:

Protein purification; monoclonal antibody production; immunochemical and immunocytochemial techniques; tissue culture; animal models; electron microscopy and molecular biology.

Keywords:

Alzheimer's disease; tauopathies; APPs; Parkinson's disease; synucleinopathies.

Research Summary:

Major research interest focuses on tau, a-synuclein and amyloid beta precursor protein (APP), and their roles in the pathobiology of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementias (FTD).  In particular, we wish to determine the pathogenesis of senile plaques, Lewy bodies and neurofibrillary tangles because these are major lesions found in the brains of AD patients and other neurodegenerative diseases.  Information obtained from research program may shed light on how neurons degenerate in AD and PD and lead to a better understanding of the etiology of these diseases.  A multi-disciplinary approach (including biochemical and molecular studies of neuronal culture systems, animal models and human tissues obtained at autopsy) is used in the laboratory to address these research issues in common with these neurodegenerative diseases.  Our other research efforts focus on an increased understanding of the normal functions of tau, synucleins, and APP.

Lab Rotation Projects:

Lab rotation projects are difficult to define in a rapidly progressing field of research. Please contact Dr. Lee to discuss suitable projects.

Key References:

Hong, M., Zhukareva, V., Vogelsberg-Ragaglia, V., Wszolek, Z., Reed, L., Geschwind, D., Bird, T., McKeel, D., Morris, J., Wilhelmsen, K., Schellenberg, G.D., Trojanowski, J.Q., Lee, V. M-Y. Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17,  Science, 282:1914-1917, 1998.

Skovronsky, D.M., Zhang, B., Kung, M.-P., Kung, H. F., Trojanowski, J. Q., and Lee, V. M.-Y. In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease. PNAS, 97: 7609-7614, 2000.

Ishihara, T, Hong, M, Zhang, B, Nakagawa, Y, Lee, M.K., Trojanowski, JQ and Lee, V.M.-Y. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron, 24:751-762, 1999.

Giasson, B. I., Duda, J. E., Murray, I.V.J., Chen, Q., Souza, J. M., Hurtig, H. I., Ischiropoulos, H., Trojanowski, J. Q., and Lee, V. M.-Y.  Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions.  Science 290: 985-989, 2000.

Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., and Lee, V. M.-Y. Neuronal a-synucleinopathy with severe movement disorder in mice expressing A53T human a-synuclein. Neuron 34: 521-533, 2002.

Higuchi, M., Ishihara, T., Zhang, B., Hong, M., Andreadis, A., Trojanowski, J.Q., and Lee, V. M.-Y. Transgenic Mouse Model of Tauopathies with Glial Pathology and Nervous System Degeneration. Neuron 35: 433-446, 2002.

Lab Personnel:

Senior Research Investigators:

Linda K. Kwong, Ph.D.
Bin Zhang, M.D., Ph.D.
Vicki Zhukareva, Ph.D.
Kunihiro Uryu, Ph.D.
Shaohua Xu, Ph.D.

Graduate Students:

Adam Crystal
Deepa Dabir
Edward Lee
Kangning Liu
Erin Norris
Deepak M. Sampathu

Postdoctoral Fellows:

Mark S. Forman, M.D., Ph.D.
Makoto Higuchi, M.D., Ph.D.
Benoit Giasson, Ph.D.
Paul Kotzbauer, M.D., Ph.D.
Aaron Pawlyk, Ph.D.
Ian Murray, Ph.D.
Christina Wilson, Ph.D.
Yasumasa Yoshiyama, M.D., Ph.D.
Sharon Shively, M.D.

Research Specialists:

Alex Crowe
Susan Leight
Dan Martinez
Eric Greenbaum
Lisa Gill
Chi Li
Constance Page
Sonali Sundarraj
Charles L. Graves
Kristen Lindeen
Theresa Schuck
Alexxai Kravitz

Visiting Scholar:

Vanessa Morais (from Portugal)

Technical Assistants:

Sophie Hamilton
Olga Ortiz