Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Strong, Theresa V.<br>"). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters

1. Phipps, Sharla Marion Ostein. Genetic and epigenetic modulation of telomerase activity in development and disease.

Degree: PhD, 2007, University of Alabama – Birmingham

The end replication problem of linear chromosomes leads to the erosion of telomeric DNA with each cell division. A mechanism to counteract telomeric attrition involves the activity of the specialized ribonucleoprotein telomerase. Expression of the catalytic subunit of telomerase, hTERT, is tightly regulated and this regulation is achieved through both genetic and epigenetic mechanisms. Activators such as c-MYC and SP1 and repressors such as MAD1, Menin, and p53 mediate hTERT transcription. Epigenetic control mediated by DNA methylation and histone modifications such as methylation and acetylation can reversibly and potently regulate telomerase activity. Not only is there synergism between the epigenetic regulatory mechanisms of DNA methylation and histone acetylation, there is also significant interaction between the genetic and epigenetic methods of hTERT gene regulation. Understanding mechanisms that govern hTERT expression can lead to insights into cellular processes such as embryonic development, differentiation, cancer progression, and aging because of the integral role of telomerase activity in these occurrences. The studies outlined in this dissertation attempt to elucidate some of the mechanisms modulating hTERT transcription and telomerase activity in the initiation of cellular differentiation and in a human breast cancer model. To this end, we have developed a novel model system to investigate differentially-expressed genes during the course of in vitro human embryonic stem cell differentiation. We have also presented data showing a stronger correlation between hTERT expression and expression of the epigenetic regulators DNMT3a and DNMT3b than between other epigenetic regulatory mechanisms. In the breast cancer model, we have investigated the effects of prolonged all-trans retinoic acid exposure on these cells and have demonstrated changes in cellular morphology, growth rate, and anchorage-independence. We have also observed that this retinoid slowly decreases telomerase activity, possibly due to the epigenetic changes induced at the hTERT promoter. The result of these investigations is a deeper comprehension of the complexities involved in telomerase regulation in normal regulated and unregulated cancer systems. This understanding gives insight into the early events of aging and telomere shortening and could lead to improved anti-cancer therapeutics that utilize modes of hTERT down-regulation to stop the growth of telomerase-addicted neoplastic cells.

xii, 120 p. : ill. (chiefly col.), digital, PDF file.

Biology

Natural Sciences and Mathematics

Telomerase Breast cancer ATRA Human embryonic stem cells hTERT Epigenetics

UNRESTRICTED

Advisors/Committee Members: Tollefsbol, Trygve O., Ghanta, Vithal K.<br>, Ruppert, J. Michael <br>, Strong, Theresa V.<br>, Watson, R. Douglas.

Subjects/Keywords: Telomerase  – Physiological effect <; br>; Telomerase  – Inhibitors <; br>; Genetic regulation <; br>; Enzymes  – Regulation <; br>; Genetic transcription <; br>; Reverse transcriptase <; br>; Breast  – Cancer  – Genetic aspects <; br>; Tretinoin  – Physiological effect <; br>; Epigenesis.

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Phipps, S. M. O. (2007). Genetic and epigenetic modulation of telomerase activity in development and disease. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,260

Chicago Manual of Style (16th Edition):

Phipps, Sharla Marion Ostein. “Genetic and epigenetic modulation of telomerase activity in development and disease.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed September 15, 2019. http://contentdm.mhsl.uab.edu/u?/etd,260.

MLA Handbook (7th Edition):

Phipps, Sharla Marion Ostein. “Genetic and epigenetic modulation of telomerase activity in development and disease.” 2007. Web. 15 Sep 2019.

Vancouver:

Phipps SMO. Genetic and epigenetic modulation of telomerase activity in development and disease. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2019 Sep 15]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,260.

Council of Science Editors:

Phipps SMO. Genetic and epigenetic modulation of telomerase activity in development and disease. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,260

2. Pandya, Ashka Y. Structural and functional analysis of KLF4.

Degree: PhD, 2007, University of Alabama – Birmingham

KLF4, a C2H2 type zinc finger transcription factor, plays an essential role in maturation of normal stratified squamous epithelium. In normal squamous epithelium its expression is confined to the differentiating, non-proliferating cell layers. By oncogene expression cloning, we identified KLF4 as a major transforming activity. In breast and oral tumors the compartment specificity of KLF4 expression is lost and KLF4 mRNA and protein expression is markedly increased in dysplasia and carcinoma in situ. These results suggest that specific genetic mechanisms could activate KLF4 in a large subset of breast and oral tumors, and that a transcription factor that functions in normal differentiation can contribute to tumor progression and may predict the clinical outcome of the disease. To test this hypothesis, 146 cases of human primary infiltrating ductal carcinoma of the breast were examined by immuno-staining. Staining patterns were then correlated with clinical outcome and with established prognostic factors. Tumors with high nuclear staining and low cytoplasmic staining were termed as Type 1. For patients with early stage disease, Type 1 staining was associated with eventual death due to breast cancer. In vitro, KLF4 was localized within the nucleus of transformed RK3E epithelial cells, consistent with its nuclear function as a transcription factor during induction of malignant transformation. This study identifies KLF4 as a marker of an aggressive phenotype in early-stage infiltrating ductal carcinoma. Using a combination of nested cDNA deletions and site-directed mutation, specific functional domains of KLF4 that are required for transformation in vitro were examined. Transformation defective mutants were examined for sub-cellular localization, transcriptional regulation of a promoter-reporter and dominant negative activity. KLF4 dominant negatives termed Ala5 and Ala6 were identified, by stably expressing the lossof- function mutants in RK3E cells and challenging them with wild type KLF4. Study of the mechanism involved in dominant interference, revealed that the dominant negative mutants failed to induce downstream target genes of KLF4 such as Notch1 and p21. The novel discovery of this research study was involvement of two different mechanisms in exhibiting identical phenotype. Ala5 stably associates with co-repressor Sin3A and exhibits dominant interference in activating downstream target genes. In contrast, Ala6 is more highly expressed and associates with co-repressor Sin3A similar to wild type KLF4, thus by mass action it exhibits its dominant interference in transformation by KLF4.

xii, 120 p. : ill., digital, PDF file

Cell Biology

Joint Health Sciences

KLF4 Zinc Finger Transcription Factor Dominant Negative Breast Cancer Mutagenesis Prognostic Marker

UNRESTRICTED

Advisors/Committee Members: Ruppert, J. Michael, Ruppert, Susan M.<br>, Strong, Theresa V.<br>, Engler, Jeffrey A.<br>, Frank, Stuart J.<br>, Lin, Weei-Chin<br>, Detloff, Peter J..

Subjects/Keywords: Breast Neoplasms  – metabolism<; br>; Breast Neoplasms  – pathology<; br>; Cell Nucleus  – metabolism<; br>; DNA-Binding Proteins  – biosynthesis<; br>; Kruppel-Like Transcription Factors<; br>; Prognosis Transcription Factors  – biosynthesis

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Pandya, A. Y. (2007). Structural and functional analysis of KLF4. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,531

Chicago Manual of Style (16th Edition):

Pandya, Ashka Y. “Structural and functional analysis of KLF4.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed September 15, 2019. http://contentdm.mhsl.uab.edu/u?/etd,531.

MLA Handbook (7th Edition):

Pandya, Ashka Y. “Structural and functional analysis of KLF4.” 2007. Web. 15 Sep 2019.

Vancouver:

Pandya AY. Structural and functional analysis of KLF4. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2019 Sep 15]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,531.

Council of Science Editors:

Pandya AY. Structural and functional analysis of KLF4. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,531

3. Tang, Yizhe. Modification of adenovirus capsid proteins for gene therapy applications.

Degree: PhD, 2009, University of Alabama – Birmingham

Adenovirus (Ad) is the most commonly used viral vector in gene therapy applications to date for a broad range of diseases. Although Ad-based viral vectors have many advantages in a variety of gene therapy designs, the commonly used adenoviral vectors have several key shortcomings. Those shortcomings include (1) inefficient transduction in cell types devoid of Ad’s native receptors and the incapability of gene delivery to targets behind physical barriers; (2) restricted accessibility to the central nerve system due to the existence of the blood-brain barrier (BBB); (3) lack of a useful strategy and platform to generate multi-functionality displaying Ad vectors as to achieve functional integration or synergism, which could improve Ad’s utility. We hypothesized that 1) incorporation of targeting ligands onto fiber protein would broaden the delivery range of Ad vectors in terms of cell types; 2) retargeting adenoviral vectors to the native transcytosis pathway in BBB endothelial cells would allow efficient gene delivery into the brain; 3) incorporation of multiple heterologous peptide ligands into a single Ad virion at the minor capsid protein IX (pIX) locales could allow for the display of multiple functionalities simultaneously, thus giving rise to functional integration or synergistic effect. To achieve the modification of Ad fiber and consequent expansion of gene delivery targets, the protein transduction domain of HIV-1 Tat protein (PTDtat) or melanotransferrin protein (MTf) was incorporated into the fiber knob protein via a genetic or non-genetic approach, respectively. The derived Ad vector incorporated with PTDtat showed expanded tropism and enhanced transduction efficiency in various tumor cells; the derived Ad vector incorporated with MTf achieved gene delivery across the BBB in an in vitro model. To incorporate three heterologous peptide ligands into a single Ad virion at the pIX locale, three modified pIX genes were genetically engineered and inserted into the Ad genome, resulting in the expression and incorporation of three different types of IX-ligand fusion proteins. The results indicated that capsid modification is a potent and useful strategy to enhance the efficacy of Ad vectors in gene therapy applications. However, this study mainly focused on the principle of capsid-modifying strategies, and further optimizations are necessary for their application for clinical trials.

3.35MB

Vision Science;

Optometry;

Adenovirus Capsid modification Gene Therapy protein IX Fiber Cancer Therapy

UNRESTRICTED

Advisors/Committee Members: Curiel, David T., Wu, Hongju<br>, Gamlin, Paul D.<br>, Keyser, Kent T.<br>, Strong, Theresa V.<br>, Wang, Shu-Zhen.

Subjects/Keywords: Adenoviridae  – genetics<; br>; Adenoviridae Infections  – metabolism<; br>; Adenoviruses, Human  – genetics<; br>; Blood-Brain Barrier  – virology<; br>; Capsid Proteins  – chemistry<; br>; Gene Products, tat<; br>; Gene Therapy  – methods<; br>; Genetic Engineering<; br>; Neoplasms<; br>; Transduction, Genetic  – methods

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Tang, Y. (2009). Modification of adenovirus capsid proteins for gene therapy applications. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,675

Chicago Manual of Style (16th Edition):

Tang, Yizhe. “Modification of adenovirus capsid proteins for gene therapy applications.” 2009. Doctoral Dissertation, University of Alabama – Birmingham. Accessed September 15, 2019. http://contentdm.mhsl.uab.edu/u?/etd,675.

MLA Handbook (7th Edition):

Tang, Yizhe. “Modification of adenovirus capsid proteins for gene therapy applications.” 2009. Web. 15 Sep 2019.

Vancouver:

Tang Y. Modification of adenovirus capsid proteins for gene therapy applications. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2009. [cited 2019 Sep 15]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,675.

Council of Science Editors:

Tang Y. Modification of adenovirus capsid proteins for gene therapy applications. [Doctoral Dissertation]. University of Alabama – Birmingham; 2009. Available from: http://contentdm.mhsl.uab.edu/u?/etd,675

.