Mechanisms of RNA repeat toxicity in neuromuscular degenerative disorders
RNA repeat toxicity disrupts essential molecular processes resulting in a number of degenerative disorders from Myotonic Dystrophies (DMs) to Amyotrophic Lateral Sclerosis. How these RNAs containing expanded repeats disrupt molecular function and lead to cellular dysfunction is not well understood. The long-term goal of my laboratory’s research is to comprehensively explore how these toxic RNAs subvert physiological cellular mechanisms to result in toxicity and to identify the full complement of cellular components and pathways that combinatorially regulate the processes of RNA toxicity. Our laboratory focuses on Myotonic dystrophy 1 (DM1) caused by a CTG expansion in the 3’untranslated region (UTR) of the dmpk gene and a paradigm for RNA toxicity diseases.
In our research we combine C. elegans genetics with mammalian approaches, including patients’ cells, to understand how expanded RNAs hijack normal cellular function to execute toxicity. Our laboratory’s research aims to contribute to an understanding of the pathogenic mechanisms that underlie RNA repeat toxicity, and provide new functional insights into known metabolic pathways. Our findings further offer the potential of new translational applications with the identification of targets for therapeutic approaches as well as the direct identification of small molecules that modulate RNA toxicity.
Start Lab in 2016