Genomics Commons^™

Investigation Of Genetic Alterations In Emt Suppressor, Dear1, Through Pan-Cancer Analysis And Ultra-Deep Targeted Sequencing In Ductal Carcinoma In Situ, Jacquelyn Reuther

Dissertations & Theses (Open Access)

Ductal carcinoma in situ (DCIS) is thought to be one of the earliest pre-invasive form of and non-obligate precursor to invasive ductal carcinoma (IDC). There is an urgent need to identify predictive and prognostic biomarkers for breast cancers with a heightened risk of progression from DCIS to IDC. Our laboratory has previously discovered a novel TRIM family member, DEAR1 (Ductal Epithelium Associated Ring Chromosome 1, annotated as TRIM62) within chromosome 1p35.1, that is mutated and homozygously deleted in breast cancer and whose expression is downregulated/lost in DCIS. Previous work has shown that DEAR1 is a novel tumor suppressor …

Igfbp2 Potentiates Egfr-Stat3 Signaling In Glioma, Yingxuan Chua

Dissertations & Theses (Open Access)

Gliomas are clinically challenging brain tumors with dismal survival rates due to its infiltrative nature and ineffective standard therapy. Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic oncogenic protein that has both extracellular and intracellular functions. Despite a clear causal role in cancer development, the contributions of intracellular IGFBP2 to tumor development and progression are poorly understood. Here we present evidence that both exogenous IGFBP2 treatment and cellular IGFBP2 overexpression lead to aberrant activation of EGFR, which subsequently activates STAT3 signaling. Furthermore, we demonstrate that IGFBP2 augments the nuclear accumulation of EGFR to potentiate STAT3 transactivation activities, via …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations & Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations & Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations & Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations & Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Molecular And Genomic Based Insights Into The Evolution Of Enterococcus Faecium From Commensal To Hospital-Adapted Pathogen, Jessica R. Galloway-Pena

Dissertations & Theses (Open Access)

The basis for the recent transition of Enterococcus faecium from a primarily commensal organism to one of the leading causes of hospital-acquired infections in the United States is not yet understood. To address this, the first part of my project assessed isolates from early outbreaks in the USA and South America using sequence analysis, colony hybridizations, and minimal inhibitory concentrations (MICs) which showed clinical isolates possess virulence and antibiotic resistance determinants that are less abundant or lacking in community isolates. I also revealed that the level of ampicillin resistance increased over time in clinical strains. By sequencing the pbp5 gene, …

Genetic Predictors Of Hyperglycemia Due To Hydrochlorothiazide Therapy, Jorge L. Del Aguila

Dissertations & Theses (Open Access)

Response to pharmacological treatment is variable among individuals. Some patients respond favorably to a drug while others develop adverse reactions. Early investigations showed evidence of variation in genes that code for drug receptors, drug transporters, and drug metabolizing enzymes; and pharmacogenetics appeared as the science that studies the relationship between drug response and genetic variation.

Thiazide diuretics are the recommended first-line monotherapy for hypertension (i.e. SBP>140 or DBP>90). Even so, diuretics are associated with adverse metabolic side effects, such as hyperglycemia, which increase the risk of developing type 2 diabetes. Published approaches testing variation in candidate genes (e.g. …

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

Dissertations & Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it …