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Leemor Joshua-Tor

Leemor Joshua-Tor

Professor & HHMI Investigator
W.M. Keck Professor of Structural Biology
Cancer Center Program Co-Leader

Ph.D., The Weizmann Institute of Science, 1991

leemor@cshl.edu | 516-367-8821

Joshua-Tor Lab Website   Faculty Profile

Our cells depend on thousands of proteins and nucleic acids that function as tiny machines: molecules that build, fold, cut, destroy, and transport all of the molecules essential for life. My group is discovering how these molecular machines work, looking at interactions between individual atoms to understand how they activate gene expression, DNA replication, and small RNA biology.

In Leemor Joshua-Tor’s lab, researchers study the molecular basis of nucleic acid regulatory processes using the tools of structural biology and biochemistry. One such regulatory process is RNA interference (RNAi), in which a small double-stranded RNA triggers gene silencing. Joshua-Tor and her team offered critical insight when they solved the crystal structure of the Argonaute protein and identified it as the long-sought Slicer. They then went on to explore the mechanism of the slicing event. The structure of human Argonaute 2 (hAgo2) bound to a microRNA (miRNA) guide allowed Joshua-Tor and her colleagues to understand how mRNA is cleaved during RNAi. This year, members of the Joshua-Tor lab explored the function of a very similar protein, called Argonaute 1, that has no slicing ability, even though it is almost identical in structure to the slicing hAgo2. Using biochemical methods and mutational analysis, they were able to identify key parts of the protein that are required for slicing activity. The lab also studies the generation of PIWI-interacting RNAs (piRNAs), which serve to protect the genome of germ cells. With colleagues in the Hannon lab, Joshua-Tor’s team also determined the structure and function of Zucchini, a key nuclease in the initial generation of piRNAs in fruit flies. In other work, the lab is exploring the mechanisms of heterochromatin formation and gene silencing through the study of a protein complex called RNA-induced initiation of transcriptional gene silencing (RITS). Joshua-Tor is also well known for her work on the E1 helicase enzyme, which acts to unwind DNA strands during the DNA replication process.

Dr. Leemor Joshua-Tor honored with Mildred Cohn Award from ASBMB
Member of the National Academy of Sciences
Member of the American Academy of Arts and Sciences
2018 Mildred Cohn Award in Biological Chemistry, ASBMB
2014 ACE Women’s Network, New York, Women in Science and Education Leadership Award
Fellow of the American Association for the Advancement of Science (AAAS)
2007 Dorothy Crowfoot Hodgkin Award (Inaugural award), The Protein Society
1996 Beckman Young Investigator Award

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Selected Publications

Asterix/Gtsf1 links tRNAs and piRNA silencing of retrotransposons.

30 Mar 2021 | Cell Reports | 34(13):108914
Ipsaro, Jonathan, O'Brien, Paul, Bhattacharya, Shibani, Palmer, Arthur, Joshua-Tor, Leemor

Evolution of DNA replication origin specification and gene silencing mechanisms.

14 Oct 2020 | Nature Communications | 11(1):5175
Hu, Y, Tareen, A, Sheu, Y, Ireland, W, Speck, C, Li, H, Joshua-Tor, L, Kinney, J, Stillman, B

The dynamic nature of the human origin recognition complex revealed through five cryoEM structures

18 Aug 2020 | eLife | 9:e58622
Jaremko, M, On, K, Thomas, D, Stillman, B, Joshua-Tor, L

SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease.

Dec 2020 | Emerging Microbes and Infections | 9(1):2091-2093
Wang, Pengfei, Liu, Lihong, Nair, Manoj, Yin, Michael, Luo, Yang, Wang, Qian, Yuan, Ting, Mori, Kanako, Solis, Axel, Yamashita, Masahiro, Garg, Ankur, Purpura, Lawrence, Laracy, Justin, Yu, Jian, Joshua-Tor, Leemor, Sodroski, Joseph, Huang, Yaoxing, Ho, David

Increasing gender diversity in the STEM research workforce.

8 Nov 2019 | Science | 366(6466):692-695
Greider, Carol, Sheltzer, Jason, Cantalupo, Nancy, Copeland, Wilbert, Dasgupta, Nilanjana, Hopkins, Nancy, Jansen, Jaclyn, Joshua-Tor, Leemor, McDowell, Gary, Metcalf, Jessica, McLaughlin, BethAnn, Olivarius, Ann, O'Shea, Erin, Raymond, Jennifer, Ruebain, David, Steitz, Joan, Stillman, Bruce, Tilghman, Shirley, Valian, Virginia, Villa-Komaroff, Lydia, Wong, Joyce

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ETV6 dependency in Ewing sarcoma by antagonism of EWS-FLI1-mediated enhancer activation

19 Jan 2023 | Nature Cell Biology
Gao, Yuan, He, Xue-Yan, Wu, Xiaoli, Huang, Yu-Han, Toneyan, Shushan, Ha, Taehoon, Ipsaro, Jonathan, Koo, Peter, Joshua-Tor, Leemor, Bailey, Kelly, Egeblad, Mikala, Vakoc, Christopher

Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release

31 May 2022 | eLife | 11
Bibel, Brianna, Elkayam, Elad, Silletti, Steve, Komives, Elizabeth, Joshua-Tor, Leemor

OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage

16 May 2022 | Nature
Wu, Xiaoli, He, Xue-Yan, Ipsaro, Jonathan, Huang, Yu-Han, Preall, Jonathan, Ng, David, Shue, Yan, Sage, Julien, Egeblad, Mikala, Joshua-Tor, Leemor, Vakoc, Christopher

Developmental roles and molecular mechanisms of Asterix/GTSF1

2 Feb 2022 | Wiley Interdisciplinary Reviews: RNA | :e1716
Ipsaro, Jonathan, Joshua-Tor, Leemor

Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release

6 Jan 2022 | eLife
Bibel, Brianna, Elkayam, Elad, Silletti, Steve, Komives, Elizabeth, Joshua-Tor, Leemor

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