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Leemor Joshua-Tor

Leemor Joshua-Tor

Professor, Director of Research & HHMI Investigator
W.M. Keck Professor of Structural Biology
Cancer Center Member

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

    image of Microprocessor pr-let-7a1

    The Microprocessor inside you

    December 2, 2024

    Stunning new images from CSHL’s Joshua-Tor lab reveal how the protein complex interacts with differently shaped primary microRNAs.


    image of video slide for 2024 raft race video

    The 2024 CSHL Raft Race

    November 12, 2024

    Ten teams brave cool harbor waters, the hot August sun, and new boat-building rules in the 9th annual CSHL Raft Race.


    image of DDX23 enzyme

    RNA splicing’s spotters

    June 10, 2024

    RNA therapeutics pioneer CSHL Professor Adrian Krainer has discovered a link between two important regulator proteins, SRSF1 and DDX23.


    image of the CSHL Hazen Tower with lightning bolts in the background sky

    Hazen Tower

    April 25, 2024

    The Italian-style bell tower anchors CSHL’s Neuroscience Center. Its bell has rung out every hour on the hour, from 8 a.m. to 8 p.m., since 1991.


    image of Cryo-EM Course instructors standing in front of the CSHL cryo-em microscope

    Up close and personal with cryo-EM

    April 11, 2024

    CSHL’s Cryo-Electron Microscopy course teaches the next generation of scientists to study life at the atomic level.


    image of Leemor Joshua-Tor

    Joshua-Tor named CSHL Director of Research

    January 2, 2024

    The Cold Spring Harbor Laboratory professor and HHMI investigator steps into her new role effective January 2, 2024.


    image of Leemor Joshua-Tor with Cold Spring Harbor waterfront in the background

    Dream big: A powerful vision for CSHL research

    January 2, 2024

    New Cold Spring Harbor Laboratory Director of Research Leemor Joshua-Tor shares her vision for the future of bioscience discovery.


    22nd Annual Women’s Partnership for Science Breaks Records

    October 19, 2023

    Cold Spring Harbor Laboratory held its 22nd Annual Women’s Partnership for Science lecture and luncheon.


    image of the video slide for Dance of epigenetic inheritance

    The dance of epigenetic inheritance

    September 27, 2023

    Making sure chromosomes get passed down correctly is hard work. Watch, through fluorescent and cryogenic lenses, how two proteins make it happen.


    Photo of Arabidopsis thaliana plant

    How plants pass down genetic memories

    August 28, 2023

    Thirty years ago, CSHL’s Rob Martienssen discovered plant gene DDM1. Now, he’s identified just how the DDM1 protein helps control inheritance.


See all Joshua-Tor news

Selected Publications

The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs

1 Oct 2024 | Molecular Cell | :S1097-2765(24)00741
Garg, Ankur;  Shang, Renfu;  Cvetanovic, Todor;  Lai, Eric;  Joshua-Tor, Leemor;  

Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation

24 Aug 2023 | Cell | 186(19):4100-4116.e15
Lee, Seung;  Adams, Dexter;  Ipsaro, Jonathan;  Cahn, Jonathan;  Lynn, Jason;  Kim, Hyun-Soo;  Berube, Benjamin;  Major, Viktoria;  Calarco, Joseph;  LeBlanc, Chantal;  Bhattacharjee, Sonali;  Ramu, Umamaheswari;  Grimanelli, Daniel;  Jacob, Yannick;  Voigt, Philipp;  Joshua-Tor, Leemor;  Martienssen, Robert;  

A shape-shifting nuclease unravels structured RNA

23 Feb 2023 | Nature Structural & Molecular Biology
Meze, Katarina;  Axhemi, Armend;  Thomas, Dennis;  Doymaz, Ahmet;  Joshua-Tor, Leemor;  

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;  

All Publications

The molecular basis of Human FN3K mediated phosphorylation of glycated substrates

22 Jan 2025 | Nature Communications | 16(1):941
Garg, Ankur;  On, Kin;  Xiao, Yang;  Elkayam, Elad;  Cifani, Paolo;  David, Yael;  Joshua-Tor, Leemor;  

The molecular basis of Human FN3K mediated phosphorylation of glycated substrate

5 Aug 2024 | bioRxiv
Garg, Ankur;  On, Kin;  Xiao, Yang;  Elkayam, Elad;  Cifani, Paolo;  David, Yael;  Joshua-Tor, Leemor;  

SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23 (correction)

2024 | Proceedings of the National Academy of Sciences of the United States of America | 121(30)
Segovia, Danilo;  Adams, Dexter;  Hoffman, Nickolas;  Tepes, Polona;  Wee, Tse-Luen;  Cifani, Paolo;  Joshua-Tor, Leemor;  Krainer, Adrian;  

SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23

21 May 2024 | Proceedings of the National Academy of Sciences of the United States of America | 121(21):e2322974121
Segovia, Danilo;  Adams, Dexter;  Hoffman, Nickolas;  Safaric Tepes, Polona;  Wee, Tse-Luen;  Cifani, Paolo;  Joshua-Tor, Leemor;  Krainer, Adrian;  

The structural landscape of Microprocessor Mediated pri-let-7 miRNAs processing

9 May 2024 | bioRxiv
Garg, Ankur;  Shang, Renfu;  Cvetanovic, Todor;  Lai, Eric;  Joshua-Tor, Leemor;  

Catalytic residues of microRNA Argonautes play a modest role in microRNA star strand destabilization in C. elegans

12 Mar 2024 | Nucleic Acids Research (NAR) | :gkae170
Kotagama, Kasuen;  Grimme, Acadia;  Braviner, Leah;  Yang, Bing;  Sakhawala, Rima;  Yu, Guoyun;  Benner, Lars;  Joshua-Tor, Leemor;  McJunkin, Katherine;  

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