Li-Huei Tsai Steps Down as Picower Institute Director, Focuses on Alzheimer’s Research & Brain Initiatives | MIT News

After sixteen years of leadership, Li-Huei Tsai, Picower Professor of Neuroscience at MIT, will step down as director of the Picower Institute for Learning and Memory in May. This shift isn’t a departure from neuroscience, but a deliberate refocusing of her considerable energy back towards fundamental research and teaching, specifically within the realms of Alzheimer’s disease and Down syndrome. The move allows her to deepen her involvement with MIT’s Aging Brain Initiative and the Alana Down Syndrome Center, initiatives she helped establish.

Tsai’s tenure at the Picower Institute, beginning in 2009, has been marked by substantial growth. When she arrived, the institute comprised 11 labs and a community of around 200. Under her direction, it has expanded to 16 labs and a team of approximately 400 scientists, students and staff, housed in MIT’s Buildings 46, and 68. This expansion wasn’t simply about numbers; Tsai fostered a culture of innovation and rigorous research, attracting highly talented neuroscientists and securing crucial funding.

Building a Neuroscience Hub

The growth of the Picower Institute wasn’t accidental. Tsai worked closely with the Freedom Together Foundation (formerly the JPB Foundation), the organization behind a “transformative gift” that led to the institute’s renaming in 2002, to implement strategic initiatives. These included programs designed to support junior faculty, encourage grant applications, and provide fellowships for postdoctoral researchers and graduate students. She likewise expanded the scope of the Picower Institute Innovation Fund, bolstering research productivity. The institute itself has a history of evolution, originally founded in 1994 as the Center for Learning and Memory.

Beyond strengthening the institute’s core research capabilities, Tsai spearheaded two campus-wide initiatives: the Aging Brain Initiative (launched in 2015) and the Alana Down Syndrome Center (established in 2019 with a gift from The Alana Foundation). These initiatives reflect a commitment to tackling complex neurological challenges that extend beyond the boundaries of a single research center. The Alana Down Syndrome Center, in particular, aims to improve understanding and treatment options for individuals with Down syndrome, who often experience early-onset Alzheimer’s disease.

A Legacy of Research into Alzheimer’s and Beyond

Throughout her time as director, Tsai maintained an active research program, making significant contributions to our understanding of Alzheimer’s disease. Her work spans multiple scales, from the molecular mechanisms driving neurodegeneration to the complex circuitry of the brain. She has identified key roles for the enzyme CDK5 in neurodegeneration and pioneered research into the impact of epigenetic changes and DNA damage on Alzheimer’s pathology.

More recently, Tsai’s lab has focused on understanding how the APOE4 gene variant – the biggest genetic risk factor for Alzheimer’s – contributes to the disease process. Her team’s research has explored potential therapeutic strategies, including the repurposing of existing medications and supplements. In collaboration with colleagues at MIT, she has also developed comprehensive atlases of gene expression and epigenetic changes in the brains of individuals with Alzheimer’s disease, providing a valuable resource for the broader research community. These atlases offer insights into brain vulnerability and resilience.

Gamma Entrainment: A Novel Therapeutic Approach

Perhaps one of the most promising avenues of research emerging from Tsai’s lab is the development of “Gamma Entrainment Using Sensory Stimuli” (GENUS). This non-invasive technology uses sensory stimulation – visual, auditory, or tactile – to enhance 40Hz gamma wave activity in the brain. Studies have shown that GENUS can preserve brain volume, improve learning and memory, and reduce signs of Alzheimer’s pathology in both animal models and human volunteers. The technology, now being developed by an MIT spinoff company, is currently undergoing a Phase III clinical trial, enrolling hundreds of participants nationwide. Further evidence supporting the potential of GENUS has been published in recent years.

Tsai’s contributions have been widely recognized within the scientific community. She is a fellow of the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Inventors, and has received numerous awards, including the Society for Neuroscience Mika Salpeter Lifetime Achievement Award and the Hans Wigzell Prize. She has authored over 230 peer-reviewed publications and holds numerous patents, and has been instrumental in launching several biotech startups.

The Search for a Successor

With Tsai stepping down, MIT has initiated a search for the next director of the Picower Institute. Nergis Mavalvala, dean of the MIT School of Science, has appointed a search committee led by Sherman Fairchild Professor Matthew Wilson, associate director of the institute. The committee also includes Picower Professor and former institute director Mark Bear, Menicon Professor Troy Littleton, Assistant Professor Sara Prescott, and Professor Fan Wang. They are expected to present a report to Mavalvala later this spring.

Tsai expressed her gratitude for the opportunity to lead the Picower Institute and build it into a leading center for neuroscience research. “I’m immensely proud of what our institute represents,” she said. “Our labs produce innovations, discoveries, and often translational strategies that have broken new ground and pushed science, medicine, and technology forward.” She now looks forward to dedicating her full attention to her research, the Aging Brain Initiative, and the Alana Down Syndrome Center, continuing her work to unravel the complexities of the brain and develop new treatments for neurological disorders.

The transition at the Picower Institute marks a new chapter for the institution, building on a strong foundation of scientific excellence and a commitment to addressing some of the most pressing challenges in human health. The ongoing clinical trials of GENUS, and the continued work of the Aging Brain Initiative and Alana Down Syndrome Center, represent tangible steps towards improving the lives of individuals affected by Alzheimer’s disease and Down syndrome.