Jennifer Phillips-Cremins, associate professor in Penn Engineering’s department of bioengineering and in the Perelman School of Medicine’s department of genetics, is among 60 researchers taking part in a $4.5 Million Chan Zuckerberg Initiative project that aims to apply novel, interdisciplinary approaches toward investigating neurodegenerative disorders. The CZI Collaborative Pairs Pilot Project will fund 30 teams that combine clinical and basic science expertise and have at least one early- or mid-career researcher.

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. Dr. Phillips-Cremins’ research 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.

Dr. 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,” 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, Dr. 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.