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Honoring Achievement
CHORI Celebrates Retirement of Senior Scientist Stuart Smith, PhD
On October 15, 2010, CHORI hosted a daylong symposium honoring the career and accomplishments of longtime CHORI senior scientist, Stuart Smith, PhD, who is retiring this year, after 48 years of scientific research. Participants included CHORI Executive Director, Alexander Lucas, PhD, a host of previous colleagues and post-doctoral fellows from Dr. Smith's lab who have since gone on to become preeminent scientists in their own right, and Dr. Smith himself, who began at CHORI in 1967.

"Stuart was one of the very first scientists to join CHORI, back when it was the Bruce Lyons Memorial Research Laboratory and there were about twelve other researchers in one small lab," says Dr. Lucas

“Stuart has been with our institute through its incredible growth and success, and has been a major contributor to what CHORI is today.”


The quintessential lab scientist, Dr. Smith has been driven by his passion for discovery, a passion that has sustained him for nearly a half-century of ground-breaking research.

"I guess you could say that what I've been trying to do throughout my career is to discover the truth of how things work," says Dr. Smith.
“While a clinician works to figure out why and how human biology is affected by disease and environmental factors, I've been much more interested in basic biology, in the joy of discovering little kernels of truth about how one small part of the universe works.”
Dr. Smith began his scientific career in the study of lipid metabolism using classic biochemical approaches, eventually integrating the tools of molecular biology and structural biology into his program that focused increasingly on the structure and mechanism of action of the megasynthase responsible for making fat, the fatty acid synthase (FAS).

"FAS has attracted considerable attention in recent years because it appears to have significant potential as a target for the development of new anti-cancer and anti-obesity agents," says Dr. Smith.

The structural details of FAS had been elusive for years, primarily because the protein is so large and conformationally flexible.
Dr. Smith's studies over the last two decades had cast serious doubts as to the validity of the widely accepted structural model for the FAS and resulted in the proposal of a radically different model - one which was ultimately validated by a crystal structure for the megasynthase obtained by Nenad Ban's group in Switzerland. However, the crystal structure provided only a snapshot of the megasynthase in one conformation. A collaborative effort between Dr. Smith and Dr. Francisco Asturias' group at The Scripps Research Institute utilized state-of-the-art electron microscopy tools to reveal what Dr. Smtih calls " the FAS dance": the array of different conformations the megasynthase adopts as it performs the series of reactions in the biosynthetic pathway. The landmark study was featured on the cover of the February, 2009 issue of Nature Structural and Molecular Biology and has the potential to revolutionize drug development for treating obesity and cancer and other diseases. One of many significant contributions to the field of fatty acid synthesis over the years, the groundbreaking study also represents a fitting finale for Dr. Smith's decades-long research.

"There is still more work to be done of course, but there will always be more work to do," says Dr. Smith. "I'm really pleased with having been a part of solving the conformational structure of FAS. It's incredibly gratifying to have had the opportunity to make that kind of contribution."

Dr. Smith is still working to wrap up his most recent research project that focuses on a newly discovered second pathway for fatty acid synthesis that is located specifically in the mitochondrial compartment of the cell.

"We are using a variety of model systems in an attempt to ascertain the role of this pathway in supporting normal mitochondrial function," says Dr. Smith.

Dr. Smith hopes that his studies will lead to a better understanding of the importance of the mitochondrial pathway, which has been implicated in a substantial number of human diseases.
In the meantime, however, CHORI was pleased to take the opportunity to recognize the outstanding achievements of one of its own.

"Stuart has been a role model for all of us at CHORI, epitomizing the experimental scientist who is still working at the bench himself. He's never lost touch with the lab, but has been an experimental scientist all his life, dedicating his entire life to solving one of the most complex organisms in nature," says Dr. Lucas.

"He'll be greatly missed both as a major contributor of scientific achievement to his field and as a faculty member here at CHORI who has been a solid leader in our own community."

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“Stuart will be greatly missed both as a major contributor of scientific achievement to his field and as a faculty member here at CHORI who has been a solid leader in our own community.”

Tuesday, May 17, 2011 8:19 AM

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