Assistant Professor, 2016

The long-term research pursuits of our laboratory are to enhance the mechanistic knowledge of nucleotide repeat expansions (NREs) in human disease and to identify therapeutic strategies for NRE-linked diseases. The current incomplete human genome is filled with tandem or satellite repeat DNAs, much of which has not been correctly assembled due to sequencing technological limitations. Such repetitive DNA regions can vary in magnitudes among individuals, and these inherent DNA polymorphisms may underlie diseases of fundamental importance that remain unassigned or undiagnosed. Still, over forty neurological disorders have been linked to the expansion of short repetitive DNA sequences, NREs. These disorders are typically neurological or neuromuscular disorders, such as the NRE-linked Fragile X, Huntington’s, amyotrophic lateral sclerosis (ALS), frontal temporal dementia (FTD), and many ataxias. However, identification of the primary mechanism(s) that lead to NRE-linked diseases remain(s) unclear, and therapeutic liberations are indeterminate. Our complimentary research strategy focuses on NRE-linked disease and spans in vitro biochemical characterization to in vivo pathological validation primarily employing the ALS/FTD-linked NRE paradigm recently discovered in a classically non-coding region on chromosome 9 open reading frame 72 (C9orf72). The comprehensive research performed in our laboratory will further the mechanistic knowledge of how repetitive DNA sequences function in basic human biology and contribute to human disease, and it will identify therapeutic potentials to attenuate disease.