Yannis Grammatikakis
Ph.D. Student, Department of Molecular and Cellular Biology
grammati@bcm.edu
713-798-5021
Started in the lab: June 2007
Research Interests
Myotonic Dystrophy I is caused by extended CTG repeats at the 3' UTR of the DMPK gene. These repeats are transcribed and form CUG-containing RNA foci in the nucleus and bind to a splicing factor called Muscleblind-Like 1 (MBNL1). Under normal conditions activated MBNL1 protein results in inclusion of exon 11 of the Insulin Receptor (IR) gene whereas in Myotonic Dystrophy patients, where MBNL1 is sequestered in RNA foci, exon 11 is skipped. My project focuses on the regulation of exon 11 splicing of the IR gene by MBNL1. I will first map the binding site of MBNL1 on the IR mRNA by using in vivo and in vitro splicing systems. I am also using deletion mutants of the MBNL1 protein to identify protein regions that are required for splicing regulation as well as regions that form protein-protein interactions. In the long term, I will identify the proteins that interact with MBNL1 to activate inclusion of IR exon 11. I expect that my results will help us understand how MBNL1 regulates alternative splicing in Myotonic Dystrophy.
Publications:
Lin Q, Lai R, Chirieac LR, Li C, Thomazy VA , Grammatikakis I , Rassidakis GZ, Zhang W, Fujio Y, Kunisada K, Hamilton SR, Amin HM. Constitutive activation of JAK3/STAT3 in colon carcinoma tumors and cell lines: inhibition of JAK3/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells. Am J Pathol. 2005 Oct;167(4):969-80
Rassidakis GZ, Feretzaki M, Atwell C, Grammatikakis I , Lin Q, Lai R, Claret FX, Medeiros LJ, Amin HM. Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma. Blood. 2005 Jan 15;105(2):827-9.