Virginia Man-Yee Lee

Photo: Getty Images North America

If you watched the Breakthrough Prize (sometimes called the “Oscars for scientists”) last weekend – Dr. Virginia Man-Yee Lee likely stood out – she was one of the few female awardees, but throughout her career, she has been standing out for a much more important reason – her amazing scientific contributions. Lee is a neuroscientist who has spent her career discovering and characterizing the misfolded proteins involved in neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and ALS, upending dogmas and opening up new therapeutic targets.

Lee was born and raised in China, then emigrated to London to train in piano at the Royal Academy of Music. She didn’t feel she had the passion or talent for the piano required to “make it big” – but she did have a strong passion for science. She started an undergraduate chemistry program at the University of London while continuing at the Royal Academy then switched full-time to science. She earned a Master’s degree in Biochemistry from the University of London in 1968, then moved to the US to pursue a PhD in biochemistry at the University of California, San Francisco (UCSF) where she learned biochemistry, pharmacology, and other topics that would aid her career; but it wasn’t until a postdoctoral fellowship at the University of Utrecht in the Neverlands that she turned her sights on the brain.

She returned to the US to carry out research at Boston Children’s Hospital and it was here that she met her husband and future research partner, pathologist John Q. Trojanowski. She did a stint in industry, working as Associate Senior Research Investigator at Smith-Kline & French, Inc. (what is now called GlaxoSmithKline) – but it didn’t sate her curiosity for neuroscience, so she returned to academia, joining the faculty at the University of Pennsylvania’s Perelman School of Medicine in 1981, where she remains to this day.

It can be hard transitioning from industry to academia, so “as a backup plan” she earned an MBA from the University of Pennsylvania’s Wharton School in 1984. But her scientific research took off quickly and this “backup” wasn’t needed (although the business training comes in handy managing a large lab, directing the Center for Neurodegenerative Disease Research, and co-directing of the Marian S. Ware Alzheimer Drug Discovery Program.

She and her husband partnered up to search out the diseased proteins involved in neurodegenerative diseases – with his pathology training and access to patient samples and her biochemistry know-how they have been able to make remarkable discoveries. In 1991, they showed that that the tangles seen in the brains of Alzheimer’s patients were made up of Tau protein. Alzheimer’s disease is characterized by two types of aggregated proteins – It was long believed that Alzheimer’s is caused by “plaques” of beta-amyloid protein – but Lee helped upend that dogma, her “tau hypothesis” points to “tangles” of a different protein – tau. She showed how misfolded proteins can spread throughout the central nervous system and how similar misfolded protein spreading underlies multiple neurodegenerative diseases.

In 2006, she showed that two crippling neurodegenerative diseases – frontotemporal dementia (FTD) and ALS (Lou Gehrig’s disease) were actually characterized by misfolding and “clumping” of the same type of protein – a protein called TDP43. She also showed that different forms of another protein, alpha-synuclein, in different cell types, play a role in Parkinson’s disease and Multiple System Atrophy.

The Breakthrough Prize comes with a $3 million payout and Lee plans to use some of it to pursue some of the more “out of the box” (and thus difficult to find traditional funding for) experimental ideas she has. Congratulations Dr. Lee!

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