Niemann-Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder caused by mutations in the NPC1 gene, resulting in cholesterol accumulation and severe hepatic and neurological dysfunction. The most common disease-causing mutation is an isoleucine-to-threonine substitution at position 1061, known as NPC1-I1061T. Although NPC1-I1061T retains functional activity when correctly localized to the lysosome, it is rapidly degraded in the endoplasmic reticulum (ER). My research focuses on identifying genetic and molecular regulators of NPC1 protein folding, trafficking, and function, with the goal of developing therapeutic strategies to restore NPC1 activity. I investigate intrinsic determinants of NPC1 processing by examining how glycosylation influences the folding and trafficking of human and mouse NPC1-WT and NPC1-I1061T using biochemical and molecular approaches. I also investigate extrinsic regulators of NPC1 processing through forward genetic screening approaches, including CRISPRi and Sleeping Beauty-based insertional mutagenesis. These approaches allow me to perturb ER quality control and other components of the protein-folding and trafficking machinery to identify molecular pathways that could be modulated to correct NPC1-I1061T trafficking. Additionally, I have identified lipid nanoparticle-mediated delivery of Npc1 mRNA as a promising therapeutic approach for treating NPC1 phenotypes, demonstrating efficacy in both an in vitro model and the mouse liver.

Publications:

Co-first author paper, 'Codon-Optimized Npc1 mRNA corrects Niemann-Pick type C1 disease phenotypes in vitro and in vivo' accepted into the September 2026 issue of Molecular Therapy: Nucleic Acids. My ink pen illustration interepreting mRNA integeation and translation into NPC1 was chosen as the cover for this issue.

Honors/Awards:

Best Graduate Student Poster Award, Stead Family Pediatrics Research Day, April (2026)

Genetics T-32 Pre-doctoral Training Grant (2025 - 2026)

Genetics T-32 Pre-doctoral Training Grant (2024 - 2025)

The Ara Parseghian Medical Research Fund Travel Award (2025)

The Ara Parseghian Medical Research Fund Travel Award (2024)