Virginia Man-Yee Lee
李文渝
Born	1945[2] Chongqing,China[3]
Education	University of London (BSc) Imperial College London (MSc) University of California, San Francisco (PhD) University of Pennsylvania (MBA)
Known for	Research ofAlzheimer's disease
Spouse	John Q. Trojanowski
Scientific career
Fields	Neuroscience Biochemistry
Institutions	University of Utrecht Boston Children's Hospital Harvard University Smith, Kline & French University of Pennsylvania
Thesis	Studies on the in vitro lipolytic activity of pituitary growth hormone (1973)
Doctoral advisor	Choh Hao Li[1]

Virginia Man-Yee Lee (Chinese:李文渝; born 1945) is a Chinese-born Americanbiochemist andneuroscientist who specializes in the research ofAlzheimer's disease. She is the currentJohn H. Ware 3rd Endowed Professor in Alzheimer's Research at the Department ofPathology and Laboratory Medicine, and the director of the Center for Neurodegenerative Disease Research and co-director of the Marian S. Ware Alzheimer Drug Discovery Program at thePerelman School of Medicine,University of Pennsylvania.^[4] She received the 2020Breakthrough Prize in Life Sciences.^[1]

Lee was born in 1945 inChongqing,Republic of China, and moved toHong Kong with her family at age five. She lived with her extended family and studied at aprimary school that taught inChinese. After a year at asecondary school with Chinese as its language of instruction, she switched to a secondary school that taught inEnglish. Her mother, together with most of her relatives, moved to theUnited States when she was about 11, but she stayed in Hong Kong with one of her brothers and her paternal grandmother.^[3]

Lee had been learning thepiano at the insistence of her mother, who as a result encouraged her to study at theRoyal Academy of Music inLondon. Lee was eager to leave Hong Kong and explore other countries, and so she began her piano study in 1962.^[3] Eventually, her interest inscience led her to start aBSc degree inchemistry at theUniversity of London.^[5] Two years into her piano program, she decided to fully commit to science, obtaining a BSc in 1967 and then anMSc inbiochemistry in 1968 fromImperial College London (which at that time was still a member of the University of London).^[3][4]

Afterwards, Lee moved to the United States to be closer to her mother, who was livingLos Angeles, and pursued herPhD at theUniversity of California, San Francisco under the supervision ofChoh Hao Li.^[3] She completed it in 1973.^[4]

Following herPhD, she worked as apostdoctoral fellow at theRudolf Magnus Institute of theUniversity of Utrecht in theNetherlands for a year. In 1974, at the invitation of Michael L. Shelanski and Lloyd A. Greene, who were setting up a research group atBoston Children's Hospital, she returned to theUnited States and became a postdoctoral fellow at the Boston Children's Hospital andHarvardMedical School.^[3][6]

She then entered thebiotechnology sector in 1979, when she became the associate senior research investigator at thePhiladelphia-based pharmaceutical companySmith, Kline & French, now a part ofGlaxoSmithKline. Upset about the restrictions in industry, a year later, she returned to academia, joining the Department ofPathology and Laboratory Medicine of theUniversity of PennsylvaniaSchool of Medicine (nowPerelman School of Medicine).^[3][6] Fearing the transition, she took anMBA from theWharton School of the University of Pennsylvania in 1982 as a "back-up plan" to be at the pharmaceutical industry, completing two years later.^[5][6]

Lee became aprofessor in 1989, and theJohn H. Ware 3rd Endowed Professor in Alzheimer's Research in 1999.^[6]

Since 2002, Lee has been the director of the Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania.^[7]

In 2004, the Marian S. Ware Center for Alzheimer's Drug Discovery Program was established at the University of Pennsylvania, and Lee has been directing it since.^[8]

Lee's research focuses on thepathology ofneurodegenerative diseases, especiallyAlzheimer's disease,Parkinson's disease,frontotemporal lobar degeneration, andamyotrophic lateral sclerosis. Together with her late husbandJohn Q. Trojanowski, Lee's studies challenged conventional belief that Alzheimer's disease is caused by aggregation ofamyloid plaques, and pointed to thetau protein as a major player.^[5][9][10]

The pair first reported in 1988 that the tau protein is a central component of protein aggregates associated with Alzheimer's disease (known as paired helical filaments).^[11] They also determined that abnormalphosphorylation of the tau protein is responsible for the formation ofneurofibrillary tangles, which are aggregates of the tau protein,^[12] and found that healthymice had tau aggregates inside neurons and exhibited Alzheimer's symptoms when injected with pathological tau protein.^[13] In a more recent study, they connected the two major types of protein aggregates,amyloid plaques and tau protein aggregates, where the former facilitates tau aggregation in mice.^[14]

For Parkinson's disease, Lee and Trojanowski reported that another protein,alpha-synuclein, is a major component ofLewy bodies, which are protein aggregates found inneurons of Parkinson's patients.^[15] They also discovered a type ofchaperoneprotein can reduce the death of neurons caused by alpha-synuclein built-up,^[16] and that similar to the tau protein and Alzheimer's, healthy neurons may take upextracellular alpha-synuclein and become defective in function.^[17]

Apart from these two relatively well-known neurodegenerative diseases, Lee and Trojanowski also studied frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), andmultiple system atrophy. In 2004, they associated alpha-synuclein in thebrain with multiple system atrophy.^[18] Two years later, they showed for the first time theTDP43 protein was abnormally modified by phosphorylation andubiquitylation in FTLD and ALS.^[19]

Lee met her late husbandJohn Q. Trojanowski inBoston in 1976.^[20] At the time she was apostdoctoral fellow atBoston Children's Hospital and he was aresident inpathology atHarvard University.^[20] They married in 1979.^[21] Together they carried out research ofAlzheimer's disease at theUniversity of Pennsylvania, where they co-founded the Center for Neurodegenerative Disease Research (CNDR) in 1991.^[9] They co-directed CNDR until 2002, when Lee became director and Trojanowski the co-director.^[7] Trojanowski died from a fall and relatedspinal cord injuries in February 2022.^{[22][23][24][25]}

• Potamkin Prize,American Academy of Neurology (1998)^[26]
• Member of theNational Academy of Medicine (2005)^[27]
• Alzheimer's Association International Conference Lifetime Achievement Awards in Alzheimer's Disease Research,Alzheimer's Association (2009)^[28]
• John Scott Medal (2012)^[29]
• Robert J. and Claire Pasarow Foundation Medical Research Award in Psychiatry (2012)^[30]
• Member of theAmerican Academy of Arts and Sciences (2013)^[31]
• J. Allyn Taylor International Prize in Medicine,University of Western Ontario (2014)^[32]
• Robert A. Pritzker Prize,The Michael J. Fox Foundation (2018)^[33]
• Breakthrough Prize in Life Sciences (2020)^[1]
• Clarivate Citation Laureate (2022)^[34]

• 1945 births
• Living people
• Alumni of the Royal Academy of Music
• Alumni of Imperial College London
• Alumni of the University of London
• Alzheimer's disease researchers
• American neuropathologists
• American women biochemists
• Biologists from Chongqing
• Chinese emigrants to the United States
• Chinese women biologists
• Fellows of the American Academy of Arts and Sciences
• Academic staff of Utrecht University
• Harvard Medical School faculty
• Perelman School of Medicine at the University of Pennsylvania faculty
• University of California, San Francisco alumni
• University of Pennsylvania faculty
• Wharton School alumni
• American women academics
• 21st-century American women
• Members of the National Academy of Medicine

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