+publisher:"University of Houston" +contributor:("Gunaratne, Preethi H.")

University of Houston

1. Jonsson, Philip 1985-. Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors.

Degree: PhD, Biology, 2014, University of Houston

URL: http://hdl.handle.net/10657/1949

► The estrogen receptors are fundamental factors in human biology. As transcriptional factors regulating gene programs controlling many processes in the body, they are key in… (more)

▼ The estrogen receptors are fundamental factors in human biology. As transcriptional factors regulating gene programs controlling many processes in the body, they are key in both development and disease. Also, as nuclear receptors they can be activated or blocked by specific ligands, making them excellent targets for therapeutics. This dissertation focuses on the study of the estrogen receptors, both the alpha and beta isoforms (ERα and ERβ, respectively), and how they regulate gene transcription in human breast cancer. The proliferative role of ERα in breast cancer remains poorly understood. Here we show that the ion channel KCNK5 is a direct transcriptional target of ERα in breast cancer cell lines MCF7 and T47D. Also, we show that this is reflected by changes in the ion channel’s protein. Furthermore, silencing of the ion channels expression reduces cellular proliferation, as well as the estrogen-induction of proliferation. This uncovers ion channels as potential factors in the proliferation of breast cancer, as well as potential targets in novel treatment approaches. ERα’s role as a transcription factor has predominantly been studied in regards to its regulation of protein-coding genes. Herein, we show that ERα also regulates non-coding RNAs, such as long non-coding RNAs and pseudogenes. We also potentially uncover novel protein-coding targets, by the use of novel RNA- sequencing technology, and the use of microarrays. The other estrogen receptor, ERβ, is less characterized, but it is considered to be anti-proliferative in breast cancer and its activation suggested as a potential future therapy. However, discordant results of expression in breast tumors, correlation to prognosis, and tumor-suppressive function in cell lines have made this a debated field. We explore its role in breast cancer cells further and show that, in certain contexts, ERβ is not able to suppress breast cancer cell proliferation, nor, as often suggested, counteract ERα-mediated signaling. This warrants further studies into whether its activation in breast cancer is a desirable treatment. Advisors/Committee Members: Williams, Cecilia M. (advisor), Gunaratne, Preethi H. (committee member), Webb, Paul (committee member), Willson, Richard C. (committee member).

Subjects/Keywords: Estrogen receptors; Breast cancer

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APA (6^th Edition):

Jonsson, P. 1. (2014). Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1949

Chicago Manual of Style (16^th Edition):

Jonsson, Philip 1985-. “Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors.” 2014. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1949.

MLA Handbook (7^th Edition):

Jonsson, Philip 1985-. “Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors.” 2014. Web. 19 Jan 2021.

Vancouver:

Jonsson P1. Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1949.

Council of Science Editors:

Jonsson P1. Transcriptional Control of Oncogenic Processes in Breast Cancer Cells by the Estrogen Receptors. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/1949

University of Houston

2. Rajapaksa, R. P. Gayani Kumudu 1981-. Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer.

Degree: PhD, Biology, 2014, University of Houston

URL: http://hdl.handle.net/10657/1919

► Estrogen receptors play a key role in breast cancer, and understanding the mechanisms of action is important in clinical management of the disease. Here we… (more)

▼ Estrogen receptors play a key role in breast cancer, and understanding the mechanisms of action is important in clinical management of the disease. Here we attempted to comprehend the role of the second estrogen receptor (ERβ) in two fundamental cellular mechanisms vital in the development and progression of breast cancer, unfolded protein response (UPR) and epithelial-to-mesenchymal transition (EMT). UPR confers therapeutic resistance and cellular survival in breast cancer in response to endoplasmic reticulum (EnR) stress that is induced by poorly vascularized tumor microenvironment. ERα regulates UPR-driven cell survival; however the role of ERβ is unknown. Here wild-type ERβ (ERβ1) decreased the survival of triple-negative and ERα-positive breast cancer cells in response to pharmacological stress inducers thapsigargin and bortezomib. ERβ1 enhanced cellular apoptosis by down regulating the UPR transducer inositol-requiring enzyme 1 (IRE1) and the splicing of X box-binding protein-1 (XBP-1). Further, expression of ERβ1 in EnR-stressed tamoxifen-resistant cells decreased survival by down regulating the IRE1/XBP-1s pathway. Interestingly, up regulation of ERβ1 increased the sensitivity of tamoxifen-resistant cells to tamoxifen, indicating the role of ERβ1 in regulating resistance of breast cancer to a variety of stressors including anti-estrogens through regulating the UPR. In addition, ERβ1 suppressed the activation of (PKR)-like endoplasmic reticulum kinase (PERK) pathway of UPR in breast cancer cells. Given the association of the PERK pathway with the inhibition of protein synthesis and the activation of pro-survival autophagy, ERβ1 may affect the survival of breast cancer cells by regulating the translational machinery and autophagy. In addition to the down regulation of UPR, ERβ1 was found to imbed EMT and decrease the invasiveness of breast cancer cells. ERβ1 inhibited EMT by up-regulating members of the microRNA-200 family and repressing transcriptional repressors (ZEB1, SIP1) leading to increased expression of epithelial marker E-cadherin. Furthermore, clinical breast cancer specimens showed a positive correlation between ERβ1 and E-cadherin, further supporting that ERβ1 regulates EMT and invasion in breast cancer. The repression of UPR and EMT by ERβ1 strongly supports its tumor suppressive role in breast cancer and suggests its potential utility as a prognostic marker and therapeutic target for the clinical management of the disease. Advisors/Committee Members: Gustafsson, Jan-Åke (advisor), Thomas, Christoforos (committee member), Gunaratne, Preethi H. (committee member), Williams, Cecilia M. (committee member), Webb, Paul (committee member).

Subjects/Keywords: Breast cancer; ERÎ²; Unfolded protein response; Epithelial-to-mesenchymal transition; Tumor repressor

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APA (6^th Edition):

Rajapaksa, R. P. G. K. 1. (2014). Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1919

Chicago Manual of Style (16^th Edition):

Rajapaksa, R P Gayani Kumudu 1981-. “Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer.” 2014. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1919.

MLA Handbook (7^th Edition):

Rajapaksa, R P Gayani Kumudu 1981-. “Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer.” 2014. Web. 19 Jan 2021.

Vancouver:

Rajapaksa RPGK1. Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1919.

Council of Science Editors:

Rajapaksa RPGK1. Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/1919

University of Houston

3. Wang, Jun 1988-. The Mechanisms of Tumor-suppressive miRNAs in Mammary Stem Cell Development and Triple-negative Breast Cancer.

Degree: PhD, Biology, 2015, University of Houston

URL: http://hdl.handle.net/10657/4876

► In this thesis, we investigated the mechanisms of two tumor-suppressive miRNAs in triple-negative breast cancer (TNBC). This undifferentiated subtype of breast cancer shows similarity of… (more)

▼ In this thesis, we investigated the mechanisms of two tumor-suppressive miRNAs in triple-negative breast cancer (TNBC). This undifferentiated subtype of breast cancer shows similarity of gene expression profiles as mammary epithelial progenitor cells HC11. Therefore, we first systematically explored the tumor suppressive miR-206 function in HC11 cell proliferation and differentiation. The levels of miR-206 are regulated during HC11 development. We demonstrated that miR-206 can block cell proliferation by inducing a G1-S cell cycle arrest. To elucidate how miR-206 modulates the HC11 development, we performed a microarray assay and found 106 genes affected by miR-206 could contribute to the cell cycle regulation. Furthermore, we found that miR-206 can also repress the epithelial-to-mesenchymal transition and promote the adipogenesis and cell differentiation through the Melk signaling pathways. The understanding of miR-206 function in mammary gland development leads us to study its tumor suppressive role in also undifferentiated TNBC. In TNBC, miR-206 is lost and one of its predicted target, Coronin actin-binding protein 1C (CORO1C) is up-regulated. CORO1C was found to be associated with TNBC patient survival and an anti-correlation between miR-206 and CORO1C was illustrated in both clinical samples and breast cancer cell lines. Furthermore, we shown the overexpression of miR-206 can suppress the level of CORO1C in TNBC cells and confirmed that the 3’UTR of CORO1C is directly targeted by miR-206. The miR-206-CORO1C pathway was then found to block cell proliferation, migration and also affect the actin filaments dynamics in TNBC cells. The dysregulation of actin cytoskeleton could result in the progression of tumor metastasis. Finally, we also demonstrate the anti-migratory effect of miR-200a in TNBC cells. miR-200a can directly silence the oncogene EPHA2 and thereby inhibiting the tumor metastatic potential. Our findings add important knowledge about miRNAs effect on mammary gland development and new approaches against TNBC. It also highlights the possibility to utilize tumor suppressive miRNA-206 and miRNA-200a as breast cancer biomarkers and miRNAs delivery therapy. Advisors/Committee Members: Williams, Cecilia M. (advisor), Frigo, Daniel E. (committee member), Gunaratne, Preethi H. (committee member), Landis, Melissa D. (committee member).

Subjects/Keywords: MicroRNAs (miRNA); Breast cancer

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APA (6^th Edition):

Wang, J. 1. (2015). The Mechanisms of Tumor-suppressive miRNAs in Mammary Stem Cell Development and Triple-negative Breast Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4876

Chicago Manual of Style (16^th Edition):

Wang, Jun 1988-. “The Mechanisms of Tumor-suppressive miRNAs in Mammary Stem Cell Development and Triple-negative Breast Cancer.” 2015. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/4876.

MLA Handbook (7^th Edition):

Wang, Jun 1988-. “The Mechanisms of Tumor-suppressive miRNAs in Mammary Stem Cell Development and Triple-negative Breast Cancer.” 2015. Web. 19 Jan 2021.

Vancouver:

Wang J1. The Mechanisms of Tumor-suppressive miRNAs in Mammary Stem Cell Development and Triple-negative Breast Cancer. [Internet] [Doctoral dissertation]. University of Houston; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/4876.

Council of Science Editors:

Wang J1. The Mechanisms of Tumor-suppressive miRNAs in Mammary Stem Cell Development and Triple-negative Breast Cancer. [Doctoral Dissertation]. University of Houston; 2015. Available from: http://hdl.handle.net/10657/4876

University of Houston

4. Anderson, Marc 1981-. An Account of Chemical and Mechanical Regulation of TRPC6 Channels in Podocytes.

Degree: PhD, Biology, 2013, University of Houston

URL: http://hdl.handle.net/10657/921

► Podocytes play a dynamic role in regulating glomerular filtration. The focus here is on the regulatory mechanisms of podocyte expressed transient receptor potential 6 (TRPC6)… (more)

▼ Podocytes play a dynamic role in regulating glomerular filtration. The focus here is on the regulatory mechanisms of podocyte expressed transient receptor potential 6 (TRPC6) channels, an ion channel implicated in certain forms of proteinuric kidney disease. TRPC6 channels are polymodal and can be activated by either chemical or mechanical stimuli. Chemical stimulation is mediated by surface-expressed receptors, and the roles of angiotensin II type 1 receptors (AT1R), insulin receptors, and N-methyl-D-aspartate receptors (NMDAR) on TRPC6 activity are studied here. In acutely isolated rat glomeruli, angiotensin causes an upregulation of TRPC6 activity, and this is mediated by the Gαq /PLC pathway. This angiotensin-evoked upregulation is partially dependent on the formation of reactive oxygen species (ROS). In mouse podocyte cell lines, insulin causes upregulation of TRPC6 through increasing ROS formation via NADPH oxidase 4 (NOX4). Similarly, NMDAR activation upregulates TRPC6, albeit through NOX2. The previously uncharacterized podocyte NMDAR has unusual properties with strong physiological implications. Specifically, podocyte NMDA receptors are essentially unresponsive to L-glutamate and L-aspartate and do not show glycine-mediated potentiation. These receptors respond to the agonists L-homocysteate and D-aspartate with large ionic currents that are potentiated by D-serine. Given their resistance to L-glutamate-induced activation, podocyte NMDA receptors likely do not act in a localized glomerular signaling system. However, their response to ligands that circulate in both the normal and pathological state suggests a role for podocyte NMDA receptors in normal glomerular function. Receptor-driven upregulation of TRPC6 comprises a class of potential targets for prevention and treatment of multiple acquired kidney diseases. Independent of receptor-mediated response, TRPC6 channels are mechanosentive and can be activated by membrane deformation in both podocyte cell lines and isolated glomeruli. This mechanosensitivity is repressed by podocin, a cholesterol-binding, membrane-associated partner of the TRPC6 channel. In addition, podocin mediates diacylglycerol activation of TRPC6, suggesting that podocin determines the favored mode of TRPC6 activation in podocytes. It is possible that disruption of the podocin-TRPC6 complex at the slit diaphragm contributes to Ca2+ overload and eventual foot process effacement. Drugs that selectively target and suppress TRPC6 mechanosensitivity could potentially serve as treatments for glomerular diseases. Advisors/Committee Members: Dryer, Stuart E. (advisor), Gunaratne, Preethi H. (committee member), Sheikh-Hamad, David (committee member), Ziburkus, Jokubas (committee member).

Subjects/Keywords: Podocytes; TRPC6 channels; N-methyl-D-aspartate (NMDA); Receptors; Biology

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APA (6^th Edition):

Anderson, M. 1. (2013). An Account of Chemical and Mechanical Regulation of TRPC6 Channels in Podocytes. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/921

Chicago Manual of Style (16^th Edition):

Anderson, Marc 1981-. “An Account of Chemical and Mechanical Regulation of TRPC6 Channels in Podocytes.” 2013. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/921.

MLA Handbook (7^th Edition):

Anderson, Marc 1981-. “An Account of Chemical and Mechanical Regulation of TRPC6 Channels in Podocytes.” 2013. Web. 19 Jan 2021.

Vancouver:

Anderson M1. An Account of Chemical and Mechanical Regulation of TRPC6 Channels in Podocytes. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/921.

Council of Science Editors:

Anderson M1. An Account of Chemical and Mechanical Regulation of TRPC6 Channels in Podocytes. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/921

University of Houston

5. Folly-Kossi, Helena 1984-. Nuclear Receptors in Breast Cancer.

Degree: PhD, Cell and Molecular Biology, 2017, University of Houston

URL: http://hdl.handle.net/10657/4586

► Breast cancer (BC) is classified into four major molecular subtypes. The most predominant subtypes, luminal A and B are hormone receptor-positive BC (ERα +/PR+) which… (more)

Subjects/Keywords: Nuclear receptors; Breast cancer; Survival analysis; Endocrine therapy; Tamoxifen resistance; Glucocorticoid receptors; Estrogen receptors; Clinical data

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APA (6^th Edition):

Folly-Kossi, H. 1. (2017). Nuclear Receptors in Breast Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4586

Chicago Manual of Style (16^th Edition):

Folly-Kossi, Helena 1984-. “Nuclear Receptors in Breast Cancer.” 2017. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/4586.

MLA Handbook (7^th Edition):

Folly-Kossi, Helena 1984-. “Nuclear Receptors in Breast Cancer.” 2017. Web. 19 Jan 2021.

Vancouver:

Folly-Kossi H1. Nuclear Receptors in Breast Cancer. [Internet] [Doctoral dissertation]. University of Houston; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/4586.

Council of Science Editors:

Folly-Kossi H1. Nuclear Receptors in Breast Cancer. [Doctoral Dissertation]. University of Houston; 2017. Available from: http://hdl.handle.net/10657/4586

University of Houston

6. Lama, Chamala 1979-. Identification and Characterization of Sex-Specific Transcripts in the Blood-Brain Barrier of Drosophila melanogaster.

Degree: PhD, Biology, 2013, University of Houston

URL: http://hdl.handle.net/10657/1236

► In Drosophila, a male displays a series of complex stereotypic acts in courting a female. This behavior is mainly controlled by male specific transcription factors… (more)

▼ In Drosophila, a male displays a series of complex stereotypic acts in courting a female. This behavior is mainly controlled by male specific transcription factors that define male neuronal circuits inside the brain. In our lab, we have shown that male factors which are secreted outside of the CNS are also required for normal mating behavior. How these endocrine factors interact with the CNS is unknown. We have evidence that the Blood-Brain Barrier (bbb) plays an important role in this communication. Specific feminization of the bbb in otherwise normal males severely reduces their courtship. This suggests that male specific factors in the bbb play an important role in mating behavior. To identify these factors, I have used several genomic screens on dissected brains and isolated bbb cells. Studies that include mRNA sequencing and microarray hybridizations have identified several male-specific candidate genes with possible novel roles in courtship. I examined and found an adult role for one of the male preferentially expressed bbb-specific candidate genes, Hr46 in the regulation of male courtship behavior in the bbb. In addition, I have identified bbb-expressed microRNAs and their possible targets. I explored a role for miR-184, the most abundant miRNA in the bbb of Drosophila in male courtship. Alterations of the miR-184 levels in the adult bbb resulted in significant reduction in courtship suggesting its importance for normal male courtship in the bbb. Conditional RNAi knockdown of sinu, a miR-184 target in the adult bbb showed significant reduction in courtship indicating a physiological requirement in the bbb. Dye injection analysis shows that the the bbb permeability of miR-184 and sinu mutants is intact. quiver, another putative miR-184 target and a gene down-regulated in the mRNA sequencing experiment, was also found to affect male courtship behavior. Taken together, these data are the first to identify sex-specific transcripts in the bbb and bbb-specific miRNAs; and to reveal a novel role for miR-184 in the bbb for male courtship behavior of Drosophila melanogaster. Advisors/Committee Members: Dauwalder, Brigitte (advisor), Roman, Gregg (committee member), Gunaratne, Preethi H. (committee member), Beckingham, Kathleen M. (committee member).

Subjects/Keywords: Blood-Brain Barrier; Drosophila; Courtship; Sex-specific transcripts; MiRNAs; Sinu; Hr46; Qvr; MiR-184

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APA (6^th Edition):

Lama, C. 1. (2013). Identification and Characterization of Sex-Specific Transcripts in the Blood-Brain Barrier of Drosophila melanogaster. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1236

Chicago Manual of Style (16^th Edition):

Lama, Chamala 1979-. “Identification and Characterization of Sex-Specific Transcripts in the Blood-Brain Barrier of Drosophila melanogaster.” 2013. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1236.

MLA Handbook (7^th Edition):

Lama, Chamala 1979-. “Identification and Characterization of Sex-Specific Transcripts in the Blood-Brain Barrier of Drosophila melanogaster.” 2013. Web. 19 Jan 2021.

Vancouver:

Lama C1. Identification and Characterization of Sex-Specific Transcripts in the Blood-Brain Barrier of Drosophila melanogaster. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1236.

Council of Science Editors:

Lama C1. Identification and Characterization of Sex-Specific Transcripts in the Blood-Brain Barrier of Drosophila melanogaster. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/1236

University of Houston

7. Petkova, Tihomira D. 1974-. TOWARDS RETINA REGENERATION: THE EPIGENETIC BASIS OF NEURONAL AND AXON GUIDANCE GENE REGULATION.

Degree: PhD, Physiological Optics and Vision Science, 2012, University of Houston

URL: http://hdl.handle.net/10657/1560

► Degenerative disorders, such as glaucoma are among the leading causes of irreversible blindness worldwide. With these disorders affecting a larger fraction of the population yearly,… (more)

▼ Degenerative disorders, such as glaucoma are among the leading causes of irreversible blindness worldwide. With these disorders affecting a larger fraction of the population yearly, the need for regenerative retina and optic nerve therapy is self-evident. Increasing evidence suggests that Müller glia are potential stem cells in the adult mammalian retina but have a limited potential to differentiate into retinal ganglion cell (RGC). Understanding the mechanisms regulating expression of RGC specific and axon-guidance genes during development and in retinal stem cells is key for successful optic nerve regeneration. I proposed that dedifferentation of Müller glia to RGCs is restricted by silencing of RGC specific and axon guidance genes by chromatin remodeling mechanisms such as DNA methylation. The DNA methylation pattern of RGC determining gene Atoh7 and axon guidance genes EphA5 and EphB1 in Müller glia derived spheres were investigated prior to and following demethylation. Bisulfite sequencing (BS) showed that in ImM10 spheres, the promoters of these genes exhibited a high frequency of methylation and quantitative RT-PCR showed that the genes are not transcribed. Demethylation with 5-azadeoxycytidine (AzadC) resulted in a significant decrease of methylation at the gene promoters and expression of their mRNA. Priming ImM10 derived spheres in the presence of EGF and differentiating the cells in the presence of BDNF resulted in increased expression of pluripotent, RGC developmental and retinal pigment epithelium specific genes. These gene expression changes were associated with cell morphology changes consistent with that of cells of epithelial identity. Furthermore, I showed that DNA methylation is required for this BDNF driven morphological change. Additional evidence for the role of DNA methylation in the regulation of the retinal temporal-nasal gradient of EphA5 was found in BS analysis of the P0 mouse retina. In the nasal retina a modest, but statistically significant increase in methylation was correlated with lower levels of receptor mRNA expression compared to the temporal retina. The inverse relationship between EphA5 promoter methylation and mRNA expression is consistent with a role for DNA methylation in modulating the spatial patterns of EphA5 gene expression in the retina and in silencing EphA5 expression in ImM10 cells. In addition to regulation by DNA methylation, the EphA5 proximal promoter contains four predicted TCF/LEF binding sites, suggesting a potential role for WNT signaling in the transcriptional regulation of EphA5. In luciferase assays, activation of the canonical WNT signaling pathway increased the activity of mouse EphA5 promoter constructs in HEK293. WNT signaling activation increased expression of the endogenous EphA5 gene in retinal progenitor cells in vitro but failed to upregulate expression of the gene in retinal explants ex vivo, possibly due to the lack of one or several WNT signaling components in the P7 retina. Taken together these data provide the first evidence for a direct role… Advisors/Committee Members: Otteson, Deborah C. (advisor), McDermott, Alison M. (committee member), Wang, Steven (committee member), Gunaratne, Preethi H. (committee member), Fox, Donald A. (committee member).

Subjects/Keywords: Retinal gene regulation; DNA methylation; Math5/Atoh7; EphA5; Wnt signaling; Müller glia; Stem cells; Retinal regeneration

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APA (6^th Edition):

Petkova, T. D. 1. (2012). TOWARDS RETINA REGENERATION: THE EPIGENETIC BASIS OF NEURONAL AND AXON GUIDANCE GENE REGULATION. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1560

Chicago Manual of Style (16^th Edition):

Petkova, Tihomira D 1974-. “TOWARDS RETINA REGENERATION: THE EPIGENETIC BASIS OF NEURONAL AND AXON GUIDANCE GENE REGULATION.” 2012. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1560.

MLA Handbook (7^th Edition):

Petkova, Tihomira D 1974-. “TOWARDS RETINA REGENERATION: THE EPIGENETIC BASIS OF NEURONAL AND AXON GUIDANCE GENE REGULATION.” 2012. Web. 19 Jan 2021.

Vancouver:

Petkova TD1. TOWARDS RETINA REGENERATION: THE EPIGENETIC BASIS OF NEURONAL AND AXON GUIDANCE GENE REGULATION. [Internet] [Doctoral dissertation]. University of Houston; 2012. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1560.

Council of Science Editors:

Petkova TD1. TOWARDS RETINA REGENERATION: THE EPIGENETIC BASIS OF NEURONAL AND AXON GUIDANCE GENE REGULATION. [Doctoral Dissertation]. University of Houston; 2012. Available from: http://hdl.handle.net/10657/1560

University of Houston

8. Shen, Xiaopeng 1990-. miR-322/503 Cluster Drives Cardiac Differentiation by Inhibiting CUG-binding Protein 1.

Degree: PhD, Biochemistry, 2014, University of Houston

URL: http://hdl.handle.net/10657/5669

► Understanding the mechanisms of early cardiac fate determination may lead to better approaches in promoting heart regeneration after injury. MicroRNAs (miRNAs) involved in the process… (more)

▼ Understanding the mechanisms of early cardiac fate determination may lead to better approaches in promoting heart regeneration after injury. MicroRNAs (miRNAs) involved in the process are particularly interesting due to their small profile and relatively shorter path to clinic. With Mesp1 as the marker, we used a Mesp1-Cre/Rosa-EYFP reporter system to track the earliest cardiac progenitors, and identified the miRNAs enriched in these cells. Among them, the miR-322/503 cluster is found to be a powerful regulator of the cardiac program: (1) in a screening of more than 20 cardiac progenitor cell (CPC) enriched miRNAs, miR-322/503 was the most powerful in driving calcium flux activity in mouse embryonic stem cells (mESCs) differentiation; (2) induced ectopic expression of miR-322/503 to mimic the natural course in mESCs led to α-actinin expression and significant increases of cardiac transcription factors (Tbx5, Mef2C, Nkx2-5 and α-MHC); and (3) inhibitors of miR-322 and miR-503 significantly reduced expression of α-actinin and the above cardiac TFs. Remarkably, miR-322/503 regulates the cardiac program by inhibiting an RNA-alternative splicing/decay factor, CUG-binding protein 1 (Celf1), which is also known for a role in myotonic dystrophy pathogenesis. The evidences include: (i) miR-322 and miR-503 had a shared target site at the 3’UTR of Celf1; (ii) expression patterns of miR-322/503 and Celf1 were mutually exclusive, with the highest Celf1 expression in the brain; (iii) miR-322/503 repressed Celf1 protein expression in a dose-dependent manner; (iv) Celf1-shRNA induced up-regulation of cardiac transcription factors and α-actinin, mimicking the function of miR-322/503; and (v) the ectopic expression of Celf1 repressed expression of cardiac transcription factors, while promoted expressions of early neural markers, including Sox1, Notch3, Nestin and Pax6. In summary, we have identified a miR-322/503-Celf1 pathway that promotes cardiac differentiation by preventing activation of other lineages. This new regulatory mechanism may be used to direct cardiac regeneration after heart injury, and treat myotonic dystrophy where Celf1 up-regulation is responsible for skeletal muscle wasting and other symptoms. Advisors/Committee Members: Schwartz, Robert J. (advisor), Liu, Yu (committee member), Gunaratne, Preethi H. (committee member), Widger, William R. (committee member), Cooney, Austin J. (committee member).

Subjects/Keywords: MicroRNAs (miRNA); Celf1; Cardiac differentiation; Neural differentiation

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APA (6^th Edition):

Shen, X. 1. (2014). miR-322/503 Cluster Drives Cardiac Differentiation by Inhibiting CUG-binding Protein 1. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/5669

Chicago Manual of Style (16^th Edition):

Shen, Xiaopeng 1990-. “miR-322/503 Cluster Drives Cardiac Differentiation by Inhibiting CUG-binding Protein 1.” 2014. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/5669.

MLA Handbook (7^th Edition):

Shen, Xiaopeng 1990-. “miR-322/503 Cluster Drives Cardiac Differentiation by Inhibiting CUG-binding Protein 1.” 2014. Web. 19 Jan 2021.

Vancouver:

Shen X1. miR-322/503 Cluster Drives Cardiac Differentiation by Inhibiting CUG-binding Protein 1. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/5669.

Council of Science Editors:

Shen X1. miR-322/503 Cluster Drives Cardiac Differentiation by Inhibiting CUG-binding Protein 1. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/5669

University of Houston

9. Kim, Jong Hwan 1983-. MESP1's Epigenetic and Transcriptional Role during Mesendoderm Formation.

Degree: PhD, Biochemistry, 2016, University of Houston

URL: http://hdl.handle.net/10657/5393

► MESP1 is a basic helix loop helix transcription factor that is essential for the survival and development of mouse embryogenesis. It is the earliest marker… (more)

▼ MESP1 is a basic helix loop helix transcription factor that is essential for the survival and development of mouse embryogenesis. It is the earliest marker for identifying the nascent mesoderm that is fated to becoming the myocardium, head mesenchyme, and somites. In spite of the advancements in our knowledge of MESP1, it is, however, still very unclear how it directs the activation of the cardiac program. It is important to understand MESP1’s epigenetic, and transcriptional function during development to increase efficiency in somatic and stem cells cardiac reprogramming. ChIP-seq analysis of endogenous targets of endogenously expressed MESP1 affected neuro-ectoderm specific GO terms over mesendoderm specific terms predominantly. To analyze MESP1’s effect on target genes, a comparison to RNA-seq data of FACsorted YFP cells from ESC and day 5, 6, 7, and 8 was done. YFP protein marks endogenously activated MESP1 expressing cells during EB differentiation which resulted in identifying MESP1’s effect on target genes. Analysis of the transcriptome of YFP positive cells provided evidence that MESP1 is indirectly activating the core cardiac program and directly repressing the non-mesoderm program such as neuro-ectoderm. MESP1 directly represses the neuro-ectoderm developmental program by targeting, Sox2, Neurod1, Neurog1, Neurog2, and Neurog3 by reducing the expression levels within the first 12 hours of Dox induction. Meta-data analysis of MESP1-binding regions with H3K27acetylation and tri-methylation show strong overlap with H3K27acetyaltion favoring Mesendoderm specific genes and H3K27me3 favoring neuro-ectoderm target genes. H3K27acetylation suggest a potential mechanism in indirectly activating the core cardiac program. ChIP-qPCR of Neurog3 adjacent enhancers show that MESP1 guides the deposit of H3K27me3 through the PRC2 complex in an ebox variant-dependent manner. Analysis of MESP1 binding sites for potential bias in the ebox variant show that CACCTG variant is favored in regards to both repressive function and H3K27me3 marking,. Advisors/Committee Members: Schwartz, Robert J. (committee member), Sater, Amy K. (committee member), Gunaratne, Preethi H. (committee member), McConnell, Bradley K. (committee member).

Subjects/Keywords: Helix loop; Mesendoderm

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APA (6^th Edition):

Kim, J. H. 1. (2016). MESP1's Epigenetic and Transcriptional Role during Mesendoderm Formation. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/5393

Chicago Manual of Style (16^th Edition):

Kim, Jong Hwan 1983-. “MESP1's Epigenetic and Transcriptional Role during Mesendoderm Formation.” 2016. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/5393.

MLA Handbook (7^th Edition):

Kim, Jong Hwan 1983-. “MESP1's Epigenetic and Transcriptional Role during Mesendoderm Formation.” 2016. Web. 19 Jan 2021.

Vancouver:

Kim JH1. MESP1's Epigenetic and Transcriptional Role during Mesendoderm Formation. [Internet] [Doctoral dissertation]. University of Houston; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/5393.

Council of Science Editors:

Kim JH1. MESP1's Epigenetic and Transcriptional Role during Mesendoderm Formation. [Doctoral Dissertation]. University of Houston; 2016. Available from: http://hdl.handle.net/10657/5393

University of Houston

10. Tennakoon, Jayantha 1969-. Impact of Dicer on the Embryonic Stem Cell Epigenome and Androgen Mediated AMPK-PGC-1α Signaling in Prostate Cancer.

Degree: PhD, Biology, 2013, University of Houston

URL: http://hdl.handle.net/10657/1027

► What mechanisms govern a cellular phenotype is a fascinating question for which answers are yet being sought. The work presented in this dissertation is an… (more)

▼ What mechanisms govern a cellular phenotype is a fascinating question for which answers are yet being sought. The work presented in this dissertation is an effort to address two fundamental questions, which relate to cellular transition of pluripotent stem cells to a differentiated state and the ability of prostate cancer to have increased proliferative potential. Dicer is an evolutionary conserved RNAse III type endoribonuclease enzyme, which plays a pivotal role in the biogenesis of microRNAs and silencing RNAs (siRNAs). Within the first chapter herein using in vitro cultures of embryonic stem cells, I show that loss of Dicer leads to changes in the ES cell epigenome resulting in a shift in transcriptionally favorable versus transcriptionally unfavorable histone modifications and thereby affect gene expression critical for precise cellular differentiation. In the second chapter, employing a combination of molecular biological and modern metabolomics approaches I show that androgen signaling deregulated in almost all forms of metastatic prostate cancers can lead to increased mitochondrial biogenesis and ATP production affording a distinct proliferative advantage. The underlying mechanism is linked to androgen mediated AMPK- PGC-1α signaling which results increased oxidative capacity in addition to elevated glycolytic capacity quite well established in numerous types of cancers. The pathway uncovered provides an interesting option for targeted therapeutics of prostatic cancers that are particularly resistant to androgen ablation therapies. Finally in the third chapter I show the significance of Dicer in maintaining expression levels of developmentally critical mammalian imprinted genes. The combined results of this thesis provide mechanistic insights into developmentally critical cellular pathways in embryonic stem cells and cancer having high potential to be manipulated in stem cell and molecular intervention based therapeutics. Advisors/Committee Members: Gunaratne, Preethi H. (advisor), Frigo, Daniel E. (advisor), Wells, Dan E. (committee member), Gao, Xiaolian (committee member), Zwaka, Thomas P. (committee member).

Subjects/Keywords: Dicer; Mouse embryonic stem cells; Epigenome; Androgen signaling; AMPK; PGC1a; Prostate cancer; Biology

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APA (6^th Edition):

Tennakoon, J. 1. (2013). Impact of Dicer on the Embryonic Stem Cell Epigenome and Androgen Mediated AMPK-PGC-1α Signaling in Prostate Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1027

Chicago Manual of Style (16^th Edition):

Tennakoon, Jayantha 1969-. “Impact of Dicer on the Embryonic Stem Cell Epigenome and Androgen Mediated AMPK-PGC-1α Signaling in Prostate Cancer.” 2013. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1027.

MLA Handbook (7^th Edition):

Tennakoon, Jayantha 1969-. “Impact of Dicer on the Embryonic Stem Cell Epigenome and Androgen Mediated AMPK-PGC-1α Signaling in Prostate Cancer.” 2013. Web. 19 Jan 2021.

Vancouver:

Tennakoon J1. Impact of Dicer on the Embryonic Stem Cell Epigenome and Androgen Mediated AMPK-PGC-1α Signaling in Prostate Cancer. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1027.

Council of Science Editors:

Tennakoon J1. Impact of Dicer on the Embryonic Stem Cell Epigenome and Androgen Mediated AMPK-PGC-1α Signaling in Prostate Cancer. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/1027

University of Houston

11. Valenzuela, Nicolas 1988-. A Role for the Histone Chaperone Hira in Muscle Hypertrophy, Cellular Stress Responses, and Developmental Gene Expression.

Degree: PhD, Biochemistry, 2016, University of Houston

URL: http://hdl.handle.net/10657/1938

► Chromatin modifications play a pivotal role in regulating gene expression. The deposition of histone variants by histone chaperones into the nucleosome plays a large role… (more)

▼ Chromatin modifications play a pivotal role in regulating gene expression. The deposition of histone variants by histone chaperones into the nucleosome plays a large role in influencing gene expression. Histone incorporation can be separated into two categories: replication-coupled and replication independent. The histone chaperone HIRA deposits the variant histone H3.3 into promoters and gene bodies of active genes in a replication-independent manner. HIRA is also responsible for H3.3 deposition into the “bivalent” promoters of regulatory genes in embryonic stem cells, required for transcription restart after DNA repair, and required for the formation of senescence associated heterochromatin foci. Hira null mutation in mice resulted in embryonic lethality by E11 which largely resulted from gastrulation defects including abnormalities in the heart. Cardio- and skeletal myocytes are post mitotic cells and thus the majority of chromatin remodeling should be performed in a replication-independent manner. Additionally, skeletal myocytes must alter gene expression in response to physiological signals. Because of this we hypothesized that HIRA is likely to play a large role in epigenetically regulating gene expression in myocytes. The objective of this study was to determine the consequence of HIRA ablation in cardio- and skeletal myocytes in vivo. We accomplished this by using Myf6-cre to delete Hira from myofibers, and αMHC-cre for cardiomyocytes, both of which remove Hira after these cells have terminally differentiated. Both HIRA CKO cardio- and skeletal myocytes exhibited hypertrophy, sarcolemmal damage, upregulation of fetal/developmental genes, and downregulation of genes associated with responses to cellular stresses and DNA damage. This resulted in focal replacement fibrosis and altered cardiac function in the heart, while mice lacking HIRA from myofibers exhibited decreased body weight, increased lean mass, increased grip strength and endurance, increased abundance of type I fibers, and centralized nuclei. Comparative analysis of gene expression sets suggest that loss of HIRA impaired transcriptional response to cellular stresses. The major discrepancies in these phenotypes can largely be attributed to each tissues mode of regeneration in which cardiomyocytes lack regenerative potential while skeletal myocytes can rapidly regenerate damage. Thus HIRA is an important factor in epigenetically maintaining myocyte homeostasis. Advisors/Committee Members: Schwartz, Robert J. (advisor), Stewart, M. David (advisor), Gunaratne, Preethi H. (committee member), McConnell, Bradley K. (committee member), Wells, Dan E. (committee member).

Subjects/Keywords: Cardiomyocyte; Myocyte; H3.3; HIRA; Heart health; Skeletal muscle; Histone; Histone Chaperone

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

APA (6^th Edition):

Valenzuela, N. 1. (2016). A Role for the Histone Chaperone Hira in Muscle Hypertrophy, Cellular Stress Responses, and Developmental Gene Expression. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1938

Chicago Manual of Style (16^th Edition):

Valenzuela, Nicolas 1988-. “A Role for the Histone Chaperone Hira in Muscle Hypertrophy, Cellular Stress Responses, and Developmental Gene Expression.” 2016. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1938.

MLA Handbook (7^th Edition):

Valenzuela, Nicolas 1988-. “A Role for the Histone Chaperone Hira in Muscle Hypertrophy, Cellular Stress Responses, and Developmental Gene Expression.” 2016. Web. 19 Jan 2021.

Vancouver:

Valenzuela N1. A Role for the Histone Chaperone Hira in Muscle Hypertrophy, Cellular Stress Responses, and Developmental Gene Expression. [Internet] [Doctoral dissertation]. University of Houston; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1938.

Council of Science Editors:

Valenzuela N1. A Role for the Histone Chaperone Hira in Muscle Hypertrophy, Cellular Stress Responses, and Developmental Gene Expression. [Doctoral Dissertation]. University of Houston; 2016. Available from: http://hdl.handle.net/10657/1938

University of Houston

12. -8465-3791. Defining Anti-Tumorigenic and Anti-Inflammatory Effects Mediated By Estrogen Receptor Beta In Colon Epithelial Cells.

Degree: PhD, Biology and Biochemistry, 2015, University of Houston

URL: http://hdl.handle.net/10657/2018

► Despite its slow development and our capacity for early detection using endoscopy, colorectal cancer remains the second leading cause of cancer death in the United… (more)

▼ Despite its slow development and our capacity for early detection using endoscopy, colorectal cancer remains the second leading cause of cancer death in the United States. Epidemiological studies indicate a role for estrogen in protecting against colorectal cancer. Estrogen receptor β (ERβ) has been found to be the main ER in the colon. Cell line studies have implicated that ERβ has anti-tumorigenic and anti-proliferative effects on colon cancer cells lines while human epidemiological data suggest that polymorphisms in the ERβ gene are associated with greater cancer risk and lower survival. Overexpression of ERβ changes the miRnome. Here we show that ERβ can alleviate the progression of colon cancer by inhibiting proliferation through decreasing MYC transcription and therefore decreasing levels of miR-17-92 (OncomiR-1). This is reflected in a decrease in cell number, decrease in migration, and increase in apoptosis. Furthermore, addition of miR-17 using miRNA mimics reverses the effects of ERβ. This demonstrates that ERβ influences not only the transcriptome, but also the miRnome and that the miRnome can be potential targets for novel treatment approaches. ERβ upregulates miR-205 and downregulates PROX1. This study uncovers the pathway in which ERβ downregulates the transcription factor PROX1 by upregulating miR-205 directly. MiR-205 then targets PROX1 mRNA for degradation. This results in the cells adopting a more adhesive phenotype and reduces the metastatic potential. This study uncovers the potential for ERβ to be anti-metastatic in addition to being anti-proliferative and anti-inflammatory. ERβ modulates the NFkB inflammatory cascade. One of ERβ’s attributes is that it has anti-inflammatory capabilities. Using a whole genome approach, this study reveals that ERβ can modulate the NFkB inflammatory network. In SW480 cells, ERβ downregulates NFkB transcription factors and induces apoptosis. In HT29 cells, ERβ prevents p65 subunit of NFkB from translocating to the nucleus. Overall, ERβ attenuates the NFkB signaling cascade by attenuating genes related to inflammation while enhancing genes related to apoptosis and cellular defenses. This makes ERβ a useful target for anti-inflammatory drug treatments for patients suffering from chronic inflammatory diseases. Advisors/Committee Members: Williams, Cecilia M. (advisor), Lin, Chin-Yo (committee member), Gunaratne, Preethi H. (committee member), Lee, Mong-Hong (committee member).

Subjects/Keywords: Estrogen receptor beta; Colon cancer epithelial cells

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APA (6^th Edition):

-8465-3791. (2015). Defining Anti-Tumorigenic and Anti-Inflammatory Effects Mediated By Estrogen Receptor Beta In Colon Epithelial Cells. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/2018

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Chicago Manual of Style (16^th Edition):

-8465-3791. “Defining Anti-Tumorigenic and Anti-Inflammatory Effects Mediated By Estrogen Receptor Beta In Colon Epithelial Cells.” 2015. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/2018.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

MLA Handbook (7^th Edition):

-8465-3791. “Defining Anti-Tumorigenic and Anti-Inflammatory Effects Mediated By Estrogen Receptor Beta In Colon Epithelial Cells.” 2015. Web. 19 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-8465-3791. Defining Anti-Tumorigenic and Anti-Inflammatory Effects Mediated By Estrogen Receptor Beta In Colon Epithelial Cells. [Internet] [Doctoral dissertation]. University of Houston; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/2018.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Council of Science Editors:

-8465-3791. Defining Anti-Tumorigenic and Anti-Inflammatory Effects Mediated By Estrogen Receptor Beta In Colon Epithelial Cells. [Doctoral Dissertation]. University of Houston; 2015. Available from: http://hdl.handle.net/10657/2018

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

University of Houston

13. Hernandez Herrera, Anadulce 1982-. A Genome-Wide Search for Tumor Suppressor MicroRNAs in Ovarian Cancer.

Degree: PhD, Biochemistry, 2014, University of Houston

URL: http://hdl.handle.net/10657/4756

► Ovarian cancer is one of the most lethal cancers among women. The Cancer Genome Atlas (TCGA) is a collaborative effort, which seeks to characterize the… (more)

▼ Ovarian cancer is one of the most lethal cancers among women. The Cancer Genome Atlas (TCGA) is a collaborative effort, which seeks to characterize the complete set of molecular changes associated with cancer and provide a public resource that will allow the development of new therapies and better diagnostic tools for cancer. Much of the focus is on protein coding genes and our understanding of the contribution from non-coding RNAs is lagging behind. MicroRNAs are small non-coding RNAs that can bind and repress hundreds of gene targets to regulate gene networks. Therefore, defining and understanding the miRNA-regulated genes offer new insights that can be clinically applied for many of the disease. In order to identify new tumor suppressors for ovarian cancer and downstream targets that drive key aspects of this disease such as drug resistance and metastatic spread, 3 candidates were selected from the microRNA-mRNA bioinformatic analyses from the TCGA. A combination of molecular and functional studies confirmed that miR-29a that can regulate genes from the histone modifier and cell cycle pathways, inhibit proliferation and moderately increase cisplatin response in the p53-WT HEYA8; miR-509-3p which targets genes from the ECM/EMT networks, inhibits cell proliferation in p53-WT HEYA8 and p53-mut OVCAR8 and correlated with improved overall survival when analyzed by in situ hybridization in an independent cohort; miR-130b increases apoptosis by 3-fold in p53-mutant OVCAR8 and p53-wild-type HEYA8 and significantly induces TAp63 and BCL2L11 (BIM). Forced expression of TAp63 decreases cell viability by 60-80% and miR-130b-ABT-737 (BCL2L11-mimetics) combination increases apoptosis by 9-fold suggesting TAp63 and BIM are critical effectors of the tumor-suppressive mechanisms driven by miR-130b, and can be used to develop new therapeutic strategies that will target p53 WT and p53 mutant tumors. Advisors/Committee Members: Gunaratne, Preethi H. (advisor), Flores, Elsa R. (committee member), Wang, Yuhong (committee member), Zhang, Xiaoliu Shaun (committee member), Widger, William R. (committee member).

Subjects/Keywords: MicroRNAs (miRNA); Ovarian cancer; The cancer genome atlas (TCGA)

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APA (6^th Edition):

Hernandez Herrera, A. 1. (2014). A Genome-Wide Search for Tumor Suppressor MicroRNAs in Ovarian Cancer. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/4756

Chicago Manual of Style (16^th Edition):

Hernandez Herrera, Anadulce 1982-. “A Genome-Wide Search for Tumor Suppressor MicroRNAs in Ovarian Cancer.” 2014. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/4756.

MLA Handbook (7^th Edition):

Hernandez Herrera, Anadulce 1982-. “A Genome-Wide Search for Tumor Suppressor MicroRNAs in Ovarian Cancer.” 2014. Web. 19 Jan 2021.

Vancouver:

Hernandez Herrera A1. A Genome-Wide Search for Tumor Suppressor MicroRNAs in Ovarian Cancer. [Internet] [Doctoral dissertation]. University of Houston; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/4756.

Council of Science Editors:

Hernandez Herrera A1. A Genome-Wide Search for Tumor Suppressor MicroRNAs in Ovarian Cancer. [Doctoral Dissertation]. University of Houston; 2014. Available from: http://hdl.handle.net/10657/4756

University of Houston

14. Ghosh, Rajib 1979-. Redefining tumor suppressor microRNAs: functional complexities & nanoparticle mediated delivery.

Degree: PhD, Biology, 2012, University of Houston

URL: http://hdl.handle.net/10657/836

► MicroRNAs (miRNAs) are 22-24 nucleotides non-coding RNAs that can simultaneously influence the levels of multiple target genes and have the potential to strongly silence multiple… (more)

▼ MicroRNAs (miRNAs) are 22-24 nucleotides non-coding RNAs that can simultaneously influence the levels of multiple target genes and have the potential to strongly silence multiple gene networks. MYCN and ALK are well established oncogenes implicated in the pathogenesis and progression of neuroblastoma. We have identified the miRNAs that are directly repressed by the oncogene MYCN; however, overexpression of a MYCN-repressed miRNA resulted in an unexpected oncogenesis. Then using web-based algorithms I have identified miR-1323 as potential tumor suppressor that can control the pathogenesis and/or progression of neuroblastoma by targeting both MYCN and ALK. Over-expression of miR-1323 led to a decrease in MYCN and ALK expression; however, it revealed increased proliferation, colony formation, and tumor growth of xenograft tumors. SiRNA against MYCN-ALK strongly limits proliferation indicating miR-1323 targets an alternative tumor suppressor which by-passes the growth suppressive effects of MYCN-ALK inhibition and drives proliferation. Bio-informatics analysis of putative miR-1323 targets revealed PAG1 as a possible tumor suppressor target of miR-1323. Analyses of PAG1 in clinical cohorts of neuroblastoma revealed that low expression of PAG1 strongly correlates with poor overall survival compared to patients with high PAG1 expression. We therefore propose that miR-1323 mediated repression of PAG1 activates the Src-dependent oncogenic pathways, overriding its effect on MYCN or ALK. These studies further demonstrate the complexity of microRNA functions in normal and cancer cells and mandate careful evaluation of putative ‘tumor suppressive’ microRNAs as therapeutic tools. Lastly, the large number of miRNAs and genes that are typically dysregulated in the majority of diseases makes it impractical to systematically analyze the impact of each gene and miRNA candidate on disease phenotypes. To overcome these challenges, we developed a miR-AuNP delivery system that can overcome the toxicity and low miRNA entrapment capacity of liposomal delivery and release functional miRNAs into living cells quite efficiently. In vitro studies indicated that the AuNP platform was able to release functional miRNAs, those efficiently down regulate target genes and modulate the rate of proliferation. Advisors/Committee Members: Gunaratne, Preethi H. (advisor), Schwartz, Robert J. (committee member), Shohet, Jason M. (committee member), Otteson, Deborah C. (committee member), Williams, Cecilia M. (committee member).

Subjects/Keywords: MicroRNAs (miRNA); Cancer; Neuroblastoma; Neurosciences; Ovarian cancer; Gold nanoparticles; In vitro; Biology

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APA (6^th Edition):

Ghosh, R. 1. (2012). Redefining tumor suppressor microRNAs: functional complexities & nanoparticle mediated delivery. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/836

Chicago Manual of Style (16^th Edition):

Ghosh, Rajib 1979-. “Redefining tumor suppressor microRNAs: functional complexities & nanoparticle mediated delivery.” 2012. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/836.

MLA Handbook (7^th Edition):

Ghosh, Rajib 1979-. “Redefining tumor suppressor microRNAs: functional complexities & nanoparticle mediated delivery.” 2012. Web. 19 Jan 2021.

Vancouver:

Ghosh R1. Redefining tumor suppressor microRNAs: functional complexities & nanoparticle mediated delivery. [Internet] [Doctoral dissertation]. University of Houston; 2012. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/836.

Council of Science Editors:

Ghosh R1. Redefining tumor suppressor microRNAs: functional complexities & nanoparticle mediated delivery. [Doctoral Dissertation]. University of Houston; 2012. Available from: http://hdl.handle.net/10657/836

15. Chaney, Shawnta Y. Retinal development and age related degeneration following gestational lead exposure.

Degree: PhD, Biochemistry, 2013, University of Houston

URL: http://hdl.handle.net/10657/1041

► PURPOSE: Gestational lead exposure (GLE) increased and prolonged retinal progenitor cell proliferation in mice, resulting in a dose-dependent increase in two late-born retinal neurons: rod… (more)

Subjects/Keywords: Retinal development; Toxicology; Lead; Biochemistry

11 more images…

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APA (6^th Edition):

Chaney, S. Y. (2013). Retinal development and age related degeneration following gestational lead exposure. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/1041

Chicago Manual of Style (16^th Edition):

Chaney, Shawnta Y. “Retinal development and age related degeneration following gestational lead exposure.” 2013. Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/1041.

MLA Handbook (7^th Edition):

Chaney, Shawnta Y. “Retinal development and age related degeneration following gestational lead exposure.” 2013. Web. 19 Jan 2021.

Vancouver:

Chaney SY. Retinal development and age related degeneration following gestational lead exposure. [Internet] [Doctoral dissertation]. University of Houston; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/1041.

Council of Science Editors:

Chaney SY. Retinal development and age related degeneration following gestational lead exposure. [Doctoral Dissertation]. University of Houston; 2013. Available from: http://hdl.handle.net/10657/1041

University of Houston

16. Rababa'H, Abeer 1981-. Human Signaling Scaffold Protein (mAKAP) Polymorphisms: Role in Heart Failure.

Degree: Pharmacology, Pharmacology PhD, University of Houston

URL: http://hdl.handle.net/10657/2616

► Protein kinase-A (PKA) substrate phosphorylation is facilitated through its co-localization with its signaling partner by A-kinase anchoring proteins (AKAPs). mAKAP (muscle-selective AKAP) localizes PKA and… (more)

▼ Protein kinase-A (PKA) substrate phosphorylation is facilitated through its co-localization with its signaling partner by A-kinase anchoring proteins (AKAPs). mAKAP (muscle-selective AKAP) localizes PKA and its substrates such as phosphodiesterase-4D3 (PDE4D3), ryanodine receptor and protein phosphatase (PP2A) to the cardiomyocytes sarcoplasmic reticulum and perinuclear space. We have recently identified potentially important human mAKAP coding non-synonymous polymorphisms located within or near key protein binding sites critical to β-adrenergic receptor signaling. Three mutations (P1400S, S2195F and L717V) were cloned and transfected into a mammalian cell line for the purpose of comparing whether those substitutions disrupt mAKAP binding to both the PKA or PDE4D3 binding domain and understanding their role in altered signaling. Our immunopreciptation study of mAKAP-P1400S, a mutation in the mAKAP-PDE4D3 binding site, displayed a significant reduction in binding affinity to PDE4D3 after stimulation, with no significant change in PKA binding and activity. Conversely, mAKAP-S2195F, a mutation located in mAKAP-PP2A binding site and flanking PKA-RII binding domain, showed significant increase in both binding affinity to PKA as well as PKA activity. Although, mAKAP-L717V (a mutation flanking the mAKAP-spectrin repeat domain) exhibited an enhanced binding propensity to PKA, it showed similar pattern of PKA activity as the wild-type mAKAP. All three mutations have similar total phosphodiesterase enzyme activity. Binding results were quantified using surface plasmon resonance (Biacore-2000). We demonstrated specific binding of wild-type mAKAP to PDE4D3. Additionally, human mAKAP mutants S2195F and L717V displayed increased expression for downstream PKA substrates and hypertrophic markers such as CREB and calcineurin. These data suggest that S2195F or L717V-mAKAP may enhance cardiac hypertrophy through persistent binding of mAKAP to PKA. Furthermore, these mutants increased the phosphorylation of ERK5 compared to the wild-type mAKAP suggesting that mAKAP also orchestrates the cross-talk of mitogen activated protein kinase (MAPK) signaling pathway with cAMP/PKA signaling pathways. Generally, PKA-PDE4D3-mAKAP complexes exemplify how protein kinases and phosphodiesterase may contribute in molecular signaling to dynamically normalize localized intracellular signaling. Consequently, comparative analysis of the binding responses of mutations to mAKAP could provide important information about how these mutations modulate signaling. Advisors/Committee Members: McConnell, Bradley K. (advisor), Salim, Samina (committee member), Hussain, Tahir (committee member), Hwa, John (committee member), Gunaratne, Preethi H. (committee member), Tikunova, Svetlana B. (committee member).

Subjects/Keywords: Heart failure; Protein kinase A; MAKAP; Hypertrophy

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APA (6^th Edition):

Rababa'H, A. 1. (n.d.). Human Signaling Scaffold Protein (mAKAP) Polymorphisms: Role in Heart Failure. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/2616

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16^th Edition):

Rababa'H, Abeer 1981-. “Human Signaling Scaffold Protein (mAKAP) Polymorphisms: Role in Heart Failure.” Doctoral Dissertation, University of Houston. Accessed January 19, 2021. http://hdl.handle.net/10657/2616.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7^th Edition):

Rababa'H, Abeer 1981-. “Human Signaling Scaffold Protein (mAKAP) Polymorphisms: Role in Heart Failure.” Web. 19 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Rababa'H A1. Human Signaling Scaffold Protein (mAKAP) Polymorphisms: Role in Heart Failure. [Internet] [Doctoral dissertation]. University of Houston; [cited 2021 Jan 19]. Available from: http://hdl.handle.net/10657/2616.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Rababa'H A1. Human Signaling Scaffold Protein (mAKAP) Polymorphisms: Role in Heart Failure. [Doctoral Dissertation]. University of Houston; Available from: http://hdl.handle.net/10657/2616

Note: this citation may be lacking information needed for this citation format:
No year of publication.

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