David M. Sabatini

David M. Sabatini (born January 27, 1968) is an American scientist and a former Professor of Biology at the Massachusetts Institute of Technology. From 2002 to 2021, he was a member of the Whitehead Institute for Biomedical Research. He was also an investigator of the Howard Hughes Medical Institute from 2008 to 2021 and was elected to the National Academy of Sciences in 2016. He is known for his contributions in the areas of cell signaling and cancer metabolism, most notably the discovery and study of mTOR.

David M. Sabatini
Born (1968-01-27) January 27, 1968
New York, United States
NationalityAmerican
CitizenshipUnited States
Alma materBrown University
Johns Hopkins School of Medicine
Known forDiscovery and study of mTOR
Scientific career
FieldsBiochemistry
Cell Biology
InstitutionsWhitehead Institute
Massachusetts Institute of Technology
Broad Institute
Doctoral advisorSolomon H. Snyder

In August 2021, Sabatini was fired from the Whitehead Institute and Howard Hughes Medical Institute, and placed on administrative leave from MIT following an investigation related to sexual harassment during his work at the Whitehead Institute.[1][2][3] Sabatini later resigned his tenured professorship position at MIT.[4]

Biography

David M. Sabatini was born and raised in New York to David D. Sabatini and 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, where he worked in the lab of Solomon H. Snyder. He joined the Whitehead Institute as a Whitehead Fellow in 1997, the same year he matriculated from Johns Hopkins.[5] 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 gardener. 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 Medical School.[5][6]

Sabatini is the scientific founder of Navitor,[7] Raze Therapeutics,[8] and KSQ Therapeutics.[9]

Allegations of sexual misconduct

On August 20, 2021, an investigation conducted by an independent law firm, Hinckley, Allen & Snyder, concluded that Sabatini violated several of the Whitehead Institute's policies, including policies on sexual harassment.[3] Following the results of this investigation, both the Whitehead Institute and Howard Hughes Medical Institute ended their association with Sabatini. Sabitini resigned from MIT following the recommendation of three senior MIT officials to revoke his tenure.[1]

In October 2021, Sabatini filed a lawsuit against the Whitehead Institute, its director Ruth Lehmann, and one of his accusers, claiming that he was the victim of false claims made to “exact revenge against a former lover.”[10]

In December 2021, Sabatini's accuser filed a civil lawsuit claiming that Sabatini coerced her into sex and that his laboratory had a “toxic and sexually-charged” environment.[11] Sabatini's attorneys denied the new allegations that had been made against him.

As of April 2022, Sabatini has resigned from his position as professor of Biology at the Massachusetts Institute of Technology, following internal investigations, review, and recommendation that Sabatini’s tenure be revoked.[4] According to an email sent to faculty by President Leo Rafael Reif on April 1st, the reviewers found that “Professor Sabatini behaved in ways incompatible with the responsibilities of faculty membership and that Professor Sabatini violated MIT’s Consensual Sexual or Romantic Relationships in the Workplace or Academic Environment policy.”[12][13]

In April 2022, the NYU Grossman School of Medicine was considering hiring Sabatini.[14][15]

Scientific contributions

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.[5] Although the TOR/DRR genes had been identified in 1993 as conferring rapamycin resistance in budding yeast, the direct target of rapamycin and its mechanism of action in mammals was unknown.[16][17] 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.[5]

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.[18] For example, his lab discovered the mTORC1[19] and mTORC2[20] multi-protein complexes, the nutrient sensing Rag GTPase pathway upstream of mTORC1,[21] as well as the direct amino acid sensors Sestrin[22][23] and CASTOR.[24][25]

mTOR signaling pathway.

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[26] and the CRISPR-Cas9 system.[27] As of 2016, Sabatini has authored over 250 publications and has an h-index of 142 as of April 2022.[28]

Selected awards and honors

Selected publications
  • 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. PMC 5692607. PMID 29078414.
  • 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. S2CID 33647539.

References
  1. DeAngelis, Allison. "MIT's David Sabatini on Leave Following Sexual Harassment Investigation". Business Insider. Retrieved August 20, 2021.
  2. Stocio, Nick (August 21, 2021). "MIT professor, biotech founder placed on leave following investigation into sexual harassment". Boston Globe. Retrieved August 21, 2021.
  3. Wadman, Meredith (August 21, 2021). "HHMI fires prominent biologist for sexual harassment". Science | AAAS.
  4. Wadman, Meredith (April 1, 2022). "Prominent biologist David Sabatini out at MIT after breaching sexual relationship policy". Science. Retrieved April 9, 2022.
  5. Viegas, Jennifer (December 26, 2017). "Profile of David M. Sabatini". Proceedings of the National Academy of Sciences of the United States of America. 115 (3): 438–440. doi:10.1073/pnas.1721196115. PMC 5777013. PMID 29279397.
  6. Ware, Lauren (2013). "Science in their Blood". HHMI Bulletin. Howard Hughes Medical Institute. Retrieved April 5, 2017.
  7. "Navitor Pharmaceuticals". Archived from the original on November 14, 2017. Retrieved September 12, 2015.
  8. Raze Therapeutics
  9. Kendall Square Therapeutics
  10. Fox, Jeremy (October 20, 2021). "MIT professor sues after he was forced to resign from institute following sexual harassment allegations". Boston Globe. Retrieved November 15, 2021.
  11. Fox, Jeremy C. "Lawsuit alleges MIT professor 'groomed' young women, ran 'sexually charged' lab - The Boston Globe". BostonGlobe.com. Retrieved December 8, 2021.
  12. Wadman, Meredith (April 1, 2022). "Prominent biologist David Sabatini out at MIT after breaching sexual relationship policy". ScienceInsider. American Association for the Advancement of Science. Retrieved April 2, 2022.
  13. Fox, Jeremy C. (April 2, 2022). "MIT professor accused of sexually harassing grad student resigns". Boston Globe. Retrieved April 29, 2022.
  14. "NYU may hire biologist pushed out of MIT, Whitehead for sexual misconduct". www.science.org. Retrieved April 27, 2022.
  15. Wong, Ashley (April 27, 2022). "Backlash Erupts as N.Y.U. Weighs Hiring Scientist Accused of Harassment". New York Times. Retrieved April 29, 2022.
  16. 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. S2CID 42926249.
  17. 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.
  18. Saxton RA, Sabatini, DM (2017). "mTOR Signaling in Growth, Metabolism, and Disease". Cell. 169 (2): 361–371. doi:10.1016/j.cell.2017.03.035. PMID 28388417.
  19. 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. S2CID 4656930.
  20. 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. S2CID 4658268.
  21. 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. Bibcode:2008Sci...320.1496S. doi:10.1126/science.1157535. PMC 2475333. PMID 18497260.
  22. Wolfson RL, Chantranupong L, Saxton RA, et al. (2016). "Sestrin2 is a leucine sensor for the mTORC1 pathway". Science. 351 (6268): 43–8. Bibcode:2016Sci...351...43W. doi:10.1126/science.aab2674. PMC 4698017. PMID 26449471.
  23. Saxton RA, Knockenhauer KE, Wolfson RL, et al. (2016). "Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway". Science. 351 (6268): 53–8. Bibcode:2016Sci...351...53S. doi:10.1126/science.aad2087. PMC 4698039. PMID 26586190.
  24. 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.
  25. 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. Bibcode:2016Natur.536..229S. doi:10.1038/nature19079. PMC 4988899. PMID 27487210.
  26. 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. S2CID 630641.
  27. 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. Bibcode:2014Sci...343...80W. doi:10.1126/science.1246981. PMC 3972032. PMID 24336569.
  28. "David M. Sabatini". scholar.google.com. Retrieved April 9, 2022.
  29. "The Louisa Gross Horwitz Prize". Columbia University Irving Medical Center. June 14, 2018.
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