Johanna Lee
Ph.D. Student, Interdepartmental Program in Cell and Molecular Biology
jelee@bcm.edu
713-798-5021
Started in the lab: June 2007
Research Interests
Myotonic dystrophy 1 (DM1) is a multisystemic neuromuscular disorder that affects multiple organ systems. Major symptoms include cardiac conduction defects, myotonia, cataracts, and defects in the central nervous system. Interestingly, the main cause of DM1 pathogenesis is not a mutation resulting in loss of gene function. Instead, it results from expanded CTG repeats located in the 3' UTR of the DMPK gene. This transcribes into RNA that contains a CUG repeat expansion localized in nuclear foci. There is plenty of evidence suggesting that CUGBP1, a splicing regulator, is involved in the pathogenesis of DM1. It is also known that steady state levels of CUGBP1 are increased in the muscle of DM1 patients. Recently, we have shown that the stability of CUGBP1 is increased through phosphorylation by protein kinase C. My research directly focuses on how this repeat-containing RNA contributes to the phosphorylation of CUGBP1. More specifically, I would like to answer the following: Is the DMPK context important for the RNA repeats to induce CUGBP1 phosphorylation? What is unique about the repeats to induce CUGBP1 phorphosphorylation? What factors bind to the 3' UTR (or the repeats) and are required for CUGBP1 phosphorylation?