+publisher:"University of Illinois – Chicago" +contributor:("Burdette, Joanna")

University of Illinois – Chicago

1. Jindal, Siddharth. Identification of Novel Lead Inhibitors for Bacillus anthracis Adenylosuccinate Synthetase.

Degree: 2014, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19078

► Anthrax is an infectious disease caused by the bacterium Bacillus anthracis. It came into public notability in 2001 during the bioterrorism attack in the United… (more)

▼ Anthrax is an infectious disease caused by the bacterium Bacillus anthracis. It came into public notability in 2001 during the bioterrorism attack in the United States. Because of the potential threat and the emergence of antibiotic resistance B. anthracis, novel antibiotics are needed to overcome this problem. One way is to develop antibiotics that inhibit novel targets. One such target is the de novo purine biosynthesis pathway. The enzyme, Adenylosuccinate synthetase (PurA), catalyses the first committed step in the synthesis of adenosine, an important component for bacterial purine biosynthesis pathway. This metallo-enzyme is a homo-dimer which catalyses formation of adenylosuccinate from IMP in presence of GTP and aspartate and releases an inorganic phosphate (Pi). PurA is found in all life forms with few exceptions and because of its essential role in the biosynthesis of adenine nucleotides and ultimately nucleic acids, it is potentially an excellent target for anti-bacterial drug development. The goal of this project is to identify inhibitors that exhibit antibacterial activity against the Category A pathogen, B. anthracis. We used combination of different approaches to identify novel lead inhibitors against B. anthracis adenylosuccinate syntheatse. The purA gene was cloned and the enzyme was expressed and purified. MESG assay was employed to determine the substrate kinetics for PurA. Subsequently, malachite green assay was optimized for high throughput screening of the Chembridge and the Life Chemicals library totaling 75,000 compounds to identify inhibitors against PurA. The hits were validated and assay interference from the hits from high throughput screening was corrected using the artifact assay. To confirm the hits from artifact assay, an independent binding assay was performed to determine the binding and equilibrium dissociation constant of these compounds. Here we present data describing the optimization of the assays and various strategies for identification and characterization of inhibitors of PurA. We have identified two compounds as promising hits for further development in a hit-to-lead optimization process. Both these compounds have good inhibition in HTS, a good MIC and bind to the enzyme. Advisors/Committee Members: Johnson, Michael E. (advisor), Federle, Michael (committee member), Burdette, Joanna (committee member).

Subjects/Keywords: adenylosuccinate synthetase; novel lead inhibitors

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

APA (6^th Edition):

Jindal, S. (2014). Identification of Novel Lead Inhibitors for Bacillus anthracis Adenylosuccinate Synthetase. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jindal, Siddharth. “Identification of Novel Lead Inhibitors for Bacillus anthracis Adenylosuccinate Synthetase.” 2014. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jindal, Siddharth. “Identification of Novel Lead Inhibitors for Bacillus anthracis Adenylosuccinate Synthetase.” 2014. Web. 12 Apr 2021.

Vancouver:

Jindal S. Identification of Novel Lead Inhibitors for Bacillus anthracis Adenylosuccinate Synthetase. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jindal S. Identification of Novel Lead Inhibitors for Bacillus anthracis Adenylosuccinate Synthetase. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/19078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

2. Pham, Vy T. Nitric Oxide: An Epigenetic Regulator.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19326

► Methylation and acetylation of Lysine 9 on Histone 3 (H3K9me2/ac) has been shown to play an important role in the epigenetic regulation of gene expression.… (more)

▼ Methylation and acetylation of Lysine 9 on Histone 3 (H3K9me2/ac) has been shown to play an important role in the epigenetic regulation of gene expression. The methylation status of H3K9 is regulated by methyltransferases (HMT) and demethylases. Demethylation of these epigenetic marks is performed predominantly by a family of JMJC domain Fe(II)-dependent enzymes which use alpha-ketoglutarate and O2 as substrates. Nitric oxide (•NO), a biological free radical with a similar chemical structure as O2, has been shown by our lab to inhibit the JMJC class of lysine-specific demethylases (KDM) and affect global histone methylation. Here, we will demonstrate that the removal of •NO on MDA-MB-231 can reverse the expression of HMT and KDM caused by •NO exposure. Also, levels of H3K9me2/ac returned to basal level after •NO had been removed from the cellular environment. Furthermore, H3K4mono/di/tri methylation are all shown to be affected by •NO. This study provides important insights on how this endogenously-produced molecule can possibly regulate transcription of genes by changing global methylation and acetylation levels of histones. TETs are dioxygenase enzymes that convert 5-methylcytosine (5mC) containing DNA to 5-hydroxymethylcytosine (5hmC) containing DNA. 5mC has been associated with transcription repression whereas, elevated 5hmC levels are associated with gene activation. TET-mediated conversion of 5mC to 5hmC is considered as an important epigenetic component of transcriptional regulation. Similar to JMJC domain-containing demethylases, TETs are oxygen-dependent and require α-ketoglutarate and Fe(II) for their catalytic activities. In addition to determining the modifications of histones by •NO, we will demonstrate the ability of •NO to inhibit TETs functions and decrease the overall conversion of 5mC to 5hmC. Overall, our study reveals novel roles of •NO in regulating the epigenetics landscape via altering DNA modifications and histone modifications. Advisors/Committee Members: Thomas, Douglas D. (advisor), Petukhov, Pavel (committee member), Burdette, Joanna (committee member).

Subjects/Keywords: Nitric oxide; Free radicals; Epigenetics; Histone modifications; Lysine methyltransferase; Lysine demethylase; DNA modifications; 5-methylcytosine; 5-hydroxymethylcytosine; TETs

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

APA (6^th Edition):

Pham, V. T. (2015). Nitric Oxide: An Epigenetic Regulator. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19326

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pham, Vy T. “Nitric Oxide: An Epigenetic Regulator.” 2015. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19326.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pham, Vy T. “Nitric Oxide: An Epigenetic Regulator.” 2015. Web. 12 Apr 2021.

Vancouver:

Pham VT. Nitric Oxide: An Epigenetic Regulator. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19326.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pham VT. Nitric Oxide: An Epigenetic Regulator. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19326

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

3. Snelten, Courtney S. Modulation of Estrogen Metabolism by Hops Extracts and Bioactive Compounds as Analyzed by LC-MS-MS.

Degree: 2013, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/10249

► The oxidative metabolism of estrogens into estrogen quinones that damage DNA, contributes to the carcinogenicity of estrogens. In order to circumvent using hormone replacement therapy,… (more)

▼ The oxidative metabolism of estrogens into estrogen quinones that damage DNA, contributes to the carcinogenicity of estrogens. In order to circumvent using hormone replacement therapy, many women in the United States use botanical dietary supplements as a means to alleviate menopausal symptoms and avoid associated cancer risks. Little is known about the ability of these botanicals to alter estrogen metabolism leading to breast cancer. The hypothesis of this thesis is that botanicals used by women for menopausal symptom relief have beneficial chemopreventive activities by reducing exposure to genotoxic estrogen metabolites and improving overall wellness by reducing the negative effects of estrogen. Our previous studies have shown that hops (Humulus lupulus), a component of popular European botanical dietary supplements used for relief of menopausal symptoms, inhibits estradiol metabolism to the 2- and 4-methoxyestrone (MeOE1) metabolites. Utilizing an optimized LC-MS-MS assay I investigated 3 major constituents within hops ability to alter estrogen metabolism and the CYP1B1 and CYP1A1 activity and mRNA expression which are responsible for estrogen metabolite oxidation. The hypothesis was supported by the observation that five hops extracts altered estrogen metabolism and the one with the highest amount of isoxanthohumol and 8-prenylnaringenin increased the benign metabolite marker 2-methoxyestrone while simultaneously decreasing the genotoxic metabolite marker 4-methoxyestrone. While xanthohumol did not alter estrogen metabolism, 8-prenylnaringenin and isoxanthohumol altered the amount of the genotoxic metabolite 4-methoxyestrone although in opposite manners. 8-prenylnaringenin treatment increased the genotoxic metabolite 4-methoxyestrone by increasing the mRNA for the enzyme responsible for its production (CYP1B1). On the other hand, isoxanthohumol treatment decreased the genotoxic metabolite 4-methoxyestrone by directly inhibiting the enzyme. The data suggests that hops extracts, specifically those with high levels of isoxanthohumol, have beneficial chemopreventive activities by reducing the genotoxic pathway of estrogen metabolism and could potentially improve overall wellness by reducing the negative effects of estrogen. Advisors/Committee Members: Bolton, Judy L. (advisor), Burdette, Joanna (committee member), Dietz, Birgit (committee member).

Subjects/Keywords: estrogen metabolism; hops; breast cancer

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

APA (6^th Edition):

Snelten, C. S. (2013). Modulation of Estrogen Metabolism by Hops Extracts and Bioactive Compounds as Analyzed by LC-MS-MS. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/10249

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Snelten, Courtney S. “Modulation of Estrogen Metabolism by Hops Extracts and Bioactive Compounds as Analyzed by LC-MS-MS.” 2013. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/10249.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Snelten, Courtney S. “Modulation of Estrogen Metabolism by Hops Extracts and Bioactive Compounds as Analyzed by LC-MS-MS.” 2013. Web. 12 Apr 2021.

Vancouver:

Snelten CS. Modulation of Estrogen Metabolism by Hops Extracts and Bioactive Compounds as Analyzed by LC-MS-MS. [Internet] [Thesis]. University of Illinois – Chicago; 2013. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/10249.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Snelten CS. Modulation of Estrogen Metabolism by Hops Extracts and Bioactive Compounds as Analyzed by LC-MS-MS. [Thesis]. University of Illinois – Chicago; 2013. Available from: http://hdl.handle.net/10027/10249

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

4. Madriaga, Antonett P. Evaluation of Photoreactive and Phenothiazine-based HDAC Inhibitors.

Degree: 2014, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/11303

► Increased histone deacetylase (HDAC) activity and decreased acetylation status have been implicated in a wide array of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s disease.… (more)

▼ Increased histone deacetylase (HDAC) activity and decreased acetylation status have been implicated in a wide array of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s disease. For this reason, developing HDAC inhibitors has risen as a promising therapeutic strategy to treat these ailments. While several HDAC inhibitors have proven quite effective in clinical and pre-clinical studies, there are still some critical barriers for developing successful inhibitors, including lack of HDAC isoform selectivity and potential drug resistance in cells. We hypothesize that we can improve the therapeutic potential of HDAC inhibitors for neurological diseases by (1) evaluating isoform selectivity in a disease-relevant system to aid in the design of selective inhibitors and (2) developing multifunctional HDAC inhibitors to reduce potential drug resistance. The first half of this thesis addresses the first goal, and focuses on optimizing the Binding Ensemble Profiling with Photoaffinity Labeling (BEProFL) approach, developed in our lab, to evaluate the selectivity of photoreactive HDAC inhibitors in a cell-based system. We chose the novel, biologically active HDAC probe, HD-55, as our model compound to optimize this methodology. We report that HD-55 crosslinks to HDAC8 in both a recombinant and cell-based system. Interestingly, this probe also binds the other Class I HDACs and additional proteins, which are currently unidentified. The next half of this thesis covers how we sought to evaluate novel phenothiazine-containing compounds as potential polypharmacological neuroprotective agents that inhibit HDAC function and counter oxidative stress. First, we evaluated these compounds for HDAC activity, radical scavenging ability, and DNA intercalation. Then, we evaluated whether these compounds could induce a neuroprotective effect in differentiated SH-SY5Y cells exposed to oxidative stress; a known model for neurodegenerative disease states. We report that the novel phenothiazine-containing compounds can inhibit HDACs with varying selectivity and scavenge radicals with similar efficacy to known antioxidants without intercalating DNA. We also found that these compounds induce differential increases in the viability of stressed neuronal-like cells. Due to these findings, we conclude that these novel compounds may be potential neuroprotective drugs. Advisors/Committee Members: Petukhov, Pavel A. (advisor), Burdette, Joanna (committee member), Thomas, Douglas (committee member).

Subjects/Keywords: histone deacetylase; HDAC; HDAC inhibitor; photoaffinity probes; neuroprotection; oxidative stress

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

APA (6^th Edition):

Madriaga, A. P. (2014). Evaluation of Photoreactive and Phenothiazine-based HDAC Inhibitors. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/11303

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Madriaga, Antonett P. “Evaluation of Photoreactive and Phenothiazine-based HDAC Inhibitors.” 2014. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/11303.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Madriaga, Antonett P. “Evaluation of Photoreactive and Phenothiazine-based HDAC Inhibitors.” 2014. Web. 12 Apr 2021.

Vancouver:

Madriaga AP. Evaluation of Photoreactive and Phenothiazine-based HDAC Inhibitors. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/11303.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Madriaga AP. Evaluation of Photoreactive and Phenothiazine-based HDAC Inhibitors. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/11303

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

5. Pan, Xian. Transcriptional Regulation of Cytochrome P450 2D6 by Small Heterodimer Partner.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19796

► Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme, responsible for eliminating ~20% of marketed drugs. Of note, CYP2D6 activity exhibits large interindividual variability, but… (more)

▼ Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme, responsible for eliminating ~20% of marketed drugs. Of note, CYP2D6 activity exhibits large interindividual variability, but the factors leading to this variability remain poorly understood. Accumulating clinical data indicate that CYP2D6-mediated drug metabolism is increased during pregnancy. However, the underlying mechanism was completely unknown in part due to a lack of study models that could recapitulate the clinical finding. Here, we established CYP2D6-humanized transgenic (Tg-CYP2D6) mice as such a model, by showing enhanced CYP2D6 expression at term pregnancy in the mice. Using Tg-CYP2D6 mice, we found that transcription factor small heterodimer partner (SHP) was downregulated in the liver during pregnancy and established SHP as a transcriptional repressor of CYP2D6 expression. Furthermore, we identified that all-trans retinoic acid (atRA), an endogenous compound that induces SHP expression, exhibited decreased hepatic levels during pregnancy in Tg-CYP2D6 mice. Administration of atRA led to a significant decrease in CYP2D6 expression in Tg-CYP2D6 mice. Based on the finding that SHP is a novel transcriptional regulator of CYP2D6 expression, we further examined whether known modulators of SHP expression alter CYP2D6 expression. SHP is a known representative target gene of farnesoid X receptor (FXR), a bile acid sensor. Administration of a synthetic agonist of FXR, GW4064, to Tg-CYP2D6 mice led to significant decreases in CYP2D6 expression in an SHP-dependent manner. Estrogen-induced cholestasis also led to increased SHP and decreased CYP2D6 expression in Tg-CYP2D6 mice. Together, these results suggest that differential levels of SHP modulators may contribute to interindividual variability in CYP2D6 activity. Our study potentially provides a basis to better predict CYP2D6 activity level in humans and thus to enable personalized medicine for CYP2D6 substrates. Advisors/Committee Members: Jeong, Hyunyoung (advisor), He, Xiaolong (advisor), McLachlan, Alan (advisor), Burdette, Joanna E. (advisor), Lee, Hyunwoo (committee member), He, Xiaolong (committee member), McLachlan, Alan (committee member), Burdette, Joanna E. (committee member).

Subjects/Keywords: CYP2D6; SHP; transcriptional regulation; pregnancy; interindividual variability

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

APA (6^th Edition):

Pan, X. (2015). Transcriptional Regulation of Cytochrome P450 2D6 by Small Heterodimer Partner. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19796

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pan, Xian. “Transcriptional Regulation of Cytochrome P450 2D6 by Small Heterodimer Partner.” 2015. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19796.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pan, Xian. “Transcriptional Regulation of Cytochrome P450 2D6 by Small Heterodimer Partner.” 2015. Web. 12 Apr 2021.

Vancouver:

Pan X. Transcriptional Regulation of Cytochrome P450 2D6 by Small Heterodimer Partner. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19796.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pan X. Transcriptional Regulation of Cytochrome P450 2D6 by Small Heterodimer Partner. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19796

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

6. Chen, Wei-Lun. Identification and Characterization of Potential New Anticancer Drugs from Natural Sources.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21620

► In 2014, the World Health Organization (WHO) reported that cancer was the leading cause of death worldwide, accounting for 8.2 million deaths in 2012. According… (more)

▼ In 2014, the World Health Organization (WHO) reported that cancer was the leading cause of death worldwide, accounting for 8.2 million deaths in 2012. According to the National Cancer Institute (NCI) and the Centers for Disease Control and Prevention (CDC), cancer ranks second among all causes of death in the United States. The American Cancer Society estimates that there will be 1,685,210 new cases of cancer in 2016, and 595,690 cancer related deaths.14 Cancer chemotherapy is an established adjuvant to surgery and radiation to treat successfully solid tumors, lymphomas, and leukemias. Although many anticancer drugs are approved and clinically available, the problems of resistance to and toxicity of existing agents necessitates the discovery of new drug leads. For decades, secondary metabolites from plants, fungi and bacteria have been found to exhibit potent anticancer activity. Natural products are selected by evolution to reach their molecular target within cells and to interact with biologically active protein folds. Secondary metabolites may serve their producing organisms by improving their competitive strength. Natural products have been essential components of drug discovery and are direct sources of small molecule therapies and scaffolds for semisynthesis. Driven by the need for new anticancer targets, this thesis focuses on exploring new molecules for the novel regulation in cell death to find compounds with good specificity and potency against cancer cells without altering normal cells. Silvestrol is a cyclopenta[b]benzofuran that was isolated from the fruits and twigs of Aglaia foveolata, which is indigenous to the island states of Southeast Asia. Previous testing of silvestrol revealed that it is a potent inhibitor of protein synthesis and hascytotoxic activity similar to or more potent than many Food and Drug Administration (FDA) approved anticancer agents. Silvestrol treatment of cultured human cell lines derived from melanoma (MDA-MB-435) or colon cancer (HT-29) induced cell cycle arrest at the G2 stage. Silvestrol treatment also induced caspase-3 activation and apoptotic cell death in a time- and concentration-dependent manner. Treatment of ATG7-null mouse embryonic fibroblast (MEF) cells with silvestrol resulted in impaired transformation of LC3-I to LC3-II. This suggests that silvestrol caused a conventional autophagy response that ultimately progressed to apoptosis. Strebloside was isolated from the stem bark of Streblus asper in Southeast Asia, and its chemical structure shares a common cardiac glycoside structural motif. Strebloside was studied in a hollow fiber assay to determine if it had any potency in vivo. Strebloside was able to inhibit the growth of ovarian cancer cell model OVCAR3 and also triple negative breast cancer cell model MDA-MB-231. From these data, ovarian cancer models were chosen due to its high sensitivity to strebloside. Strebloside was active in OVSAHO, OVCAR4 and OVCAR5, but was most potent in OVCAR3. Furthermore, strebloside blocked cell cycle progression at the… Advisors/Committee Members: Burdette, Joanna E (advisor), Swanson, Steven M (committee member), Orjala, Jimmy (committee member), Murphy, Brian T (committee member), Hong, Seungpyo (committee member), Burdette, Joanna E (chair).

Subjects/Keywords: silvestrol; strebloside; apoptosis; autophagy; natural products

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

APA (6^th Edition):

Chen, W. (2016). Identification and Characterization of Potential New Anticancer Drugs from Natural Sources. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21620

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Wei-Lun. “Identification and Characterization of Potential New Anticancer Drugs from Natural Sources.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/21620.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Wei-Lun. “Identification and Characterization of Potential New Anticancer Drugs from Natural Sources.” 2016. Web. 12 Apr 2021.

Vancouver:

Chen W. Identification and Characterization of Potential New Anticancer Drugs from Natural Sources. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/21620.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen W. Identification and Characterization of Potential New Anticancer Drugs from Natural Sources. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21620

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

7. Karthikeyan, Subbulakshmi. Signaling Pathways Contributing to High-Grade Serous Ovarian Cancer and Metastasis from Fallopian Tube.

Degree: 2018, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/22970

► The fallopian tube epithelium (FTE) gives rise to high grade serous ovarian cancer (HGSOC), the most lethal gynecological malignancy. A mutation in p53 is reported… (more)

▼ The fallopian tube epithelium (FTE) gives rise to high grade serous ovarian cancer (HGSOC), the most lethal gynecological malignancy. A mutation in p53 is reported in 96% of HGSOC. A transgenic mouse model and a cellular model with p53 mutation was developed and determined that p53 mutation alone is not sufficient to form tumors, however it significantly induced the cell migration. In vitro and In vivo analyses revealed that in FTE, mutant p53 reduced CDH6 (cell adhesion protein), through direct binding on CDH6 promoter, but CDH6 is not expressed in the ovaries. The existence of a FTE specific mutant p53 marker, may add to the existing tools for finding the cell of origin of HGSOC and may improve personalized therapies that work better in tumors arising from the FTE. In order to identify key drivers of HGSOC tumorigenesis, a spontaneous model of FTE derived cancer (MOEhigh - murine oviductal epithelium high passage, equivalent to human FTE) was made that contained gene alterations concordant to HGSOC. A human prolactin (PRL) like gene, Prl2c2 was amplified >100 fold in the model. Prl2c2 stable knockdown in MOEhigh cells demonstrated a significant reduction in cell proliferation, 2-dimensional foci, anchorage independent growth, and completely blocked tumor formation. The overall survival of ovarian cancer patients from transcriptome analysis of 1868 samples was lower when abundant PRL and prolactin receptors (PRL-R) were expressed. A HGSOC cell line (OVCAR3) and a tumorigenic human FTE cell line (FT33-Tag-Myc) were treated with recombinant PRL and a significant increase in cellular proliferation was detected. A CRISPR/Cas9 mediated PRL-R deletion in OVCAR3 and FT33-Tag-Myc cells demonstrated significant reduction in cell proliferation and eliminated tumor growth using the OVCAR3 model. PRL phosphorylated STAT5, m-TOR and ERK in ovarian cancer cells. Until now, PRL serum levels were only identified as a diagnostic marker for screening OVCA. However, this study for the first time, report that PRL is expressed and mediates tumorigenesis in human FTE. Small molecules were identified to block PRL-R activity and thereby providing a novel strategy, which with further clinical validation can be used to prevent HGSOC tumor formation from fallopian tube. Advisors/Committee Members: Burdette, Joanna E (advisor), Stocco, Carlos (committee member), Hanakahi, Leslyn (committee member), Thomas, Douglas (committee member), Jeong, Hyunyoung (Young) (committee member), Burdette, Joanna E (chair).

Subjects/Keywords: High grade serous ovarian cancer; p53 mutation; Prolactin; Prolactin receptor; Spontaneous fallopian tube derived cancer model; p53 phosphorylation; Cadherins; Fallopian tube; Mutant p53 transgenic mouse model

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

APA (6^th Edition):

Karthikeyan, S. (2018). Signaling Pathways Contributing to High-Grade Serous Ovarian Cancer and Metastasis from Fallopian Tube. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22970

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Karthikeyan, Subbulakshmi. “Signaling Pathways Contributing to High-Grade Serous Ovarian Cancer and Metastasis from Fallopian Tube.” 2018. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/22970.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Karthikeyan, Subbulakshmi. “Signaling Pathways Contributing to High-Grade Serous Ovarian Cancer and Metastasis from Fallopian Tube.” 2018. Web. 12 Apr 2021.

Vancouver:

Karthikeyan S. Signaling Pathways Contributing to High-Grade Serous Ovarian Cancer and Metastasis from Fallopian Tube. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/22970.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Karthikeyan S. Signaling Pathways Contributing to High-Grade Serous Ovarian Cancer and Metastasis from Fallopian Tube. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/22970

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

8. Quartuccio, Suzanne M. Modeling Early Events Associated with Serous Ovarian Cancer Formation from Fallopian Tube Epithelium.

Degree: 2014, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19135

► Epithelial ovarian cancer is the most lethal gynecological malignancy and fifth leading cause of cancer death among US women. High mortality rates can be attributed… (more)

▼ Epithelial ovarian cancer is the most lethal gynecological malignancy and fifth leading cause of cancer death among US women. High mortality rates can be attributed to the lack of early detection strategies and an incomplete understanding of disease etiology. Historically, ovarian cancer was thought to arise from the ovarian surface epithelium (OSE) but evidence suggests that the epithelial cells of the distal fallopian tube (TEC) may be progenitors to some high-grade serous ‘ovarian’ cancers. Although a heterogeneous disease, 96% of high-grade serous ovarian tumors contain mutations in p53 and the “p53 signature”, or overexpression of p53 is a potential precursor lesion to the disease. In order to examine the role of both cell types in the development of serous cancer, as well as potential initiation factors that might be involved in early disease formation, a three-dimensional culture system was developed to study normal mouse and human epithelium in contact with its stromal microenvironment. This system allowed for the discovery that transforming growth factor beta (TGFβ) leads to growth inhibition of normal mouse ovarian surface epithelium, but not normal mouse tubal epithelial cells despite transcriptional activation by TGFβ. In addition, ex vivo cultures of human fimbriae resulted in induction of p53 expression and could be used in the future to model the p53 signature. Mouse models to conditionally target floxed genes in the TEC were also optimized. Intraoviductal injection of adenovirus expressing Cre recombinase lead to limited infectivity of the TEC. Tissue specific promoters should be employed to target these cells while the OSE is best targeted through intrabursal injections. A mouse oviductal epithelial cell line that spontaneously immortalized and was stably transfected with the R273H TP53 mutation was used to study the role of mutant p53 in ovarian tumorigenesis. Mutation in p53 led to increased migration and upregulation of pro-migratory genes in TEC, but not OSE. The R273H TP53 mutation combined with oncogenic KRAS (G12V) expression transformed TEC. Understanding the mechanisms required to transform normal fallopian tube epithelium may help identify early biomarkers, develop chemoprevention strategies, and elucidate novel treatments to improve overall survival rates. Advisors/Committee Members: Burdette, Joanna E. (advisor), Swanson, Steven M. (committee member), Thomas, Douglas D. (committee member), Barbolina, Maria (committee member), Bosland, Maarten C. (committee member).

Subjects/Keywords: ovarian cancer; fallopian tube; p53 signature; precursor lesion; 3D culture

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

APA (6^th Edition):

Quartuccio, S. M. (2014). Modeling Early Events Associated with Serous Ovarian Cancer Formation from Fallopian Tube Epithelium. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19135

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Quartuccio, Suzanne M. “Modeling Early Events Associated with Serous Ovarian Cancer Formation from Fallopian Tube Epithelium.” 2014. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19135.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Quartuccio, Suzanne M. “Modeling Early Events Associated with Serous Ovarian Cancer Formation from Fallopian Tube Epithelium.” 2014. Web. 12 Apr 2021.

Vancouver:

Quartuccio SM. Modeling Early Events Associated with Serous Ovarian Cancer Formation from Fallopian Tube Epithelium. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19135.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Quartuccio SM. Modeling Early Events Associated with Serous Ovarian Cancer Formation from Fallopian Tube Epithelium. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/19135

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

9. Pearson, Ryan M. Impact of Dendritic Polymer Architecture on Self-assembly, Cellular Interactions, and Protein Adsorption.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19378

► Nanocarriers have demonstrated their great potential to revolutionize the diagnosis, treatment, and prevention of a variety of diseases, especially cancer. In this dissertation research, we… (more)

▼ Nanocarriers have demonstrated their great potential to revolutionize the diagnosis, treatment, and prevention of a variety of diseases, especially cancer. In this dissertation research, we systematically explored the role of dendritic polymer architecture on the self-assembly and cellular interactions of nanocarriers. A set of novel PEGylated dendron-based copolymers (PDC) were synthesized and characterized along with self-assembled dendron micelles (DM) with various surface functional groups and hydrophilic-lipophilic balances (HLB). The critical micelle concentration (CMC) of PDCs varied from 6.50 × 10-8 to 9.3 × 10-7 M and compared to synthesized linear-block copolymer (LBC) counterparts, the CMCs of PDCs were up to 100-times lower at similar HLBs, demonstrating their superior thermodynamic stability. Molecular dynamics (MD) simulations revealed that the hydrophobic core of the DM was more completely covered by dense poly(ethylene glycol) (PEG) compared to the linear micelle (LM). In vitro analyses of the DMs revealed that both the formation of non-specific and specific cellular interactions were controllable through modulation of the PEG corona length. Using folic acid (FA) as the model targeting agent, variation of the PEG corona length and PDC-FA content resulted in targeted DMs that achieved modular cellular interactions, ranging from minimal to 27-fold enhancements, compared to non-targeted DMs. The targeting efficiency of FA-targeted DMs was then compared to FA-targeted LMs at physiologically relevant (high serum) culture conditions. DMs and LMs exhibited similar targeting efficiencies in non-serum containing media; however, the use of serum containing media substantially reduced the targeting ability of LM, while DMs remained unaffected. Further studies provided evidence for the positive role of dendritic polymer architectures for overcoming the negative effect of protein corona formation on targeted cellular interactions. The controlled, high stability self-assembled structures produced by PDCs as well as the ability to engineer the cellular interactions of DMs through simple manipulation of physicochemical properties such as PEG corona length provide compelling evidence for the future development of DMs as targeted drug delivery platforms. Advisors/Committee Members: Hong, Seungypo (advisor), Kral, Petr (committee member), Onyuksel, Hayat (committee member), Burdette, Joanna (committee member), Swanson, Steven (committee member).

Subjects/Keywords: Nanocarriers; dendrimers; dendron micelles; cell interactions; polymer; self-assembly; active targeting

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APA (6^th Edition):

Pearson, R. M. (2015). Impact of Dendritic Polymer Architecture on Self-assembly, Cellular Interactions, and Protein Adsorption. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19378

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pearson, Ryan M. “Impact of Dendritic Polymer Architecture on Self-assembly, Cellular Interactions, and Protein Adsorption.” 2015. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19378.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pearson, Ryan M. “Impact of Dendritic Polymer Architecture on Self-assembly, Cellular Interactions, and Protein Adsorption.” 2015. Web. 12 Apr 2021.

Vancouver:

Pearson RM. Impact of Dendritic Polymer Architecture on Self-assembly, Cellular Interactions, and Protein Adsorption. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19378.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pearson RM. Impact of Dendritic Polymer Architecture on Self-assembly, Cellular Interactions, and Protein Adsorption. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19378

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Carlson, Skylar. Secondary Metabolite Regulation And Drug-Lead Discovery From Aquatic Actinomycetes.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19520

► Chapter 1 provides an introduction to the field of natural products, drug discovery from the aquatic environment, and the development of Actinobacteria as a resource… (more)

Subjects/Keywords: actinomycete; drug discovery; coculture; co-cultivation; aquatic actinomycetes

11 more images…

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APA (6^th Edition):

Carlson, S. (2015). Secondary Metabolite Regulation And Drug-Lead Discovery From Aquatic Actinomycetes. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19520

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Carlson, Skylar. “Secondary Metabolite Regulation And Drug-Lead Discovery From Aquatic Actinomycetes.” 2015. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19520.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Carlson, Skylar. “Secondary Metabolite Regulation And Drug-Lead Discovery From Aquatic Actinomycetes.” 2015. Web. 12 Apr 2021.

Vancouver:

Carlson S. Secondary Metabolite Regulation And Drug-Lead Discovery From Aquatic Actinomycetes. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19520.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Carlson S. Secondary Metabolite Regulation And Drug-Lead Discovery From Aquatic Actinomycetes. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19520

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

11. O hAinmhire, Eoghainin. Identification and Characterization of Potential Drug Targets In Serous Ovarian Cancer.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19811

► Ovarian cancer is the most lethal gynecological disease in women in the US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade… (more)

▼ Ovarian cancer is the most lethal gynecological disease in women in the US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade serous ovarian carcinomas, demonstrating a critical role. Additionally, the Transforming Growth Factor Beta (TGFβ) pathway is dysfunctional in various malignancies, including ovarian cancer. This study investigated how expression of wild-type, mutant, or the absence of p53 alters ovarian cancer cell response to TGFβ signaling. It also investigated the response of the ovarian surface epithelium and the fallopian tube epithelium to TGFβ. Only ovarian cancer cells expressing wild-type p53 were growth inhibited by TGFβ, while ovarian cancer cells that were mutant or null for p53 were not growth inhibited. TGFβ induced migration in p53 null SKOV3 cells, which was not observed in SKOV3 cells with stable expression of mutant p53 (specifically the R273H mutation). Knockdown of wild-type p53 in the ovarian cancer cells, OVCA 420, enhanced cell migration in response to TGFβ. Increased protein expression of DKK1 and TMEPAI, two pro-invasive genes with enhanced expression in late stage metastatic ovarian cancer, was observed in p53 knockdown and null cells, while cells stably expressing mutant p53 demonstrated lower DKK1 and TMEPAI induction. Expression of mutant p53 or loss of p53 permit continued proliferation of ovarian cancer cell lines in the presence of TGFβ; however, cells expressing mutant p53 exhibit reduced migration as compared to wild-type and null cells, and they expressed decreased protein levels of DKK1 and TMEPAI. The cell of origin of ovarian cancer has come into question in recent years, with both the ovarian surface epithelium and the fallopian tube epithelium hypothesized to give rise to high-grade serous histotype. PAX8 is a Müllerian-expressed developmental transcription factor in the fallopian tube and high grade serous ovarian tumors, but PAX8 is not expressed in the ovarian surface epithelium. Loss of PAX8 in high-grade serous ovarian cancer leads to decreased proliferation and apoptosis. Additionally, murine models of high-grade serous ovarian cancer derived from the ovarian surface epithelium demonstrate acquired expression of PAX8 protein. This study investigated the functional and mechanistic role of PAX8 in progenitor cells of ovarian cancer. Murine OSE cells stably expressing PAX8 showed morphological and functional changes. Specifically, MOSE-PAX8 cells had increased levels of proliferation and migration, but no increase in anchorage independence. Protein and mRNA levels of pro-migratory genes, N-cadherin, fibronectin and slug, were increased in MOSE-PAX8 cells compared to control cells. Stable knockdown and knockout of PAX8 in murine oviductal epithelium could not be maintained, however, transient suppression of PAX8 did not induce cell cycle arrest or apoptosis in these cells but did slow proliferation. PAX8 is often expressed in HGSC, and several pathways associated with HGSC were shown to upregulate PAX8 regardless of the cell of origin.… Advisors/Committee Members: Burdette, Joanna E. (advisor), Murphy, Brian T. (committee member), Barbolina, Maria (committee member), Stocco, Carlos (committee member), Beck, William T. (committee member).

Subjects/Keywords: Ovarian cancer; drug discovery; p53; TGFbeta; PAX8

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

APA (6^th Edition):

O hAinmhire, E. (2015). Identification and Characterization of Potential Drug Targets In Serous Ovarian Cancer. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19811

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

O hAinmhire, Eoghainin. “Identification and Characterization of Potential Drug Targets In Serous Ovarian Cancer.” 2015. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19811.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

O hAinmhire, Eoghainin. “Identification and Characterization of Potential Drug Targets In Serous Ovarian Cancer.” 2015. Web. 12 Apr 2021.

Vancouver:

O hAinmhire E. Identification and Characterization of Potential Drug Targets In Serous Ovarian Cancer. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19811.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

O hAinmhire E. Identification and Characterization of Potential Drug Targets In Serous Ovarian Cancer. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19811

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

12. Hart, Peter C. Manganese Superoxide Dismutase (MnSOD): A Driver of Metabolism Critical for Breast Cancer Progression.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20243

► Manganese superoxide dismutase (MnSOD) is a critical mitochondrial resident enzyme responsible for the conversion of the mild oxidant superoxide anion (O2-•) to hydrogen peroxide (H2O2),… (more)

Subjects/Keywords: MnSOD; manganese superoxide dismutase; cancer metabolism; glycolysis; Warburg Effect; hydrogen peroxide; reactive oxygen species

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APA (6^th Edition):

Hart, P. C. (2016). Manganese Superoxide Dismutase (MnSOD): A Driver of Metabolism Critical for Breast Cancer Progression. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20243

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hart, Peter C. “Manganese Superoxide Dismutase (MnSOD): A Driver of Metabolism Critical for Breast Cancer Progression.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/20243.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hart, Peter C. “Manganese Superoxide Dismutase (MnSOD): A Driver of Metabolism Critical for Breast Cancer Progression.” 2016. Web. 12 Apr 2021.

Vancouver:

Hart PC. Manganese Superoxide Dismutase (MnSOD): A Driver of Metabolism Critical for Breast Cancer Progression. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/20243.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hart PC. Manganese Superoxide Dismutase (MnSOD): A Driver of Metabolism Critical for Breast Cancer Progression. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20243

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

13. Xie, Jia. Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20256

► High-grade serous carcinoma (HGSC) is the most common and lethal histotype of ovarian cancer. Radiation is usually used as a second-line treatment against the disease.… (more)

▼ High-grade serous carcinoma (HGSC) is the most common and lethal histotype of ovarian cancer. Radiation is usually used as a second-line treatment against the disease. In spite of numerous clinical studies indicating efficacy of radiation therapy in patients suffering from disease recurrence, it is seldom used clinically due to severe dose-related toxicity. Discovery and utilization of novel radiosensitizers could control the toxicity and enable effective therapeutic application of radiation. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors. Our previous publications showed that CX3CR1 is not expressed in normal ovarian surface epithelium and is expressed in primary and metastatic epithelial ovarian carcinoma. Moreover, transient downregulation of CX3CR1 in ovarian cancer cells will impair their proliferation as well as their migration and adhesion to peritoneal mesothelial cells. Therefore, we proposed combining CX3CR1 downregulation and radiation as a strategy for reducing the dose of radiation while maintaining the therapeutic efficacy. The experimental observations indicated that transient downregulation of CX3CR1 in most HGSC cell lines can lead to radiosensitization, as determined by clonogenic assay. However, loss of CX3CR1 does not affect radiosensitivity in ovarian cancer cells that express wild-type p53. There are several altered characteristics that may contribute to resistance to ionizing radiation, including enhanced DNA damage repair, and adaptive response to the radiation-induced ROS (Reactive Oxygen Species). Specifically, my results indicated that downregulation of CX3CR1 can abrogate the phosphorylation and activation of DNA double-strand break repair related proteins following ionizing radiation. The unrepaired DNA damage leads to damage persistence and ultimately contributes to radiosensitization. Another mechanism by which CX3CR1 knockdown alters radiosensitivity is the regulation of cellular redox capacity, where loss of CX3CR1 leads to elevated ROS levels. Taken together, my study demonstrated for the novel findings that loss of CX3CR1 can sensitize HGSC cells to ionizing radiation through the regulation of DNA damage response and intracellular redox status. Advisors/Committee Members: Barbolina, Maria (advisor), Nitiss, John (committee member), Jeong, Hyun-Young (committee member), Burdette, Joanna (committee member), Diamond, Alan (committee member).

Subjects/Keywords: high-grade serous ovarian cancer; ionizing radiation; fractalkine receptor; DNA damage repair; reactive oxygen species

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

APA (6^th Edition):

Xie, J. (2016). Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20256

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xie, Jia. “Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/20256.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xie, Jia. “Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells.” 2016. Web. 12 Apr 2021.

Vancouver:

Xie J. Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/20256.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xie J. Fractalkine Receptor Regulates Cellular Response to X-Ray Radiation in Ovarian Cancer Cells. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20256

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

14. Hajirahimkhan, Atieh. Estrogenic And Chemopreventive Properties of Licorice Species Used For Menopausal Symptoms.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20952

► Hormone therapy (HT) has been the most efficacious treatment for relieving menopausal symptoms. However, Women’s Health Initiative showed an increased breast cancer risk associated with… (more)

▼ Hormone therapy (HT) has been the most efficacious treatment for relieving menopausal symptoms. However, Women’s Health Initiative showed an increased breast cancer risk associated with HT. Therefore, menopausal women have turned to alternative options such as licorice. Glycyrrhiza glabra (GG), Glycyrrhiza uralensis (GU), and Glycyrrhiza inflata (GI) have been considered medicinal licorice; however, their estrogenic efficacy and their role in chemoprevention have not been well documented. In this study GG, GU, and GI induced estrogen responsive alkaline phosphatase activity in Ishikawa cells, estrogen responsive element (ERE)-luciferase in MCF-7 cells, and Tff1 mRNA in T47D cells. The estrogenic activity decreased as GU > GI > GG. Liquiritigenin (LigF) the principle phytoestrogen of licorice showed better binding affinity for estrogen receptor (ER) β. Isoliquiritigenin (LigC) the precursor chalcone of LigF demonstrated estrogenic activity which could be the result of its cyclization to LigF under physiological conditions. GG, GU, and LigF did not exhibit uterine proliferation in immature rats; however, LigF suppressed E2-induced uterine growth which could be associated with its ERβ as well as partial agonist effects. Licorice species were studied for activating a chemoprevention marker, NAD(P)H:quinone oxidoreductase 1 (NQO1) as they contain Michael acceptors such as LigC and also licochalcone A (LicA) from GI. Extracts activated NQO1 in hepa1c1c7 cells with the rank order GI > GG ≅ GU. The rank order for the compounds was LigC > LicA ≫ LigF. GG, GU, and LigC enhanced NQO1 levels in MCF-10A cells. Activation of antioxidant response element in HepG2-ARE-C8 cells suggested the involvement of Keap1-Nrf2 pathway. When GG and GU were orally administered to mature female rats LigC and LigF were detected in liver, serum, and mammary tissues with a significant increase in NQO1 activity in mammary glands. LigC did not enhance NQO1 activity in vivo likely due to rapid metabolism. This study showed the impact of chemical profile on the biological activities of licorice species and further supported the importance of simultaneous chemical and biological evaluation as well as standardization of botanicals. Advisors/Committee Members: Bolton, Judy L. (advisor), van Breemen, Richard (committee member), Burdette, Joanna (committee member), Che, Chun-Tao (committee member), Tonetti, Debra (committee member).

Subjects/Keywords: Breast cancer; Chemoprevention; Estrogen; Isoliquiritigenin; Licorice; Licochalcone A; Liquiritigenin; Menopause

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

APA (6^th Edition):

Hajirahimkhan, A. (2016). Estrogenic And Chemopreventive Properties of Licorice Species Used For Menopausal Symptoms. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20952

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hajirahimkhan, Atieh. “Estrogenic And Chemopreventive Properties of Licorice Species Used For Menopausal Symptoms.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/20952.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hajirahimkhan, Atieh. “Estrogenic And Chemopreventive Properties of Licorice Species Used For Menopausal Symptoms.” 2016. Web. 12 Apr 2021.

Vancouver:

Hajirahimkhan A. Estrogenic And Chemopreventive Properties of Licorice Species Used For Menopausal Symptoms. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/20952.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hajirahimkhan A. Estrogenic And Chemopreventive Properties of Licorice Species Used For Menopausal Symptoms. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20952

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

15. Modi, Dimple A. Modeling Precursor Lesions by Targeting Key Molecular Pathways in High-Grade Serous Ovarian Cancer.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20958

► High-Grade Serous Ovarian Cancer (HGSC) is the deadliest gynecological malignancy that affects women worldwide. A major confounding factor in the field is that the epithelial… (more)

▼ High-Grade Serous Ovarian Cancer (HGSC) is the deadliest gynecological malignancy that affects women worldwide. A major confounding factor in the field is that the epithelial subtype responsible for HGSC is unclear and could either be the ovarian surface epithelium (OSE) or the fallopian tube epithelium (FTE) or both. Regardless of organ site, elevated levels of gonadotropin hormones are associated with increased incidence of ovarian cancer. Gonadotropins increased proliferation in both 3D ovarian organ culture and in a 2D normal mouse OSE cell line. Activation of pathways, such as Akt, EGFR, Birc5, Cdk2, Cdk4, and Cdkn2a identified in the 3D organ cultures, were also validated in 2D MOSE cells. Akt and EGFR inhibitors blocked gonadotropin-induced cell proliferation in 3D organ and 2D cell culture. These data suggested that the gonadotropins stimulate some of the same proliferative pathways in normal OSE that are activated in ovarian cancers. Rapid advances have been made in modeling serous pathogenesis from the FTE. However, the existing models fail to recapitulate the molecular basis of early precursor lesion development from the FTE. Loss of PAX2 is one of the earliest reported changes identified in the FTE that may define the transition of the normal FTE into benign lesions. Combination of PAX2 loss and mutant TP53 in murine oviductal epithelium (MOE) cells altered functional characteristics in vitro but was insufficient to drive tumorigenesis in vivo. Re-expression of PAX2 in PAX2-null human HGSC cells reduced tumorigenic properties via apoptosis. Reduced levels of PTEN negatively regulated PAX2 expression in MOE cells and stable re-expression of PAX2 reduced the tumorigenic effects from PTEN silencing. A novel biological screen identified a molecule that can activate PAX2 expression in MOE cells. A novel targeted delivery system conjugated to Follicle Stimulating Hormone (FSH) peptide was designed to specifically target FSH receptor in ovarian cancer cells. The selectivity of the FSH-targeted dendrimers was validated in 3D ovarian organ cultures, in vivo and in a HGSC cell line. In summary, it is critical to determine the mechanism of early precursor formation and design delivery systems to accurately target ovarian cancer cells. Advisors/Committee Members: Burdette, Joanna E. (advisor), Bolton, Judy (committee member), Stocco, Carlos (committee member), Barbolina, Maria (committee member), Thomas, Douglas (committee member).

Subjects/Keywords: gonadotropins; serous ovarian cancer; PAX2; p53; fallopian tube; dendrimer

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

APA (6^th Edition):

Modi, D. A. (2016). Modeling Precursor Lesions by Targeting Key Molecular Pathways in High-Grade Serous Ovarian Cancer. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20958

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Modi, Dimple A. “Modeling Precursor Lesions by Targeting Key Molecular Pathways in High-Grade Serous Ovarian Cancer.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/20958.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Modi, Dimple A. “Modeling Precursor Lesions by Targeting Key Molecular Pathways in High-Grade Serous Ovarian Cancer.” 2016. Web. 12 Apr 2021.

Vancouver:

Modi DA. Modeling Precursor Lesions by Targeting Key Molecular Pathways in High-Grade Serous Ovarian Cancer. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/20958.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Modi DA. Modeling Precursor Lesions by Targeting Key Molecular Pathways in High-Grade Serous Ovarian Cancer. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20958

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

16. Choi, Su-Young. Hormonal Regulation of Hepatic CYP Expression: Implications in Altered Drug Metabolism during Pregnancy.

Degree: 2012, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/9282

► Pregnancy alters hepatic drug metabolism in a cytochrome P450 (CYP) isoform-specific manner, and rising concentrations of female hormones are potentially responsible for the changes. The… (more)

▼ Pregnancy alters hepatic drug metabolism in a cytochrome P450 (CYP) isoform-specific manner, and rising concentrations of female hormones are potentially responsible for the changes. The objective of this study is to determine the effects of estradiol (E2) and progesterone (PRG) on the expression and activities of hepatic CYPs. In chapter 2, human hepatocytes were treated with E2, PRG, their combination, or known CYP inducers and the mRNA expression and activity levels of CYP were determined. The roles of orphan nuclear receptors in hormone-mediated CYP regulation were also determined by promoter activity assays. The results show that E2 enhances CYP2A6, CYP2B6, and CYP3A4 expression whereas PRG enhances CYP2A6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 expression. E2 also increased the activities of CYP2C9 and CYP2E1 without affecting the mRNA levels. A combination of estrogens and PRG exhibited an additive effect on CYP3A4 expression, but not on CYP2A6 and CYP2B6 expression. The promoter assays showed that E2 is a constitutive androstane receptor activator, and PRG is a pregnane X receptor activator. When these results were compared with the clinical observations, increased activities of CYP2A6, CYP2C9 and CYP3A4/5 during pregnancy can be, at least in part, attributable to increased female hormone levels. In Chapter 3, we characterized effects of E2 on the expression of rat hepatic CYPs in vivo. Female Sprague-Dawley rats were treated with estradiol benzoate or known CYP inducers, and the expression and activities of CYPs and their modulators were determined. The results showed that E2 enhanced the expression of CYP1A2, CYP2C6, CYP2C7, CYP2C12, and CYP3A9 while the expression of CYP3A1, PXR, CAR, and POR was downregulated. The directional changes observed in female rats are mostly different from those clinically observed during human pregnancy. In chapter 4, we evaluated DMSO-treated Huh 7 cells as an in vitro model system for drug metabolism studies. The results showed that 2% DMSO treatment dramatically induced the mRNA expression levels and activities of most DMEs in Huh7 cells. However, compared to human hepatocytes, the overall expression and activities of DMEs were still low, limiting the utility of DMSO-treated Huh7 cells as a substitution for hepatocytes. Advisors/Committee Members: Jeong, Hyunyoung (advisor), Bolton, Judy (committee member), Burdette, Joanna (committee member), Fischer, James (committee member), van Breemen, Richard (committee member).

Subjects/Keywords: Cytochrome P450; pregnancy; estradiol; progesterone; primary human hepatocytes; drug metabolism

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

APA (6^th Edition):

Choi, S. (2012). Hormonal Regulation of Hepatic CYP Expression: Implications in Altered Drug Metabolism during Pregnancy. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9282

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Choi, Su-Young. “Hormonal Regulation of Hepatic CYP Expression: Implications in Altered Drug Metabolism during Pregnancy.” 2012. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/9282.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Choi, Su-Young. “Hormonal Regulation of Hepatic CYP Expression: Implications in Altered Drug Metabolism during Pregnancy.” 2012. Web. 12 Apr 2021.

Vancouver:

Choi S. Hormonal Regulation of Hepatic CYP Expression: Implications in Altered Drug Metabolism during Pregnancy. [Internet] [Thesis]. University of Illinois – Chicago; 2012. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/9282.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Choi S. Hormonal Regulation of Hepatic CYP Expression: Implications in Altered Drug Metabolism during Pregnancy. [Thesis]. University of Illinois – Chicago; 2012. Available from: http://hdl.handle.net/10027/9282

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

17. Hilliard, Tyvette S. Gonadotropins Regulate Oncogenic Pathways in Ovarian Surface Epithelium in a Three-Dimensional Model.

Degree: 2012, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/9298

► Ovarian cancer is the most lethal gynecological malignancy among American women, killing 70% of women diagnosed due to the lack of signs and symptoms leading… (more)

▼ Ovarian cancer is the most lethal gynecological malignancy among American women, killing 70% of women diagnosed due to the lack of signs and symptoms leading to late diagnosis. Epithelial ovarian carcinomas are primarily derived from a single layer of epithelial cells surrounding the ovary, the ovarian surface epithelium (OSE). Ovarian surface proliferation associated with ovulation, and the gonadotropins that regulate ovulation have been suggested to play a role in ovarian surface transformation and cancer progression. The elevated levels of gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH), during ovulation, menopause, and premature ovarian failure have been hypothesized to play a role in the initiation and progression of ovarian cancer. Aspects of ovarian surface repair following ovulation include proliferation, migration, and surface regeneration. In order to study ovarian surface repair, an organ culture system was developed that supports the proliferation, encapsulation, and repair of an artificially wounded surface. Wounded mouse ovaries embedded into an alginate hydrogel matrix have normal OSE cells as demonstrated by expression of cytokeratin 8, vimentin, N-cadherin, and a lack of E-cadherin. Normal OSE cells began proliferating and migrating around wounded surfaces after 1 day of culture. Organ cultures were propagated in medium supplemented with bovine serum albumin (BSA) or fetal bovine serum (FBS) to determine optimal growth conditions. OSE from BSA cultured organs proliferated significantly more than controls until day 4 while organs cultured in FBS had significantly more surface area encapsulated by OSE. The role of the gonadotropins in normal OSE is not well characterized; however, previous in vivo studies demonstrated that the gonadotropins increased OSE proliferation but in vitro studies were inconclusive because the OSE cells studied were usually immortalized and underwent morphological changes. Using a three-dimensional (3D) organ culture system, the role of gonadotropins in normal OSE in the absence of ovulation was investigated to test the hypothesis that the gonadotropins increase OSE proliferation by activating oncogenic pathways that may lead to induction of ovarian cancer. The 3D ovarian organ culture confirmed previous in vivo studies that demonstrated FSH and LH promote proliferation of the OSE. Transcriptional array analyses demonstrated the gonadotropins activated pathways that control cell cycle, angiogenesis and metastasis. Akt and epidermal growth factor receptor (EGFR) signaling were integral to gonadotropin induced OSE proliferation as demonstrated by abrogation by specific chemical inhibitors of these pathways. Western blots confirmed that Akt expression is not only enhanced, but Akt is also phosphorylated from FSH and LH treatment. However, inhibition of Akt signaling did not completely suppress Akt expression in LH treated ovaries, likely due to upregulation of both Akt1 and Akt2. Soft agar transformation experiments indicated menopausal… Advisors/Committee Members: Burdette, Joanna E. (advisor), Bolton, Judy (committee member), Swanson, Steven (committee member), Thomas, Douglas (committee member), Barbolina, Maria (committee member).

Subjects/Keywords: gonadotropins; ovarian surface epithelium; ovarian cancer

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

APA (6^th Edition):

Hilliard, T. S. (2012). Gonadotropins Regulate Oncogenic Pathways in Ovarian Surface Epithelium in a Three-Dimensional Model. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9298

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hilliard, Tyvette S. “Gonadotropins Regulate Oncogenic Pathways in Ovarian Surface Epithelium in a Three-Dimensional Model.” 2012. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/9298.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hilliard, Tyvette S. “Gonadotropins Regulate Oncogenic Pathways in Ovarian Surface Epithelium in a Three-Dimensional Model.” 2012. Web. 12 Apr 2021.

Vancouver:

Hilliard TS. Gonadotropins Regulate Oncogenic Pathways in Ovarian Surface Epithelium in a Three-Dimensional Model. [Internet] [Thesis]. University of Illinois – Chicago; 2012. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/9298.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hilliard TS. Gonadotropins Regulate Oncogenic Pathways in Ovarian Surface Epithelium in a Three-Dimensional Model. [Thesis]. University of Illinois – Chicago; 2012. Available from: http://hdl.handle.net/10027/9298

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

18. Mistry, Tina L. SpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabI.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21583

► This dissertation includes work on three projects. The first project was focused on conducting a high-throughput screen (HTS) with a 25000 compound library to discover… (more)

Subjects/Keywords: PurC; HTS; malachite green; FabI; mechanism of action; S. aureus

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APA (6^th Edition):

Mistry, T. L. (2016). SpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabI. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21583

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mistry, Tina L. “SpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabI.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/21583.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mistry, Tina L. “SpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabI.” 2016. Web. 12 Apr 2021.

Vancouver:

Mistry TL. SpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabI. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/21583.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mistry TL. SpPurC Hit Selection Optimization and Evaluation of Benzimidazole-based Inhibitors of S. aureus FabI. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21583

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

19. Gauntner, Timothy. Stromal Cell Regulation of the Prostate Epithelial Stem Cell Niche.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21592

► The molecular mechanisms underlying developmental morphogenesis have long been suspected to also play important roles in cancer. Stem cells, being fundamental to both of these… (more)

▼ The molecular mechanisms underlying developmental morphogenesis have long been suspected to also play important roles in cancer. Stem cells, being fundamental to both of these processes, can be the cells-of-origin in those cancers whose pathogeneses involve subversion of developmental signaling pathways. Therefore, cells and signaling pathways that regulate stem cells during development are likely to also play a role in carcinogenesis. The prostate stroma is essential for normal androgenic development of the prostate gland, including epithelial growth and differentiation. Thus, it stands to reason that key aspects of stromal regulation of epithelial development are mediated through control of the epithelial stem cells, but this has yet to be proven. Given the compelling evidence that stem cells are preferential cells-of-origin in many cancers, it is essential that the regulatory mechanisms governing normal prostate stem cell homeostasis are elucidated so that this knowledge can be exploited towards development of novel treatments for prostate cancer growth regulation. Recent evidence from our laboratory suggests that estrogens are key modulators of prostate epithelial stem and progenitor cells. Furthermore, it has been shown by our laboratory and others that estrogens can act as carcinogens in rodent and human models of prostate cancer. When these two facts are considered along with the well-documented role of estrogen receptor signaling in prostate stromal cells, an intriguing model emerges whereby aberrant stromal estrogenic control of epithelial stem cells may contribute to prostate carcinogenesis. To test the hypothesis that prostate stromal cells secrete paracrine factors that regulate epithelial stem and progenitor cells in both normal and cancer niches, and that 17β-estradiol modulates the secretion of these factors, the following specific aims were proposed for this thesis work: 1. Elucidate how stromal cells modulate prostate stem and progenitor cell homeostasis within the normal adult human stem cell niche. 2. Determine how estrogen signaling modulates the stromal-epithelial signaling axis within the normal adult human stem cell niche. 3. Delineate the role of stromal cells in the prostate cancer stem cell niche. This work was performed using patient- and donor-derived primary cells in order to maximize the translational relevance of this work, while at the same time reducing artifacts often introduced by monoclonal, immortalized cell lines. Advisors/Committee Members: Prins, Gail S (advisor), Bosland, Maarten (committee member), Nonn, Larisa (committee member), Burdette, Joanna (committee member), Diamond, Alan M (chair).

Subjects/Keywords: Prostate cancer; stem cells; cancer-associated fibroblasts; stem cell niche; stromal-epithelial interactions, estrogen, estrogen receptor alpha; ERalpha; ERα; CAF; CAFs; TCGA; bioinformatics; IL6; LAMA5; prostasphere

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

APA (6^th Edition):

Gauntner, T. (2016). Stromal Cell Regulation of the Prostate Epithelial Stem Cell Niche. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21592

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gauntner, Timothy. “Stromal Cell Regulation of the Prostate Epithelial Stem Cell Niche.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/21592.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gauntner, Timothy. “Stromal Cell Regulation of the Prostate Epithelial Stem Cell Niche.” 2016. Web. 12 Apr 2021.

Vancouver:

Gauntner T. Stromal Cell Regulation of the Prostate Epithelial Stem Cell Niche. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/21592.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gauntner T. Stromal Cell Regulation of the Prostate Epithelial Stem Cell Niche. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21592

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

20. Baumgarten, Sarah Catherine. Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation.

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21843

► Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation Infertility affects more than 7% of couples in the United States. Approximately… (more)

▼ Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation Infertility affects more than 7% of couples in the United States. Approximately 40% of these infertility cases can be attributed to ovarian dysfunction, where a woman is unable to produce and/or ovulate mature oocytes for fertilization. For those who seek assisted reproductive technologies such as in vitro fertilization (IVF), anovulation is often overcome by the administration of follicle stimulating hormone (FSH) to induce the development of the oocyte-containing ovarian follicles. During follicle development to the preovulatory stage, undifferentiated granulosa cells proliferate and differentiate into two distinct populations: mural granulosa cells that line the wall of the follicle and cumulus granulosa cells that surround the oocyte. These cells work together to foster steroid hormone synthesis and oocyte development, respectively, both of which are required for normal fertility. In humans, little is understood about the process of granulosa cell differentiation because access to undifferentiated granulosa cells is extremely rare. However, cumulus and mural granulosa cells can be collected from the follicular aspirates of women undergoing IVF. Studies in rodents have revealed that the cumulus granulosa cells are protected from FSH-induced differentiation by factors secreted from the oocyte. Thus, we hypothesized that cumulus cells obtained from patients undergoing in vitro fertilization (IVF) treatment could be cultured to study human granulosa cell differentiation, once separated from the oocyte and its influence. In a novel approach, cumulus and mural granulosa cells were collected from the follicular aspirates of IVF patients and cultured in serum-free, phenol red-free media. Gene expression analysis revealed that cumulus granulosa cells expressed significantly lower levels of differentiation genes including the luteinizing hormone receptor (LHR) and steroidogenic genes such as CYP19A1 (aromatase), CYP11A1 (P450 side chain cleavage), and STAR (steroidogenic acute regulatory protein) than the mural granulosa cells. Additionally, in cumulus, but not in mural, cells, treatment with FSH stimulated the expression of key differentiation genes including CYP19A1, CYP11A1, and StAR at both the mRNA and protein level. The fact that cumulus cells are less differentiated than mural cells in culture and differentiate in response to FSH treatment indicate the cultured cumulus granulosa cells can be used as an experimental approach to study human granulosa cell differentiation. Using cultured cumulus granulosa cells, we sought to understand the role of locally produced ovarian factors, such as insulin-like growth factors (IGFs), in granulosa cell differentiation and follicle maturation. Previous studies demonstrated that IGFs enhance FSH-induced granulosa cell differentiation. We found that FSH upregulated IGF2 at both the RNA and protein level, and that this stimulation was driven specifically by the P3-promoter of… Advisors/Committee Members: Stocco, Carlos (advisor), Burdette, Joanna (committee member), Heydemann, Ahlke (committee member), Unterman, Terry (committee member), Rao, Mrinalini (chair).

Subjects/Keywords: cumulus granulosa cells; FSH; IGF2; IGF1R

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APA (6^th Edition):

Baumgarten, S. C. (2017). Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21843

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Baumgarten, Sarah Catherine. “Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation.” 2017. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/21843.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Baumgarten, Sarah Catherine. “Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation.” 2017. Web. 12 Apr 2021.

Vancouver:

Baumgarten SC. Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/21843.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Baumgarten SC. Role of Insulin-like Growth Factors in Granulosa Cell Differentiation and Ovarian Follicle Maturation. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/21843

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

21. Li, Jing. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/22078

► The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. Major DSB repair pathways in mammalian cells include homologous recombination… (more)

▼ The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. Major DSB repair pathways in mammalian cells include homologous recombination and non-homologous end joining (NHEJ). NHEJ is a template-independent mechanism, yet many NHEJ repair products carry limited genetic changes, which suggest that NHEJ includes mechanisms to minimize error. In yeast, mutations of tyrosyl-DNA phosphodiesterase 1 (TDP1) reduced NHEJ fidelity. We are investigating the role of TDP1 in NHEJ in human cells. Using affinity capture chromatography, we found human TDP1 physically interacted with the required NHEJ protein -XLF. This interaction also stimulated DNA binding for both TDP1 and XLF, and formation of TDP1:XLF:DNA complexes. TDP1 can remove adducts from DNA 3’ ends, and TDP1:XLF interactions stimulated this activity on double-stranded, but not on single-stranded DNA. To investigate role of TDP1 in NHEJ in human cells, we used CRISPR/Cas9-mediated genome editing to generate TDP1-knockout HEK 293 cells, which showed an expected increase sensitivity to Topoisomerase 1 poisoning and ionizing radiation. Using a chromosomally- integrated end-joining reporter substrate, we observed an average 4-fold reduction in repair of I-SceI-induced DSBs in TDP1-KO cells as compared to wild type cells. These data indicate that, in human cells, TDP1 contributes to repair of DSBs that lack 3’ end damage. NextGen sequencing of end-joining junctions generated in this reporter system showed that TDP1 deficiency resulted in increased use of microhomology in joining. Within the N-terminal domain of TDP1, phosphorylation at serine 81 (S81) has been reported to regulate interaction with DNA repair factors, including DNA ligase III, XRCC4 and PARP1. We observed that the TDP1-S81 phosphomimetic, TDP1-S81E, had 10-fold reduced XLF binding, and ectopic expression of TDP1-S81E in TDP1-knockout cells failed to restore NHEJ activity. These data suggest that phosphorylation of TDP1-S81 regulates TDP1 participation in NHEJ, and may also direct TDP1 towards DNA ligase III-related pathways. Our observations support the hypothesis that TDP1 participates in mammalian NHEJ, and contribute important details to our understanding of DNA repair. Advisors/Committee Members: Hanakahi, Les (advisor), Nitiss, John (committee member), Mankin, Alexander (committee member), Burdette, Joanna (committee member), Thomas, Douglas (committee member), Hanakahi, Les (chair).

Subjects/Keywords: tyrosyl-DNA phosphodiesterase 1 (TDP1); non-homologous end joining (NHEJ); DNA double-strand breaks (DSB)

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APA (6^th Edition):

Li, J. (2017). Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Li, Jing. “Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).” 2017. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/22078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Li, Jing. “Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).” 2017. Web. 12 Apr 2021.

Vancouver:

Li J. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/22078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Li J. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

22. Muhammad, Maryam Bint. Synthetic Biology Tools for Polyketide Engineering.

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/22166

► This thesis discusses the advancement of synthetic biology tools for polyketide engineering, specifically in the construction of a genetic device for the biosynthesis of a… (more)

Subjects/Keywords: Synthetic biology; polyketides; fluorine chemistry; Streptomyces

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APA (6^th Edition):

Muhammad, M. B. (2017). Synthetic Biology Tools for Polyketide Engineering. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22166

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Muhammad, Maryam Bint. “Synthetic Biology Tools for Polyketide Engineering.” 2017. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/22166.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Muhammad, Maryam Bint. “Synthetic Biology Tools for Polyketide Engineering.” 2017. Web. 12 Apr 2021.

Vancouver:

Muhammad MB. Synthetic Biology Tools for Polyketide Engineering. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/22166.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Muhammad MB. Synthetic Biology Tools for Polyketide Engineering. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22166

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

23. Convissar, Scott M. Role of GATA4, GATA6, and SP1 on Luteal Function and LH Receptor Expression.

Degree: 2018, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/23039

► Infertility is defined by the inability to achieve pregnancy after 1 year of trying to conceive. According to the most recent report from the Center… (more)

▼ Infertility is defined by the inability to achieve pregnancy after 1 year of trying to conceive. According to the most recent report from the Center for Disease Control approximately 10% of woman ages 15-44 have difficulties getting pregnant or staying pregnant accounting for around 6.1 million women in the United States. An aption for couples seeking infertility treatment is the use of assisted reproductive technologies (ART) of which in vitro fertilization (IVF) accounts for over 99% of the ART procedures. The demand for IVF is increasing every year. In fact, the number of ART cycles has risen by 32% between the years 2006 and 2015. Primarily based on patients age, weight, and ovarian reserve, standardized IVF protocols are selected to maximize the likelihood to achieve pregnancy. Most protocols involved the administration of follicle-stimulating hormone (FSH) to induce the maturation of several ovarian follicles, which it is followed by human chorionic gonadotropin (hCG), an analog of LH, to trigger ovulation and the subsequent collection of eggs for in vitro fertilization. Although fertilization may be successful, inherent obstacles remain with achieving embryo transfer and maintaining pregnancy. Therefore, luteal phase support, in the form of progesterone or hCG supplementation, is required to prime the uterus for implantation and to maintain embryogenesis until the placenta become the main source of progesterone. However, luteal phase treatments increase the risk of a potentially life-threatening condition called ovarian hyperstimulation syndrome (OHSS), which is marked by ovarian vasodilation in response to hCG treatment. Chapters three and four of my thesis explored mechanisms involved with luteal cell function. Within chapter five, I have investigated the interaction between the oocyte and cumulus granulosa in primary human cumulus cells and focuses on the regulation of anti- Anti-Müllerian hormone (AMH), which is an important marker for ovarian reserve and OHSS risk. First, we focused our attention on the role of GATA factors in luteal cell function. Previous studies in our lab showed that GATA4 and GATA6 are essential for granulosa cell steroidogenesis, preovulatory follicle formation, and fertility. Therefore, the lack of preovulatory follicle formation in the granulosa cell GATA knockout mice precluded the investigation of the role of GATA in the corpus luteum. To overcome this problem, we used a Cre-lox mouse model in which protein-coding exons of GATA4 and GATA6 were deleted with progesterone receptor (PR) driven Cre Recombinase expression. PR expression only occurs in the ovary at the time of ovulation. Therefore, we were able to investigate the effect of the knockdown of GATA4 and GATA6 as granulosa cells luteinize and the corpus luteum is formed. We observed that the deletion of either GATA4 or GATA6 alone results in subfertility while the elimination of both GATA factors renders female mice infertile. This experimental approach also revealed that although estrous cyclicity and ovulation are… Advisors/Committee Members: Stocco, Carlos (advisor), Wolska, Beata (committee member), Liew, Chong Wee (committee member), Burdette, Joanna (committee member), Rasenick, Mark (chair).

Subjects/Keywords: GATA; corpus luteum; luteal; progesterone; steroidogenesis; LHR; progesterone; SP1; GDF9; BMP15; AMH; granulosa; reproduction; ovary; mRNA

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APA (6^th Edition):

Convissar, S. M. (2018). Role of GATA4, GATA6, and SP1 on Luteal Function and LH Receptor Expression. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23039

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Convissar, Scott M. “Role of GATA4, GATA6, and SP1 on Luteal Function and LH Receptor Expression.” 2018. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/23039.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Convissar, Scott M. “Role of GATA4, GATA6, and SP1 on Luteal Function and LH Receptor Expression.” 2018. Web. 12 Apr 2021.

Vancouver:

Convissar SM. Role of GATA4, GATA6, and SP1 on Luteal Function and LH Receptor Expression. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/23039.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Convissar SM. Role of GATA4, GATA6, and SP1 on Luteal Function and LH Receptor Expression. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23039

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

24. Summerlin, Matthew Brock. Small Molecule And Protein Modifiers of The NHEJ Pathway.

Degree: 2018, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/23046

► Non-Homologous End Joining (NHEJ) is a pathway for the repair of DNA doube-strand breaks (DSBs) that is active throughout the cell cycle and does not… (more)

▼ Non-Homologous End Joining (NHEJ) is a pathway for the repair of DNA doube-strand breaks (DSBs) that is active throughout the cell cycle and does not use a template to direct the repair. NHEJ is dependent upon the Ku70/80, DNA-PKcs,XRCC4, Ligase IV, and XLF proteins, and deficiency in any one of these factors results in failure of DSB repair by NHEJ. Additionally, proteins and small molecules have been shown to contribute to NHEJ. Deficiencies in these so-called “accessory” factors generally results in reduced NHEJ efficiency, rather than loss of NHEJ function. This dissertation examines the roles of two types of NHEJ accessory molecules, and the work presented here represents two studies. The first study focused on the small molecule myo-inositol hexakisphosphate (IP6), which has previously been shown to contribute to NHEJ in vitro. A biotinylated version of IP6 (IP6-bio) was developed and characterized as a possible tool to study the role of IP6 in NHEJ and other cellular processes. IP6-bio was similar to native IP6 in its ability to contribute to NHEJ in vitro and interacted with the required NHEJ factor Ku70/80, which had previously been reported to bind IP6. IP6-bio was not bound by other NHEJ factors. We concluded from the se data that IP6-bio can be used as a tool to study the role of IP6 in NHEJ. IP6-bio was also shown to interact with the known IP6-binding protein casein kinase 2 (CK2). Binding of IP6-bio by established IP6-binding proteins Ku70/80 and CK2 indicated that the critical determinants for IP6—binding were present in IP6-bio, and suggested that IP6-bio might be used to identify new IP6-binding proteins. Competition experiments using IP6 and less phosphorylated inositol phosphates as competitors showed that IP6-bio-binding proteins were preferentially competed off by IP6 and not by other inositol phosphates. These data indicate that proteins that bound IP6-bio may be bona fide IP6-binding proteins. Along these lines, one protein from the HEK293 extract that bound IP6-bio was the nucleolar protein nucleolin, which has been shown to participate in chromatin remodeling to facilitate DSB repair. Taken together the results of this study demonstrate that IP6-bio can by synthesized and used as a tool to investigate the role of IP6 in cellular processes, and to identify new IP6-binding proteins. The second study investigated the role of the small proteins encoded by the Cell Cycle Regulator of NHEJ (CYREN) gene in NHEJ. CYREN-deficient cells had reduced end-joining and increased sensitivity to agents that cause DNA damage that requires NHEJ for repair. Additionally, extracts prepared from CYREN-deficient cells had reduced NHEJ activity in vitro. CYREN-encoded proteins were found to physically interact with the required NHEJ protein XLF. Further, CYREN-XLF interaction impacted DNA-binding by XLF, and reduced XLF-XRCC4-DNA interactions. We interpret these data as a role for CYREN in regulating the number of DNA ends that are processed during NHEJ to minimize error. Overall, this study identifies… Advisors/Committee Members: Hanakahi, Leslyn (advisor), Nitiss, John (committee member), Burdette, Joanna (committee member), Thomas, Doug (committee member), Mankin, Alexander (committee member), Hanakahi, Leslyn (chair).

Subjects/Keywords: NHEJ IP6 CYREN

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

APA (6^th Edition):

Summerlin, M. B. (2018). Small Molecule And Protein Modifiers of The NHEJ Pathway. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Summerlin, Matthew Brock. “Small Molecule And Protein Modifiers of The NHEJ Pathway.” 2018. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/23046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Summerlin, Matthew Brock. “Small Molecule And Protein Modifiers of The NHEJ Pathway.” 2018. Web. 12 Apr 2021.

Vancouver:

Summerlin MB. Small Molecule And Protein Modifiers of The NHEJ Pathway. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/23046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Summerlin MB. Small Molecule And Protein Modifiers of The NHEJ Pathway. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

25. Toh, May Fern. Identification and Biological Characterization of Progestins from Botanicals In Vitro and In Vivo.

Degree: 2014, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/18868

► Extensive studies have been conducted on botanicals for the presence of estrogenic molecules, unfortunately, very little has ever been done to identify plant-based progestins. This… (more)

▼ Extensive studies have been conducted on botanicals for the presence of estrogenic molecules, unfortunately, very little has ever been done to identify plant-based progestins. This underexplored area is troubling especially since there is a body of scientific evidence supporting the presence of progesterone receptor (PR) modulators in plant material that may affect endocrine function. The goal of this dissertation was to identify and characterize natural progesterone (P4)-like compounds from botanical extracts for the improvement of women’s health. Red clover, hops, angelica, black cohosh, kudzu, dogwood, and chaste-tree berry were investigated for their ability to interact with purified PR, to activate PRE-luciferase transcription in human breast cancer cells, and for tissue specific regulation of P4 inducible genes. Kaempferol was identified as having P4-like activity and may function in a cell-specific manner. In vivo studies revealed that kaempferol exhibited P4-like effects in ovariectomized Sprague-Dawley rat model. Since genistein is a phytoestrogen that previously demonstrated to increase uterine weight and proliferation, the ability of kaempferol to block genistein action in the uterus was investigated. Analyses of proliferation, steroid receptor expression, and induction of well-established PR-regulated targets Areg and Hand2 were completed. In addition, kaempferol in silico binding analysis was completed for PR, as was the activation of ER and AR signaling in vitro in order to determine receptor specificity. The data from this dissertation suggest that kaempferol interacts with PR, activates the receptor without stimulating its degradation, induces known PR target genes in vitro and in vivo and blocked genistein-induced proliferation in the luminal epithelial cells in Sprague-Dawley rat uteri. The toxicity of hops extracts in cell-based assays precluded further investigation in vitro, but an initial bioassay screen suggested that natural progestins can be identified from hops extracts. Further chemical and biological analyses are warranted to identify and characterize progestins from hops. The comprehensive framework outlined in this thesis will provide a promising avenue for the identification of potentially better and safer compounds capable of activating PR signaling from botanical extracts used for women's health. Advisors/Committee Members: Burdette, Joanna E. (advisor), Murphy, Brian T. (committee member), Moore, Terry W. (committee member), Thomas, Douglas D. (committee member), Stocco, Carlos D. (committee member).

Subjects/Keywords: Kaempferol; Progestin; Hormone replacement therapy; Genistein; Red clover; Progesterone receptor

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

APA (6^th Edition):

Toh, M. F. (2014). Identification and Biological Characterization of Progestins from Botanicals In Vitro and In Vivo. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/18868

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Toh, May Fern. “Identification and Biological Characterization of Progestins from Botanicals In Vitro and In Vivo.” 2014. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/18868.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Toh, May Fern. “Identification and Biological Characterization of Progestins from Botanicals In Vitro and In Vivo.” 2014. Web. 12 Apr 2021.

Vancouver:

Toh MF. Identification and Biological Characterization of Progestins from Botanicals In Vitro and In Vivo. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/18868.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Toh MF. Identification and Biological Characterization of Progestins from Botanicals In Vitro and In Vivo. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/18868

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

26. Vasudevan, Divya. Nitric Oxide is an Epigenetic Regulator of Transcription via Alteration of Histone Modification Profiles.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19545

► Nitric oxide (•NO) production has long been associated with aggressive cancers and is considered a negative prognostic indicator; however, its role in disease etiology has… (more)

▼ Nitric oxide (•NO) production has long been associated with aggressive cancers and is considered a negative prognostic indicator; however, its role in disease etiology has remained promiscuous. The aim of this project was to identify significant molecular mechanisms of •NO-signaling that drive cancer progression. Methylation and acetylation of histone lysine residues are important epigenetic regulators of cellular transcription. Aberrant histone methylation or acetylation patterns are often detected in high-grade tumors. Therefore, we tested the ability of •NO to mediate oncogenic phenotypes by acting as an epigenetic regulator. We generated a comprehensive map of histone modification changes at 15 different lysine residues in response to •NO via high-resolution mass spectrometry. Our data revealed that lysine K9 on histone H3 was extensively modified by •NO. Specifically, we saw an increase in dimethylation (H3K9me2), attributable to inhibition of demethylase activity at this site. •NO also significantly lowered acetylation at H3K9 (H3K9ac), potentially precluded due to increased methylation at the same residue. Next, we examined the ability of •NO to regulate gene expression downstream of histone modification changes. Genes differentially expressed due to association with •NO-altered H3K9me2/ac were identified by combined bioinformatic analysis of microarray and ChIP-seq data across the genome. Almost 6500 genes were differentially expressed in response to •NO and a significant proportion of transcription was regulated via epigenetic mechanisms. Our data revealed that differential enrichment of H3K9me2/ac at specific genes correlated with corresponding changes in their expression levels. These data demonstrate a unique mechanism of •NO signaling via regulation of multiple posttranslational histone modifications, which ultimately dictate gene expression changes leading to an oncogenic phenotype. Advisors/Committee Members: Thomas, Douglas D. (advisor), Bolton, Judy L. (committee member), Burdette, Joanna E. (committee member), Thatcher, Gregory R. (committee member), Sodhi, Monsheel S. (committee member).

Subjects/Keywords: Nitric oxide; epigenetics; histones; posttranslational modifications

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

APA (6^th Edition):

Vasudevan, D. (2015). Nitric Oxide is an Epigenetic Regulator of Transcription via Alteration of Histone Modification Profiles. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19545

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vasudevan, Divya. “Nitric Oxide is an Epigenetic Regulator of Transcription via Alteration of Histone Modification Profiles.” 2015. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/19545.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vasudevan, Divya. “Nitric Oxide is an Epigenetic Regulator of Transcription via Alteration of Histone Modification Profiles.” 2015. Web. 12 Apr 2021.

Vancouver:

Vasudevan D. Nitric Oxide is an Epigenetic Regulator of Transcription via Alteration of Histone Modification Profiles. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/19545.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vasudevan D. Nitric Oxide is an Epigenetic Regulator of Transcription via Alteration of Histone Modification Profiles. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19545

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

27. Lei, Hao. Inhibitor Development for Bacterial N5-CAIR Mutase and MERS Coronavirus Papain-like Protease.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/20892

► The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial… (more)

▼ The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial for Bacillus anthracis survival in serum. In this study, we adopted a fragment-based hit discovery approach, using three screening methods − saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR), against B. anthracis PurE (BaPurE) to identify active site binding fragments by initially testing 352 compounds in a Zenobia fragment library. Competition STD NMR with the BaPurE product effectively eliminated non-active site binding hits from the primary hits, selecting active site binders only. Binding affinities (dissociation constant, KD) of these compounds varied between 234 and 301 μM. Based on test results from the Zenobia compounds, we subsequently developed and applied a streamlined fragment screening strategy to screen a much larger library consisting of 3,000 computationally pre-selected fragments. Fifteen final fragment hits were confirmed to exhibit binding affinities varying from 14 μM to 900 μM, which were categorized into five different basic scaffolds. All fifteen fragment hits have ligand efficiencies higher than 0.30. We demonstrated that at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme. Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) is known to be essential for viral replication, making it an attractive target in antiviral drug discovery. In our study, we explored and optimized the MERS-PLpro crystallization condition. Two structures were solved with resolutions at 2.59 Å and 1.79 Å, respectively. The overall structure of MERS-PLpro resembles that of SARS-PLpro. The MERS-PLpro blocking loop 2 (BL2) structure differs significantly from that of SARS-PLpro, where it plays a crucial role in inhibitor binding. Four SARS-PLpro lead inhibitors with IC50 values ranging from 0.2 to 2.0 µM were tested against MERS-PLpro, none of which were effective against MERS-PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-PLpro were replaced by T274 and A275 in MERS-PLpro, eliminating critical binding interactions for similar types of inhibitors. High-throughput screening (HTS) of 25,000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. This newly identified compound acts as a competitive inhibitor with an IC50 of 6 µM against MERS-PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-PLpro with an IC50 of 11 µM. Docking studies were performed to predict the possible interactions between inhibitor and both SARS and MERS-PLpro. These results demonstrate that inhibitor recognition specificity of MERS-PLpro differs from that of SARS-PLpro. In addition, mutagenesis studies… Advisors/Committee Members: Johnson, Michael E. (advisor), Moore, Terry W. (committee member), Burdette, Joanna E. (committee member), Caffrey, Michael S. (committee member), Murphy, Brian T. (committee member).

Subjects/Keywords: PurE; Purine biosynthesis; Bacillus anthracis; STD-NMR; WaterLOGSY NMR; SPR; Fragment-based drug design; Coronavirus; MERS; Papain-like protease; Crystallography; High throughput screening; Enzyme inhibitor

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

APA (6^th Edition):

Lei, H. (2016). Inhibitor Development for Bacterial N5-CAIR Mutase and MERS Coronavirus Papain-like Protease. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/20892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lei, Hao. “Inhibitor Development for Bacterial N5-CAIR Mutase and MERS Coronavirus Papain-like Protease.” 2016. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/20892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lei, Hao. “Inhibitor Development for Bacterial N5-CAIR Mutase and MERS Coronavirus Papain-like Protease.” 2016. Web. 12 Apr 2021.

Vancouver:

Lei H. Inhibitor Development for Bacterial N5-CAIR Mutase and MERS Coronavirus Papain-like Protease. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/20892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lei H. Inhibitor Development for Bacterial N5-CAIR Mutase and MERS Coronavirus Papain-like Protease. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/20892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

28. Speltz, Thomas E. Developing Hydrocarbon Stapled Peptides for Inhibiting Estrogen Receptor/Coactivator Interactions.

Degree: 2018, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/23175

► A current limitation in treating estrogen receptor positive breast cancer is the development of resistance to endocrine therapy. Among the many possible mechanisms of resistance,… (more)

Subjects/Keywords: Stapled peptide; estrogen receptor; molecular dynamics; breast cancer

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

APA (6^th Edition):

Speltz, T. E. (2018). Developing Hydrocarbon Stapled Peptides for Inhibiting Estrogen Receptor/Coactivator Interactions. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23175

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Speltz, Thomas E. “Developing Hydrocarbon Stapled Peptides for Inhibiting Estrogen Receptor/Coactivator Interactions.” 2018. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/23175.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Speltz, Thomas E. “Developing Hydrocarbon Stapled Peptides for Inhibiting Estrogen Receptor/Coactivator Interactions.” 2018. Web. 12 Apr 2021.

Vancouver:

Speltz TE. Developing Hydrocarbon Stapled Peptides for Inhibiting Estrogen Receptor/Coactivator Interactions. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/23175.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Speltz TE. Developing Hydrocarbon Stapled Peptides for Inhibiting Estrogen Receptor/Coactivator Interactions. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23175

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

29. Manoel Crnkovic, Camila. Metabolomics for the Discovery of Natural Products from Cyanobacteria.

Degree: 2018, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/23299

► Cyanobacteria are chemically rich microorganisms shown to produce natural products with relevant biotechnological applications. The discovery of natural products has been traditionally based on bioassay-guided… (more)

▼ Cyanobacteria are chemically rich microorganisms shown to produce natural products with relevant biotechnological applications. The discovery of natural products has been traditionally based on bioassay-guided approaches. Recently, omics techniques have added new tools to the field of natural product discovery. In this study, we applied mass spectrometry metabolomics to explore the chemistry of cultured cyanobacteria, leading to the discovery of new metabolites. Comparative metabolomics was used to analyze cyanobacterial strains growing in media with different levels of phosphate and nitrate. Among many relevant observations, these experiments revealed a new linear peptide, named scytodecamide, produced in increased amounts by strain Scytonema sp. UIC 10036 under low nitrate and high phosphate conditions. In a second approach, in situ dereplication using the droplet–liquid microjunction–surface sampling probe (droplet probe) coupled with UPLC-UV-HRMS/MS led to the discovery of calothrixamides A and B from strain Calothrix sp. UIC 10520. Calothrixamides and scytodecamide were elucidated by HRMS, MS/MS, and 1D and 2D NMR, along with chemical degradation and derivatization reactions. Calothrixamides are the first functionalized fatty acid amides found in freshwater cyanobacteria and one of the few natural products described from the genus Calothrix. Their discovery inspired the investigation of other Calothrix strains for new natural products. A combination UPLC-HRMS profiling, UPLC-MS/MS, and stable isotope labeling experiments with PCA, molecular networking, and comparative metabolomics led to the identification of known and new natural products in Calothrix strains. This study presented metabolomic strategies that can be incorporated into natural product discovery workflows to select strains and identify new compounds from microbial sources. Advisors/Committee Members: Orjala, Jimmy (advisor), Murphy, Brian T. (committee member), Burdette, Joanna E. (committee member), Sanchez, Laura M. (committee member), Cologna, Stephanie M. (committee member), Orjala, Jimmy (chair).

Subjects/Keywords: cyanobacteria; metabolomics, structure elucidation; natural products; secondary metabolites

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

APA (6^th Edition):

Manoel Crnkovic, C. (2018). Metabolomics for the Discovery of Natural Products from Cyanobacteria. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/23299

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Manoel Crnkovic, Camila. “Metabolomics for the Discovery of Natural Products from Cyanobacteria.” 2018. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/23299.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Manoel Crnkovic, Camila. “Metabolomics for the Discovery of Natural Products from Cyanobacteria.” 2018. Web. 12 Apr 2021.

Vancouver:

Manoel Crnkovic C. Metabolomics for the Discovery of Natural Products from Cyanobacteria. [Internet] [Thesis]. University of Illinois – Chicago; 2018. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/23299.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Manoel Crnkovic C. Metabolomics for the Discovery of Natural Products from Cyanobacteria. [Thesis]. University of Illinois – Chicago; 2018. Available from: http://hdl.handle.net/10027/23299

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

30. Bai, He. Exploration of Histone Deacetylase Ligand Binding Modes by Photoaffinity Probes.

Degree: 2013, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/9803

► Histone deacetylases (HDACs) regulate chromatin structure and function. Since much of the literature has reported aberrant expression and recruitment of HDAC in malignant tissues, the… (more)

▼ Histone deacetylases (HDACs) regulate chromatin structure and function. Since much of the literature has reported aberrant expression and recruitment of HDAC in malignant tissues, the role of HDACs in regulating the genes that are involved in cell cycle progression and arrest makes them attractive therapeutic targets for the treatment of cancer. Even though the pan-HDAC inhibitor showed promising antiproliferative activity, their application may be limited due to their toxicity and negative side-effects. To address this gap, design of isoform-selective HDAC inhibitors might be of significant importance for the treatment of cancer, making the knowledge of how inhibitors interact with HDACs and their binding mode crucial for isoform-specific inhibitor discovery. This study focused on investigating the interaction between HDAC probes and HDACs at the molecular level by using a combination of in vitro bioassays, immunoblotting, fluorescence spectroscopy, and protein mass spectrometry. In this dissertation, a binding ensemble profiling with (f)photoaffinity labeling approach that utilizes photolabeling of HDAC8 or HDAC3/NCoR2-DAD with a probe containing a UV-reactive aromatic azide, mapping of the covalent modification by liquid chromatography-tandem mass spectrometry, and a computational method to characterize the binding poses of the probe is described. 1) Two distinct binding poses of the HDAC8 probe were identified. An “upside-down” pose with the surface binding group of the probe bound in an alternative pocket near the catalytic site may contribute to the binding. 2) Modification sites on HDAC3 and NCoR2-DAD were identified and the interaction between HDAC3 and its corepressor NCoR2-DAD was explored. The results presented in this study showed that our combined approach could not only delineate the regions involved in the interface between two interacting proteins but also lead to structural models where the relative orientation of the proteins and their accessibility by small molecule inhibitors are defined. Advisors/Committee Members: Petukhov, Pavel A. (advisor), van Breemen, Richard B. (committee member), Burdette, Joanna E. (committee member), Murphy, Brian T. (committee member), Frasor, Jonna (committee member).

Subjects/Keywords: Histone Deacetylase; Photolabeling; BeProFL

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APA (6^th Edition):

Bai, H. (2013). Exploration of Histone Deacetylase Ligand Binding Modes by Photoaffinity Probes. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/9803

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bai, He. “Exploration of Histone Deacetylase Ligand Binding Modes by Photoaffinity Probes.” 2013. Thesis, University of Illinois – Chicago. Accessed April 12, 2021. http://hdl.handle.net/10027/9803.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bai, He. “Exploration of Histone Deacetylase Ligand Binding Modes by Photoaffinity Probes.” 2013. Web. 12 Apr 2021.

Vancouver:

Bai H. Exploration of Histone Deacetylase Ligand Binding Modes by Photoaffinity Probes. [Internet] [Thesis]. University of Illinois – Chicago; 2013. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10027/9803.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bai H. Exploration of Histone Deacetylase Ligand Binding Modes by Photoaffinity Probes. [Thesis]. University of Illinois – Chicago; 2013. Available from: http://hdl.handle.net/10027/9803

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations