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Untangling the mysteries of Alzheimer’s

Drs. Virginia M.-Y. Lee and John Q. Trojanowski are on the front lines of a battle with one of the biggest global threats of the 21st century – one that continues to escalate and impact millions around the world.

As renowned neuroscientists and leading Alzheimer’s researchers, they are fighting the debilitating effects of neurological disorders, including Amyotrophic lateral sclerosis (ALS), Parkinson’s disease and frontal lobe dementia.

“Alzheimer’s disease, and related disorders, they are the scourge of our millennium,” said Dr. Trojanowski. “We desperately need a very vigorous campaign to shutdown these diseases. I fear they will bankrupt our countries and lead to horrible social disruption.”

The researchers direct the Centre for Neurodegenerative Disease Research at the University of Pennsylvania. Among the 10 most cited neuroscientists in the world, they have made major contributions to understanding the molecular basis of neurological disorders.

It is because of these important contributions that they were named the 2014 J. Allyn Taylor International Prize in Medicine co-recipients by Robarts Research Institute.

“Their work has had an immense impact on our understanding of neurological disorders and on our ability to develop focused therapies,” said Arthur Brown, PhD, Robarts Research Institute scientist and chair of the Taylor Prize committee. “They have made an unparalleled contribution to the field of neuroscience.”

Creating protein road maps

Together, this energetic duo has solved the composition of the signature pathologies of four neurological diseases by identifying protein building blocks.

Their first major contribution to the field was the mapping and purification of the tau protein in the early 1990s, a central component of the neurofibrillary tangles in Alzheimer’s disease.

This discovery was controversial at the time, as many in the scientific community were looking to the beta amyloid peptide to solve the Alzheimer’s puzzle. By explaining the biology of the tau protein, Drs. Lee and Trojanowski opened a whole new field of Alzheimer’s research.

“We gave the letter code to the protein that forms the tangles,” Dr. Trojanowski explained. “That launched us on a career that continues today – to try to find biomarkers to measure Tau and diagnose disease.”

They have also led research in Parkinson’s and ALS. In 1998, they showed that alpha-synuclein is the building block of lewy bodies in Parkinson’s disease. Then in 2006, they showed that the protein TDB 43 is the building block for ALS.

“These discoveries enabled them to open up new avenues to understanding and potentially treating these highly prevalent and debilitating diseases,” said Dr. Larry Jameson, dean, Perelman School of Medicine, University of Pennsylvania, in his Taylor Prize nomination letter.

Despite these prominent successes, Drs. Lee and Trojanowski are focused on moving their work forward.

“It’s a quest to mitigate, eliminate and prevent the relentless accumulation of these pathological proteins, to prevent or reverse the disease, and to provide a target for drug and biomarker discoveries,” said Dr. Trojanowski.

Love and the lab

As both lab and life partners for more than 30 years, Drs. Lee and Trojanowski appear to be each other’s secrets to success.

Dr. Lee, PhD, MBA, a biochemist, was born in Chongqing, China and is a trained classical pianist. She studied at the Royal Academy of Music in London, but abandoned her musical training to pursue scientific endeavors.

Dr. Trojanowski, MD, PhD, is a neuropathologist with a medical degree and doctorate from Tufts University.

The two met in a Boston bar in 1976. She was a postdoctoral fellow at Boston Children’s Hospital and he was beginning a residency in pathology at Harvard University. They have been happily married since 1979.

Both became faculty members at the University of Pennsylvania by 1981, the catalyst to their impressive collaboration – although the move to Philadelphia took some convincing on Dr. Lee’s part.

“I wanted to stay in Boston,” explained Dr. Trojanowski. “We had a huge fight, but it was the right time for her. And it eventually brought us together and led to this collaboration.”

Disagreements are not an uncommon occurrence in their professional lives together. A 2006 article in Nature Medicine noted their “scientific arguments are legendary and public – but productive.”

The husband-and-wife team say these infamous arguments are a necessary part of their process as researchers and life partners. “I think because we’re married, a special thing is listening to each other and compromising,” said Dr. Trojanowski.

With a love of travel, the couple often extends their frequent business trips for personal visits to global cities and tours of historic sites. But jet setting to glamorous locales isn’t a priority when one is contributing significantly to the field of neurological disorders research.

“You have to immerse yourself in the science,” said Dr. Lee. “You need to work really hard and be creative. Being smart is not enough.”

Recognition for a wider cause

As co-recipients of the 2014 J. Allyn Taylor International Prize in Medicine, Drs. Lee and Trojanowski are pleased their work and their team is being recognized.

“It’s a great honour, but it’s a team effort,” said Dr. Lee.

Dr. Trojanowski enthusiastically agrees. “I get excited because it is so important for the public to appreciate milestone advances,” he said. “These are made by people and research teams, and they should be recognized. The most important thing to me is it gives visibility to the importance of these diseases.”

Robarts Research Institute has been awarding the prestigious Taylor Prize to leading scientists since 1985. The award will be presented at the Leaders in Innovation Dinner on Thursday, November 20 at the Lamplighter Inn and Conference Centre. The event is proudly supported by the C.H. Stiller Memorial Foundation and the Family of J. Allyn Taylor. Click here for more information and to purchase tickets.