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Adrian R. Krainer

Ph.D., Harvard University, 1986

(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 is able to correct this defect using a potentially powerful therapeutic approach. It is possible to stimulate protein production by altering mRNA splicing through the introduction of chemically modified pieces of RNA called antisense oligonucleotides (ASOs) into the spinal cords of mice. Previously, using ASOs in mice carrying a transgene of human SMN2, they developed a model for SMA using a technique they called TSUNAMI (shorthand for targeting splicing using negative ASOs to model illness). This year, they used the method to develop a mouse model for adult onset SMA, and they are currently working to develop models for the study of other diseases caused by splicing defects, including familial dysautonomia. The Krainer lab has also worked to shed light on the role of splicing proteins in cancer. They have found that the splicing factor SRSF1 functions as an oncogene stimulating the proliferation of immortal cells. This year, they were surprised to find that SRSF1 can actually stop cell growth by stabilizing a powerful tumor suppressor protein, called p53—suggesting that the cell is responding to the aberrant SRSF1 activity. This discovery offers insight into how tumors arise and the pathways that lead to transformation.
National Institutes of Health MERIT Award
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