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 cancer and genetic diseases, and the means by which faulty splicing can be corrected. For example, 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 antisense technology to develop therapies for other diseases caused by splicing defects, including familial dysautonomia, and to target a cancer-specific alternative-splicing event that controls the Warburg effect. 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, e.g., for a nonsense allele in cystic fibrosis. The Krainer lab has also worked to shed light on how splicing factors and alternative splicing promote cancer progression in the context of breast, liver, brain, pancreatic, and blood malignancies. Finally, the lab continues to study fundamental mechanisms of splicing and its regulation, focusing on the precise recognition of highly diverse intronic and exonic pre-mRNA features by various spliceosome components.
2021 Wolf Prize in Medicine from the President of Israel
2020 Takeda Pharmaceuticals & NY Academy of Sciences Innovators in Science Senior Scientist Award in Rare Diseases
2020 Ross Prize in Molecular Medicine, Feinstein Institute
2020 Member, National Academy of Sciences
2019 Member, National Academy of Medicine
2019 Adrian Krainer wins 2019 Peter Speiser Award
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
2018 National Academy of Inventors Fellow, Adrian Krainer
2018 Breakthrough Prize to CSHL professor for SMA research
2017 Inventor of the Year, New York Intellectual Property Law Association
Fellow of the American Academy of Arts and Sciences
National Institutes of Health MERIT Award
A new treatment approach for cystic fibrosis
July 14, 2022
Molecules called antisense oligonucleotides may help lung cells make a protein missing in people with cystic fibrosis.
The promising drug duo that may improve SMA treatment
July 11, 2022
Pairing Spinraza® with a second FDA-approved drug may be a new way to improve the drug’s therapeutic effects in spinal muscular atrophy patients.
Krainer awarded Watanabe Prize in Translational Research
June 16, 2022
Indiana University School of Medicine honored Krainer for his pioneering work on RNA splicing, which led to the first FDA-approved SMA therapeutic.
Cutting off liver cancer’s nutrient supply chain
February 3, 2022
CSHL researchers developed a way to interfere with the energy pathway that allows liver cancer to grow and spread.
Editing RNA to fix protein problems in cystic fibrosis
January 27, 2022
CSHL researchers found a new way to address a previously untreatable class of mutations in the cystic fibrosis gene.
The rise of RNA therapeutics
October 14, 2021
RNA has been making waves as a new approach to prevent or treat diseases, including COVID-19 and spinal muscular atrophy.
Krainer wins Pew grant to study fetal alcohol syndrome
September 15, 2021
CSHL Professor Adrian Krainer will study RNA splicing errors that occur in people with the disease and look for treatment targets.
CSHL serves up its 30th season of volleyball
August 3, 2021
People have been playing volleyball at CSHL for decades. The league returned for its 30th season in the summer of 2021.
Krainer wins Gabbay Award for SMA research
June 28, 2021
CSHL Professor Adrian Krainer won the Jacob and Louise Gabbay Award in Biotechnology and Medicine for his work on spinal muscular atrophy (SMA).
Envisagenics and Biogen partner for RNA splicing research
June 9, 2021
CSHL spin-out company Envisagenics teams up with Biogen to advance research in RNA-based therapeutics for central nervous system diseases.
1 Mar 2020 | Genes and Development | 34(5-6):413-427
Rahman, M, Lin, K, Bradley, R, Abdel-Wahab, O, Krainer, A
28 May 2019 | Bioinformatics | 35(23):5048-5054
Lin, K, Krainer, A
16 Aug 2018 | Molecular Cell | 71(6):1012-1026.e3
Wong, M, Kinney, J, Krainer, A
Antisense oligonucleotides correct the familial dysautonomia splicing defect in IKBKAP transgenic mice
1 Jun 2018 | Nucleic Acids Research | 46(10):4833-4844
Sinha, R, Kim, Y, Nomakuchi, T, Sahashi, K, Hua, Y, Rigo, F, Bennett, C, Krainer, A
Feb 2016 | Nature Biotechnology | 34(2):164-166
Nomakuchi, T, Rigo, F, Aznarez, I, Krainer, A
27 Sep 2022 | Proceedings of the National Academy of Sciences of USA | 119(39):e2204233119
Zhou, Juannan, Wong, Mandy, Chen, Wei-Chia, Krainer, Adrian, Kinney, Justin, McCandlish, David
Counteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy
9 Jun 2022 | Cell | 185(12):2057-2070.e15
Marasco, Luciano, Dujardin, Gwendal, Sousa-Luís, Rui, Liu, Ying, Stigliano, Jose, Nomakuchi, Tomoki, Proudfoot, Nick, Krainer, Adrian, Kornblihtt, Alberto
27 May 2022 | Nature Communications | 13(1):2978
Kim, Young, Nomakuchi, Tomoki, Papaleonidopoulou, Foteini, Yang, Lucia, Zhang, Qian, Krainer, Adrian
18 Jan 2022 | Proceedings of the National Academy of Sciences of USA | 119(3):e2114858118
Kim, Young, Sivetz, Nicole, Layne, Jessica, Voss, Dillon, Yang, Lucia, Zhang, Qian, Krainer, Adrian
8 Jan 2022 | Nucleic Acids Research
Gao, Yuan, Lin, Kuan-Ting, Jiang, Tao, Yang, Yang, Rahman, Mohammad, Gong, Shuaishuai, Bai, Jialin, Wang, Li, Sun, Junjie, Sheng, Lei, Krainer, Adrian, Hua, Yimin