Medications used to treat disease often come with unwanted side effects.
That is where 新澳门六合彩内幕信息College of Arts and Sciences researcher Dr. Libin Ye, assistant professor in the Department of Molecular Biosciences is focusing his latest research.
Ye鈥檚 lab concentrates on a fundamental scientific question, which he said he hopes will aid in drug development: how can we rationally design a biased drug for the G-protein coupled receptor (GPCR)?
They are examining the roles of different GPCR conformations in the human body and their relations to biased signaling for biased drug development.
GPCRs mediate most cellular responses to hormones and neurotransmitters and are responsible for vision, olfaction and taste, according to the National Institutes of Health.
Specifically, they are researching GPCR-biased signaling to aid in the development of drugs that he says could exclusively target therapeutic signaling with minimized side effects.
G protein-coupled receptors. (Photo courtesy of Dr. Ye)
鈥淲e are working toward drug discovery by fundamentally understanding how the drugs act on the receptor and how the receptor responds to drugs through shape-changing,鈥� Ye said. 鈥淥ne-third of medications actually touch on the larger family of the GPCRs, which are everywhere in our body.鈥�
Ye and his colleagues are being highlighted in for their work in advancing the conformational resolution of the GPCR by creating a set of confirmation-biased mutants in collaboration with William A. Goddard from California Institute of Technology and Chris Neale from Los Alamos National Laboratory.
Ye says that the discovery of GPCR-biased signaling (one signaling pathway over others) will aid in the development of drugs that can exclusively target a specific signal while minimizing unwanted side effects.
鈥淔or example, you drink coffee every day, but how is the drink effective? Some people cannot drink coffee because it has a negative side effect on their heart,鈥� Ye said. 鈥淪o, if you can design a caffeine analog that can give you energy but not give you heart problems, that would be great for the people who can鈥檛 have coffee currently.鈥�
Ye says that he and his colleagues have demonstrated the ability to delineate and quantify conformational states of a GPCR at a high resolution, which allows us to study the functions of individual conformational states. The preliminary data further demonstrated that different conformational states exhibit different functions in directing signaling bias related to either the therapeutic or side-effect outputs.
鈥淭he ongoing study will enable us to address a series of fundamental scientific questions in the GPCR signaling process and drive biased drug design based on the receptor conformational selectivity upon different drug bindings,鈥� he said.
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