
Adrian R. Krainer
Professor
St. Giles Foundation Professor
Cancer Center Deputy Director of Research
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 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
Laying the groundwork for drug discoveries
August 8, 2023
A new partnership between CSHL and one of the world’s leading biotech investors could streamline this process and help change society for the better.
Eight serving one: CSHL volleyball mid-season report
August 2, 2023
CSHL’s 32nd Volleyball League season sees eight teams battling for the coveted Tiernan Cup and a year’s worth of bragging rights.
Adrian Krainer awarded honorary IADR membership
June 21, 2023
Krainer was recognized for his pioneering research on spinal muscular atrophy and RNA therapeutics.
President’s essay: Bringing bold visions to life
May 26, 2023
CSHL President & CEO Bruce Stillman sees the Laboratory as a global hub for scientific expertise and a powerful launchpad for early-career scientists.
This killer protein causes pancreatic cancer
April 26, 2023
CSHL researchers have found that high levels of a protein called SRSF1 can cause pancreatitis and jumpstart tumor development.
Krainer named Society for RNA Therapeutics board member
April 18, 2023
He helped pioneer the field. It changed medicine. Now, he joins a group of renowned scientists and physicians aiming to take it to the next level.
From tragedy, a potential pediatric cancer treatment
April 12, 2023
CSHL Professor Adrian Krainer, the man behind the “miracle drug” known as Spinraza®, has found a way to fight a deadly pediatric brain cancer in mice.
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.
Selected Publications
Recurrent SRSF2 mutations in MDS affect both splicing and NMD
1 Mar 2020 | Genes and Development | 34(5-6):413-427
Rahman, M, Lin, K, Bradley, R, Abdel-Wahab, O, Krainer, A
PSI-Sigma: a comprehensive splicing-detection method for short-read and long-read RNA-seq analysis
28 May 2019 | Bioinformatics | 35(23):5048-5054
Lin, K, Krainer, A
Quantitative Activity Profile and Context Dependence of All Human 5' Splice Sites
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
Antisense oligonucleotide-directed inhibition of nonsense-mediated mRNA decay
Feb 2016 | Nature Biotechnology | 34(2):164-166
Nomakuchi, T, Rigo, F, Aznarez, I, Krainer, A
All Publications
Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer
7 Jul 2023 | Cancer Discovery | 13(7):1678-1695
Wan, Ledong, Lin, Kuan-Ting, Rahman, Mohammad, Ishigami, Yuma, Wang, Zhikai, Jensen, Mads, Wilkinson, John, Park, Youngkyu, Tuveson, David, Krainer, Adrian
RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
May 2023 | Nature | 617(7959):147-153
Jbara, Amina, Lin, Kuan-Ting, Stossel, Chani, Siegfried, Zahava, Shqerat, Haya, Amar-Schwartz, Adi, Elyada, Ela, Mogilevsky, Maxim, Raitses-Gurevich, Maria, Johnson, Jared, Yaron, Tomer, Ovadia, Ofek, Jang, Gun, Danan-Gotthold, Miri, Cantley, Lewis, Levanon, Erez, Gallinger, Steven, Krainer, Adrian, Golan, Talia, Karni, Rotem
Antisense oligonucleotide therapy for H3.3K27M diffuse midline glioma
12 Apr 2023 | Science Translational Medicine | 15(691):eadd8280
Zhang, Qian, Yang, Lucia, Liu, Ying, Wilkinson, John, Krainer, Adrian
RNA therapeutics
Apr 2023 | RNA | 29(4):393-395
Hastings, Michelle, Krainer, Adrian
Specificity, cooperativity, synergy, and mechanisms of splice-modifying drugs
10 Feb 2023 | Biophysical Journal | 122(3S1):271a
Ishigami, Y, Wong, M, Aldaravi, C, Kooshkbaghi, M, Ayaz, A, McCandlish, D, Krainer, A, Kinney, J