Maurice S. Swanson, Ph.D. is professor of molecular genetics and microbiology at the University of Florida. Swanson studies how genomic microsatellite instability resulting in sequence expansions and repeats are associated with nearly 30 hereditary disorders, including Huntington’s disease, fragile X-associated tremor ataxia syndrome and several types of myotonic dystrophy. Swanson’s lab proposed the RNA-mediated disease model in which mutant DM1 and DM2 mRNAs are trapped in the nucleus and sequester (C)CUG repeat binding proteins that are essential for normal tissue development and maintenance. His lab also identified these sequestered factors as the muscleblind-like (MBNL) proteins. His ongoing efforts are focused on elucidating the normal functions of these proteins as well as investigating whether RNA toxicity has a pathogenic role in other hereditary disorders. Swanson’s research focuses on three main areas: 1) the roles of genomic repetitive elements in embryonic and postnatal development; 2) novel pathomechanisms of neurological diseases caused by the expansion of short tandem repeats (STRs); 3) RNA-based mechanisms of enhanced tissue repair in a mammalian model of optimized regeneration. Swanson earned his doctorate at the University of California, Berkeley.
Tandem Repeats in RNA Processing and Disease
More than half of the human genome consists of repetitive DNA sequences including both interspersed transposable elements and tandem repeats (TRs). Short tandem repeats (STRs), or microsatellites, are 1-6 bp in length, comprise ~3% of the human genome and are highly unstable genetic elements and thus polymorphic in the general population. While STR expansions cause more than 60 hereditary neurological and neuromuscular diseases, these expansion mutations have also provided novel mechanistic insights into RNA processing, localization and translation. Here, we discuss recent studies focused on the cell type specific impacts of STR expansions on the developmental regulation of RNA alternative splicing.