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

Fellow of the American Academy of Arts and Sciences

National Institutes of Health MERIT Award