Position #063
Examining SUGP1 Overexpression on Intracellular Lipid Accumulation in iPSCs
Mentors: Shahrbanoo Keshavarz Aziziraftar, PhD and Aras N. Mattis, MD, PhD
Metabolic dysfunction–associated steatotic liver disease (MASLD) is a growing liver disorder characterized by excess fat accumulation unrelated to alcohol use. Recent studies suggest the splicing factor gene SUGP1 plays a role in regulating cholesterol metabolism by altering the splicing of HMGCR, a key cholesterol synthesis gene. This project explores how overexpressing SUGP1 in induced pluripotent stem cells (iPSCs) affects lipid metabolism under fatty acid stress. Lentivirus carrying SUGP1 was produced using HEK-293 cells and used to transduce iPSCs. Antibiotic selection ensured only successfully modified cells were retained. SUGP1 expression was validated through qPCR, and lipid accumulation was measured after oleate exposure in SUGP1-knockout and SUGP1-overexpressing lines. We anticipate that SUGP1 overexpression will reduce lipid buildup, supporting its role in regulating fat metabolism. This research aims to clarify how splicing factors like SUGP1 contribute to diseases like MASLD and could identify new therapeutic targets for liver fat reduction and cholesterol control.