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Adrian R. Krainer

Adrian R. Krainer

Professor
St. Giles Professorship of Neuroscience

Ph.D., Harvard University, 1986

krainer@cshl.edu | (516) 367-8417 (p)

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 recently 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.

    Therapeutic RNA corrects splicing defect that causes familial dysautonomia

    Therapeutic RNA corrects splicing defect that causes familial dysautonomia

    April 30, 2018

    Cold Spring Harbor, NY — Scientists at Cold Spring Harbor Laboratory (CSHL) have identified a therapeutic RNA molecule that corrects the error in genetic processing that leads to familial dysautonomia, a rare inherited neurodegenerative disorder. The experiments, conducted in cells sampled from patients and in a mouse model of the disease, provide proof of the...


    New method identifies splicing biomarkers for liver cancer

    New method identifies splicing biomarkers for liver cancer

    March 2, 2018

    Cold Spring Harbor, NY — Because liver cancer is particularly diverse, genetically, and prone to relapse, identifying biomarkers that can predict disease progression is a critical goal in the fight against it. Researchers at Cold Spring Harbor Laboratory (CSHL), led by CSHL Professor Adrian Krainer, now report in Genome Research that they have developed a...


    Welcome to the real world of science, I’ll be your guide

    Welcome to the real world of science, I’ll be your guide

    February 5, 2018

    LabDish blog Science is not too hard for you to understand. That was Jackie Novatt’s attitude during every tour she gave at CSHL, where she herself was a researcher, and it showed. She wasn’t interested in merely dazzling visitors with high-tech equipment and triumphant success stories. She was determined to show the people on her...


    FDA approval of life-saving SMA drug is hailed by its researcher-inventor at CSHL

    FDA approval of life-saving SMA drug is hailed by its researcher-inventor at CSHL

    December 24, 2016

    ‘A perfect example of why we do basic research,’ says Dr. Bruce Stillman, CSHL president Cold Spring Harbor, NY — Within a week of Christmas day, a drug called nusinersen (Spinraza) will be in the hands of doctors across the nation, who will use it, most urgently, to treat young children with a severe and...


    One experiment: A drug for SMA visibly repairs defective cells

    One experiment: A drug for SMA visibly repairs defective cells

    December 1, 2016

    Think of this pair of images as the scientific equivalent of an exclamation point. Here is proof positive of an idea first advanced in 2003 by CSHL Professor Adrian Krainer and colleagues. In a paper entitled “Correction of disease-associated exon skipping,” they suggested a way to make a drug to treat spinal muscular atrophy. A...


    “Sink or swim”

    “Sink or swim”

    October 15, 2016

    Base Pairs podcast For most scientists, the path to running a lab is a long one. It can require well over a decade of school and training. This episode of Base Pairs is about a scientist whose path to scientific independence was about as short as possible. Professor Adrian Krainer was offered the opportunity to...


    Candidate drug for spinal muscular atrophy, with roots in CSHL research, passes major hurdle

    Candidate drug for spinal muscular atrophy, with roots in CSHL research, passes major hurdle

    August 4, 2016

    Basic research by Adrian Krainer and colleagues formed the basis for development of nusinersen Cold Spring Harbor, NY — In an announcement that delighted the families of patients and surprised many pharmaceutical industry analysts, the biotechnology firms Biogen and Ionis Pharmaceuticals on Monday said they had decided to cut short a phase-3 clinical trial for...


    Adrian Krainer of Cold Spring Harbor Laboratory elected to American Academy of Arts and Sciences

    Adrian Krainer of Cold Spring Harbor Laboratory elected to American Academy of Arts and Sciences

    April 20, 2016

    Cold Spring Harbor, NY and Cambridge, MA – The American Academy of Arts and Sciences today announced the election of 213 new members. They include some of the world’s most accomplished scholars, scientists, writers, artists. Among those elected into this newest class is Professor Adrian Krainer of Cold Spring Harbor Laboratory (CSHL). “On behalf of...


    New method prevents cells from prematurely halting protein production in certain genetic illnesses

    New method prevents cells from prematurely halting protein production in certain genetic illnesses

    December 14, 2015

    Cold Spring Harbor, NY — Improperly formed proteins can cause a host of serious illnesses, from muscular dystrophy to cystic fibrosis. A question of enormous import in research, beyond the challenge of determining how malformed proteins contribute to specific disease processes, is figuring out ways to prevent or reduce the pathologies they cause. Today, a...


    Breaking down breast cancer at CSHL

    Breaking down breast cancer at CSHL

    October 30, 2015

    LabDish blog Breast cancer awareness is important, but it’s action that saves lives. Whether developing more accurate and affordable tests for patients or mapping out the treacherous landscape of breast cancer genetics, researchers at CSHL certainly aren’t putting the fight on pause even as the pink ribbons dissipate. Explore how they’re attacking breast cancer from...


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.

Roca, X. and Akerman, M. and Gaus, H. and Berdeja, A. and Bennett, C. F. and Krainer, A. R. (2012) Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes and Development, 26(10) pp. 1098-109.

Hua, Y. and Sahashi, K. and Rigo, F. and Hung, G. and Horev, G. and Bennett, C. F. and Krainer, A. R. (2011) Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature, 478(7367) pp. 123-6.

Additional materials of the author at
CSHL Institutional Repository