Biochemist Yueming Li studies the function and regulation of transmembrane proteases and the development of novel protease-based cancer therapies. We spoke to him soon after he joined the Sloan Kettering Institute’s Molecular Pharmacology Program in 2002.
Since moving to the US from China in 1986, Yueming Li has been on the fast-track. In 1997, after receiving his doctorate in biochemistry from the UC-Berkeley and a postdoctoral degree from Harvard Medical School, Dr. Li went to work for Merck Research Laboratories.
At Merck, he led a team in the emerging areas of understanding the molecular mechanism of the gamma-secretase pathway and the development of inhibitors for potential Alzheimer’s disease therapy.
“At first, I liked that my work had direct clinical applications,” said Dr. Li, referring to his pharmaceutical work. “I did a lot of research and made a good contribution to drug development.”
In addition to drug discovery, his group provided compelling evidence that presenilins — proteins that, when mutated, can lead to Alzheimer’s disease — contain the active site of g-secretase and represent a novel class of aspartyl proteases that catalyze intramembrane proteolysis and signaling. This work led to a seminal paper in Nature, which was recently recognized as a “hot paper” by The Scientist because of the large volume of citation.
“But then, in the last two years, I felt like I would do better back in academia,” he continued. “I missed the freedom of research. Sometimes, research, on its own, moves in other directions than you had originally planned. But when you work for a big pharmaceutical company, you can’t always follow it.”
His search for a research institution brought him to Memorial Sloan Kettering, where he was recruited to head Sloan Kettering Institute’s new Laboratory of Biochemistry and Molecular Pharmacology. Dr. Li is extending his pioneering work on the intramembrane protease catalysis into cancer research. Using the disparate tools of molecular biology, protein chemistry, chemistry and proteomics, Dr. Li’s lab studies regulated intramembrane proteolysis and signal transduction.
“In many ways, this was the perfect step for me — it’s the best of both worlds here,” Dr. Li commented. “At Memorial Sloan Kettering, I can do both basic research and drug development. I find this translational element to be essential.”
And as part of the Center’s recently instituted Experimental Therapeutics Center (ETC), Dr. Li hopes to develop new agents that inhibit an unusual class of intramembrane proteases that are associated with cancer — a perfect example of the ETC’s mission to streamline the development of new therapeutics, from conception through early-stage clinical trials. “Right now I have a good team in place and I’m excited about our prospects for doing some important work here at SKI,” said Dr.Li.