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Leemor Joshua-Tor

Leemor Joshua-Tor

Professor & HHMI Investigator
W.M. Keck Professor of Structural Biology

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

leemor@cshl.edu | (516) 367-8821

Joshua-Tor Lab

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.

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

    Dr. Leemor Joshua-Tor honored with Mildred Cohn Award from ASBMB

    Dr. Leemor Joshua-Tor honored with Mildred Cohn Award from ASBMB

    February 2, 2018

    The idea that understanding the form and function of molecules that make up life is essential to understanding life itself has guided Professor Leemor Joshua-Tor throughout more than 25 years of research. The latest honor in her distinguished career is the American Society for Biochemistry and Molecular Biology’s 2018 Mildred Cohn Award in Biological Chemistry,...


    Research profile: Leemor Joshua-Tor

    Research profile: Leemor Joshua-Tor

    November 27, 2017

    When she was in the 7th grade, Leemor Joshua-Tor came upon a fragrant box that once held her mother’s perfume. It proved the perfect container for a set of flash cards that she was using to learn properties of the chemical elements. “I think my brain connected doing chemistry to good feelings, good smells,” she...


    Structural view suggests RNAi machinery multiplies its efficiency in repressing gene expression

    Structural view suggests RNAi machinery multiplies its efficiency in repressing gene expression

    August 3, 2017

    Cold Spring Harbor, NY — Continuously throughout our lives, our cells are expressing genes. It’s the first step in making proteins, the stuff of all the structures in the body and molecular players in the countless dramas unfolding every second as cells execute tasks that enable our organs to function. Many specialized and overlapping mechanisms...


    Freeze-frames of enzymes in action have implications for a new cancer treatment concept

    Freeze-frames of enzymes in action have implications for a new cancer treatment concept

    July 3, 2017

    Tutases are a class of enzymes that regulate the microRNA let-7—a gene that is commonly downregulated in cancers. The Joshua-Tor lab used x-ray crystallography to capture images of the enzyme in action, offering insight into how these potential cancer targets function.


    CSHL’s Dr. Leemor Joshua-Tor is elected to The National Academy of Sciences

    CSHL’s Dr. Leemor Joshua-Tor is elected to The National Academy of Sciences

    May 2, 2017

    Washington, D.C. and Cold Spring Harbor, NY — Cold Spring Harbor Laboratory Professor Leemor Joshua-Tor, Ph.D., a structural biologist whose work is known and respected worldwide, has been elected to The National Academy of Sciences (NAS). Dr. Joshua-Tor, who since 2008 has been an Investigator of the Howard Hughes Medical Institute, joins a new class whose...


    CSHL’s Dr. Leemor Joshua-Tor Elected to American Academy of Arts and Sciences

    CSHL’s Dr. Leemor Joshua-Tor Elected to American Academy of Arts and Sciences

    April 14, 2017

    Cambridge, MA and Cold Spring Harbor, NY — Professor Leemor Joshua-Tor, Ph.D., of Cold Spring Harbor Laboratory is among 228 newly elected members of The American Academy of Arts and Sciences, it was announced today. Dr. Joshua-Tor is a Howard Hughes Medical Institute Investigator. The new class of Academy members will be inducted at a ceremony...


    Protein complex that takes first steps in human DNA replication dance is captured at high atomic resolution

    Protein complex that takes first steps in human DNA replication dance is captured at high atomic resolution

    March 16, 2017

    The Stillman and Joshua-Tor labs collaborated to obtain the structure of the active human Origin Recognition Complex (ORC), the proteins that control the initiation of DNA replication. Using both cyro-EM and x-ray crystallography, the labs obtained a high-resolution image of the ORC proteins bound to DNA, providing insights into the most fundamental process in cell proliferation.


    “Science is our candle in the dark”

    “Science is our candle in the dark”

    May 29, 2015

    LabDish blog In this edition of LabDish, we feature the thought-provoking remarks of Dr. Jack Walleshauser, on the occasion of his graduation from the Watson School of Biological Sciences on April 19. That day, Jack shared his passion for science and his desire to see scientists communicate more readily with the public. As a U.S. Army...


    In a role reversal, RNAs proofread themselves

    In a role reversal, RNAs proofread themselves

    January 29, 2015

    Molecular photographs of an enzyme bound to RNA reveal a new, inherent quality control mechanism Cold Spring Harbor, NY — Building a protein is a lot like a game of telephone: information is passed along from one messenger to another, creating the potential for errors every step of the way. There are separate, specialized enzymatic...


    Knowing what to keep and what to trash: how an enzyme distinguishes cellular messages

    Knowing what to keep and what to trash: how an enzyme distinguishes cellular messages

    August 3, 2014

    Molecular structure reveals how a protein reads RNAs to preserve stem cell identity Cold Spring Harbor, NY – Every once in a while, we are forced to sort that stack of papers on the kitchen counter. Interspersed between the expired coupons and dozens of takeout menus are important documents like your car insurance or electric...


Faehnle, C. R. and Walleshauser, J. and Joshua-Tor, L. (2017) Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis. Nat Struct Mol Biol, 24(8) pp. 658-665.

Tocilj, A. and On, K. F. and Yuan, Z. and Sun, J. and Elkayam, E. and Li, H. and Stillman, B. and Joshua-Tor, L. (2017) Structure of the active form of human Origin Recognition Complex and its ATPase motor module. Elife, 6

Kuhn, C. D. and Wilusz, J. E. and Zheng, Y. and Beal, P. A. and Joshua-Tor, L. (2015) On-Enzyme Refolding Permits Small RNA and tRNA Surveillance by the CCA-Adding Enzyme. Cell, 160(4) pp. 644-658.

Faehnle, C. R. and Walleshauser, J. and Joshua-Tor, L. (2014) Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway. Nature, 514(7521) pp. 252-6.

Elkayam, E. and Kuhn, C. D. and Tocilj, A. and Haase, A. D. and Greene, E. M. and Hannon, G. J. and Joshua-Tor, L. (2012) The structure of human argonaute-2 in complex with miR-20a. Cell, 150(1) pp. 100-110.

Additional materials of the author at
CSHL Institutional Repository