Home Department: Bioengineering
Mentor: Ravi Majeti (Medicine)

"Protein Engineering to Investigate Developmental and Leukemic Phenotypes in ASXL1 Mutant Disease"

Germline gain-of-function mutations in ASXL1 cause a rare, untreatable developmental disorder, while somatic mutations are common founding mutations in blood cancers and associated with poor prognosis. My project aims to determine if depleting the mutant ASXL1 protein can eliminate the disease phenotype in both germline and somatic contexts. I will use a targeted degradation strategy to selectively and rapidly eliminate the mutant ASXL1 protein in pluripotent stem cells differentiating into neurons (germline) or blood cells (somatic). This approach will help to identify a therapeutic window for ASXL mutation-linked conditions while also deepening our understanding of how these mutations drive disease.