2017 Dickson Prize Winner
David Sabatini, MD, PhD
Professor of Biology
Massachusetts Institute of Technology
Investigator, Howard Hughes Medical Institute
Biography
As a graduate student in the MD/PhD program at Johns Hopkins University in 1994, David M. Sabatini identified a protein in mammalian cells that anchors a master growth-regulating pathway. This protein was dubbed mTOR—mechanistic target of rapamycin.
Rapamycin had been discovered in a soil sample from a Pacific island in the 1970s. 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 cellular pathway that rapamycin targets opened the door to the molecular and physiological study of a rich field. mTOR is conserved in eukaryotes, not just in mammals. The signaling network anchored by mTOR, it turns out, is a central regulator of growth, metabolism, and aging; and it is deregulated in some very common diseases, including diabetes and cancer.
Sabatini earned his bachelor of science at Brown University and, in 1997, received his MD and PhD from Johns Hopkins. That same year, he became a fellow at the Whitehead Institute for Biomedical Research in Cambridge, Mass., where he continued his groundbreaking investigations into mTOR. In 2002, he was named a member of the Whitehead Institute and joined the faculty of the Massachusetts Institute of Technology (MIT). Over the years, the Sabatini Lab has been responsible for the identification of most of the established components of the mTOR pathway, including the mTORC1 and mTORC2 complexes, and has led the way in uncovering the cellular and organismal functions of many pathway components. More recently, the 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 is also interested in how small molecule metabolism affects growth control and has studied the role of the serine synthesis pathway in cancer and used genetic screens to find that aspartate synthesis is an essential function of mitochondria in cell proliferation.
In an offshoot of the work on mTOR, Sabatini's group has been developing new technologies that will permit researchers to identify the components of signaling networks in mammalian cells. Sabatini and his colleagues have developed "cell-based microarrays"—microscopic slides printed with spots of mammalian cells that over- or underexpress particular gene products. This technology allows researchers to look at the cellular effects of perturbing thousands of genes simultaneously. Sabatini's group is now using the technique to identify candidate genes that underlie phenotypes of interest, such as cell size.
In 2005, the RNAi Consortium, led by Sabatini and colleagues at several Boston-area research institutions, created a library of RNA-interference (RNAi) reagents that researchers can use to block the function of every human gene. Sabatini and his colleagues are using those RNAi tools in a new project that gets him back to his roots in cell growth studies: a systematic effort to identify the metabolic processes that allow tumor cells with common cancer-causing mutations to survive.
Sabatini's ambitious goal is to use RNAi and CRISPR technology to identify all of the human metabolic genes necessary for cancer cells to survive in standard tissue-culture conditions and in conditions that mimic oxygen-deprived regions of a tumor. Ultimately, this knowledge could lead to myriad therapeutic approaches to preventing and curing cancer.
Currently, Sabatini is a professor of biology at MIT, a senior associate member of the Broad Institute of Harvard University and MIT, and a member of the Koch Institute for Integrative Cancer Research at MIT. He remains a member of the Whitehead Institute and is an investigator of the Howard Hughes Medical Institute.
Sabatini’s honors include being named a W. M. Keck Foundation Distinguished Young Scholar and a Pew Scholar. He has received numerous awards, including the 2009 Paul Marks Prize for Cancer Research, 2013 Feodor Lynen Award from Nature, and the 2014 National Academy of Sciences Award in Molecular Biology. In 2017, he was awarded the Lurie Prize in Biomedical Sciences by the Foundation for the National Institutes of Health. In 2016, he was elected to the National Academy of Sciences.
Sabatini is scheduled to deliver the Dickson Prize in Medicine Lecture on Friday, October 20, as a plenary session for Science 2017, the University of Pittsburgh’s annual celebration of science and technology.