LI-HUEI TSAI
Picower Professor of Neuroscience,Department of Brain and Cognitive Sciences, MIT
Director of the Picower Institute for Learning and Memory, MIT
Senior Associate Member, Broad Institute of MIT and HarvardMITIn 1991, Li-Huei Tsai was a postdoctoral fellow in Edward Harlow’s cancer biology laboratory at Massachusetts General Hospital Cancer Center in Boston. She was working on mammalian orthologs of yeast cyclin-dependent kinases, which regulate cell cycle transitions and are important in tumors, where these enzymes can be mutated and deregulated. She had already cloned and characterized almost an entire family of genes for these kinases, and the gene for one protein in particular, Cdk5, stood out. “Even though this kinase was structurally similar to mitotic kinases, in all of the human and murine cell lines available at the time, there was no Cdk5 activity,” says Tsai, now a professor of neuroscience at MIT. “Others in the lab told me it was probably a pseudogene, but I didn’t give up. Instead, I started a big, crazy effort.”
While everyone in her lab was working on cancer cell lines, Tsai decided to systematically dissect out every mouse tissue and organ and perform an in vitro protein kinase assay to test for Cdk5 activity. If Cdk5 was active as a kinase, it would attach a radioactive phosphate to a test substrate, a histone H1 protein that’s a component of chromatin in eukaryotes.
“There are few times in my life when there has been a defining moment, and this was one. It was late at night, and I was exhausted, waiting for the autoradiograph to come out of the developer. I didn’t expect much because all of my other experiments had been negative. Instead, I couldn’t believe my eyes!” Tsai recalls. On the film, she ...
