December 10, 1999

Exton honored for signal transduction research

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Dr. John Exton

Exton honored for signal transduction research

Dr. John H. Exton has been named a Fellow of the American Association for the Advancement of Science (AAAS).

Exton, professor of Molecular Physiology and Biophysics and Pharmacology and investigator of the Howard Hughes Medical Institute, is the second Vanderbilt University Medical Center scientist elected to the rank of AAAS Fellow. He joins F. Peter Guengerich, Ph.D., professor of Biochemistry and director of the Center in Molecular Toxicology.

The AAAS elects those members whose "efforts on behalf of the advancement of science or its applications are scientifically or socially distinguished," according to the association. Exton is being honored for his research in the area of signal transduction — how hormones, neurotransmitters, and growth factors 'talk' to cells in order to regulate cell functions.

"John has made many seminal observations over the years," said Alan D. Cherrington, Ph.D., Charles H. Best Professor of Diabetic Research and Chair of Molecular Physiology and Biophysics. "He has made major contributions to our understanding of signaling pathways, and this recognition is certainly well-deserved."

Exton came to Vanderbilt as a post-doctoral fellow to study with Dr. Charles R. ('Rollo') Park, Professor of Physiology, Emeritus, and the late Dr. Earl W. Sutherland, 1971 Nobel Laureate in Physiology or Medicine.

"He was outstanding from the very beginning, and we were fortunate to keep him here on the faculty," Park said. "He is a very prominent member of the scientific community, and his work has substantially extended our knowledge of basic physiological mechanisms underlying hormone action."

In extending scientific knowledge, Exton sometimes found himself challenging the accepted version of how things work.

He was among those who first realized that there was more than one way for hormones to send a signal across the cell membrane. At the time, the single accepted signaling pathway involved the messenger molecule cyclic AMP. Exton and others found another pathway at work that included the action of an enzyme called phospholipase C that breaks down lipids in the cell membrane.

He went on to participate in the identification of a key molecular member of this second signaling pathway: the G protein Gq.

"The discovery of Gq came about because of an amazing constellation of research by three labs," Exton said. "We all got part of the picture, and it was an incredible bit of scientific collaboration."

Exton bumped up against accepted models again when he realized that phospholipase C wasn't the only enzyme breaking down lipids in the cell membrane. His data led to the discovery that the enzyme phospholipase D was also at work in a second lipid signaling pathway.

"I haven't deliberately gone against conventional understanding," Exton said. "I just find what I find. I have confidence in my data, so I don't hesitate to challenge dogma."

His laboratory currently focuses on the 'Rho' family of small GTP-binding proteins, which are important participants in signaling pathways regulating cell growth, shape, and movement.

Exton attributes his willingness to challenge scientific dogma to excellent scientific training since the beginning: as a medical student at the University of New Zealand, as a graduate student at the University of Otago, New Zealand, and as a post-doctoral fellow and young faculty member at Vanderbilt.

Exton adds his election as an AAAS Fellow to a long list of honors including the Lilly Award from the American Diabetes Association, a Doctor Honoris Causa from the Autonomous University of Barcelona, the Drummond Award from the University of Calgary, and the Sutherland Award, Vanderbilt's highest research award. He is also a University National Scholar, New Zealand and a Commonwealth Scholar, United Kingdom.

The AAAS, founded in 1848, is the world's largest federation of scientists, with more than 144,000 members. The tradition of AAAS Fellows distinction began in 1874. AAAS Fellows, including Exton and Timothy P. McNamara, Ph.D., professor and chair of Psychology in the College of Arts and Science, will be recognized at the AAAS annual meeting in February, 2000.