David M. Sabatini
David M. Sabatini
|Alma mater||Brown University|
Johns Hopkins School of Medicine
|Known for||Discovery and study of mTOR|
Massachusetts Institute of Technology
|Doctoral advisor||Solomon Snyder|
David M. Sabatini is an American scientist and Professor of Biology at the Massachusetts Institute of Technology as well as a member of the Whitehead Institute for Biomedical Research. He has been an investigator of the Howard Hughes Medical Institute since 2008 and was elected to the National Academy of Sciences in 2016. He is known for his important contributions in the areas of cell signaling and cancer metabolism, most notably the discovery and study of mTOR, a protein kinase that is an important regulator of cell and organismal growth that is deregulated in cancer, diabetes, as well as the aging process.
David M. Sabatini was born and raised in New York to Dr. David D. Sabatini and Dr. Zulema Sabatini, both Argentine immigrants from Buenos Aires. He obtained his B.S. from Brown University followed by both his MD and his Ph.D. at Johns Hopkins School of Medicine in Baltimore, Maryland, where he worked in the lab of Solomon H. Snyder. He joined the Whitehead Institute as a Whitehead Fellow in 1997, and in 2002 he became an Assistant Professor at MIT and a Member of the Whitehead Institute. He was promoted to tenured professor in 2006.
Sabatini currently resides in Cambridge, Massachusetts and is an avid biker and also enjoys gardening. His father, David D. Sabatini is a cell biologist and Professor at New York University. His younger brother, Bernardo L. Sabatini is a neuroscientist and Professor at Harvard University Medical School.
As a graduate student in Solomon Snyder’s Lab at Johns Hopkins, Sabatini began working on understanding the molecular mechanism of rapamycin; a macrolide antibiotic discovered in the soil of Easter Island that has potent antifungal, immunosuppressive, and anti-tumorigenic properties. Although the TOR/DRR genes had been identified in 1993 as conferring rapymycin resistance in budding yeast, the direct target of rapamycin and its mechanism of action in mammals was unknown. In 1994, Sabatini used rapamycin and its binding partner FKBP12 to purify the mechanistic Target of Rapamycin (mTOR) protein from rat brain, showing it to be the direct target of rapamycin in mammals and the homolog of the yeast TOR/DRR genes.
Since starting his own lab at the Whitehead Institute in 1997, Sabatini has made numerous key contributions to the understanding of mTOR function, regulation, and importance in diseases such as cancer. For example, his lab discovered the mTORC1 and mTORC2 multi-protein complexes, the nutrient sensing Rag GTPase pathway upstream of mTORC1, as well as the direct amino acid sensors Sestrin and CASTOR.
Sabatini’s research interests have expanded in recent years to include cancer metabolism as well as technology development surrounding the use of high-throughput genetic screens in human cells, most notably through the use of RNA interference and the CRISPR-Cas9 system. As of 2016, Sabatini has authored over 250 publications and has an h-index of 100.
Selected Awards and Honors
- Ware, Lauren (2013). "Science in their Blood". HHMI Bulletin. Howard Hughes Medical Institute. Retrieved 5 April 2017.
- Navitor Pharmaceuticals
- Raze Therapeutics
- Kendall Square Therapeutics
- Sabatini, DM (2017). "Twenty-five years of mTOR: Uncovering the link from nutrients to growth". Proc Natl Acad Sci U S A. 114 (45): 11818–11825. doi:10.1073/pnas.1716173114. PMID 29078414.
- Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M, Movva NR, Hall MN (1993). "Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression". Cell. 73 (3): 585–96. doi:10.1016/0092-8674(93)90144-f. PMID 8387896.
- Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y, Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP (1993). "Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity". Mol. Cell. Biol. 13 (10): 6012–23. doi:10.1128/mcb.13.10.6012. PMC 364661. PMID 8413204.
- Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH (1994). "RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs". Cell. 78 (1): 35–43. doi:10.1016/0092-8674(94)90570-3. PMID 7518356.
- Saxton RA, Sabatini, DM (2017). "mTOR Signaling in Growth, Metabolism, and Disease". Cell. 168 (6): 960–976. doi:10.1016/j.cell.2017.02.004. PMID 28388417.
- Kim DH, Sarbassov DD, Ali SM, et al. (2002). "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery". Cell. 110 (2): 163–75. doi:10.1016/s0092-8674(02)00808-5. PMID 12150925.
- Sarbassov DD, Ali SM, Kim DH, et al. (2004). "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr. Biol. 14 (14): 1296–302. doi:10.1016/j.cub.2004.06.054. PMID 15268862.
- Sancak Y, Peterson TR, Shaul YD, et al. (2008). "The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1". Science. 320 (5882): 1496–501. doi:10.1126/science.1157535. PMC 2475333. PMID 18497260.
- Wolfson RL, Chantranupong L, Saxton RA, et al. (2016). "Sestrin2 is a leucine sensor for the mTORC1 pathway". Science. 351 (6268): 43–8. doi:10.1126/science.aab2674. PMC 4698017. PMID 26449471.
- Saxton RA, Knockenhauer KE, Wolfson RL, et al. (2016). "Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway". Science. 351 (6268): 53–8. doi:10.1126/science.aad2087. PMC 4698039. PMID 26586190.
- Chantranupong L, Scaria SM, Saxton RA, et al. (2016). "The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway". Cell. 165 (1): 153–64. doi:10.1016/j.cell.2016.02.035. PMC 4808398. PMID 26972053.
- Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM (2016). "Mechanism of arginine sensing by CASTOR1 upstream of mTORC1". Nature. 536 (7615): 229–33. doi:10.1038/nature19079. PMC 4988899. PMID 27487210.
- Moffat J, Grueneberg DA, Yang X, et al. (2006). "A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen". Cell. 124 (6): 1283–98. doi:10.1016/j.cell.2006.01.040. PMID 16564017.
- Wang T, Wei JJ, Sabatini DM, Lander ES (2014). "Genetic screens in human cells using the CRISPR-Cas9 system" (PDF). Science. 343 (6166): 80–4. doi:10.1126/science.1246981. PMC 3972032. PMID 24336569.