Leemor Joshua-Tor
Professor, Director of Research & 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
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.
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.
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.
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.
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.
A molecular machine’s secret weapon exposed
February 23, 2023
A shape-shifter with a protruding arm and an appetite for unwanted RNA! CSHL biochemists identify the hidden talents of a mysterious molecule.
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.
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
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
The catalytic activity of microRNA Argonautes plays a modest role in microRNA star strand destabilization in C. elegans
9 Jan 2024 | bioRxiv
Kotagama, Kasuen, Grimme, Acadia, Braviner, Leah, Yang, Bing, Sakhawala, Rima, Yu, Guoyun, Benner, Lars, Joshua-Tor, Leemor, McJunkin, Katherine
Manipulating PTPRD function with ectodomain antibodies
5 Sep 2023 | Genes & Development
Qian, Zhe, Song, Dongyan, Ipsaro, Jonathan, Bautista, Carmelita, Joshua-Tor, Leemor, Yeh, Johannes, Tonks, Nicholas
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 circadian-like gene network programs the timing and dosage of heterochronic miRNA transcription during C. elegans development
22 Aug 2023 | Developmental Cell | :S1534-5807(23)00402
Kinney, Brian, Sahu, Shubham, Stec, Natalia, Hills-Muckey, Kelly, Adams, Dexter, Wang, Jing, Jaremko, Matt, Joshua-Tor, Leemor, Keil, Wolfgang, Hammell, Christopher