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Full-Text Articles in Molecular Biology

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr May 2020

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits ...


Analysis Of Cyclin E In Fibrolamellar Hepatocellular Carcinoma, Hannah Gustafson, Katrina Vang, Tim Vogt, Sara Stickler Apr 2020

Analysis Of Cyclin E In Fibrolamellar Hepatocellular Carcinoma, Hannah Gustafson, Katrina Vang, Tim Vogt, Sara Stickler

Research and Scholarship Symposium Posters

Fibrolamellar Hepatocellular Carcinoma (FL-HCC), a rare primary liver cancer, differs from the most common liver cancer, hepatocellular carcinoma, as FL-HCC is not correlated with chronic liver diseases. Mayo Clinic conducted a proteomic screening and found the proline biosynthetic pathway to be dysregulated in FL-HCC patients. In liver cells, free proline has been shown to induce the mTOR pathway, which stimulates cell proliferation through upregulation of full-length Cyclin E (FL-E). In addition, FL-E can be partially cleaved by an enzyme called serine protease neutrophil elastase, creating low molecular weight cyclin E (LMW-E) that has been linked to tumorigenesis. To further investigate ...


Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia Apr 2020

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Symposium of Student Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of ...


Peptidylarginine Deiminase Isozyme-Specific Pad2, Pad3 And Pad4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures And Cell Invasion In Two Glioblastoma Multiforme Cell Lines, Pinar Uysal-Onganer, Amy Maclatchy, Rayan Mahmoud, Igor Kraev, Paul R. Thompson, Jameel M. Inal, Sigrun Lange Feb 2020

Peptidylarginine Deiminase Isozyme-Specific Pad2, Pad3 And Pad4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures And Cell Invasion In Two Glioblastoma Multiforme Cell Lines, Pinar Uysal-Onganer, Amy Maclatchy, Rayan Mahmoud, Igor Kraev, Paul R. Thompson, Jameel M. Inal, Sigrun Lange

Open Access Articles

Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 ...


The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Kyle Kenney, Amanda Bohn, Angela Asirvatham Jan 2020

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Kyle Kenney, Amanda Bohn, Angela Asirvatham

Student Research Poster Presentations 2020

The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The quantity of cAMP available to Schwann cells can determine if they become a myelinating or proliferating phenotype. The abundance of intracellular cAMP available to the cell is widely regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of cAMP in the cell. This study was undertaken to determine the concentration of rolipram that would ...


Functional Analysis Of Dnmt3a Dna Methyltransferase Mutations Reported In Patients With Acute Myeloid Leukemia, Daria A. Khrabrova, Andrei G. Loiko, Anastasia A. Tolkacheva, Natalia A. Cherepanova, Maria I. Zvereva, Olga V. Kirsanova, Elizaveta S. Gromova Dec 2019

Functional Analysis Of Dnmt3a Dna Methyltransferase Mutations Reported In Patients With Acute Myeloid Leukemia, Daria A. Khrabrova, Andrei G. Loiko, Anastasia A. Tolkacheva, Natalia A. Cherepanova, Maria I. Zvereva, Olga V. Kirsanova, Elizaveta S. Gromova

Open Access Articles

In mammals, DNA methylation is necessary for the maintenance of genomic stability, gene expression regulation, and other processes. During malignant diseases progression, changes in both DNA methylation patterns and DNA methyltransferase (MTase) genes are observed. Human de novo MTase DNMT3A is most frequently mutated in acute myeloid leukemia (AML) with a striking prevalence of R882H mutation, which has been extensively studied. Here, we investigate the functional role of the missense mutations (S714C, R635W, R736H, R771L, P777R, and F752V) found in the catalytic domain of DNMT3A in AML patients. These were accordingly mutated in the murine Dnmt3a catalytic domain (S124C, R45W ...


Modulating Mcm Levels Causes Differential Loading At Origins Of Replication And Changes Replication Timing, Livio Dukaj Dec 2019

Modulating Mcm Levels Causes Differential Loading At Origins Of Replication And Changes Replication Timing, Livio Dukaj

GSBS Dissertations and Theses

DNA replication is a highly complex part of cell metabolism that ensures safe propagation of the genome through tight regulation of the expression, localization, and activity of a large number of factors. Replication starts from distinct sites in the genome and initiation events are temporally ordered in a manner that is, on average, highly reproducible across cell populations. The specific order with which different parts of the genome are replicated has been proposed to be important to processes such as gene expression, cell differentiation, development, and genome evolution. Nevertheless, the fundamental mechanisms that are responsible for establishing these timing programs ...


Yap/Taz Activation Drives Uveal Melanoma Initiation And Progression, Huapeng Li, Qi Li, Kyvan Dang, Shan Ma, Jennifer L. Cotton, Sun Yang, Lihua Julie Zhu, April C. Deng, Y. Tony Ip, Randy L. Johnson, Xu Wu, Claudio Punzo, Junhao Mao Dec 2019

Yap/Taz Activation Drives Uveal Melanoma Initiation And Progression, Huapeng Li, Qi Li, Kyvan Dang, Shan Ma, Jennifer L. Cotton, Sun Yang, Lihua Julie Zhu, April C. Deng, Y. Tony Ip, Randy L. Johnson, Xu Wu, Claudio Punzo, Junhao Mao

Open Access Articles

Uveal melanoma (UM), the most common ocular malignancy, is characterized by GNAQ/11 mutations. Hippo/YAP and Ras/mitogen-activated protein kinase (MAPK) emerge as two important signaling pathways downstream of G protein alpha subunits of the Q class (GalphaQ/11)-mediated transformation, although whether and how they contribute to UM genesis in vivo remain unclear. Here, we adapt an adeno-associated virus (AAV)-based ocular injection method to directly deliver Cre recombinase into the mouse uveal tract and demonstrate that Lats1/2 kinases suppress UM formation specifically in uveal melanocytes. We find that genetic activation of YAP, but not Kras, is ...


Mechanisms And Consequences Of Myb Gene Activation In Salivary Gland Tumors, Candace Frerich Dec 2019

Mechanisms And Consequences Of Myb Gene Activation In Salivary Gland Tumors, Candace Frerich

Biomedical Sciences ETDs

Salivary gland adenoid cystic carcinoma (ACC) is an aggressive tumor with a tendency to infiltrate surrounding nerves and metastasize to distant sites. The standard treatment often fails to control local tumor recurrence and distant metastases and no approved targeted therapeutic options exist for these tumors. The goal of our studies was to reveal the molecular mechanisms driving ACC tumor development and novel drug targets to improve patient morbidity and mortality.

We first analyzed clinical and RNA-sequencing (RNA-seq) data for 68 formalin-fixed paraffin-embedded (FFPE) ACC tumor samples and described previously unappreciated molecular heterogeneity that predicts patient outcome. The poor outcome subgroup ...


Hydrophobically Modified Let-7b Mirna Enhances Biodistribution To Nsclc And Downregulates Hmga2 In Vivo, Meirav Segal, Annabelle Biscans, Maud-Emmanuelle Gilles, Eleni Anastasiadou, Roberto De Luca, Jihoon Lim, Anastasia Khvorova, Frank J. Slack Nov 2019

Hydrophobically Modified Let-7b Mirna Enhances Biodistribution To Nsclc And Downregulates Hmga2 In Vivo, Meirav Segal, Annabelle Biscans, Maud-Emmanuelle Gilles, Eleni Anastasiadou, Roberto De Luca, Jihoon Lim, Anastasia Khvorova, Frank J. Slack

RNA Therapeutics Institute Publications

MicroRNAs (miRNAs) have increasingly been shown to be involved in human cancer, and interest has grown about the potential use of miRNAs for cancer therapy. miRNA levels are known to be altered in cancer cells, including in non-small cell lung cancer (NSCLC), a subtype of lung cancer that is the most prevalent form of cancer worldwide and that lacks effective therapies. The let-7 miRNA is involved in the regulation of oncogene expression in cells and directly represses cancer growth in the lung. let-7 is therefore a potential molecular target for tumor therapy. However, applications of RNA interference for cancer research ...


Discovery Of An Egfr Inhibitor For The Treatment Of Lung And Other Cancers, Jodie Meng '20 Nov 2019

Discovery Of An Egfr Inhibitor For The Treatment Of Lung And Other Cancers, Jodie Meng '20

Student Publications & Research

The Epidermal Growth Factor Receptor (EGFR), a transmembrane protein involved in the regulation of signaling pathways, is frequently overexpressed in epithelial tumors. First generation EGFR TKIs, such as erlotinib and gefitinib, traditionally improved outcomes for non-small-cell lung carcinoma and pancreatic cancer patients by attaching competitively and reversibly to the ATP binding domain of EGFR. Second-generation EGFR TKIs have been developed to combat resistance among patients, despite demonstrating toxic side effects. In the present study, 1400 selective inhibitors were designed based on the molecular scaffolds of first and second generation EGFR TKIs. Results were refined by parameters outlined in Lipinski’s ...


Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani Sep 2019

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani

Sure-J: Science Undergraduate Research Journal

Background
Breast cancer is a heterogeneous disease that consists of varying genetic, cellular and molecular subtypes with unique characteristics. Due to the multiple subtypes and molecular markers of breast cancer, successful clinical treatment is hampered by the lack of reliable biomarkers. HER2-positive breast cancer is an aggressive subtype associated with poor patient prognosis. Although survival rates have dramatically increased due to the development of Trastuzumab in 1997, many patients develop a resistance to this therapeutic treatment and relapse over time. Rani et al. (2014), have associated the acquirement of resistance to HER2-treatment with Neuromedin U, but the mechanisms by which ...


Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw Aug 2019

Insulin Receptor Substrate-1 (Irs-1) And Irs-2 Expression Levels Are Associated With Prognosis In Non-Small Cell Lung Cancer (Nsclc), Andrew J. Piper, Jennifer L. Clark, Jose R. Mercado-Matos, Asia N. Matthew-Onabanjo, Chung-Cheng Hsieh, Ali Akalin, Leslie M. Shaw

Open Access Articles

The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma ...


Deubiquitinating Enzymes Promote Cancer Progression And Metastasis Via Regulating Protein Stability, Zhenna Xiao Aug 2019

Deubiquitinating Enzymes Promote Cancer Progression And Metastasis Via Regulating Protein Stability, Zhenna Xiao

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Deubiquitinating enzymes (DUBs, also called deubiquitinases) are enzymes that remove monoubiquitin or polyubiquitin chains from target proteins. DUBs have critical roles in cell homeostasis and signal transduction, as they regulate protein degradation, subcellular localization, and protein-protein interaction. Deregulation of DUBs contributes substantially to tumor formation and progression, and therefore targeting DUBs may be a promising cancer therapy strategy. My dissertation focuses on identifying the DUBs of EZH2 and SNAI1, two proteins critical for cancer progression and metastasis, and establishing these DUBs as promising anti-cancer targets.

EZH2, the catalytic component of the PRC2 complex, silences gene transcription by histone methylation. High ...


Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii May 2019

Extraction, Purification And Evaluation Of Prmt5-Inhibitory Phytochemical Compounds For The Treatment Of Prostate Adenocarcinoma, Oliver H. Richmond Iii

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

The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and protein post-translational modifications within protein signaling pathways. PRMT5 functions by catalyzing the symmetric dimethylation of terminal arginine residues on target protein substrates. Under abnormal conditions of overexpression and upregulation, PRMT5 methyltransferase activity constitutively drives the growth and proliferation of dysregulated cells. Overexpression or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate ...


Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot May 2019

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I ...


The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy May 2019

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

All Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims ...


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

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

Electronic Theses and Dissertations

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


Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey Apr 2019

Mechanisms Of Oriented Cell Division And Their Roles In Tissue Development, Evan Blake Dewey

Biology ETDs

Properly executed cell division is crucial to development, maintenance, and longevity of multicellular organisms. Defects in both symmetric and asymmetric divisions can lead to improper developmental patterning, as well as genomic instability, disruption of tissue homeostasis, and cancer. Our research focuses on how regulators orchestrate proper cell divisions. Mushroom Body Defect (Mud) is one such regulator, and here we describe how Mud is regulated via the Hippo signaling pathway kinase Warts (Wts), showing Wts phosphorylates Mud to enhance interaction with the polarity protein Partner of Inscuteable, promoting spindle orientation activity. We next focus on another regulator, Shortstop (Shot), describing a ...


Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma Jan 2019

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D3 levels have better prognoses than patients with low serum vitamin D3. However, double-blind clinical trials on the efficacy of vitamin D3 supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D3 supplements who had ‘estrogen receptor ...


Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D. Jan 2019

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of ...


The Functional Role Of Rna Binding Protein Rbms3 As A Tumor Promoter In Triple-Negative Breast Cancer Cells, Yuting Zhou Jan 2019

The Functional Role Of Rna Binding Protein Rbms3 As A Tumor Promoter In Triple-Negative Breast Cancer Cells, Yuting Zhou

Theses and Dissertations--Molecular and Cellular Biochemistry

RBMS3 belongs to the family of c-myc gene single-strand binding proteins (MSSPs) that play important roles in transcriptional regulation. Here, we show that RBMS3 functions as a tumor promoter in triple-negative breast cancer (TNBC), a highly aggressive BC subtype. Analysis of RBMS3 expression shows that RBMS3 is upregulated at both mRNA and protein levels in TNBC cells. Functionally, overexpression of RBMS3 increases cell migration, invasion and cancer stem cell (CSC) behaviors. Moreover, RBMS3 induces expression of epithelial-mesenchymal transition (EMT) and CSC markers. Conversely, loss of RBMS3 in TNBC BT549 cells inhibits cell proliferation, migration and mesenchymal phenotype. Correlation analysis shows ...


Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko Jan 2019

Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko

Theses and Dissertations

According to the American Cancer Society, it has been estimated that in 2019 alone, there will be approximately 53,000 new cases of oropharyngeal cancers. Oropharyngeal cancers are the largest subset of head and neck squamous cell carcinomas (HNSCCs), which are the sixth most common cancer across worldwide populations. They, along with other HNSCCs, fall under a category of cancers known as Human papillomavirus (HPV)-associated cancers, and it has been found that upwards of 70% of these cancers can be attributed to high-risk HPV infections.

Specifically, the high-risk HPV gene, E7, plays a key role in relieving cell cycle ...


Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue Dec 2018

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3 ...


Structural Analysis Of The Active Site And Dna Binding Of Human Cytidine Deaminase Apobec3b, Shurong Hou, Tania V. Silvas, Florian Leidner, Ellen A. Nalivaika, Hiroshi Matsuo, Nese Kurt Yilmaz, Celia A. Schiffer Nov 2018

Structural Analysis Of The Active Site And Dna Binding Of Human Cytidine Deaminase Apobec3b, Shurong Hou, Tania V. Silvas, Florian Leidner, Ellen A. Nalivaika, Hiroshi Matsuo, Nese Kurt Yilmaz, Celia A. Schiffer

Schiffer Lab Publications

APOBEC3s proteins (A3s), a family of human cytidine deaminases, protect the host from endogenous retro-elements and exogenous viral infections by introducing hypermutations. However, overexpressed A3s can modify genomic DNA to promote tumorigenesis, especially A3B. Despite overall similarity, A3 proteins have distinct deamination activity. Recently determined A3 structures have revealed the molecular determinants of nucleotide specificity and DNA binding. However, for A3B, the structural basis for regulation of deamination activity and the role of active site loops in coordinating DNA had remained unknown. Using advanced molecular modeling followed by experimental mutational analysis and dynamics simulations, we investigated molecular mechanism of DNA ...


Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater Nov 2018

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study ...


Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke Nov 2018

Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke

Shared Knowledge Conference

Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a high-speed ...


Signaling Pathways Induced By Leptin During Epithelial(-)Mesenchymal Transition In Breast Cancer, Monserrat Olea-Flores, Juan Carlos Juarez-Cruz, Miguel A. Mendoza-Catalan, Teresita Padilla-Benavides, Napoleon Navarro-Tito Nov 2018

Signaling Pathways Induced By Leptin During Epithelial(-)Mesenchymal Transition In Breast Cancer, Monserrat Olea-Flores, Juan Carlos Juarez-Cruz, Miguel A. Mendoza-Catalan, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Leptin is an adipokine that is overexpressed in obese and overweight people. Interestingly, women with breast cancer present high levels of leptin and of its receptor ObR. Leptin plays an important role in breast cancer progression due to the biological processes it participates in, such as epithelial(-)mesenchymal transition (EMT). EMT consists of a series of orchestrated events in which cell(-)cell and cell(-)extracellular matrix interactions are altered and lead to the release of epithelial cells from the surrounding tissue. The cytoskeleton is also re-arranged, allowing the three-dimensional movement of epithelial cells into the extracellular matrix. This transition provides ...


Synthesis And Biological Evaluation Of Phaeosphaeride A Derivatives As Antitumor Agents, Victoria Abzianidze, Petr Beltyukov, Sofya Zakharenkova, Natalia Moiseeva, Jennifer Mejia, Alvin Holder, Yuri Trishin, Alexander Berestetskiy, Victor Kuznetsov Nov 2018

Synthesis And Biological Evaluation Of Phaeosphaeride A Derivatives As Antitumor Agents, Victoria Abzianidze, Petr Beltyukov, Sofya Zakharenkova, Natalia Moiseeva, Jennifer Mejia, Alvin Holder, Yuri Trishin, Alexander Berestetskiy, Victor Kuznetsov

Chemistry & Biochemistry Faculty Publications

New derivatives of phaeosphaeride A (PPA) were synthesized and characterized. Anti-tumor activity studies were carried out on the HCT-116, PC3, MCF-7, A549, К562, NCI-Н929, Jurkat, THP-1, RPMI8228 tumor cell lines, and on the HEF cell line. All of the compounds synthesized were found to have better efficacy than PPA towards the tumor cell lines mentioned. Compound 6 was potent against six cancer cell lines, HCT-116, PC-3, K562, NCI-H929, Jurkat, and RPMI8226, showing a 47, 13.5, 16, 4, 1.5, and 7-fold increase in anticancer activity comparative to those of etoposide, respectively. Compound 1 possessed selectivity toward the NCI-H929 cell ...