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Cancer

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Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren Sep 2019

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren

All Dissertations, Theses, and Capstone Projects

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil. Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, we ...


Investigating The Role Of Cd109 In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen Aug 2019

Investigating The Role Of Cd109 In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

UT GSBS Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer death in the US. We performed loss of function genomic screening on a cohort of four patient derived PDAC cell populations and our data shows a cell surface receptor CD109 to be a common vulnerability, the biologic role of which in PDAC is yet unstudied and largely unknown. We hypothesized that CD109 expression provides PDAC cells with a survival advantage, and promotes cancer progression through activation of downstream signaling. We believe therefore that targeting CD109 could improve PDAC patients’ survival. Here we report that CD109 plays a role in ...


Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw Jul 2019

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Thesis Collection

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal ...


Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore May 2019

Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The largest U.S. cancer health disparity exists in prostate cancer, with African American men having the highest incidence and mortality rates. The present study evaluated the effects of ZIC2 and the underlying mechanisms in the E006 parental African-American cell line that produces tumors at accelerated growth rates because of the increase of ZIC2 genes in African-American males. We analyzed the experimental research that the overexpression of ZIC2 contributes to progression of prostate cancer. E006AA cells with overexpressed or suppressed ZIC2 were analyzed to determine phenotypic differences, PCR, cell proliferation and immunoblot assays. The expression levels of ZIC2 were analyzed ...


The Role Of Fos And Junb In The Reprogramming Of Acute Myeloid Leukemia Cells, Kayla Bendinelli May 2019

The Role Of Fos And Junb In The Reprogramming Of Acute Myeloid Leukemia Cells, Kayla Bendinelli

Student Honors Theses By Year

Acute Myeloid Leukemia (AML) is the most common form of leukemia in adults and while it has a high remission rate, relapse with therapy resistance is common, indicating the need for more targeted and effective therapies. It is possible to reprogram AML cells in culture to undergo cell cycle arrest, differentiation into “normal” macrophage-like cells, and apoptosis using phorbol 12-myristate 13-acetate (PMA), a diacyl glycerol (DAG) mimic. While this is effective in “curing” leukemia in culture, PMA is too toxic to serve as a therapy in AML patients. During these PMA-induced changes, approximately 1250 genes change in expression. The goal ...


Relationships Of Protein Biomarkers Of The Urokinase Plasminogen Activator System With Expression Of Their Cognate Genes In Primary Breast Carcinomas., Seth B. Sereff May 2019

Relationships Of Protein Biomarkers Of The Urokinase Plasminogen Activator System With Expression Of Their Cognate Genes In Primary Breast Carcinomas., Seth B. Sereff

College of Arts & Sciences Senior Honors Theses

Background: Urokinase plasminogen activator (uPA), its receptor uPAR and serine protease inhibitors PAI-1 or PAI-2 play key roles in tissue membrane remodeling and invasion of basement membranes by induction of a fibrinolytic pathway. Earlier studies reported that uPA and PAI-1 protein levels in breast carcinomas assist in prediction of response to chemotherapy. Our goal is to develop molecular signatures of candidate genes and identify novel relationships with these four protein biomarkers that demonstrate clinical utility for assessment of breast carcinoma outcomes.

Methods: This retrospective study used de-identified biomarker results and clinical outcomes from primary breast cancers that were stored in ...


The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud May 2019

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

All Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death ...


Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt May 2019

Paraoxonase 2 Is Critical For Non-Small Cell Lung Carcinoma Proliferation., Aaron Whitt

Electronic Theses and Dissertations

Non-small cell lung carcinoma (NSCLC) comprises 85% of lung cancer diagnoses and is plagued by drug resistance. Thus, elucidating the underlying mechanisms of NSCLC is paramount to expand future treatment options. Paraoxonase 2 (PON2), an intracellular enzyme with arylesterase and lactonase functions, has well-established anti-atherosclerotic activity. Recent studies show PON2 is overexpressed in a variety of tumors and confers drug resistance, although these interactions have not been thoroughly examined in NSCLC. Thus, we sought to investigate the role of PON2 in cellular proliferation using PON2-knockout mice, primary mouse cells, and NSCLC cell lines. Using these approaches, we demonstrate that PON2 ...


The Regulation Of Skeletal Muscle Fatigue During The Progression Of Cancer Cachexia, Brandon N. Vanderveen Apr 2019

The Regulation Of Skeletal Muscle Fatigue During The Progression Of Cancer Cachexia, Brandon N. Vanderveen

Theses and Dissertations

Cachexia is the unintentional loss of body weight secondary to chronic disease and is prevalent is roughly 50% of cancer patients. The loss of body weight and skeletal muscle mass is reduced functional capacity associated with reduced life quality. The etiology of cachexia is multimodal and complex; however, cachexia has been linked to several systemic (e.g. chronic inflammation, hypogonadism, anemia, insulin resistance) and behavioral (e.g. anorexia, inactivity) changes that can compound to accelerate muscle mass and body weight loss. While several inflammatory cytokines are associated with cachexia’s disease progression, our laboratory has established that Interleukin-6 (IL-6) is ...


Synthetic Lectins, A Diagnostic And Prognostic Tool For Detecting Glycans In Breast Cancer, Daniel James Gordon Apr 2019

Synthetic Lectins, A Diagnostic And Prognostic Tool For Detecting Glycans In Breast Cancer, Daniel James Gordon

Theses and Dissertations

Cancer diagnostic tools have been pushed to the forefront of medical research because a person’s chance of survival is directly correlated with how early the tumor is identified and treatment is begun. In searching for the subtle differences between healthy and tumor cells, almost every type of cancer has been shown to under, over, or neo express glycans, and these changes in the glycan fingerprint can continue as the disease progresses. This provides a powerful diagnostic opportunity that’s works by screening for glycoproteins and glycosylation patterns that deviate from normal cells.

Boronic acids have a useful and tunable ...


Exploring Patient Perceptions And Misconceptions: Beliefs Regarding Hereditary Cancer, Margaret Flach Apr 2019

Exploring Patient Perceptions And Misconceptions: Beliefs Regarding Hereditary Cancer, Margaret Flach

Theses and Dissertations

Many patients who enter a genetic counseling session have preconceived notions about why they or their family members developed a genetic condition. Often these perceptions are deeply rooted in personal, familial, and/ or cultural beliefs; individuals typically have a personal framework, or schema, into which they incorporate new information. There is limited research on what information patients are retaining during a genetic counseling session and how they are assimilating that knowledge into their existing views. We attempted to characterize these patient perceptions with respect to hereditary cancer, in order to assess how patients are adopting the information presented in a ...


Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail Jan 2019

Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail

Honors Undergraduate Theses

The causality dilemma between dysbiosis and cancer has given rise to numerous studies both exploring the mechanisms behind cancer progression and the associative shifts in the microbiota upon carcinogenesis. Aside from the hallmark study of Dr. Barry Marshall in establishing the true causal relationship between Helicobacter pylori and gastric adenocarcinoma, studies have only been successful in adding associative links of carcinogenesis mediated by bacteria to the literature. The current field is limited in its ability to establish causative relationships, and further work is needed to construct a reference community whose physiological responses reflect global community responses. In this thesis, the ...


Discovering Pathway And Cell Type Signatures In Transcriptomic Compendia With Machine Learning, Gregory Philip Way Jan 2019

Discovering Pathway And Cell Type Signatures In Transcriptomic Compendia With Machine Learning, Gregory Philip Way

Publicly Accessible Penn Dissertations

Gene expression measurements capture downstream biological responses to molecular perturbations. This systems biology perspective can be investigated using both supervised and unsupervised machine learning approaches to rapidly derive insight, including cell type and pathway signatures, from transcriptomic compendia. Machine learning applied to transcriptomic compendia can aid in biological discovery, hypothesis generation, and precision medicine. We introduce these topics and discuss their impact in Chapter 1. In Chapters 2-4, we describe and extend a supervised learning approach to detect aberrant gene and pathway activity in cancer. We apply this approach to identify patient tumors, cell lines, and patient derived xenograft models ...


Role Of The Nuclear Receptor Pparγ In Clear Cell Renal And Bladder Urotheial Carcinoma, Danielle Sanchez Jan 2019

Role Of The Nuclear Receptor Pparγ In Clear Cell Renal And Bladder Urotheial Carcinoma, Danielle Sanchez

Publicly Accessible Penn Dissertations

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) has a well-characterized role in the developmental process of adipogenesis and transcriptional regulation of lipid metabolism. However, its expression patterns and functions in various cancer subtypes are less understood. My studies investigate the role of PPARγ in two distinct cancers of the urinary tract: clear cell renal cell carcinoma (ccRCC) and bladder urothelial carcinoma (UC). In ccRCC, I hypothesized that PPARγ activity contributes to the aberrant lipid accumulation phenotype characteristic of this disease, thereby promoting tumor progression. Through ChIP-seq, I demonstrated that PPARγ and its heterodimeric DNA binding partner retinoid X receptor ...


Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher Jan 2019

Development And Characterization Of An Immunologically Humanized And Cancer Xenograft Model In Pigs With Severe Combined Immunodeficiency (Scid), Adeline Nicole Boettcher

Graduate Theses and Dissertations

Swine with severe combined immunodeficiency (SCID) are an emerging large animal model for biomedical research. There have been several SCID pig models described since our first discovery of naturally occurring SCID with mutations in Artemis (DCLRE1C) in 2012. SCID animals are particularly useful in biomedical research due to their lack of T, B, and sometimes NK cells. Absence of the adaptive immune system allows for human cell and tissue xenotransplantation into these SCID animals. The works described within this thesis are categorized under four main goals: (1) further characterization of the immune system of Art-/- SCID pigs, (2) development of ...


Effects Of H-Ras Disease Mutations On Binding To The Ras Binding Domain Of Pi3ky Measured By Micro-Scale Thermophoresis, Justin Martyr Jan 2019

Effects Of H-Ras Disease Mutations On Binding To The Ras Binding Domain Of Pi3ky Measured By Micro-Scale Thermophoresis, Justin Martyr

Undergraduate Honors Theses

H-Ras is a G-protein responsible for the activation of multiple signaling pathways that control cell growth. Our primary interest is examining its role in the regulation of the phosphoinositide-3-kinase (PI3K) signaling cascade, as H-Ras has been previously shown to recruit PI3K to the plasma membrane where this lipid kinase phosphorylates PIP2 to PIP3, a signal for cellular growth. The H-Ras-PI3K-PIP3 signaling pathway is known to be highly oncogenic, with constitutive activation of H-Ras leading to increased PIP3 production and cell growth. We hypothesize that disease-linked mutations on the binding interface between Ras and PI3K increase the ...


The Grass Is Always Greener On The Other Side (Of The Basement Membrane): Prostate Cancer Metastasis As Intracorporeal Dispersal, Matthew Oh Jan 2019

The Grass Is Always Greener On The Other Side (Of The Basement Membrane): Prostate Cancer Metastasis As Intracorporeal Dispersal, Matthew Oh

Undergraduate Honors Theses

Dispersal ecology offers a possible explanation for the behavior of prostate cancer (PCa), which disproportionately metastasizes to the bone. Organisms become more likely to leave their home patch when conditions are unfavorable, with the goal of becoming established in more favorable patches. Similarly, PCa cells are pushed from the prostate tumor by hypoxic stress and pulled toward the bone by the presence of bone stromal cells (BSCs), which support PCa growth and proliferation. When PCa settles in the bone, it leads to the formation of a feedforward loop in which PCa enhances osteoblast differentiation; osteoblasts in turn promote PCa proliferation ...


Genes Regulating Cell Movement During Regeneration In Drosophila Melanogaster Following Radiation Damage, Michelle Ledru Jan 2019

Genes Regulating Cell Movement During Regeneration In Drosophila Melanogaster Following Radiation Damage, Michelle Ledru

Undergraduate Honors Theses

Each year, 1.7 million people are diagnosed with cancer and 610,000 people die from the disease (“Cancer Statistics,” 2018). Ionizing radiation therapy is a commonly used method of treatment for many cancers because it kills cancer cells (Baskar et al., 2012). However, cancer cells that have not been eradicated can proliferate, leading to resistance to treatment (Hanahan & Weinberg, 2011). Drosophila melanogasteris an excellent model organism because they have a short life cycle and share 75% of human disease-causing genes, while the larvae can withstand high amounts of radiation and have regenerative properties. Different genes were investigated to ...


Effects Of A Plant-Based Vegan Diet On The Risk Of Cancer: An Integrative Review Of The Literature, Chelsie M. Silavent Jan 2019

Effects Of A Plant-Based Vegan Diet On The Risk Of Cancer: An Integrative Review Of The Literature, Chelsie M. Silavent

Honors Undergraduate Theses

Cancer, an aggressive chronic disease, impacts the lives of millions of people every day. There are numerous proposed triggers related to the diagnosis and much remains to be learned about the causes. Associated with this disease's variability is the challenge to identify a single causative agent that lead to its prevention. Specific topics that need additional evidence relate to environmental factors and lifestyle behaviors in the development, treatment and, in some instances, even suppression of disease progression. Specifically, a diet that excludes animal-based products but consists of a variety of fruits and vegetables (i.e., plant-based vegan diet) is ...


Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer Dec 2018

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling ...


The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le Dec 2018

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

UT GSBS Dissertations and Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS ...


Cd147 As A Potential Therapeutic Target In Glioblastoma Treatment, Beau Adams Nov 2018

Cd147 As A Potential Therapeutic Target In Glioblastoma Treatment, Beau Adams

All NMU Master's Theses

Glioblastoma (GBM) tumors are the most common and lethal form of cancer in the central nervous system (CNS). GBM tumors appear to contain a mixture of different cell types, which makes them difficult to treat. GBM cells exhibit altered morphology from normal cells on several different levels, which highlights different pathways to potentially target for therapeutic treatments. The human surface glycoprotein CD147, also known as basigin, is expressed at significantly higher levels in GBMs compared to non-neoplastic brain tissue. Furthermore, levels of CD147 expression correlate with brain tumor progression and show the highest expression in GBM. Here, we suppressed tumor ...


Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry Oct 2018

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry

GSBS Dissertations and Theses

Tumor heterogeneity observed between patients has made it challenging to develop universal or broadly effective cancer therapies. Therefore, an ever-growing movement within cancer research aims to tailor cancer therapies to individual patients or specific tumor subtypes. Tumor stratification is generally dictated by the genomic mutation status of the tumor cells themselves. Importantly, non-genetic influences – such as interactions between tumor cells and other components of the tumor microenvironment – have largely been ignored. Therefore, in an effort to increase treatment predictability and efficacy, we investigated how tumor-stroma interactions contribute to drug sensitivity and drug resistance.

I designed a high throughput co-culture screening ...


Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller Aug 2018

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug ...


Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost Jul 2018

Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost

Pence-Boyce STEM Student Scholarship

Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha ...


Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah May 2018

Regulation Of The Pi3-Kinase/Pten Signaling Pathway By Tgf-Β In Prostate Cancer Cells, Mawiyah Kimbrough-Allah

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Transforming growth factor -β (TGF-β) plays an important role in the progression of prostate cancer. It acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. The PI3-kinase pathway has been shown to play integral roles in many cellular processes including cell proliferation, survival, and cell migration in many cell types. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. In this present study, we investigated possible roles of ...


The Role Of Mafb In Reversing The Transformed Phenotype Of Human Acute Myeloid Leukemia Cells, Tulley Shofner May 2018

The Role Of Mafb In Reversing The Transformed Phenotype Of Human Acute Myeloid Leukemia Cells, Tulley Shofner

Student Honors Theses By Year

The five-year survival rate for patients with acute myeloid leukemia is 27.4%, with most patients who achieve temporary remission relapsing, despite chemotherapeutic treatments (National Cancer Institute, 2014). With the inadequacy of current drug therapies for human acute myeloid leukemia patients, the genetic changes in AML cells’ genomes and transcriptomes have been studied for insights as to more effective targeted therapies. Data obtained by the Roberts lab demonstrates that treatment of HL-60 cells with PMA, which leads to cell cycle arrest, differentiation and apoptosis, is accompanied by upregulation of approximately 100 transcription factor genes. For this project, the basic leucine ...


The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland May 2018

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

UT GSBS Dissertations and Theses (Open Access)

DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is ...


Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal May 2018

Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal

UT GSBS Dissertations and Theses (Open Access)

Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual phosphorylation ...


Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu May 2018

Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu

UT GSBS Dissertations and Theses (Open Access)

Deviations from a diploid configuration of the human genome, spanning single genes or entire chromosomes, can have wide-ranging impacts on the variation of human phenotypes, including Mendelian and complex forms of diseases. These chromosomal alterations — such as duplications, deletions or copy-neutral loss-of-heterozygosity — are thus important forms of genetic variation for phenotyping populations of individuals as well as populations of cells. Indeed, copy number variants (CNVs) serve as hallmarks of critical changes in the development of particular diseases such as cancer and thus may be used as biomarkers. These CNVs may be either inherited (transmitted by germ cells, originating in meiosis ...