Virginia Man-Yee Lee, PhD

The John H. Ware 3rd Endowed Professor in Alzheimer's Research
University of Pennsylvania Perelman School of Medicine
Director, Center for Neurodegenerative Disease Research
Co-Director, Marian S. Ware Center for Alzheimer's Drug Discovery Program

Contact InformationCenter for Neurodegenerative Disease Research
3rd Floor, Maloney Building
3600 Spruce Street
Philadelphia, PA 19104-4283
Office: (215) 662-6427
Fax: (215) 349-5909


Specialty Division

Neuropathology, Cancer and Immunobiology

Research Expertise

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.

Description of Research
Dr. Lee’s research focuses on disease proteins that form pathological inclusions in hereditary and sporadic Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders of aging. Her work demonstrated that tau, alpha-synuclein and TDP-43 proteins form unique brain aggregates in neurodegenerative diseases and provided critical evidence that aggregation of brain proteins is a common mechanistic theme in diverse neurodegenerative diseases including AD, PD, FTLD, ALS and related disorders. Significantly, Dr. Lee’s studies implicated the abnormal aggregation of tau, alpha-synuclein and TDP-43 in mechanisms that compromise neuronal viability. Most importantly, this research has opened up new avenues of research to identify targets for drug discovery to develop better treatments for these disorders.

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

Rotation Projects
Lab rotation projects are difficult to define in a rapidly moving field. Please contact Dr. Lee to discuss possible rotation projects.

Graduate Groups

Biochemistry and Molecular Biophysics
Cell and Molecular Biology


Royal Academy of Music, London, England, 1964
B.Sc (Chemistry), Univ. of London, England, 1967
M.Sc (Biochemistry), Univ. of London, England, 1968
Ph.D. (Biochemistry), University of California at San Francisco, 1973
M.B.A. Wharton School, University of Pennsylvania, Philadelphia, 1984

Specialty Certification

Postgraduate Training

Rudolf Magnus Institute for Pharmacology, University of Utrecht, Utrecht, The Netherlands, 1973-1974
Dept. of Neuropathology, Children's Hospital Medical Center and Harvard Medical School, Boston, MA, 1974-1979

Awards and Honors

ZWO (The Netherlands Organization for Scientific Research) Postdoctoral Fellowship, 1973-1974
American Cancer Society Postdoctoral Fellowship, 1974-1975
U.S.P.H.S. Postdoctoral Fellowship NS-05273, 1975-1978
N.C.I. MERIT (Method To Extend Research In Time) Award as Co-Principal Investigator of CA-36245, 1986-1996
Weil Award For Best Experimental Neuropathology Paper, American Association of Neuropathologists, 1988
N.I.N.C.D.S. Senator Jacob Javits Award as Principal Investigator of RO1 NS-18616, 1988-1995
Zenith Award for Alzheimer's Disease Research, Alzheimer's Association, Inc, 1991-1994
Metropolitan Life Foundation Award for Alzheimer Disease Research, 1991
Allied Signal Award for Aging Research, 1992
Recognized by Thompson Scientific as the 12th “Highly Cited Neuroscientist” for 1995-2005, 1995-2005
Metropolitan Life Foundation Award for Medical Research in Alzheimer's Disease, 1996
Rita Hayworth Award for Medical Research in Alzheimer's Disease, 1997
Potamkin Prize for Medical Research in Alzheimer's Disease, 1998
Stanley Cohen Biomedical Research Award, 2000
Recognized by ISI as a "Highly Cited Researcher" (top 250 most highly cited neuroscientists for 1981-1999), 2000
Bristol Meyer Squibb Unrestricted Biomedical Research Grant in Neuroscience, 2003
US Department of Health and Human Services, National Advisory Council on Aging, Member, 2004-2007
AAUW Founders distinguished Senior Scholar Award, 2004-present
AAUW Founders Distinguished Senior Scholar Award, 2004-2004
Franklin Founder Award 2008: Celebrating Women in Science, 2008-2008
3rd Leon Thal Prize, Keep Memory Alive Foundation, Las Vegas, NV, 2009
Life Time Achievement Award in Alzheimer’s Disease Research, Alzheimer’s Association., 2009
John Scott Award (establishd by John Scott in 1822 and given for inventions that have contributed in some outstanding way to the "comfort, welfare and happiness" of mankind by the City of Philadelphia since 1822), 2012
National Academy of Inventors, Charter Fellow, 2012
24th Annual Robert J. and Claire Pasarow Foundation Award in Neuropsychiatry Research, Los Angeles, CA, 2012
10th Parkinson Society Canada’s Donald Calne Award and Lectureship, 2013
American Academy of Arts and Sciences, Member, 2013
J. Allyn Taylor International Prize in Medicine, 2014
Robert A. Pritzker Award for Leadership in Parkinson’s Disease Research from the Michael J. Fox Foundation, 2018-2018
Helis Foundation Award for Parkinson’s and Neurodegenerative Disease Research, 2018-2018
Breakthrough Prize in Life Sciences, 2019

Memberships and Professional Organizations

Alzheimer 100 Scientific Advisory Board, Centenial of Alois Alzheimer’s First Description of Alzheimer’s Disease on November 3, 1906, Tübingen, Germany, 2006 - 2006
Institue of Medicine, 2006 - 2008
Lou Ruvo Brain Instutite, Scientific Advisory Board, 2006 - 2008
Institute of Medicine, 2006 - Present
Scientific Advisory Board, ISTAART, 2008 - Present
Institute Of Medicine, 2008 - 2010
NIA Board of Scientific Counselors, 2009 - 2013
Challenge grants editorial review (neuroscience)., 2009 - 2011
American Academy of Arts and Sciences, 2013 - Present
American Association for the Advancement of Science, - Present
American Association for Neuropathologists, - Present
Society for Neuroscience, - Present
Society for Neuro-chemistry, - Present
American Society for Cell Biology, - Present
New York Academy of Sciences, - Present
US Department of Health and Human Services, National Advisory Council on Aging, - Present
Medical Advisory Board of the Society for Progressive Supranuclear Palsy, - Present
Human Frontier Program, Strasbourg, France,, - Present
Society for Neuroscience, - Present
Alzheimer's Association Zenith Award,, - Present
National Institutes on Aging Subcommittee B, - Present
Research Foundation University of Pennsylvania, - Present
Allied Signal Research Award for Aging, - Present
American Health Assistance Foundation, - Present
N. I. N. D. S. and N.C.I, - Present
National Institutes on Aging Awards Applications, - Present
Neurology C, - Present
American Society for Neural Transplantation and Repair, - Present

Web Links

Selected Publications

An acetylation switch controls TDP-43 function and aggregation propensity.

Cohen TJ, Hwang AW, Restrepo C, Yuan CX, Trojanowski JQ, Lee VM-Y., Nat Commun 6(): 5845, 2015

TDP-43 as a possible biomarkers for frontotemporal lobar degeneration: a systematic review of existing antibodies.

Goosens J, Vanmechelen E, Trojanowski JW, Lee VM, Van Broeckhoven C, van der Zee J, Engelborghs S., Acta Neuropathol Commun. 3(): 15, 2015

Drosha Inclusions Are New Components of Dipeptide-Repeat Protein Aggregates in FTLD-TDP and ALS C9orf72 Expansion Cases.

Porta S, Kwong LK, Trojanowski JQ, Lee VM, J Neuropathol Exp Neurol 74(): 380-387, 2015

Spreading of pathology in neurodegenerative diseases: a focus on human studies.

Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ., Nat Rev Neurosci 16(): 109-120, 2015

Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the carboxylic acid functional group.

Ballatore C, Gay B, Huang L, Robinson KH, James MJ, Trojanowski JQ, Lee VM-Y, Brunden KR, Smith AB 3rd., Bioorg Med Chem Lett 24(): 4171-4175, 2014

In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy.

Crescenzi R, DeBrosse C, Nanga RP, Reddy S, Haris M, Hariharan H, Iba M, Lee VM-Y, Detre JA, Borthakur A, Reddy R., Neuroimage 101C(): 185-192, 2014

Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice.

Peeraer E, Bottelvergs A, Van Kolen K, Mahieu M, Duyschaever H, Verdonck L, Torremans A, Sluydts E, Van Acker N, Kemp JA, Brunden KR, Trojanowski JQ, Dewachter I, Lee VM-Y, Moechars D., Neurobiol Dis 73(): 83-95, 2014

A comparison of Aβ amyloid pathology staging systems and correlation with clinical diagnosis.

Boluda S, Toledo JB, Irwin DJ, Raible KM, Byrne MD, Lee EB, Lee VM-Y, Trojanowski JQ, Acta Neuropath 128(): 543-550, 2014

Aminothienopyridazines as imaging probes of tau pathology: a patent evaluation of WO2013090497.

Ballatore C, Smith AB 3rd, Lee VM-Y, Trojanowski JQ, Brunden KR., Expert Opin Ther Pat 24(): 355-360, 2014

α-Synuclein immunotherapy blocks uptake and templated propagation of misfolded α-Synuclein and neurodegeneration.

Tran HT, Chung CH, Luk KC, Iba M, Zhang B, Trojanowski JQ, Lee VM-Y., Cell Reports 72(): 1-12, 2014

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