Masahiko Negishi, Ph.D., head of the NIEHS Pharmacogenetics Group, has been named the 2016 recipient of the Bernard B. Brodie Award in Drug Metabolism by the American Society for Pharmacology and Experimental Therapeutics (ASPET). This prestigious award recognizes outstanding original research contributions in drug metabolism and disposition, particularly those with a major impact on future research in the field.
In selecting Negishi, ASPET acknowledged his landmark contributions in multiple aspects of drug metabolism. The society noted, “Your discovery of CAR and elucidation of the molecular mechanism of induction of cytochromes P450 by phenobarbital was considered by several reviewers as one of the most important accomplishments in our field over the past 40 years.” The constitutive androstane receptor (CAR) is an orphan nuclear receptor that is essential for metabolism, including detoxifying substances that are foreign to the body, such as drugs.
Negishi’s work has had profound implications on understanding a number of human health issues associated with abnormal growth factor and nuclear receptor signaling. More importantly, by resolving the mechanism by which phenobarbital activates CAR, Negishi addressed an issue that had plagued biochemists and pharmacologists. Negishi’s laboratory determined that phenobarbital directly binds to the epidermal growth factor receptor, or EFGR, thus blocking a signaling cascade that normally prevents the activation of CAR.
Negishi’s laboratory has also solved and reported the X-ray crystallography structure of a number of enzymes, including estrogen sulfotransferase, which was the first crystal structure solved at NIEHS.
A long list of honors
The society listed several of his honors in giving Negishi the award. In 2000, Negishi was selected to be a member of the Senior Biomedical Research Service at the National Institutes of Health. His research accomplishments were acknowledged with the Scientific Achievement Award from the International Society for Study of Xenobiotics in 2002. Negishi received an honorary doctorate degree from the University of Kuopio, Finland in 2005 and was designated a Fellow of the Japanese Society for the Study of Xenobiotics in 2012.
Negishi has authored and co-authored numerous scientific publications, many of which are highly cited. He has trained more than 100 postdocs and students in the past 32 years, he said, and many have become professors and institute directors. Several former trainees, prominent scientists in their own right, continue to collaborate with Negishi on a number of research projects.
Negishi will receive the Brodie Award on April 2, at the ASPET annual meeting in San Diego, during the 2016 Experimental Biology conference. The award, which is given every other year, includes an honorarium, a commemorative medal, and publication of his work in the journal Drug Metabolism and Deposition. He will also present a keynote speech at the conference on April 4, describing his research on P450 regulation.
(Tara Ann Cartwright, Ph.D., is a former postdoctoral fellow in the NIEHS Intracellular Regulation Group).