Adrian R. Krainer
Professor
St. Giles Foundation Professorship
Ph.D., Harvard University, 1986
krainer@cshl.edu | (516) 367-8417
Our DNA carries the instructions to manufacture all the molecules needed by a cell. After each gene is copied from DNA into RNA, the RNA message is "spliced" - an editing process involving precise cutting and pasting. I am interested in how splicing normally works, how it is altered in genetic diseases and cancer, and how we can correct these defects for therapy.
Adrian Krainer’s lab studies the mechanisms of RNA splicing, ways in which they go awry in disease, and the means by which faulty splicing can be corrected. In particular, they study splicing in spinal muscular atrophy (SMA), a neuromuscular disease that is the leading genetic cause of death in infants. In SMA, a gene called SMN2 is spliced incorrectly, making it only partially functional. The Krainer lab found a way to correct this defect using a powerful therapeutic approach. It is possible to stimulate SMN protein production by altering mRNA splicing through the introduction into cells of chemically modified pieces of RNA called antisense oligonucleotides (ASOs). Following extensive work with ASOs in mouse models of SMA, one such molecule, known as nusinersen or Spinraza, was taken to the clinic, and at the end of 2016 it became the first FDA-approved drug to treat SMA, by injection into the fluid surrounding the spinal cord. The Krainer lab is currently using this approach for the study of other diseases caused by splicing defects, including familial dysautonomia. In addition, they are applying antisense technology to stabilize mRNAs that are destroyed by a process called nonsense-mediated mRNA decay (NMD), both to learn about the underlying mechanisms and to develop new therapies. The Krainer lab has also worked to shed light on the role of splicing proteins in cancer. They found that the splicing factor SRSF1 functions as an oncogene, and characterized the splicing changes it elicits when overexpressed in the context of breast cancer; several of these changes contribute to various aspects of cancer progression. Finally, the lab continues to study fundamental mechanisms of splicing and its regulation, and they identified novel ways in which the U1 snRNA can recognize natural 5’ splice sites that deviate from the consensus.
2020 Ross Prize in Molecular Medicine, Feinstein Institute
2020 Member, National Academy of Sciences
2019 Member, National Academy of Medicine
2019 Life Sciences Breakthrough Prize
2019 Fellow of the National Academy of Inventors
2019 Doctorate Honoris Causa, Tel Aviv University
2019 Klaus Joachim Zülch Prize for Basic Neurological Research, Gertrud Reemtsma Foundation and Max Planck Society
2019 RNA Society Lifetime Achievement Award
2019 Bermuda Principles Award
2019 Peter Speiser Award in Pharmaceutical Sciences, ETH Zurich
2017 Inventor of the Year, New York Intellectual Property Law Association
CSHL tops Bush Center’s Innovation Impact Productivity Score
July 13, 2020
Cold Spring Harbor Laboratory ranks #1 in Innovation Impact Productivity Score among Pure Research/Health Care Institutions by the Bush Center.
Krainer wins 2020 NYAS Innovators prize for SMA research
July 8, 2020
Professor Adrian Krainer is the 2020 Senior Scientist Winner of the Innovators in Science Award for his work on SPINRAZA®.
Adrian Krainer elected to the National Academy of Sciences
April 28, 2020
Professor Adrian Krainer was elected to the National Academy of Science as part of its 2020 election.
CSHL featured in new Ken Burns documentary, The Gene
April 6, 2020
The documentary will feature CSHL Professor Adrian Krainer, materials from the CSHL Library & Archives, and glimpses of the CSHL campus.
Adrian Krainer wins Ross Prize in Molecular Medicine
March 2, 2020
Professor Adrian Krainer wins the Ross Prize for his pioneering work on antisense therapy and its application to treating SMA.
Mutation’s role in blood cancers revealed by ideal team-up
January 31, 2020
Researchers from CSHL and MSKCC have determined how a mutation implicated in many blood cancers reduces the proteins that make healthy blood cells.
Mutation’s role in blood cancers revealed by ideal collaboration
January 31, 2020
Researchers from CSHL and MSKCC have determined how a mutation implicated in many blood cancers reduces the proteins that make healthy blood cells.
Researchers identify gene behind spread of deadly breast cancer
December 9, 2019
Jackson Laboratory and Cold Spring Harbor Laboratory researchers uncovered novel targets for therapies related to deadly triple negative breast cancers.
Adrian Krainer wins 2019 Peter Speiser Award
November 27, 2019
Professor Adrian Krainer was awarded the Peter Speiser Award for advances in the pharmaceutical sciences.
High school senior wins big in Breakthrough Junior Challenge
November 5, 2019
Winning the 2019 Breakthrough Junior Challenge, student Jeffery Chen earned his high school a $100,000 science lab designed by the DNA Learning Center.
Rahman, M. A. and Lin, K. T. and Bradley, R. K. and Abdel-Wahab, O. and Krainer, A. R. (2020) Recurrent SRSF2 mutations in MDS affect both splicing and NMD. Genes Dev, 34(5-6) pp. 413-427.
Lin, K. T. and Krainer, A. R. (2019) PSI-Sigma: a comprehensive splicing-detection method for short-read and long-read RNA-seq analysis. Bioinformatics,
Wong, M. S. and Kinney, J. B. and Krainer, A. R. (2018) Quantitative Activity Profile and Context Dependence of All Human 5' Splice Sites. Mol Cell, 71(6) pp. 1012-1026.e3.
Sinha, R. and Kim, Y. J. and Nomakuchi, T. and Sahashi, K. and Hua, Y. and Rigo, F. and Bennett, C. F. and Krainer, A. R. (2018) Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice. Nucleic Acids Res, 46(10) pp. 4833-4844.
Nomakuchi, T. T. and Rigo, F. and Aznarez, I. and Krainer, A. R. (2016) Antisense oligonucleotide-directed inhibition of nonsense-mediated mRNA decay. Nat Biotechnol, 34(2) pp. 164-166.
Additional materials of the author atCSHL Institutional Repository