Medicine and Health Sciences Commons^™

Genetics Of Obesity In Starr County, Texas Mexican Americans, Heather M. Highland

Dissertations & Theses (Open Access)

Currently, over two-thirds of Americans are classified as over-weight or obese. Obesity increases risk for many other diseases including type 2 diabetes, heart disease, stroke, and cancer, making obesity the largest public health problem in America and most other Westernized nations. Hispanics have a higher rate of both obesity and type 2 diabetes, making them a particularly interesting population in which to study obesity. For the last 33 years, the Starr County Health Studies has collected an array of phenotypes and biological samples from residents of Starr County, along Texas-Mexico border. This study includes 825 subjects who were not known …

Rest Regulatory Circuit Controls Distinct Oncogenic Properties Of Glioblastoma Stem Cells Through Specific Micrornas, Anantha L Marisetty

Dissertations & Theses (Open Access)

Glioblastoma Multiforme (GBM) is the most common and aggressive primary malignant brain tumor in adults. With an average survival of only 12-16 months the prognosis for GBM patients remains dismal, with less than 5% of patients surviving 5 years. New mechanism-based approaches are necessary for the management of patients with GBM. Many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs). These GSCs are resistant to chemo- and radiation therapies, and are believed to be responsible for tumor recurrence. In a recent paper from our lab we have shown that REST, RE1-silencing transcription factor, regulates oncogenic …

Elucidating The Role Of Rumi And O-Glucosylation In The Drosophila Eye, Amanda Haltom

Dissertations & Theses (Open Access)

Rumi is a protein O-glucosyltransferase that adds the sugar O-glucose onto the serine in the target sequence C-S-X-S-(P/A)-C found within properly folded EGF repeats. It was first discovered to modify the Drosophila Notch extracellular domain and to be required for Notch signaling in a temperature dependent manner, but other targets of Rumi remained unknown. Several other proteins in the Drosophila proteome harbor multiple consensus sequence highly predictive of O-glucose, including the transmembrane protein Crumbs and the secreted protein Eyes shut (Eys). Both of these proteins are required for proper eye development and mutations in their human homologs …

Dna Polymerase Θ (Polq) And The Cellular Defense Against Dna Damage, Matthew J. Yousefzadeh

Dissertations & Theses (Open Access)

In mammalian cells, DNA polymerase θ (POLQ) is an unusual specialized DNA polymerase whose in vivo function is under active investigation. The protein is comprised of an N-terminal helicase-like domain, a C-terminal DNA polymerase domain, and a large central domain that spans between the two. This arrangement is also found in the Drosophila Mus308 protein, which helps confer resistance to DNA interstrand crosslinking agents. Homologs of POLQ and Mus308 are found in eukaryotes, including plants, but a comparison of phenotypes suggests that not all of these genes are functional orthologs. Flies with defective Mus308 are sensitive to DNA interstrand crosslinking …

Investigating The Roles Of P63 And P73 Isoforms To Therapeutically Treat P53-Altered Cancers, Avinashnarayan Venkatanarayan

Dissertations & Theses (Open Access)

Investigating the roles of p63 & p73 isoforms to therapeutically treat

p53-altered cancers

Avinashnarayan Venkatanarayan, M.S.

Supervisory Professor: Elsa R. Flores, Ph.D.

The TP53 tumor suppressor is mutated in approximately 50% of human cancers rendering cancer therapies ineffective. p53 reactivation suppresses tumor formation in mice. However, this strategy has proven difficult to implement therapeutically. An alternate approach to overcome p53 loss is to manipulate the p53-family members, p63 and p73, which interact and share structural similarities to p53. p63 and p73, unlike p53 are less frequently mutated and have two major isoforms with distinct functions …

Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra

Dissertations & Theses (Open Access)

The anaplastic lymphoma kinase (ALK) is a single chain transmembrane receptor tyrosine kinase that belongs to the insulin receptor superfamily. Other members of this superfamily include the insulin receptor (IR), type I insulin-like growth factor receptor (IGF-IR), and the leukocyte tyrosine kinase. The common structural finding among these tyrosine kinases is the YXXXYY motif present within their respective tyrosine kinase domains. Binding of its ligands causes ALK receptor homodimerization and protein kinase activation. ALK has been previously shown to play a significant role during early developmental stages. In human embryos, the expression of ALK is mainly seen in …

Developmental Origins Of Renal Connecting Tubule And Collecting Duct: Role Of Aqp2+ Progenitor Cells, Lihe Chen

Dissertations & Theses (Open Access)

The connecting tubule interconnects the nephron and collecting duct, which arise from kidney mesenchyme and the ureteric bud, respectively, to generate the functional tubular networks. The collecting duct is comprised of principal cells and intercalated cells, which bear different molecular signatures and regulate sodium/water and acid/base balance, respectively. The progenitor cells of the connecting tubule and the collecting duct remain virtually unknown.

We generated two Aqp2 lineage tracing mouse models. In these models, Aqp2Cre transgene drives Cre expression by the Aqp2 promoter to exclusively either inactivate histone H3 K79 methyltransferase Dot1l (Dot1l^f/f Aqp2Cre) or activate RFP in …

Selection Methods For Genetically-Modified T Cells: In Support Of Translational Therapy, David Rushworth

Dissertations & Theses (Open Access)

T cells are blood cells which organize the immune system of the host. These cells are necessary for the host to respond appropriately to threats from foreign organisms and cancerous growth. However, in the case of certain infections and cancer, T cells are unable to respond appropriately to a threat and establish immunity. This leads to disease when the infection or cancer is not sufficiently eliminated. On the other hand, T cells can lack tolerance for healthy tissue and perceive healthy tissue as infected. The ensuing over-reactive immune response also leads to disease. A delicate balance must exist between immunity …

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 …

Actions Of Pi3k-Delta Inhibitor, Idelalisib, And Its Combination With Bendamustine In Chronic Lymphocytic Leukemia, Prexy Modi

Dissertations & Theses (Open Access)

Class I phosphatidylinositol 3-kinase isoforms (α, β, δ, and γ) play a major role in cancer cell growth and survival. PI3K α and β are most studied. PI3K pathway is highly dysregulated in many cancers and aberrant PI3K signaling is associated with oncogene mutations and disease progression in solid tumors and in hematologic malignancies.

Chronic lymphocytic leukemia (CLL) is driven by B-cell receptor (BCR) signaling that promotes B-cell proliferation and survival. PI3K is a critical node in BCR pathway and PI3Kδ has a pivotal role in B-cell development and maintenance and this isoform is over-expressed in many B-cell malignancies, including …

Regulation Of Cell Adhesion By The Ferm Proteins, Ptpn14 And Merlin, Patty Dimarco Hewitt

Dissertations & Theses (Open Access)

Cell-cell adhesion is critical for the control of tissue organization and homeostasis. A family of proteins that regulate cell-cell adhesions is the FERM (4.1 protein, Ezrin, Radixin, Moesin) domain-containing proteins.One FERM domain protein, the non-receptor tyrosine phosphatase PTPN14, is mutated or deleted in several human cancers suggesting that it may be involved in tumor development and/or progression. Additionally, the loss of the FERM domain protein Merlin is associated with tumor development and metastasis.Both PTPN14 and Merlin have been shown to localize and possibly regulate adherens junction (AJ) functions. This work sought to determine if …

Measuring Single Cell Responses To Lapatinib In A Heterogeneous Population, Preety Priya

Dissertations & Theses (Open Access)

Cancer is notonedisease butasaga of diseases and is the outcome of disturbed homeostasis in the normal cells due to the deregulation of its genetic makeup. With advent of technologies thatallowdetailed molecular characterizationoftumors, targeted therapies have emerged as a more promising and specific mode of treatment. However, a major challenge with targeted therapy is the acquired resistance in the cancer cells to these therapies, quite often very rapidly in the course of a few months. One of the major targets in cancer has been the EGFR/ErbB2 network in breast and other cancer types. Prior work from our lab and others have …

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 …

Spiritual Exploration In The Prenatal Genetic Counseling Session, Katelynn G. Sagaser

Dissertations & Theses (Open Access)

Religion and spirituality are important components of many individuals’ lives, and spiritual needs may present among persons receiving medical care. Spirituality has been demonstrated to be significant in the coping of women experiencing pregnancy complications (Breen et al. 2006; Price et al. 2007). To characterize the manner in which prenatal genetic counselors might address spiritual issues with their patients, we surveyed 283 patients receiving prenatal genetic counseling using the Brief RCope and a series of questions that examined interest in spiritual exploration. Counselors were concurrently surveyed to identify the spiritual language used within the session and the counselor’s perceived importance …