Date Approved
2-21-2025
Embargo Period
3-24-2025
Document Type
Thesis
Degree Name
Master of Science (M.S.)
Department
Bioinformatics
College
College of Science & Mathematics
Advisor
Nathaniel Nucci, PhD
Committee Member 1
Ileana Soto-Reyes, PhD
Committee Member 2
Yong Chen, PhD
Keywords
Gene Expression;Lipid Metabolism;Mitochondria;Niemann-Pick Type C
Disciplines
Biology | Life Sciences
Abstract
Niemann-Pick Disease Type C (NPC) is a progressive lysosomal storage disorder characterized by the accumulation of lipids, particularly cholesterol, within cells, leading to severe neurological manifestations and developmental issues. This study employs RNA-seq to compare gene expression profiles between fibroblasts derived from a healthy individual and a patient with the NPC1 mutation. A total of 12,978 genes were analyzed, revealing 191 differentially expressed genes. Functional enrichment analysis disclosed significant associations with biological processes related to development, lipid metabolism, embryonic organ development, vascularization, and neuroinflammation. Additionally, the connection between mitochondrial function and lysosomal impairment was explored, revealing that NPC1 mutant fibroblasts exhibit diminished mitochondrial volume and impaired response to nutrient fluctuations. Our findings indicate that while NPC1 mutant fibroblasts retain some ability to recover from serum starvation, their overall mitochondrial and developmental dysregulation may contribute to the pathophysiology of NPC. This study underscores the potential for targeting specific gene networks and signaling pathways to mitigate symptoms of NPC, providing a foundation for future therapeutic investigations aiming at restoring lipid homeostasis and enhancing mitochondrial function.
Recommended Citation
Kim, Sarah, "MOLECULAR MECHANISMS OF NIEMANN-PICK TYPE C: INVESTIGATING GENE EXPRESSION, LIPID METABOLISM, AND MITOCHONDRIAL DYSFUNCTION IN FIBROBLASTS" (2025). Theses and Dissertations. 3325.
https://rdw.rowan.edu/etd/3325
