Overview of Reddy Lab
We are investigating how RNA dysfunction can cause neuromuscular disease and leveraging this knowledge to develop new therapeutic strategies. Our research is focused on myotonic dystrophy and on human ITPase enzyme deficiency using a combination of biochemical, cellular and genomic approaches.
Microsatellite expansion disorders are a group of more than 40 neurological, neuromuscular and neurodegenerative diseases caused by expansions of simple DNA tandem repeat sequences (microsatellites). This group includes myotonic dystrophy types 1 and 2, caused by a CTG and CCTG repeat expansion respectively, C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia, caused by a GGGGCC repeat expansion and Huntington disease caused by a CAG expansion. These repeats form toxic RNA molecules that lead to many detrimental downstream cellular consequences. We aim to understand how these toxic RNA molecules are regulated within the cell and to leverage this knowledge to design therapeutic strategies for the associated disorders.
Human ITPase enzyme deficiency can result in severe developmental anomalies and is typically fatal in childhood with dilated cardiomyopathy as a major cause of death. The ITPase enzyme prevents accumulation of inosine and deoxyinosine triphosphate within NTP and dNTP pools. In the absence of ITPase, inosine accumulation can result in misincorporation into RNA and DNA. While the biochemical activity of ITPase is well understood, the molecular and cellular basis of pathogenesis resulting from ITPase dysfunction is unknown. We are studying the molecular and cellular consequences of ITPase dysfunction during development to better understand this rare genetic condition and to better understand gene networks that are active during normal healthy development that may be disrupted due to inosine misincorporation.