Date of Award

12-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Healthcare Genetics

Committee Member

Margaret A Wetsel

Committee Member

Julie Eggert

Committee Member

Mary Beth Steck

Committee Member

Emil Alexov

Abstract

The first chapter of this dissertation provides an overview of the interdisciplinary Healthcare Genetics model, the framework for the studies described in Chapters Two, Three and Four. The model is comprised of five core constructs: Research, Environment, Clinical Practice, Ethical/Legal/Social Implications (ELSI) and Education. Each construct is defined. Chapter One also presents a brief overview of subsequent chapters.

Chapter Two details a biophysical approach to the phenotypic classification of mutations in the 7-dehydroxycholesterol reductase (DHCR7) gene, involved in Smith-Lemli-Opitz syndrome. This study utilized computer modeling to determine the biophysical effects of each mutation on structure and function of the DHCR7 protein.

The third chapter is a narrative review of the role of the cytokine interleukin 17 (IL-17) in the gynecological condition endometriosis. This review discusses the incidence, etiology and pathogenesis of endometriosis and outlines general guidelines for diagnosis and treatment are outlined. Finally, potential IL-17-targeted therapies are explored.

Chapter Four presents original bench research that evaluated the effects of the phyto-cannabinoid beta-caryophyllene (BCP) on a cell culture model of endometriosis. The effects of BCP on markers of inflammation such as cell proliferation and vascular endothelial growth factor (VEGF) production were assessed.

The final chapter, Chapter Five, summarizes the findings from Chapters Two, Three and Four. The significance and limitations of these studies are discussed. Finally, Chapter Five provides recommendations for future research.

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