ORCID

https://orcid.org/0000-0002-2319-9601

Date of Award

2021

Document Type

Dissertation

Degree Name

Philosophy (Ph.D)

Department

Biological Sciences

First Advisor

Wan S Yang

Second Advisor

Matteo Ruggiu

Third Advisor

Ivana Vancurova

Abstract

Ferroptosis is a non-apoptotic regulated form of cell death driven by the toxic accumulation of lipid peroxides and the presence of iron. The mechanism by which ferroptosis operates requires further investigation; here I will discuss the findings regarding the role of ferroptosis in different cellular models as well as the genes that may be involved with either promoting or hindering the ferroptotic pathway. NSC-34 is a hybrid cell line of neuroblastoma and primary spinal cord cells that can be differentiated into a motor neuron-like state allowing the characterization of ferroptosis in two distinct cellular conditions. Additionally, iNIL cells are a mouse embryonic stem cell line that can be efficiently differentiated into motor neurons and provides a viable cellular model to study ferroptosis in neuronal context. Contrarily, HT-1080 is the mother cell line in which ferroptosis was discovered, providing the best model to look at which genes are essential to drive ferroptosis. PPIP5K2 is a gene involved in phosphate homeostasis that, upon knockdown via siRNA transfection, showed rescue of cell death after ferroptosis induction. ACSL4 is another gene of interest since it is involved in lipid metabolism and lethal accumulation of lipid ROS is a hallmark of ferroptosis. Thus, generating stable cell lines with knockouts of such genes via lentiviral CRISPR transduction in both HT-1080 and mouse embryonic stem cells are essential to establish further connections.

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