David M. Sabatini

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David M. Sabatini
WALS David M. Sabatini 3m04s (cropped).jpg
Sabatini in 2013
Born (1968-01-27) January 27, 1968 (age 56)
New York, United States
Nationality American
Citizenship United States
Alma mater Brown University
Johns Hopkins School of Medicine
Known forCo-discovery and study of mTOR
Scientific career
Fields Biochemistry
Cell Biology
Institutions Whitehead Institute
Massachusetts Institute of Technology
Broad Institute
Doctoral advisor Solomon H. Snyder

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 co-discovery of mTOR. [1]

Contents

In 2021 and 2022, Sabatini was fired from the Howard Hughes Medical Institute and resigned his positions at the Whitehead Institute and the Massachusetts Institute of Technology, following allegations of sexual harassment. [2] [3] [4] Sabatini denies the allegations.

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 graduated 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's 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

In April 2021, after a new director of the Whitehead Institute where Sabatini worked had initiated a sexual harassment survey, a former graduate student at the institute came forward with sexual harassment allegations against him. [10]

In August 2021, following an investigation of the complaints by an outside law firm, Sabatini was forced to resign from the Whitehead Institute and was fired from the Howard Hughes Medical Institute which had funded his research. [11] [2] [12] Sabatini denies that the alleged behavior was sexual harassment, claims that the investigation was biased, and has filed a defamation lawsuit against the Whitehead Institute, its director and his accuser. [3] [10] [4] His accuser responded with a countersuit, claiming that he coerced her into sex and that the atmosphere in his lab was sexually charged and toxic. [10]

MIT placed Sabatini on administrative leave while it conducted its own investigation. [13] This investigation concluded that Sabatini had violated its policies on sexual relationships in the workplace, finding that he "engaged in a sexual relationship with a person over whom he held a career-influencing role", and gave a recommendation to revoke tenure. Sabatini resigned from his position at MIT in April 2022. [3] [13]

In 2022, Sabatini was under consideration for a position at the NYU Grossman School of Medicine. [14] After significant protests from students and some faculty over the sexual harassment allegations, he withdrew his name from consideration. [4] [15] [16]

Independent funding and IOCB Prague

In February 2023, Bill Ackman and an unnamed partner announced $25 million to fund Sabatini's research, though it is unclear if he could successfully find an institution willing to host his lab or if one could be built independently. [17] [18] By November 2023, Sabatini had accepted a position at the Institute of Organic Chemistry and Biochemistry (IOCB) of the Czech Academy of Sciences in Prague, [19] [20] and in April 2024 it was announced that IOCB would open a Boston branch, where it was planned that Sabatini would spend part of his time. [21]

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. [22] [23] 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. [24] For example, his lab discovered the mTORC1 [25] and mTORC2 [26] multi-protein complexes, the nutrient sensing Rag GTPase pathway upstream of mTORC1, [27] as well as the direct amino acid sensors Sestrin [28] [29] and CASTOR. [30] [31]

mTOR signaling pathway. MTOR-pathway-v1.7.svg
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 [32] and the CRISPR-Cas9 system. [33]

Selected awards and honors

Selected publications

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References

  1. ↑ Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH (July 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.
  2. 1 2 Wadman, Meredith (August 21, 2021). "HHMI fires prominent biologist for sexual harassment". Science. American Association for the Advancement of Science.
  3. 1 2 3 Wadman, Meredith (April 1, 2022). "Prominent biologist David Sabatini out at MIT after breaching sexual relationship policy". Science. American Association for the Advancement of Science. Retrieved April 2, 2022.
  4. 1 2 3 Wong, Ashley (May 3, 2022). "N.Y.U. Will Not Hire Scientist Accused of Harassment After Backlash". The New York Times. Retrieved May 25, 2022.
  5. 1 2 3 4 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. ↑ "Founders". Raze Therapeutics. Archived from the original on December 1, 2016. Retrieved May 4, 2022.
  9. ↑ Kendall Square Therapeutics
  10. 1 2 3 Fox, Jeremy C. (December 7, 2021). "Lawsuit alleges MIT professor 'groomed' young women, ran 'sexually charged' lab". The Boston Globe. Retrieved June 4, 2022.
  11. ↑ Fox, Jeremy C. (October 20, 2021). "MIT professor sues after he was forced to resign from institute following sexual harassment allegations". BostonGlobe.com. Retrieved June 5, 2024.
  12. ↑ Stocio, Nick (August 21, 2021). "MIT professor, biotech founder placed on leave following investigation into sexual harassment". Boston Globe. Retrieved August 21, 2021.
  13. 1 2 Fox, Jeremy C. (April 2, 2022). "MIT professor accused of sexually harassing grad student resigns". Boston Globe. Retrieved April 29, 2022.
  14. ↑ Wadman, Meredith (April 25, 2022). "NYU may hire biologist pushed out of MIT, Whitehead for sexual misconduct". Science. American Association for the Advancement of Science. Retrieved May 25, 2022.
  15. ↑ Merlan, Anna (May 3, 2022). "Biologist Accused of Sexual Misconduct Withdraws from Consideration at NYU". Vice. Retrieved May 25, 2022.
  16. ↑ El-bawab, Nadine (May 3, 2022). "Former MIT professor accused of sexual harassment withdraws from NYU hiring consideration". ABC News. Retrieved May 25, 2022.
  17. ↑ Arsenault, Mark (February 7, 2023). "New funding for controversial MIT and Whitehead Institute scientist David Sabatini draws divided reactions". The Boston Globe. Retrieved February 19, 2023.
  18. ↑ Wadman, Meredith (February 3, 2023). "David Sabatini, biologist fired for sexual misconduct, lands millions from private donors to start new lab". Science. American Association for the Advancement of Science. Retrieved February 19, 2023.
  19. ↑ Arsenault, Mark (November 13, 2023). "Former MIT biologist, who lost positions after engaging in a prohibited sexual relationship, accepts new science position in Prague". The Boston Globe. Retrieved November 13, 2023.
  20. ↑ Wadman, Meredith (November 13, 2023). "Despite sexual harassment shadow, biologist David Sabatini lands job at top Czech institute". Science. American Association for the Advancement of Science. Retrieved November 18, 2023.
  21. ↑ Arsenault, Mark (April 30, 2024). "Former MIT biologist David Sabatini, forced out after sexual harassment accusations, to lead new Boston team". The Boston Globe. Retrieved May 3, 2024.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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 . hdl: 1721.1/116766 . PMID   28388417.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ 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.
  34. ↑ "Columbia Presents Horwitz Prize to Three Scientists for Cancer Discoveries". Columbia University Irving Medical Center. January 10, 2020. Retrieved January 29, 2023.
  35. ↑ "The Louisa Gross Horwitz Prize". Columbia University Irving Medical Center. June 14, 2018.
  36. ↑ "Whitehead Institute Member David Sabatini Receives the 2020 Sjöberg Prize from the Royal Swedish Academy of Sciences". Whitehead Institute. February 4, 2020.

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