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Regulation of Growth by the mTOR Pathway
11:00 a.m., Friday, 20 October
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David M. Sabatini, MD, PhD
Professor of Biology
Massachusetts Institute of Technology

Investigator, Howard Hughes Medical Institute

As a graduate student at Johns Hopkins University, David M. Sabatini, MD, PhD, identified a key cellular regulatory metabolic pathway known as mTOR, or mechanistic target of rapamycin. His subsequent research has revealed several important roles that individual proteins in this pathway play in common diseases.

Produced by a bacterium, rapamycin is an antifungal and immunosuppressive chemical that stops cells from dividing and causes them to shrink. It became widely used in organ transplantation, and the discovery of the mTOR cellular pathway that rapamycin targets enabled the molecular and physiological study of a rich field. In fact, the signaling network anchored by mTOR is a central regulator of growth, metabolism, and aging; and it is deregulated in diabetes and cancer. The Sabatini Lab has identified key components of the mTOR pathway, including the mTORC1 and mTORC2 complexes, and has uncovered cellular and organismal functions of many pathway components.

More recently, Sabatini’s research team has discovered the amino acid sensors and signaling molecules that convey amino acid sufficiency to mTORC1. The identification of rapamycin-resistant functions of mTORC1 and mTORC2 led to the development of a new class of compounds that inhibit both and are now in clinical trials as anticancer agents. In work in vivo, Sabatini and his colleagues have uncovered molecular mechanisms through which fasting and feeding regulate organ physiology, including hepatic ketogenesis, intestinal stem cell self-renewal, and tumor growth.

Sabatini earned his bachelor’s degree at Brown University and his MD and PhD at Johns Hopkins University before continuing his investigations into mTOR as a fellow at the Whitehead Institute for Biomedical Research. His honors include W. M. Keck Foundation Distinguished Young Scholar and a Pew Scholar awards. He has received the Paul Marks Prize for Cancer Research, Feodor Lynen Award from Nature, the National Academy of Sciences Award in Molecular Biology, and the Lurie Prize in Biomedical Sciences from the Foundation for the National Institutes of Health. In 2016, he was elected to the National Academy of Sciences.

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