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Jeannie T. Lee

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Jeannie T. Lee
Alma materHarvard University, University of Pennsylvania Medical School, Massachusetts Institute of Technology
Awards2018 Harrington Rare Genetic Disease Scholar

2016 Lurie Award 2016 Centennial Award from Genetics Society of America 2015 Election to National Academy of Sciences (NAS) 2010 Molecular Biology Award from NAS 1999 Pew Scholar

1998 Basil O'Connor Scholar
Scientific career
Fieldsepigenetics, long noncoding RNA, X-inactivation, 3D genome, X-chromosome reactivation technology
Thesis (1993)
Academic advisorsNancy Kleckner, Robert Nussbaum, Rudolf Jaenisch

Jeannie T. Lee is a Professor of Genetics (and Pathology) at Harvard Medical School and the Massachusetts General Hospital, and a Howard Hughes Medical Institute Investigator. She is known for her work on X-chromosome inactivation and for discovering the functions of a new class of epigenetic regulators known as long noncoding RNAs (lncRNAs), including Xist and Tsix.

Education

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Jeannie T. Lee received an AB from Harvard College in Biochemistry & Molecular Biology and an MD/PhD in 1993[1] from the University of Pennsylvania School of Medicine.[2] While at Harvard she worked with Nancy Kleckner on antisense regulation of Tn10 transposition. While at University of Pennsylvania School of Medicine her advisor was Robert L. Nussbaum.[3] Her PhD research focused on Fragile X syndrome, and led to her strong interest in X chromosome inactivation and epigenetics.[4] Then she did postdoctoral work with Rudolf Jaenisch at the Whitehead Institute , during which she discovered the nature of the X-inactivation center.[3] She was also Chief Resident of Laboratory Medicine at the Massachusetts General Hospital.

Research career

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Lee joined the faculty at Harvard in 1997 and devoted her studies to noncoding RNA and sex chromosome dynamics during development and disease. Her major career research achievements include identifying the X inactivation center,[5][6] discovering Tsix antisense RNA,[7] determining Xist's mechanism of action,[8][9] demonstrating that a lncRNA is a regulator of Polycomb repressive complex 2,[8][10][11][12] and determining that the X chromosome folds like origami and adopts a unique conformation.

Her studies established the existence and function of a group of lncRNAs. In a 2013 interview, she stated that this group of RNAs excited her because they control gene expression in a locus-specific way, by recruiting chromatin modifying activities to the locus, making the lncRNAs excellent drug design targets. She founded RaNA Therapeutics to test this idea.[3]

Upon conferring the Lurie Prize to Lee in 2016, Dr. Charles A. Sanders of the Foundation for the National Institutes of Health remarked: “Dr. Lee’s work has revolutionized the field of epigenetics. Her research has led to groundbreaking contributions, and we now have a better understanding of the unique role that long non-coding RNAs play in gene expression, which could lead to the development of new therapeutics.”[13]

Lee was President of the Genetics Society of America,[14] Codirector of the Harvard Epigenetics Initiative, and is Vice Chair of the Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School. She delivered a set of lectures to iBiology on X chromosome inactivation.[15]

Notable publications

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  • Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. J Zhao, BK Sun, JA Erwin, JJ Song, JT Lee. Science, 2008 [8]
  • Long noncoding RNAs: past, present, and future. JTY Kung, D Colognori, JT Lee. Genetics, 2013 [16]
  • Epigenetic regulation by long noncoding RNAs. JT Lee. Science, 2012 [17]
  • Genome-wide identification of polycomb-associated RNAs by RIP-seq. J Zhao, T Ohsumi, ... JT Lee. Molecular Cell, 2010 [18]
  • YY1 tethers Xist RNA to the inactive X nucleation center. Y Jeon, JT Lee. Cell, 2011 [19]
  • Transient homologous chromosome pairing marks the onset of X inactivation. N Xu, CL Tsai, JT Lee. Science, 2006 [20]
  • Tsix, a gene antisense to Xist at the X-inactivation centre. JT Lee, LS Davidow, D Warshawsky. Nature Genetics, 1999 [7]
  • A 450 kb transgene displays properties of the mammalian X-inactivation center. JT Lee, WM Strauss, JA Dausman, R Jaenisch. Cell, 1996 [21]

Awards

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References

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  1. ^ "Jeannie T. Lee". Massachusetts General Hospital. Retrieved August 15, 2018.
  2. ^ "Jeannie T. Lee".
  3. ^ a b c "Interview with Jeannie T. Lee". Oligonucleotide Therapeutics Society. August 13, 2016.
  4. ^ Viegas, J (2015). "QnAs with Jeannie T. Lee". Proc Natl Acad Sci U S A. 112 (48): 14745–6. Bibcode:2015PNAS..11214745V. doi:10.1073/pnas.1521185112. PMC 4672782. PMID 26582793.
  5. ^ Lee, J. T.; Strauss, W. M.; Dausman, J. A.; Jaenisch, R. (1996-07-12). "A 450 kb transgene displays properties of the mammalian X-inactivation center". Cell. 86 (1): 83–94. doi:10.1016/s0092-8674(00)80079-3. ISSN 0092-8674. PMID 8689690. S2CID 17888183.
  6. ^ Lee, J. T.; Lu, N.; Han, Y. (1999-03-30). "Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain". Proceedings of the National Academy of Sciences of the United States of America. 96 (7): 3836–3841. Bibcode:1999PNAS...96.3836L. doi:10.1073/pnas.96.7.3836. ISSN 0027-8424. PMC 22381. PMID 10097124.
  7. ^ a b Lee, J. T.; Davidow, L. S.; Warshawsky, D. (April 1999). "Tsix, a gene antisense to Xist at the X-inactivation centre". Nature Genetics. 21 (4): 400–404. doi:10.1038/7734. ISSN 1061-4036. PMID 10192391. S2CID 30636065.
  8. ^ a b c Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Song, Ji-Joon; Lee, Jeannie T. (2008-10-31). "Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome". Science. 322 (5902): 750–756. Bibcode:2008Sci...322..750Z. doi:10.1126/science.1163045. ISSN 1095-9203. PMC 2748911. PMID 18974356.
  9. ^ Minajigi, Anand; Froberg, John; Wei, Chunyao; Sunwoo, Hongjae; Kesner, Barry; Colognori, David; Lessing, Derek; Payer, Bernhard; Boukhali, Myriam (2015-07-17). "A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation". Science. 349 (6245): aab2276. doi:10.1126/science.aab2276. ISSN 0036-8075. PMC 4845908. PMID 26089354.
  10. ^ Zhao, Jing; Ohsumi, Toshiro K.; Kung, Johnny T.; Ogawa, Yuya; Grau, Daniel J.; Sarma, Kavitha; Song, Ji Joon; Kingston, Robert E.; Borowsky, Mark (2010-12-22). "Genome-wide identification of polycomb-associated RNAs by RIP-seq". Molecular Cell. 40 (6): 939–953. doi:10.1016/j.molcel.2010.12.011. ISSN 1097-4164. PMC 3021903. PMID 21172659.
  11. ^ Cifuentes-Rojas, Catherine; Hernandez, Alfredo J.; Sarma, Kavitha; Lee, Jeannie T. (2014-07-17). "Regulatory interactions between RNA and polycomb repressive complex 2". Molecular Cell. 55 (2): 171–185. doi:10.1016/j.molcel.2014.05.009. ISSN 1097-4164. PMC 4107928. PMID 24882207.
  12. ^ Zovoilis, Athanasios; Cifuentes-Rojas, Catherine; Chu, Hsueh-Ping; Hernandez, Alfredo J.; Lee, Jeannie T. (2016-12-15). "Destabilization of B2 RNA by EZH2 Activates the Stress Response". Cell. 167 (7): 1788–1802.e13. doi:10.1016/j.cell.2016.11.041. ISSN 1097-4172. PMC 5552366. PMID 27984727.
  13. ^ "Foundation for the NIH to Award Lurie Prize in Biomedical Sciences to Dr. Jeannie Lee for Pioneering Work in Epigenetics | FNIH". fnih.org. Archived from the original on 2017-09-30. Retrieved 2017-09-30.
  14. ^ a b "Jeannie T. Lee".
  15. ^ "Jeannie Lee • iBiology". iBiology. Retrieved 2019-12-15.
  16. ^ Kung, Johnny T. Y.; Colognori, David; Lee, Jeannie T. (March 2013). "Long noncoding RNAs: past, present, and future". Genetics. 193 (3): 651–669. doi:10.1534/genetics.112.146704. ISSN 1943-2631. PMC 3583990. PMID 23463798.
  17. ^ Lee, Jeannie T. (2012-12-14). "Epigenetic regulation by long noncoding RNAs". Science. 338 (6113): 1435–1439. Bibcode:2012Sci...338.1435L. doi:10.1126/science.1231776. ISSN 1095-9203. PMID 23239728. S2CID 206546141.
  18. ^ Zhao, Jing; Ohsumi, Toshiro K.; Kung, Johnny T.; Ogawa, Yuya; Grau, Daniel J.; Sarma, Kavitha; Song, Ji Joon; Kingston, Robert E.; Borowsky, Mark; Lee, Jeannie T. (2010-12-22). "Genome-wide identification of polycomb-associated RNAs by RIP-seq". Molecular Cell. 40 (6): 939–953. doi:10.1016/j.molcel.2010.12.011. ISSN 1097-4164. PMC 3021903. PMID 21172659.
  19. ^ Jeon, Yesu; Lee, Jeannie T. (2011-07-08). "YY1 tethers Xist RNA to the inactive X nucleation center". Cell. 146 (1): 119–133. doi:10.1016/j.cell.2011.06.026. ISSN 1097-4172. PMC 3150513. PMID 21729784.
  20. ^ Xu, Na; Tsai, Chia-Lun; Lee, Jeannie T. (2006-02-24). "Transient homologous chromosome pairing marks the onset of X inactivation". Science. 311 (5764): 1149–1152. Bibcode:2006Sci...311.1149X. doi:10.1126/science.1122984. ISSN 1095-9203. PMID 16424298. S2CID 20362477.
  21. ^ Lee, J. T.; Strauss, W. M.; Dausman, J. A.; Jaenisch, R. (1996-07-12). "A 450 kb transgene displays properties of the mammalian X-inactivation center". Cell. 86 (1): 83–94. doi:10.1016/s0092-8674(00)80079-3. ISSN 0092-8674. PMID 8689690. S2CID 17888183.
  22. ^ "Interview with Jeannie T. Lee, MD, PHD". 6 August 2013. Archived from the original on 19 April 2017. Retrieved 18 April 2017.
  23. ^ "Centennial Awards honor outstanding GENETICS articles". EurekAlert!. Retrieved 2017-09-30.