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
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
PFF student named Regeneron scholar
January 30, 2023
CSHL Partners for the Future student Sean Krivitsky is a semifinalist in one the nation's most prestigious high school science competitions.
Decoding how a protein on the move keeps cells healthy
May 31, 2022
The Argonaute protein is a workhorse for cell regulation and CSHL researchers discovered what helps it commute from job to job.
Cold Spring Harbor Laboratory 2022 Ph.D.’s
May 1, 2022
The School of Biological Sciences awarded Ph.D. degrees to ten students this year. Here are some stories and memories from their time at CSHL.
CSHL Ph.D. program: Graduating class of 2021
August 22, 2021
The CSHL School of Biological Sciences awarded Ph.D. degrees to seven students this year, who describe some of their experiences.
Research matters
June 8, 2021
Innovative research and educational activities never stopped during the COVID-19 pandemic.
DNA replication: A game of precision
April 25, 2021
A highly choreographed complex of molecules is vital to starting and synchronizing DNA replication during cell division.
How to tame a restless genome
April 8, 2021
CSHL researchers found a mechanism to keep otherwise mobile genetic elements in place in the genome.
Joshua-Tor wins Biophysical Society honor
November 16, 2020
CSHL Professor and HHMI Investigator Leemor Joshua-Tor was named a 2021 Fellow of the Biophysical Society for her work on RNAi and DNA replication.
The “ORC” twists, pinches, and dances around DNA
September 16, 2020
The Origin Recognition Complex (ORC) is a key piece of cellular machinery, fundamental to life, yet so far mysterious.
Replicating a genome starts with a twist, a pinch, and a bit of a dance
September 16, 2020
Researchers have their first high resolution look at how “ORC,” a human protein complex essential to life, moves.
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
All Publications
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