Nutritional Requirements of Pancreatic Cancers - A Conversation with Dafna Bar-Sagi

Editor's Note: Dafna Bar-Sagi is Professor in the Departments of Biochemistry & Molecular Pharmacology and Medicine, and Senior Vice President and Vice Dean for Science at New York University's School of Medicine. In 1986 Dr. Bar-Sagi and her postdoc advisor, Dr. James Feramisco, observed that injection of oncogenic KRAS protein into fibroblasts caused morphological changes, including pronounced membrane ruffling and the accumulation of pinocytic vesicles. Recent investigations into the metabolism of cancers, especially cancers driven by mutant KRAS, have transformed macropinocytosis from a phenotypic curiosity to a key player in the nutrition of pancreatic cancer cells. RAS Central editors recently interviewed Dr. Bar-Sagi about her science and her career.

Can you describe where you were, what you were doing, and what your position was when you first observed macropinocytosis induced by RAS protein? I was a fairly new postdoc in Jim Feramisco's lab at Cold Spring Harbor. It was a cell biology lab that had essentially transformed itself into a cancer biology group with all of the excitement about the discovery of oncogenes, particularly RAS. We wanted to understand what RAS was doing—how the transfection of a piece of DNA encoding RAS into NIH3T3 cells caused them to become transformed. The challenge we faced was that it took up to 3 weeks from the time NIH3T3 cells were transfected with a mutant RAS gene to when we saw them form foci. Lots of other things might have happened over that time, many of which were probably secondary or tertiary consequences of having RAS in the cells.

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