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 they 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.
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 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
Adrian Krainer wins RNA Society’s Lifetime Achievement Award
March 8, 2019
Professor Adrian Krainer was awarded the RNA Society’s Lifetime Achievement Award for his life-saving research.
National Academy of Inventors Fellow, Adrian Krainer
December 11, 2018
Professor Adrian Krainer has been named a NAI 2018 Fellow for his work on the first FDA-approved treatment for spinal muscular atrophy.
Big bold dreamers
December 10, 2018
Dreamers drive discoveries. CSHL honors its many scientists making big impacts in their respective fields.
Breakthrough Prize laureates meet at CSHL
December 6, 2018
Breakthrough Prize winner Adrian Krainer & C. Frank Bennett reunite for the first time since their award ceremony at CSHL to discuss further project.
Breakthrough Prize to CSHL professor for SMA research
October 17, 2018
Professor Adrian Krainer has received a Breakthrough Prize in Life Sciences for his work on the first FDA-approved treatment of SMA.
Predicting how splicing errors impact disease risk
August 30, 2018
New research helps correlate genetic mutations with errors in RNA splicing that can cause serious illness
CSHL helps ring opening bell at Nasdaq
August 21, 2018
CSHL Professor Adrian Krainer and his team join the Spinal Muscular Atrophy (SMA) Foundation in ringing the Nasdaq opening bell
Therapeutic RNA corrects splicing defect that causes familial dysautonomia
April 30, 2018
A team provides proof of concept for an RNA drug correcting an error in RNA splicing that causes familial dysautonomia (FD)
New method identifies splicing biomarkers for liver cancer
March 2, 2018
Researchers have developed a method for identifying splicing-based biomarkers for liver cancer
Welcome to the real world of science, I’ll be your guide
February 5, 2018
Jackie Novatt was determined to show the people on her campus tours how science really works—and landed her dream job in the process.
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,
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.
Aznarez, Isabel and Nomakuchi, Tomoki T. and Tetenbaum-Novatt, Jaclyn and Rahman, Mohammad Alinoor and Fregoso, Oliver and Rees, Holly and Krainer, Adrian R. (2018) Mechanism of Nonsense-Mediated mRNA Decay Stimulation by Splicing Factor SRSF1. Cell Reports, 23(7) pp. 2186-2198.
Lin, K. T. and Ma, W. K. and Scharner, J. and Liu, Y. R. and Krainer, A. R. (2018) A human-specific switch of alternatively spliced AFMID isoforms contributes to TP53 mutations and tumor recurrence in hepatocellular carcinoma. Genome Res,
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.
Anczukow, O. and Akerman, M. and Clery, A. and Wu, J. and Shen, C. and Shirole, N. H. and Raimer, A. and Sun, S. and Jensen, M. A. and Hua, Y. and Allain, F. H. and Krainer, A. R. (2015) SRSF1-Regulated Alternative Splicing in Breast Cancer. Mol Cell, 60(1) pp. 105-17.
Hua, Y. and Liu, Y. H. and Sahashi, K. and Rigo, F. and Bennett, C. F. and Krainer, A. R. (2015) Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in mild and severe transgenic mouse models. Genes Dev, 29(3) pp. 288-297.
Additional materials of the author atCSHL Institutional Repository