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Dissertations & Theses (Open Access)

Theses/Dissertations

2022

Bioinformatics

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Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic May 2022

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations & Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …


An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan May 2022

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations & Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …