JoAnne Stubbe

JoAnne Stubbe is an American chemist best known for her work on ribonucleotide reductases, for which she was awarded the National Medal of Science in 2009. In 2017, she retired as a Professor of Chemistry and Biology at the Massachusetts Institute of Technology.

In 1980, she moved to the University of Wisconsin, serving as assistant professor in the Biochemistry Department and rising to full professor in 1985. She was an assistant professor for a total of 12 years. In 1987, Stubbe became a professor in the MIT Chemistry Department, where she became the first woman to receive tenure in that department. She received a joint appointment in the MIT Biology Department in 1990.

Her first two publications in scientific journals showed the mechanisms for reactions that involved the enzymes enolase that metabolizes carbohydrates, and pyruvate kinase. Her first groundbreaking experiments were carried out in the late 1970s and early 1980s, while she was at Yale, then the University of Wisconsin. She was trying to understand how the hydroxyl group at the 2’ position of the ribonucleotide's sugar was replaced by the hydrogen found in deoxyribonucleotides. To perform these experiments, she had to synthesize nucleotides that carried a heavy isotope at specific positions. Stubbe reportedly kept a bed in her office since she worked around the clock on her experiments. Stubbe pioneered the use of spectroscopic investigations of enzyme interactions and has devoted most of her career to elucidating the biochemical mechanisms behind free radicals. In her early work at Yale and then at the University of Wisconsin, Stubbe discovered how enzymes called ribonucleotide reductases use free-radical chemistry to convert nucleotides into deoxynucleotides, an essential process in DNA repair and replication. These enzymes catalyze the rate-determining step in DNA biosynthesis. Her analysis of the nucleotide reduction process shed light on the mechanism of action of the Eli Lilly & Co. anti-cancer drug gemcitabine, which is used to treat various carcinomas, such as pancreatic cancer, breast cancer, and non-small cell lung cancer.

In 1946, Stubbe was born in Champaign, Illinois. In 1968, Stubbe received a BS degree in chemistry from the University of Pennsylvania, and worked as an undergraduate in the laboratory of Professor Edward R. Thornton. After she received her PhD degree in organic chemistry under the guidance of Professor George Kenyon from the University of California, Berkeley in 1971, she did a very brief stint (1971-1972) as a postdoc at UCLA, where she worked on synthesizing LSD from tryptophan with Julius Rebek. Then, Stubbe taught at Williams College (1972-1977) discovered she didn't want to teach, but wanted to do research. Her realization sent her to Brandeis University (1975-1977), where she did a second postdoc with Bob Abeles. This is where she learned the art and science of creating mechanism-based enzyme inhibitors. She also taught at Yale School of Medicine (1977-1980) as an assistant professor in the department of pharmacology.