Lando Ringel

Date of Award

2015

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Ryba, Tyrone

Keywords

Genetics, Tumors, Treatment

Area of Concentration

Natural Sciences

Abstract

Due to the molecular heterogeneity of adenocarcinomas, conventional chemotherapy has been shown to have minimal efficacy against basal tumorigenic cells. With recent advances in epigenetic therapy, we aim to build an in vivo model, involving immunocompromised mice exposed to tobacco related carcinogens and lung adenocarcinomas engrafted orthotopically into nude rats. This model helps define tumor responsiveness and resistance to epigenetic and/or chemotherapeutic treatments. Once having distinguished the gene expression profile for adenocarcinomas in mice, we used this data to compare drug treatment combinations and their effect on cancer related gene expression. Our analysis exhibited significant evidence that epigenetic therapy allows the re-expression of many known tumor suppressor genes (TSGs). Differences between cisplatin-resistant and non-treated cancer tissues were discovered when administered epigenetic therapy. To carry out differential expression analysis between multiple samples, we created a pipeline that allows for automated data processing and analysis including: annotation, normalization, filtering, differential expression, clustering, hypergeometric tests, text mining gene ontologies, and TSG and oncogene matching. Having this automated framework, we can now expedite the creation of our model and assist researchers conducting similar experiments in the future.

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