By Queen Muse
The plan for Virginia M.-Y. Lee’s life was simple.
She would attend the Royal Academy of Music in England, study for two or three years, then she would get married and teach kids how to play piano.
This wasn't a vision she’d concocted herself, but she longed to leave her small hometown in Hong Kong and travel the world. “My mother thought that would be a good trajectory for me,” Lee recalled.
So, after high school, she trekked to the heart of London and began learning the intricate compositions of Rachmaninov and Beethoven. But after two years at the Academy, Lee knew she was destined for a different path.
“I was pretty good at it [piano], but it wasn’t really for me.”
She convinced her mother to let her refocus her studies on science instead. It’s a good thing she had the courage to go her own way.
Over the past 40 years, Virginia M.-Y. Lee, PhD, MBA, has become one of the most decorated researchers in the world and a prominent leader in research at Penn Medicine. She is the John H. Ware 3rd Endowed Professor in Alzheimer's Research in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. Lee is best known for her deep exploration of the misfolded proteins that contribute to the advancement of conditions such as Alzheimer's disease, frontotemporal degeneration (FTD), Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Lee’s groundbreaking discoveries have garnered numerous accolades, including the prestigious Breakthrough Prize in Life Sciences, and bolstered the development of new treatments for neurodegenerative diseases that were once believed to have no hope for effective therapies or cures in our lifetimes.
It’s a career made possible through sheer dedication, a passion for unraveling the mysteries of neurodegenerative diseases, and a partnership that both challenged and motivated Lee to aspire to the highest levels of achievement.
A profound personal and professional partnership
In 1976, Lee found herself at a bar in Boston. She was by then two years into a postdoctoral fellowship in Neuropathology at Boston Children’s Hospital at Harvard Medical School. She didn’t drink, but she’d been invited out that evening by her neighbor who wouldn’t take no for an answer. Lee was sipping a Coke when she saw a very tall, skinny guy come walking through the door. She recognized him as the “very handsome man” she’d seen a few times before; once at a seminar at Harvard, another time, out walking with a woman. They’d always exchanged glances but never spoke. That day, however, Lee felt compelled to finally strike up a conversation.
“Have I met you someplace before?” she asked the man, not realizing she was using probably one of the most common pick-up lines ever uttered. The man smiled. His name was John Q. Trojanowski, and he was then a student finishing up his combined MD/PhD degree at Tufts University. They talked for hours that night, realizing they’d crossed or nearly crossed paths multiple times.
“We really hit it off,” Lee recalled with a smile. “And from that day on, we’ve been together.”
Their friendship soon blossomed into a romantic union and three years later, they were married. The two kindred spirits shared not only a deep connection on a personal level but also a passion for scientific inquiry. Lee had by then earned her bachelor’s and master’s degrees in biochemistry at the University of London, then completed her PhD at the University of California San Francisco and spent a year as a postdoctoral fellow at the University of Utrecht in The Netherlands. She had studied biochemistry, pharmacology, biophysics, and endocrinology. Each training experience nudged her closer to the realization of her specialty, which by then had brought her to Boston.
“I was fascinated with the brain,” Lee said. “I really wanted to learn more about neuroscience.”
Not long after they married, the couple’s interests were pulling them in different directions. Lee received an offer to work for a pharmaceutical company in Philadelphia. Trojanowski was completing a residency in neuropathology at Massachusetts General Hospital in Boston. He didn’t want to leave. She didn’t want to stay. In a decision that came after quite a few arguments, Lee won him over.
The couple moved to Philadelphia in 1980. Trojanowski transferred to the University of Pennsylvania and eventually took on a tenure-track role in the faculty of the Perelman School of Medicine. When Lee found her new job in the pharmaceutical industry wasn’t as fulfilling as she’d expected it to be, she decided to get her MBA at the Wharton School of Business at Penn, but it wasn’t long before she found herself missing her days working in the lab. She joined Trojanowski a few years later at Penn Medicine, where their partnership extended beyond the personal into the professional realm. They joined forces to tackle some of the most pressing questions in neuroscience.
“We decided we should work together. We had different expertise, but we thought, if we put them together, maybe we could do something important,” Lee said.
Important is an understatement for what Lee and Trojanowski went on to discover.
They discovered tau, alpha-synuclein, and TDP-43 proteins, and were first to define the crucial roles these proteins play in the progression of Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative disorders. Over the next four decades, the duo founded the Center for Neurodegenerative Disease Research (CNDR) at Penn, authored numerous seminal papers, and co-led research teams that made significant strides in the field of neuroscience. Their collective research paved the way for the development of new therapeutic strategies and drug candidates aimed at combating neurodegenerative diseases.
“I didn't realize this until we were successful, that it's very unusual for anyone to be able to accomplish what we did,” Lee said.
Unfiltered collaboration between research partners
Colleagues often marveled at Lee and Trojanowski’s synergy, describing their relationship as a model of collaboration and dedication … but also, a forum for no-holds-barred arguments and debates.
Edward B. Lee, MD, PhD, now co-director of Penn’s Institute on Aging, first met Virginia Lee (no relation) and Trojanowski in 1996. He was sitting in an office, being interviewed by Virginia Lee when Trojanowski opened the door and asked her if she wanted a piece of fruit. All of a sudden, “She yelled at him and said, ‘Get out! I'm in an interview, can you see what I'm doing?!’ John apologized and left,” Edward Lee recalled.
At first he thought Virginia Lee might have been in a bad mood. But once he came to work in their lab, Edward Lee realized that was just the way they were. Back when their lab was located in the basement of the Maloney building at the Hospital of the University of Pennsylvania, he remembers the couple having full-blown arguments over the intercom system for all to hear.
“It was amusing. That's just how they interacted with each other,” he said. “It wasn't malicious, they just didn't have a filter with each other. If they were thinking something or if they felt a certain emotion, they would just let it show.”
Bickering aside, the passion they had for their work and each other was undeniable.
“Sometimes people didn't know what to think when we were at work and we’d sometimes argue in front of everybody,” Virginia Lee said, with a laugh. “During our 40-plus years’ relationship, I don’t think we’ve gone more than 24 hours without making up and speaking to each other. We were very close.”
Loss and legacy of John Q. Trojanowski
Trojanowski passed away on Feb. 8, 2022, at the age of 75. Lee returned to work shortly after his funeral. It was the one thing she says helped her cope with the loss of her lifelong companion and friend.
“That following Monday, I went back to work. It was the best thing I could think to do so I wouldn’t sit around being miserable and feeling sorry for myself,” Lee said. “I miss him but I think that, you know, we've worked together for so many years, so the work really has kept me going.”
Colleagues from around the world expressed in tributes the profound impact Trojanowski had on their lives and on the field as one of the most highly respected and most frequently cited neuroscientists in the world. His partner remains committed to carrying her part of that work forward.
Virginia Lee's legacy as a scientist, collaborator, and mentor continues to inspire future generations of researchers. Her work not only continues to deepen understanding of neurodegenerative diseases, but also exemplifies the power of collaboration and unwavering dedication to scientific inquiry.
“I don’t count my medals. I’m actually amazed,” she said with a laugh. “If you would've asked me when I was 15 years old what I would be doing now, I would be blown away by what I have accomplished. I never knew that I’d have the ability to do what I’ve done.”
Reflecting on what has kept her going all these years, fighting to make her mark in neuroscience where so few women and minorities have stood, she credits the strength of one support in particular: “My husband, John. He always believed in me.”
Before Trojanowski’s passing, the duo agreed they would continue their research for as long as they were physically able. Lee says she plans to make good on her promise.
“We decided that we were not going to retire, and that was a good decision,” she said. “To be very honest, if I stopped working, I wouldn't know what to do with myself.”
Changing the picture for dementia
Read more in this collection of stories:
- Progress after decades of research in dementia: The domino chain of discovery is finally creating a path to a cure for Alzheimer’s and related diseases of the brain. Foundational discoveries at Penn were crucial to arriving at this moment
- The gift of knowledge: The fundamental answers to the core questions of neurodegenerative diseases—how and why these diseases develop—are found within the brain itself, including from specimens donated to the Penn Medicine brain bank.
- The connection to care: With innovative memory disorder drugs on the horizon, Penn Medicine is working to address the challenges patients and families still face, from diagnosis, to treatment, to supportive care.