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
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
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
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
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
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
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
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”
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
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
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
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