Center for Brain Injury and Repair
University of Pennsylvania

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Virginia M.-Y. Lee, Ph.D.

Virginia M.-Y. Lee, PhD

Professor of Pathology and Laboratory Medicine

Co-Director of the Center for Neurodegenerative Disease Research at UPENN's School of Medicine

First recipient of the John H. Ware 3rd Chair for Alzheimer's Disease Research.

Virginia Lee’s  research interest focuses on tau, α-synuclein, TDP-43 and amyloid β precursor protein (APP), and their roles in the pathobiology of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementias (FTD) and amyotrophic lateral sclerosis (ALS).  In particular, her lab wants to determine the pathogenesis of senile plaques, Lewy bodies, neurofibrillary tangles and TDP-43 aggregates because these are major lesions found in the brains of AD patients and other neurodegenerative diseases.  Information obtained from this research 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 research issues in common with these neurodegenerative diseases.  Other research efforts focus on an increased understanding of the normal functions of tau, synuclein, APP and TDP-43. Finally, her lab is involved in research to advance drug discovery in Alzheimer's disease and Parkinson's disease.

Research Interests
Biology of tau, synucleins, TDP-43 and amyloid beta precursor proteins (APPs) in health and disease.

Key Words
Alzheimer's disease; tauopathies; APP; Parkinson’s disease; synucleinopathies, amyotrophic lateral sclerosis, Frontotemporal lobar degeneration, TDP-43 proteinopathies.

Research Techniques
Protein biochemistry; cell and molecular biology; monoclonal antibody production; immunochemical and immunocytochemical techniques; tissue culture; transgenic mouse models; and electron microscopy.

Selected Publications

Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM-Y. Initiation and synergistic fibrillization of tau and α-synuclein. Science, 300: 636-640, 2003.

Yazawa I, Giasson BI, Sasaki R, Zhang B, Joyce S, Uryu K, Trojanowski JQ, Lee VM-Y.  Mouse model of multiple system atrophy: alpha-aynuclein expression in oligodendrocytes causes glial and neuronal degeneration.  Neuron, 45: 847-859, 2005.

Neumann M, Sampathu DM, Kwong LK, Truax A, Miscenyi M, Chou TT, Bruce J, Schuck T, Grossman M, Clark C, Mccluskey L, Miller BL, Masliah E, MacKenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM-Y.  Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.  Science, 314: 130-133, 2006.

Yoshiyama Y, Higuchi M, Zhang B, Huang S-U, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM-Y. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron, 53: 337-351, 2007.

Luk KC, Song C, O’Brien P, Stieber A, Branch JR, Brunden KR, Trojanowski JQ, Lee VM-Y. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells, PNAS, 47: 20051-20056, 2009.

Hospital of the University of Pennsylvania's Department of Pathology and Laboratory Medicine
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