Scripps Research Logo

Molecular Medicine


Paul Schimmel, Ph.D.

Department of Cell and Molecular Biology
Florida Campus
Laboratory Website
(858) 784-8970

Scripps Research Joint Appointments

Department of Chemistry
The Skaggs Institute for Chemical Biology
Faculty, Graduate Program

Other Joint Appointments

Institute for Advanced Study, Hong Kong University of Science and Technology
Scripps Florida Campus

Research Focus

Decoding Genetic Information In Translation

The genetic code was established over two billion years ago and became universally adopted by all living organisms. The rules of the code--which relate specific nucleotide triplets to specific amino acids--are established by aminoacylation reactions catalyzed by aminoacyl tRNA synthetases. In these reactions, an amino acid is associated with a specific nucleotide triplet of the genetic code, by virtue of being linked to a specific tRNA that harbors the anticodon triplet cognate to the amino acid. Because of their central role in establishing the rules of the code, the tRNAs are thought to have arisen quite early, perhaps in the context of an RNA world. The synthetases may have been amongst the earliest proteins to appear, perhaps replacing ribozymes that catalyzed the aminoacylation of primordial tRNAs. The Schimmel laboratory is interested in understanding all aspects of these systems.

Our present work focuses on the discovery of the large new biology that flows out of the tRNA synthetases. These enzymes are now known to be secreted, to have nuclear functions, and to pervade most or all parts of human biology with activities that are distinct from their catalytic function of charging tRNA. The laboratory uses methods and logic of molecular and cell biology, chemistry, and structural analysis to more deeply investigate these novel functions that have a fundamental role in maintaining organismal homeostasis, and in developing and regulating nervous, vascular, and immunological systems. The research is leading to the development of a broad new class of therapeutics to treat and cure human diseases.


Ph.D., Biophysical Chemistry, Massachusetts Institute of Technology, 1966

Awards & Professional Activities

McArthur Professor, MIT; Honors: Alfred P. Sloan Fellow; American Chemical Society Pfizer Award in Enzyme Chemistry; Elected Fellow, American Association for Advancement of Science; Elected Fellow, American Academy of Arts and Sciences; Elected Member, National Academy of Sciences, Doctor of Science (Honorary), Ohio Wesleyan University; Elected Member, American Philosophical Society; Elected member, Institute of Medicine of the National Academy of Sciences; Biophysical Society Emily M. Gray Award (co-recipient), Stein and Moore Award (The Protein Society), Chinese Biopharmaceutical Association Brilliant Achievement Award, Frank Westheimer Medal (Harvard University), Nucleic Acids Award (British Biochemical Society and Royal Society of Chemistry), David Perlman Award (American Chemical Society), Editorial Boards: Accounts of Chemical Research; Archives of Biochemistry and Biophysics; Biochemistry; Biopolymers; European Journal of Biochemistry; International Journal of Biological Macromolecules; Journal of Biological Chemistry; Proceedings of the National Academy of Sciences; Protein Science; Nucleic Acids Research; Trends in Biochemical Sciences.

Selected References

For a complete list of publications:

Guo, M. and Schimmel, P. (2013). Essential Ex-translational functions of tRNA synthetases. Nature Chem. Biol. 9: 145-153.

Zhou, H., Sun, L., Yang, X.-L., and Schimmel, P. (2013). ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Nature 124: 121-125.

Xu, Z., Wei, Z., Zhou, Jie J., Ye, F., Lo, C. W. S., Wang, F., Wu, J., Lau, C. C. F., Nangle, L. A., Chiang, K. P., Yang, X.-L., Zhang, M., and Schimmel, P. (2012). Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing. Structure 20: 1470-77.

Sajish, M., Zhou, Q., Kishi, S., Valdez Jr, D. M., Kapoor, M., Guo, M., Kim, S., Lee, S., Yang, X-L. and Schimmel, P. (2012). Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to  link IFN-gamma and p53 signaling. Nature Chem. Biol. 8: 547-554.

Guo, M. and Schimmel, P. (2011). Structural Analysis Clarifies the Complex Control of Mistranslation by tRNA Synthetases. Current Op. Struct. Biol. 22:1-8.

Guo, M., Yang, X.-L., and Schimmel, P. (2010). New functions of aminoacyl tRNA synthetases beyond translation.  Nature Rev. Mol. Cell. Biol. 11: 668-674.

Guo, M., Chong, Y. E., Yang, X.-L., and  Schimmel, P. (2009). The C-Ala domain brings together editing and aminoacylation functions on a single tRNA. Science 325: 744-747.

Guo, M., Chong, Y. E., Shapiro, R., Beebe, K., Yang, X.-L., and Schimmel, P. (2009). Paradox of Mistranslation of Serine for Alanine Caused by AlaRS Recognition Dilemma. Nature  462: 808-812.

Beebe, K., Mock, M., Merriman, E., and Schimmel, P. (2008). Distinct domains of tRNA synthetase recognize the same base pair. Nature 451: 90-94


Team Finds Ancient Protein-Building Enzymes Have Evolved Diverse New Functions

HKUST-Scripps Scientists Discover Metamorphosed Protein-Building Enzymes as New Protein Therapeutics

Reprint: Human tRNA synthetase catalytic nulls with diverse functions

Full Text: Human tRNA synthetase catalytic nulls with diverse functions

Abstract: Human tRNA synthetase catalytic nulls with diverse functions

The Skaggs Institute for Chemical Biology

The Skaggs Institute Scientific Report

After the Genome Part 1: The Genome, We Are Sure, Is Packed with Subtleties

Nature's Own Medicine for Vision Loss: Inhibitor of Angiogenesis Found by Biologists at The Scripps Research Institute

Simultaneous Reports by Scientists at TSRI Show How They Made Bacteria Do What Nature Doesn't

Molecular Medicine Seminar Series
Center for Physiological Proteomics
Department Contacts

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Johnson, Eric
Kanaji, Taisuke
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Nicholson, Laura
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John

FL Faculty

Bannister, Thomas
Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Joazeiro, Claudio
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy

Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei
Ye, Li

Adjunct Faculty