J. Andy Berglund, Ph.D.

Dr. Berglund began studying biochemistry in 1990 with a focus on the structures that RNA can adopt and their role in biology. His interests expanded to determining the mechanisms through which RNA binding proteins recognize RNA motifs in pre-mRNA splicing. As a graduate student he was the first to show that proteins conserved from yeast to humans specifically recognize an RNA motif that is essential for the recognition and removal of introns in pre-mRNA splicing. In his own laboratory, he and his group began studying the molecular mechanisms of myotonic dystrophy. This led to his laboratory solving the first crystal structure of CUG repeats, the toxic RNA that causes myotonic dystrophy type 1. They have solved additional structures of CUG repeats leading to a better understanding of the dynamics of the repeats and insights into the toxicity of the repeats. One of the mechanisms through which the CUG repeats and CCUG repeats for myotonic dystrophy type 2 (DM2) are toxic is the sequestration of the muscleblind-like (MBNL) family of RNA binding proteins. The sequestration of MBNL proteins leads to many changes in splicing, which are implicated in causing the symptoms in DM. His laboratory, along with several other groups in the field, have identified some of the mechanisms through which the MBNL family of proteins regulate splicing providing a better framework for understanding the mis-splicing in myotonic dystrophy. For many years the group has investigated using small molecules to target the toxic CUG and CCUG repeats of DM. These efforts have led to the identification of molecules that rescue the mis-splicing in DM1 cell and mouse models. Recently the group has shown that targeting the production of the toxic RNA shows promise as a potential approach to identify lead compounds for developing therapeutics.