Dissertation Defense Schedule
Academic Excellence
Sharing original dissertation research is a principle to which the University of Delaware is deeply committed. It is the single most important assignment our graduate students undertake and upon completion is met with great pride.
We invite you to celebrate this milestone by attending their dissertation defense. Please review the upcoming dissertation defense schedule below and join us!
PROGRAM | Biological Sciences
Regulation of IGF-1 Receptor Signaling by Autophagy in Human Neuroblastoma Cell Lines
By: Mehrnoosh Soori Chair: Robert Mason Co-Chair: Erica Selva
ABSTRACT
This study was designed to examine the mechanism by which inhibition of lysosomal proteases causes cell death in neuroblastoma. The major lysosomal proteases are two cysteine proteases, cathepsins B and L, and an aspartic protease, cathepsin D. Inhibition of these three proteases was found to cause cellular accumulation of fragments of the IGF-1 receptor. The fragments were located in dense organelles that were characterized as autophagosomes. This novel discovery provides the first clear link between lysosIGF-1omal function, autophagy and IGF-1 mediated cell proliferation. It provides a mechanistic explanation for enhanced cytotoxicity of chemotherpautic agents when combined with inhibitors of lysosomal function and autophagy. A more in depth analysis of the IGF1 signaling pathway revealed that the MAPK pathway was particularly impaired in inhibitor treated cells, while the PKB cell survival pathway remained functional. It was discovered that Shc, an adapter protein that transmits IGF-1 signaling towards the MAPK pathway, was also sequestered in autophagosomes while IRS2, an adapter protein that transmits IGF-1 signaling towards the PKB pathway, was unaffected by cathepsin inhibition. Furthermore, Shc was sequestered in autophagasomes as its active form, indicating that autophagy is a key mechanism for down-regulating IGF-1 induced cell proliferation. Proliferating cells of neuronal origin are particularly sensitive to cathepsin inhibition. This enzyme inhibition had a greater effect on autophagic sequestration of the neuronal specific adapter protein, Shc-C, than ubiquitously expressed Shc-A, providing mechanistic support for the enhanced sensitivity of neuronally derived tumor cells. The Shc adapter proteins are central to transducing proliferation signaling by a range of receptor tyrosine kinases and consequently cathepsin inhibition may become an important therapeutic approach to treating neuroblastoma and other tumors of neuronal origin.
The Process
Step-by-Step
Visit our “Step-by-Step Graduation Guide” to take you through the graduation process.From formatting your Dissertation to Doctoral Hooding procedures.
Dissertation Manual
Wondering how to set up the format for your paper. Refer to the “UD Thesis/Dissertation Manual” for formatting requirements and more.
Defense Submission Form
This form must be completed two weeks in advance of a dissertation defense to meet the University of Delaware Graduate and Professional Education’s requirements.
