In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Bioinformatics

in the

School of Biological Sciences

Mengnan Zhang

will defend her thesis:

Analysis of the role of miRNAs in ovarian cancer metastasis

Tuesday, March 26th, 2019

1:00 PM Eastern Time

Engineered Biosystems Building, Children's Healthcare of Atlanta Seminar Room (EBB 1005)

Thesis Advisor:

Dr. John F. McDonald

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Dr. Jung H. Choi

School of Biological Sciences

Georgia Institute of Technology

Dr. I. King Jordan
School of Biological Sciences

Georgia Institute of Technology

Dr. Fredrik O. Vannberg

School of Biological Sciences

Georgia Institute of Technology

Dr. Ronghu Wu

School of Chemistry & Biochemistry

Georgia Institute of Technology

Abstract

Cancer mortality is primarily due to metastasis. Metastasis is a complex multi-step process involving, on the molecular level, regulatory control of two key development pathways: epithelial-to-mesenchymal transition (EMT) and it reciprocal, mesenchymal-to-epithelial transition (MET). MiRNAs are small regulatory RNA molecules that play key roles in the regulation of EMT/MET. In this thesis, I examine the role of miRNAs in regulating EMT/MET in ovarian cancer. In the first study, I show that sequentially divergent miRNAs converge to regulate the EMT/MET process through both direct and indirect regulatory changes. In the second study, I explore the impact of genetic difference between different cancer cell lines on the function of miRNAs to regulate the EMT/MET process. In the third study, I evaluate the importance of post-transcriptional/translational changes in the metastasis of a stage III ovarian cancer patient and the role played by miRNAs in regulating the process.