Cell and Developmental Biology Commons^™

Characterization Of E-Cadherin Regulation In Response To Zeb1 Inhibition In Endometrial Cancer Cell Lines, Chidozie Paul Chukwu

Graduate School of Biomedical Sciences Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is the process in which cells lose their epithelial structure during gastrulation. This process also affects the migration and movement of tumor cells and promotes invasion and metastases of endometrial carcinomas. Down-regulation of E-cadherin (CDH1) by transcription factors is the key target of EMT modulators and is achieved mainly by ZEB1 (zinc finger E-box binding homeobox 1). Current research looking at restoration of E-cadherin expression in vitro involves the use of small molecules such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors. Trichostatin A (TSA) and small interfering ribonucleic acid (siRNA) are tools that …

The Role Of The Expansion Segment 7 Of 25s Rrna During Oxidative Stress In Saccharomyces Cerevisiae, Ethan Gardner

Graduate School of Biomedical Sciences Theses and Dissertations

Translation is an essential process for protein expression in both eukaryotes and prokaryotes. Like any cellular process, translational factors are prone to damage when the cell is under stress. One common stressor that nearly all cells may experience is abnormal levels of reactive oxygen species (ROS). Damage caused by ROS has been associated with disease ranging from neurodegenerative impairments, to the aging process of cells. These oxygen radicals are capable of damaging a litany of molecules including nucleic acids, and molecular factors involved in translation. It has been shown that tRNA can be cleaved upon ROS-induced stress and these fragments …

Therapeutic Strategies And Drug Development For Vascular Cognitive Impairment, Eric E. Smith, Alicja Cieslak, Philip Barber, Jerry Chen, Yu-Wei Chen, Ida Donnini, Jodi D. Edwards, Richard Frayne, Thalia S. Field, Janka Hegedus, Victoria Hanganu, Zahinoor Ismail, Jamila Kanji, Makoto Nakajima, Raza Noor, Stefano Peca, Demetrios Sahlas, Mukul Sharma, Luciano A. Sposato, Richard H. Swartz, Charlotte Zerna, Sandra E. Black, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

A Review Of The Signal Transduction Pathways Involved In Epithelial Mesenchymal Transition Induced In Breast Cancer Metastasis And Their Cross-Talks, Kasey Cervantes '17

Independent Study

Epithelial-Mesenchymal Transition (EMT) is a biological process utilized by epithelial cells to transform into motile mesenchymal cells, initiating metastasis in cancer. EMT is also utilized during development and wound healing [10]. This process allows for cancerous cells to detach themselves from their primary tumor and invade normal tissue in preferred organ sites, forming secondary tumors called metastases. Metastasis is very important in the progression of cancer in patients as it the process responsible for the mortality of patients through the collection of metastases that effect vital organs like the brain, lung, or immune system. The most common metastases for malignant …

Modeling 3d Retinogenesis In Mouse Embryonic Stem Cells Following Crispr-Mediated Crx Knockdown, Pooja Prasad

Dissertations, Masters Theses, Capstones, and Culminating Projects

An emerging technology known as three-dimensional (3D) tissue engineering has allowed scientists to mimic tissues found in vivo. Previous studies indicate that it is possible to differentiate dissociated mouse embryonic stem cells (mESCs) into 3D retinal tissues in vitro (Bertacchi, 2015; Eiraku, 2012). The newly differentiated retinal tissues are said to encompass all of the major components found in retinal tissues. The generation of in vitro 3D tissues holds great potential in terms of patient-specific disease modeling. Although various diseases have been well-studied in animal models, there are limitations with regards to patient-specificity. The generation of animal models to study …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Characterization Of Myod And Myf5 Double-Knockout Muscle Stem Cells During Muscle Development, Andreea Dinicu

University Scholar Projects

MyoD and Myf5 are transcription factors that regulate myogenesis by promoting satellite cell transcription. The two genes are known to display functional redundancy. Both genes are considered myogenic determination genes and are expressed in satellite cells. The fate of myogenic precursors in the absence of both MyoD and Myf5 remains largely unknown. We aimed to begin attaining this knowledge as part of this project. We utilized a CreLoxP system to control the expression of MyoD in mice lacking Myf5. MyoD was knocked out at embryonic day (E) 11.5 during myogenesis. Limbs were collected from experimental mice following tamoxifen injection. …

Detection Of Leukocytes Stained With Acridine Orange Using Unique Spectral Features Acquired From An Image-Based Spectrometer, Courtney J. Hunter

Biomedical Engineering Undergraduate Honors Theses

A leukocyte differential count can be used to diagnosis a myriad blood disorders, such as infections, allergies, and efficacy of disease treatments. In recent years, attention has been focused on developing point-of-care (POC) systems to provide this test in global health settings. Acridine orange (AO) is an amphipathic, vital dye that intercalates leukocyte nucleic acids and acidic vesicles. It has been utilized by POC systems to identify the three main leukocyte subtypes: granulocytes, monocytes, and lymphocytes. Subtypes of leukocytes can be characterized using a fluorescence microscope, where the AO has a 450 nm excitation wavelength and has two peak emission …

The Developmental And Genetic Basis Of Differences In Cave And Surface-Dwelling Forms Of The Crustacean, Asellus Aquaticus, Hafasa Mojaddidi

Dissertations, Masters Theses, Capstones, and Culminating Projects

Currently, there are many gaps in our understanding of the genetic mechanisms responsible for human diseases. One novel method to bridge these gaps is to investigate the naturally occurring variation of wild populations, which is arguably more similar to the genetic complexity present in human disease than artificially induced mutations in model species. Species adapted to subterranean environments often share phenotypic characteristics such as the reduction or complete absence of eyes, reduced pigmentation, and enhanced sensory systems. In order to understand the evolution of these morphological changes, we selected an invertebrate model system the freshwater isopod crustacean Asellus aquaticus, …

Are Cdi Systems Multicolored, Facultative, Helping Greenbeards?, Elizabeth S. Danka, Erin C. Garcia, Peggy A. Cotter

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Competitive and cooperative interactions between organisms, including bacteria, can significantly impact the composition of a community and the fitness of its members, as well as the fitness of their hosts when communities are living on or within other organisms. Understanding the underlying mechanisms is critical to the development of strategies to control microbiological communities that impact animal and plant health and also for understanding the evolution of social behaviors, which has been challenging for evolutionary biologists. Contact-dependent growth inhibition (CDI) is a phenomenon defined by the delivery of a protein toxin to the cytoplasm of neighboring bacteria upon cell–cell contact, …

Optimizing A Standard Fasting Time For 2-Nbdg Uptake Studies In Murine Breast Cancers, Andrew C. Briley

Biomedical Engineering Undergraduate Honors Theses

Recently, there has been a larger use of 2-NBDG, a fluorescent glucose analog, to study glucose uptake in different cell types. These cell types have ranged anywhere from bacteria to human cancer cells. However, there has yet to be a standard procedure and practice for using 2-NBDG. In this study, our goal is to create a standard fasting time for the cells before introducing 2-NBDG to them. This study uses 4T07 cells, a murine breast cancer cell line, to help optimize this fasting time. These cells were fasted at different time points in order to find the ideal fasting time. …

Uncovering The Identity And Metabolism Of Bacterial Coa-Rna, Joseph R. Spangler

Dissertations

Coenzyme A is an indispensable molecule in all known life with roles in metabolism, gene regulation, and macromolecule synthesis. As CoA is derived from RNA itself, it’s incorporation into RNA by in vitro methods has proven useful in research probing the origin of life based on the RNA World theory. The discovery in contemporary bacteria of RNA modified with CoA, however, provided an unexpected twist to previously well-characterized bacterial systems. The identity of sequences associated with CoA-RNA has been elusive since their discovery in 2009 based on the difficulties in isolation while maintaining RNA quality. The aim of this study …

Identifying The Signaling Mechanisms Of Egfr-Mediated Apoptosis., Nicole Marion Jackson

Electronic Theses and Dissertations

The Epidermal Growth Factor Receptor (EGFR) is a 170-kilodalton transmembrane protein that belongs to the ErbB family of receptor tyrosine kinases. Upon ligand-mediated activation, the EGFR is responsible for cell growth, proliferation, and tissue homeostasis; however, the EGFR is overexpressed in many human malignancies, including MDA-MB-468 cells, a metastatic breast epithelial cell line. Studies within this cell line, and other cell lines characterized with high EGFR levels, have shown that EGF stimulation results in the induction of apoptosis. However, the mechanisms and signaling effectors implicated in this process have yet to be elucidated. The overarching research goal of this dissertation …

Cyclin B1 Mediates The Effect Of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma, Suet Ying Kwan

Dissertations and Theses (Open Access)

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.

We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1 …

Phopsphorylation And Ubiquitin Modification At Dna Damage Sites In Response To Double-Strand Breaks, Atanu Paul

Dissertations and Theses (Open Access)

Genomes of all organisms are continuously damaged by numerous exogenous and endogenous sources leading to different kinds of DNA lesions, which if not repaired efficiently may trigger wide-scale genomic instability, a hallmark of cancer development. To overcome this, cells have evolved a sophisticated sensory network called the DNA damage response (DDR) comprised of a large number of distinct protein complexes categorized as sensor, mediator, transducer and effector proteins that amplify the DNA damage signal and activate cell cycle checkpoint to initiate DNA repair or trigger apoptosis where the defect is beyond repair. This intricate signaling pathway is tightly regulated by …

Fluorinated N,N'-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells, Dasha E. Kenlan, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Colorectal cancer is the second-leading cause of cancer-related mortality in the United States. More than 50% of patients with colorectal cancer will develop local recurrence or distant organ metastasis. Cancer stem cells play a major role in the survival and metastasis of cancer cells. In this study, we examined the effects of novel AMP-activated protein kinase (AMPK) activating compounds on colorectal cancer metastatic and stem cell lines as potential candidates for chemotherapy. We found that activation of AMPK by all fluorinated N,N-diarylureas (FND) compounds at micromolar levels significantly inhibited the cell-cycle progression and subsequent cellular proliferation. In addition, we demonstrated …

Paracrine Regulation Of Melanocyte Genomic Stability: A Focus On Nucleotide Excision Repair, Stuart Gordon Jarrett, Katharine Marie Carter, John August D'Orazio

Markey Cancer Center Faculty Publications

UV radiation is a major environmental risk factor for the development of melanoma by causing DNA damage and mutations. Resistance to UV damage is largely determined by the capacity of melanocytes to respond to UV injury by repairing mutagenic photolesions. The nucleotide excision repair (NER) pathway is the major mechanism by which cells correct UV photodamage. This multistep process involves the basic steps of damage recognition, isolation, localized strand unwinding, assembly of a repair complex, excision of the damage‐containing strand 3′ and 5′ to the photolesion, synthesis of a sequence‐appropriate replacement strand, and finally ligation to restore continuity of genomic …

Assessment Of The Calling Detection Probability Throughout The Day Of Two Invasive Populations Of Bullfrog (Lithobates Catesbeianus) In Uruguay, Gabriel Laufer, Noelia Gobel, Alvaro Soutullo, Claudio Martinez-Debat, Rafael O. De Sá

Biology Faculty Publications

Bullfrog invasion is a major conservation concern in South America, so there is an urgent need to detect and monitor its many invasion foci. Amphibian sampling methods commonly use calling display, specifically the nuptial calls of males. With the aim of obtaining the better day period to sample and monitor Lithobates catesbeianus presence, we recorded its calls at three ponds in two invaded localities in Uruguay (Aceguá, Cerro Largo, and San Carlos, Maldonado) during the reproductive season. Then, we studied the records, obtaining a subsample of calling intensity at the first 5 minutes for each hour. We detected that vocalization …

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates …

Molecular Mechanisms Of Inward And Outward Budding From Multivesicular Endosomes, Monica Gireud Goss

Dissertations and Theses (Open Access)

Regulating the residence time of membrane proteins (e.g. transporters, ion channels, receptors) on the cell surface can modify their response to extracellular cues and allow for cellular adaptation to environmental conditions. The fate of membrane proteins that are internalized from the plasma membrane and arrive at the limiting membrane of the late endosome/multivesicular body (MVB) is dictated by whether they remain on the limiting membrane, bud into internal MVB vesicles, or bud outwardly from the membrane. The molecular details underlying the disposition of membrane proteins that transit this pathway and the mechanisms regulating these trafficking events are unclear. We established …