Tsai earns Hans Wigzell’s Prize in Medicine

The Hans Wigzell Research Foundation announced Jan. 23 that neuroscientist Li-Huei Tsai, Picower Professor and director of The Picower Institute for Learning and Memory at MIT, is the winner of Hans Wigzell´s Prize in Medicine for 2018. Tsai will travel to Stockholm to receive the prize and deliver a lecture on her research Feb. 14.

“The prize is given to professor Li-Huei Tsai for her innovative research in trying to understand the etiology and possible treatment of Alzheimer´s disease,” the Foundation stated in the announcement of the $100,000 prize. “Professor Tsai has in her research made a series of impressive findings with regard to this disease.”

In decades of research with collaborators, postdocs and students, Tsai has led several fundamental and translatable discoveries about biological mechanisms underlying neurodegeneration including specific aberrations in epigenetic gene regulation, enzyme pathways and repair of DNA damage. Tsai and collaborators have also uncovered substantial evidence that impaired neuronal synchrony may underlie Alzheimer’s progression, an insight that has allowed her to demonstrate a non-invasive treatment approach using light and sound stimuli to drive neural oscillations, engage the brain’s immune system, reduce pathology, and improve functionality in multiple mouse models. Testing of the technique has recently begun in humans.

“This treatment has resulted in dramatic improvements of the diseased animals both with regard to pathology and performance,” the foundation noted. “Her research has rapidly resulted in the start of advanced, clinical trials in Alzheimer’s patients.”

Tsai, who also directs the Aging Brain Initiative at MIT, said she was honored to earn the Wigzell Foundation’s recognition. Hans Wigzell is a former President of the Karolinska Institute and Chairman of the Nobel Prize Committee of the Institute.

“I am deeply grateful to Professor Wizgell and the Foundation for this award,” Tsai said. “The prize provides my team with great inspiration and resources to continue our work to understand the biology of neurodegeneration and to translate our findings to effective treatments for Alzheimer’s and other diseases.”

With fellowship, postdoc will work to solve Alzheimer’s myelin mystery

Growing up, Joel Blanchard watched his grandfather remain cognitively sharp past the age of 90 but his grandmother develop Alzheimer’s in her 70s. The difference sparked an interest in brain aging that motivates him today as a postdoc in MIT’s Picower Institute for Learning and Memory. As the new recipient of a 2018 Glenn Foundation for Medical Research Postdoctoral Fellowship in Aging Research, he will embark on research that could help explain why myelin, the insulation that clads the brain’s neural wiring, breaks down in Alzheimer’s disease.

“As a teenager, I wondered why these two people with shared experiences and lives had such different outcomes,” said Blanchard, whose interest in Alzheimer’s disease helped bring him to the lab of Picower Professor and Institute Director Li-Huei Tsai.

One of the main mysteries of Alzheimer’s disease – and brain aging more generally – is why myelin degenerates, Blanchard said.

“Myelin and oligodendrocytes insulate neuronal axons supporting and reinforcing neuronal networks, cognition, learning, and memory,” he said. “In aging and Alzhiemer’s disease, myelin degenerates, but it is unknown why this occurs and how it contributes to disease pathogenesis.”

With the award of $60,000 provided by the American Federation for Aging Research (AFAR) and the Glenn Foundation for Medical Research, Blanchard plans to address the question by using three-dimensional cultures of brain tissue grown from human induced pluripotent stem cells.

“We have developed a 3D model of human myelination in a tissue culture dish,” Blanchard said. “This is allowing us to investigate how genetic and environmental factors associated with cognitive aging and Alzheimer’s disease influence myelinating cells and neuronal health.”

Using the cultures, he’ll be able to observe how they grow and change, and will even be able to edit their genes to see the difference that might be made by variations associated with Alzheimer’s disease.

Blanchard said his goal is not only to improve understanding but also to identify new approaches to diagnosing and treating the disease.

“By investigating how and why myelin degenerates in Alzheimer’s disease we hope to identify new strategies for therapeutic intervention and biomarkers for identifying people at risk for cognitive impairments later in life,” he said.

With sense of humility, responsibility new MIT postdoc begins HHMI fellowship

Years before he learned that he’d be awarded a highly competitive Hanna H. Gray fellowship from the Howard Hughes Medical Institute, Matheus Victor said he was already feeling fortunate – maybe even a little guilty – simply because he had the rare opportunity to do what he loved.

As a graduate student at Washington University in St. Louis, the native of Recife, Brazil, who came to Florida at the age of 15, learned that in the United States, Latino immigrants are rare among scientific researchers. But there he was, pursuing his dreams to become a neuroscientist. The realization inspired him to lead a Latin American student group at WashU and to conduct outreach activities including creating bilingual curricula for local students.

“I was so privileged to be in a top tier graduate program pursuing my interest,” he said. “How many people get to pursue an interest? We live in a world where you have to earn money and you have to feed your family.”

And now he’s a new postdoc at MIT’s Picower Institute for Learning and Memory in the lab of Institute director Li-Huei Tsai with a prestigious fellowship that will support his career development for the next eight years. Having met other deserving postdocs who competed for the honor, he said he’s deeply grateful and humbled to be named to the HHMI program. It is designed to support accomplished life scientists from underrepresented backgrounds who can become leaders in academic research and inspire future generations to see that science could be for them, too.

Victor certainly has all that potential, Tsai said.

“I am impressed by Matheus Victor, not only by his tremendous accomplishments as a young scientist, his curiosity about science, and his courage to address the most challenging scientific questions, but also his generosity, maturity and leadership quality,” she said.

In Tsai’s lab, where he arrived in May, Victor will study the role of specific cell types in brain aging and cognitive decline. The research is part of Tsai’s efforts to combat neurodegeneration as part of MIT’s Aging Brain Initiative.

Fire ants and electric fish

But back when Victor was in high school in Orlando and he wanted to be a biologist, he figured that was someone who does field work studying plants and animals. So when he enrolled as an undergraduate at Florida State, he joined a lab that studied fire ants. That’s where the neuroscience bug started to bite (thankfully not literally). What interested him in particular was the ants’ behavior.

His mentor there, Professor Walter Tschinkel, suggested that the best way to explore his interest in science was to read papers and see what interested him most. What jumped out was research by Wash U Associate Professor Bruce Carlson, who studied fish that navigate murky waters by generating weak electrical pulses like bats or dolphins use sonar.

Victor reached out to Carlson about joining his lab when he went to graduate school. In the interim, Carlson introduced him to research colleague José Alves-Gomes who was doing fieldwork with the fish in Brazil – though in the Amazon rainforest, which is a world away from arid Recife. While Victor was studying the fish and learning about the neuroscience of how they sense with electricity, he began applying for research jobs to bridge a few years between college and graduate school.

He landed a job in a lab at Columbia University. There he learned how neural stem cells become neurons and how the cellular environment helps to determine that. He also met his wife, Alexis Hill, who is now an assistant professor of neuroscience at College of the Holy Cross in Worcester, Mass.

After two years in New York, Victor went to WashU for grad school, and Hill did her postdoc there. It was at the elite Midwestern school that Victor first realized he had a Latino identity. He had never really felt like he was a minority in Florida or New York where there were so many other Latinos. In Brazil, in fact, he was considered “white.”

“It was the first time where I felt that my race mattered,” he said.

His response was to embrace the power that he had to encourage Latino children to consider science. He and fellow minority graduate students identified a local population of mostly Mexican children.

“A lot of these kids had just arrived,” he said. “That really sparked me and made me understand my responsibility in using this awesome privilege that I have to give more opportunities like this to kids who wouldn’t otherwise have them.”

To MIT

As a graduate student, Victor rotated through labs including Carlson’s, but he realized that he had become more interested in neural cell development. He joined the lab of Andrew Yoo, who uses brain-enriched microRNAs to reprogram human skin cells into neurons. In his thesis work Victor developed a way to coax skin cells into becoming the specific kind of neuron that degenerates in Huntington’s disease, providing a testbed for research derived from cells from patients with the condition. He led two papers from the work, in Neuron and Nature Neuroscience.

During that time, Tsai came to WashU to speak and Victor learned that her lab did a substantial amount of work with cellular reprogramming, too. Not long after, he contacted her and invited her to visit his poster at the 2016 Society for Neuroscience Annual meeting in San Diego. She did, and from there they struck up a frequent correspondence. For nearly two years, she continued to encourage him to pursue his work, to apply for fellowships such as the Hanna Gray, and to come to MIT.

“She’s been very invested in my progress and my future,” he said. “It’s just really awesome.”

He interviewed to join Tsai’s lab in January 2017.

“I really enjoyed everyone I met,” he said. “I was so blown away by all the postdocs here. After every meeting I was like, ‘Wow, I want to become best friends with this person,’ or ‘Wow, I want to hang out with this person’.”

The feeling is mutual, Tsai said.

“He fits right in and meshes well with everyone in the lab,” she said. “He is kind and friendly and always willing to help.”

Now, with the support of the lab and the fellowship, Victor is interested in two projects.

In one he plans to turn human induced pluripotent stem cells (IPSCs) into microglia, an immune cell of the nervous system increasingly implicated in Alzheimer’s disease, and implant them in the brains of mice where the original microglia have been removed. With this chimera model Victor can test how microglia with different genetic variations act in a mammalian brain to see how those variations might contribute to disease pathology. In the other, he is interested in studying how inhibitory interneurons change in the aging brain. The neurons are of particular interest because they are the source of a crucial brain rhythm that is notably reduced in Alzheimer’s disease. Understanding more about how they function and falter could help explain that important change.

Then, about four years from now, Victor will start his own lab. With continued support from the fellowship, he’ll be able to embark on a career of not only reaching his own potential but also helping the next generation have the privilege of pursuing their interests, too.

Neuroscientists discover roles of gene linked to Alzheimer’s

People with a gene variant called APOE4 have a higher risk of developing late-onset Alzheimer’s disease: APOE4 is three times more common among Alzheimer’s patients than it is among the general population. However, little is known about why this version of the APOE gene, which is normally involved in metabolism and transport of fatty molecules such as cholesterol, confers higher risk for Alzheimer’s.

To shed light on this question, MIT neuroscientists have performed a comprehensive study of APOE4 and the more common form of the gene, APOE3. Studying brain cells and organoids derived from a type of induced human stem cells, the researchers found that APOE4 promotes the accumulation of the beta amyloid proteins that cause the characteristic plaques seen in the brains of Alzheimer’s patients.

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