The Persistence of Memory

Professor Li-Huei Tsai's years of hard work on Alzheimer's point to the possibility of restoring what diseased brains have forgotten.

Li-Huei Tsai was four years old when she first saw the horrors of Alzheimer's disease. She was living with her grandmother in a small seaport town north of Taipei. Late one morning, they were walking toward home when lightning cracked in the sky. That was frightening, but what followed was far worse. Her grandmother, in her early 50s at the time, became disoriented. She had no idea where they were, or how to get home; Tsai was too young to know the way herself. They were utterly lost. "It was a really, really scary experience," says Tsai, MIT's Picower Professor of Neuroscience in the Department of Brain and Cognitive Sciences. "She died two or three years later."

Credit: Mark Ostow

Decades have passed, but that experience still drives the 49-year-old scientist. In the past few years she has uncovered new details about the devastating effects of Alzheimer's on the brain and demonstrated that it's possible for mice to retrieve memories that seemed to have been lost forever--a finding that one contemporary hailed as "game-changing." At the same time, she's spearheaded research into abnormal brain development, neuropsychiatric disorders like schizophrenia, and other brain diseases. Her results have been published in top journals such as Nature, Cell, and Neuron.

"She has tremendous depth of knowledge and experience in neuro­science, learning, and memory," says Leonard Guarente, Novartis Professor of Biology, who has collaborated with Tsai. Beyond that, colleagues cite her knack for identifying the big, pressing questions in neuroscience, as well as for bringing in talented young ­researchers and managing their projects simultaneously. In chasing down those big questions, she's shown remarkable persistence--but she didn't originally set out to fight the disease that left her grandmother standing in the street, disoriented and helpless. That quest began with the discovery of a mysterious protein at the start of her career.

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Tsai's lab on the fourth floor of Building 46, which houses the Picower Institute for Learning and Memory, is a busy place: she oversees the research of a diverse mix of more than 20 graduate students and postdocs. During a recent visit, lab-coat-sporting scientists were grabbing plates full of cake from a conference room as Tsai hustled into her sunlight-filled office. A row of empty champagne bottles sat atop her bookshelf, the vestiges of postpublication celebrations. She tries to cultivate a family atmosphere in her lab, whether that means organizing birthday parties or popping champagne corks. Of course, managing all those research projects makes for a hectic life (she's so busy she sometimes brings her 11-year-old daughter to conferences so they can spend more time together). She's been known to realize on the way to the airport that she's forgotten her passport; when it comes to such administrative details, she confesses with a laugh, "I'm a disaster."

Tsai followed a circuitous career path to her gleaming corner office. She initially studied to be a veterinarian, coming to the University of Wisconsin-Madison from Taiwan in 1984 to pursue a master's in the field. But after sitting in on a series of lectures delivered by the Nobel-winning cancer researcher Howard Temin, she found herself drawn to more basic research. "I was very inspired by his work, and realized I really liked lab work," she recalls. Tsai dropped her childhood dream of becoming a vet and, following Temin's lead, switched her focus to cancer. In 1990, she earned a PhD from the University of Texas Southwestern Medical Center in Dallas.