The work owes some of its advancement to a Medical College of Georgia researcher in the 1940s.
Dr. Il-man Kim, at GHSU, is part of a group that meets weekly and includes a Nobel winner, Dr. Robert Lefkowitz, of Duke, who is a pioneer in the identification and manipulation of g-protein-coupled receptors and a similar cell signaling pathway which Kim works in involving proteins called arrestins. Kim believes there is early evidence of their activity in ovarian cancer, behaving in a way that is opposite their effect in cardiac cells.
Dr. Nevin Lambert is working on more sophisticated models for the receptors themselves, as is the Stanford honoree, Dr. Brian Kobilka, that could point toward more specific targets for drugs to enhance their function.
Kim said he is not surprised Lefkowitz got the Nobel because he was nominated a couple of times for it.
“Someday I expected he would get it,” Kim said. “It is great news.”
Kim’s mentor at Duke, Dr. Howard Rockman, founded a drug development company with Lefkowitz called Trevena that is working to develop drugs for heart failure, for instance, and for post-operative pain. Some of the older drugs stimulate both a g-protein pathway, which can be detrimental to cardiovascular disease, and a beta-arrestin pathway, which has the opposite effect and is protective, Kim’s research found. His search is to find one that only stimulates the beta-arrestin pathway, which is also what the potential heart failure drug tries to do. In ovarian cancer, however, it appears to be a different story, Kim said.
“In cardiac disease, beta-arrestin is good,” he said. “But in cancer, especially ovarian cancer, g-protein is good. It functions as a tumor suppressor.”
For Lambert, revealing the structure might hint at a far more sophisticated function than how it is believed to operate. That could mean finding a different agent that targets that receptor more specifically and with greater effect, he said.
“That might make for additional complexity as far as the pharmacology is concerned,” he said.
The work that won the Nobel has deep Augusta roots, Lambert said, because they were focusing on beta-andrenergic receptors. Medical College of Georgia researcher Raymond P. Ahlquist, in a “groundbreaking piece of work” published in 1948, first separated those receptors into alpha- and beta- type receptors, Lambert said, which led directly to the development of beta-blocker drugs.