More than 30 inherited disorders are caused by the unstable expansion of repetitive DNA sequences, including Huntington’s disease, ALS, Fragile X syndrome, and Friedreich’s ataxia. Jennifer E. Phillips-Cremins, associate professor in Penn Engineering’s Department of Bioengineering and in the Perelman School of Medicine’s Department of Genetics, has shown another link between these disorders: the location of these expanding genes relative to the complicated folding patterns the genome exhibits to fit inside the nucleus of a cell.
“We are excited to welcome the Collaborative Pairs grantees to CZI’s Neurodegeneration Challenge Network and are hopeful that the discoveries these researchers make help us understand these devastating disorders,” said CZI Head of Science, Cori Bargmann. “With this collaborative network, we’re also thrilled to support early- and mid-career scientists who bring new approaches and insights to the neurodegeneration field.”
Phillips-Cremins will collaborate with Kristen Brennand of the Icahn School of Medicine at Mount Sinai. Their project, “3D genome misfolding due to repeat instability in neurodegenerative disease,” project will investigate the emerging link between the genetic sequence’s higher-order folding patterns and pathologic repeat instability in trinucleotide repeat (TNR) expansion disorders.
In a 2018 study published in the journal Cell, Phillips-Cremins and her colleagues established a strong correlation between 3D genome misfolding, short tandem repeat instability, and pathologic gene disruption in TNR disorders, suggesting new research questions whose answers could improve diagnosis or treatment.