Principal Investigator Li-Huei Tsai
Project Website http://tsailaboratory.mit.edu/
Our primary goal is to elucidate the pathological mechanisms underlying neurological disorders affecting learning & memory. The major research areas include neuropsychiatric disorders, autism, and Alzheimer’s disease.
Dr. Li-Huei Tsai pursues two avenues of research that run to opposite ends of the human life span – from the brain as it develops in utero, to the brain as it decays in old age. Seemingly separate, they are linked by profound brain mechanisms that govern proper growth as well as proper function.
For more than a decade, in exploring possible mechanisms underlying Alzheimer’s disease, Dr. Tsai has focused on a protein kinase called Cdk5. It’s crucial to the process by which new neurons form and migrate to the outside cortical layers during development; at the same time, there’s emerging evidence that it’s key to the neuronal plasticity that allows us to remember and learn. Research in the Tsai lab suggests, for example, that briefly exposing neurons to a certain protein associated with Cdk5 boosts synaptic growth and improves certain kinds of memory; extended exposure to the same protein triggers loss of neurons and severe cognitive decline.
In addition, Dr. Tsai has both accelerated the work of her own lab and advanced the field as a whole by developing an innovative mouse model that can be induced to experience the profound neurodegeneration of Alzheimer’s, and that develops full-blown symptoms in a month or two, rather than a year or more. This adaptable mouse model is ideal for Dr. Tsai’s current work – the search for new approaches to prevent, slow, halt and even the reverse neurodegeneration. Because the model is so easy to work with, the lab can quickly test a wide variety of possibilities, from the introduction of a specific gene, to the transplantation of the stem cells, to attempts to promote growth and integration of entirely new neurons. How soon might such research offer hope for real patients suffering the poignant, debilitating losses of rapid cognitive decline? “I’m pretty optimistic,” says Dr. Tsai. “I really hope this will come to human trials in the next decade or so.”