DOI

https://doi.org/10.25772/8HZM-VD08

Author ORCID Identifier

https://orcid.org/0000-0003-3381-3959

Defense Date

2019

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Huiping Zhou

Second Advisor

Xiang-Yang Wang

Third Advisor

Joseph Landry

Abstract

Cholangiocarcinoma (CCA) has a high mortality rate and its occurrence is rising. This increase prompts the need for improved CCA treatments. Studies have suggested that CCA is highly reliant on the sphingosine-1-phosphate-receptor-2 (S1PR2) and sphingosine kinase 2 (SphK2). Recently, a competitive SphK2 inhibitor, ABC294640, has been approved for clinical trial. ABC294640 has the potential to treat CCA, which is support by a phase I clinical study that was able to temporarily treat a patient suffering from metastasized CCA with ABC294640. To determine the viability of ABC294640 as a treatment for CCA, this study focused on determining the effects of ABC294640 on rat CCA cell lines. We found that ABC294640 inhibited the growth and migration of CCA and CAFs cells. The growth and count of 3-D organotypic co-culture of CCA and CAFs, which forms the “duct-like” structures, were reduced by ABC294640. The potential of inhibiting SphK2 as a treatment for CCA is supported by our finding of increased expression of S1PR2 and SphK2 in CCA patient liver samples. In conclusion, ABC294640 represents a potential therapeutic agent for CCA.

Comments

I would like to acknowledge my PI, Dr. Huiping Zhou for helping me get through a tough point in my career and personal life. She took a risk by taking me in after my previous lab had left. Under her guidance, I improved my research and communication abilities. She gave me practical advice and reasonable objectives while pushing me forward. The lab also gave me a family away from home and this is not by accident. Dr. Zhou makes the lab feel like a family by encouraging teamwork, bringing food, having lunch celebrations for birthdays and individual’s accomplishments, and lab trips. I highly appreciate how she has treated me and my fellow lab mates. I owe unmeasurable thanks to her.

I would also like to thank my fellow lab mates. They have been teachers and friends. They have helped me learn concepts, complete experiments, and have been supported during the long nights of research. Thank you all.

I want to show appreciation for my collaborators. I appreciate Dr. Guizhi Zhu and his graduate student Shurong Zhou for developing and producing the nanoparticles used in this study. I am thankful for Guanhua Lai help in diagnosing the human samples in my study.

And thanks to my committee members, Dr. Wang and Dr. Landry.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-4-2019

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