Author ORCID Identifier

https://orcid.org/0000-0001-9404-4300

Date of Graduation

12-2018

Document Type

Dissertation (PhD)

Program Affiliation

Epigenetics and Molecular Carcinogenesis

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Dean G. Tang, Ph.D.

Committee Member

Sharon Y.R. Dent, Ph.D.

Committee Member

Vishwanath Iyer, Ph.D.

Committee Member

Yue Lu, Ph.D.

Committee Member

Jianhua Hu, Ph.D.

Abstract

Prostate cancer (PCa) is the most common non-cutaneous tumor in American men, and the second leading cause of cancer-related deaths. PCa-related deaths can be attributed to heterogeneous tumors containing metastatic and therapy-resistant cancer cells. Cancer stem cells (CSC) are an important contributor to this tumor heterogeneity, which are present in primary tumors and become enriched in castration resistant PCa (CRPC). Our lab has demonstrated that the prostate cancer stem cells (PCSCs) are enriched in the phenotypically undifferentiated PCa cell population that lacks the expression of differentiation marker prostate-specific antigen (PSA). Our work has also demonstrated that PCa cells manifest significant plasticity such that phenotypically differentiated PSA+ PCa cells can be reprogrammed to the castrationresistant, stem-like state by chronic castration or overexpression of the stemness factor NANOG. Therefore, my overarching hypothesis is that PSA-/lo cells possess intrinsic molecular and epigenetic features that regulate their aggressiveness and stemness and contribute to tumor progression and therapy resistance, and that these properties can be gained through epigenetic reprogramming of more differentiated PSA+ PCa cell population. Throughout my Ph.D. thesis research, I employed an integrative bioinformatics approach to test this hypothesis.

Keywords

Prostate cancer, Cancer heterogeneity, Cancer stem cell, Bioinformatics, PSA, AR, Nanog, Castration resistance, Differential expression genes, Epigenetics

Available for download on Thursday, December 12, 2019

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