Chris Hall '21
Major: Intergrative Neuroscience
Bio: Chris Hall, a senior integrative neuroscience major, is a DART fellow (Summers 2019 & 2020) in the Maxfield Lab at Weill Cornell Medicine to study Niemann Pick Type C, a neurodegenerative cholesterol transport disorder. Previously, he was a research assistant in the Pediatric Emotion Regulation Lab at Fordham University under Dr. Roy. In this lab, he evaluated participants to study the neurocognitive mechanisms underlying children’s heightened emotional responses.
Title of Research: Niemann Pick Type C: Stable Transfection, HSP70 Mediation, & Ineffective Arimoclomol Treatment
Mentor: Dr. Martin Di Grandi
Abstract: Niemann Pick disease Type C (NPC) is a cholesterol accumulation disorder caused by Niemann-Pick C1 (NPC1) defects in late endosomes and lysosomes. Specifically, NPC1-I1061T (I1061T) is the most prevalent of all reported mutations. Research on the disease is usually done on patient-derived fibroblasts, transiently transfected cells, or mouse models. Therefore, we successfully created a stably transfected I1061T cell line from U2OS osteosarcoma cells that responds to Vorinostat, as indicated by previous research. We also examined the role of HSP70 as a potential therapeutic target for managing NPC: we found that silencing HSP70 will increase cholesterol accumulation, and its overexpression will reduce the NPC phenotype. Orphazyme claims that Arimoclomol, a drug currently in a clinical trial, can manipulate levels of heat shock proteins like HSP70. However, the drug had no effect on cholesterol storage or HSP70 expression levels in our human fibroblasts. Overall, this research provides novel models to study NPC and evaluates the role of Arimoclomol on the HSP70 chaperone protein.