Cell and Developmental Biology Commons^™

Prolactin Drives A Dynamic Stat5a/Hdac6/Hmgn2 Cis-Regulatory Landscape Exploitable In Er+ Breast Cancer, Justin M. Craig

Theses and Dissertations

The hormone prolactin has been implicated in breast cancer pathogenesis and regulates chromatin engagement by the transcription factor, STAT5A. STAT5A is known to inducibly bind promoters and cis-regulatory elements genome-wide, though the mechanisms by which it exerts specificity and regulation of target gene expression remain enigmatic. We previously identified HDAC6 and HMGN2 as cofactors that facilitate prolactin induced, STAT5A mediated gene expression. Here, multi-condition STAT5A, HDAC6, and HMGN2 ChIP-seq with parallel condition RNA-seq are utilized to reveal the cis-regulatory landscape and cofactor dynamics underlying prolactin stimulated gene expression in breast cancer. We find that prolactin regulated genes are …

The Role Of Autophagy And Senescence In The Responses Of Non-Small Cell Lung Cancer Cells To Chemotherapy And Radiation, Nipa H. Patel

Theses and Dissertations

Cancer-associated deaths account for the second-highest mortality rates in the United States. Primary modalities of treatment often include surgery, radiation, and chemotherapy, and may also incorporate targeted therapy and immunotherapy. However, resistance to these treatments remains high, resulting in disease reoccurrence and poor survival rates. While apoptosis or cell death of tumor cells is the ideal outcome for anti-cancer therapy, this is often not the case, and in fact cancer cells may upregulate several pathways, such as autophagy and senescence, as a means to undergo alternative cell fate and evade apoptotic cell death. An essential tumor suppressor gene, TP53, …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

The Rho1 Gtpase-Activating Protein Sac7 Is A Negative Regulator Of Clathrin-Independent Endocytosis In Yeast, La'tila Abbott

Theses and Dissertations

Endocytosis, or internalization of material from the plasma membrane, is an important process for many aspects of eukaryotic cell function. Although clathrin-mediated endocytosis (CME), which requires the coat protein clathrin to facilitate endocytic vesicle formation, is the predominant mechanism for internalization, numerous clathrin-independent (CIE) pathways exist that remain poorly characterized. While the budding yeast Saccharomyces cerevisiae has been a powerful model organism for studying CME, it was long thought to lack any CIE pathways. Recently, a mutant yeast strain defective in CME was used to discover the first known yeast CIE pathway, which requires the small GTPase Rho1. Rho1 regulates …

A New Mathematical Theory For The Dynamics Of Large Tumor Populations, A Potential Mechanism For Cancer Dormancy & Recurrence And Experimental Observation Of Melanoma Progression In Zebrafish, Adeyinka A. Lesi

Dissertations and Theses

Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they …

Molecular And Genetic Studies On A Sipd/Ipad-Related Virulence Spike Protein From Immune-Suppressive Particles Of A Drosophila Parasitoid, Carlo Miguel A. Sevilla

Dissertations and Theses

Parasitoid wasps are effective biological control agents that have evolved intricate host immune suppression strategies to overcome host immune defenses. The most important anti-parasite defense mechanism is encapsulation, where the host’s blood cells surround the wasp egg. In the Drosophila/Leptopilina host-parasitoid system, extracellular vesicles (EVs) are oviposited along with the wasp egg. The EVs possess spikes and contain hundreds of proteins, some of which enable wasp eggs to escape encapsulation by changing the morphology and function of hemocytes, or killing them. Previous studies have identified an abundant surface/spike protein (SSp40) from Leptopilina heterotoma EVs. While p40, a predicted …

The Therapeutic Potential Of Glycosaminoglycan Directed Metalloglycomics: Elucidating New Targets And Mechanisms For Polynuclear Platinum Complexes, James D. Hampton

Theses and Dissertations

Cancer remains a serious clinical problem and in order to continue to improve patient health outcomes, novel treatment strategies must continue to be developed. Platinum chemotherapies remain as one of the most widely successful classes of cancer therapeutic, with over 50% of cancer patients receiving a platinate at some point over the span of their treatment. However, intrinsic and extrinsic resistances limit their effectiveness, long term efficacy, and broad applicability to multiple cancer subtypes. Therefore, the development of new agents and strategies which can overcome these limitations are crucial for patient health. To this end a novel class of polynuclear …

Larval Anatomy Of Monotypic Painted Ant Nest Frogs Lithodytes Lineatus Reveals Putative Homoplasies With The Leptodactylus Pentadactylus Group (Anura: Leptodactylidae), Filipe A.C Do Nascimento, Rafael O. De Sá, Paulo C. De A. Garcia

Biology Faculty Publications

The morphological diversity of anuran larvae made them an important source of information for evolutionary and systematic studies. For the monotypic frog genus Lithodytes, which has an interesting taxonomic history, including its past synonymizing with Adenomera and its placement as a subgenus of Leptodactylus, the information provided from its larvae can help to understand its systematics interrelationships and also provide insights about its evolutionary trajectories. Herein, we provide a detailed description of the larval morphology of Lithodytes lineatus, including novel data of internal morphology (buccopharyngeal cavity and skeleton), and discuss some morphological and evolutionary aspects in relation …

Investigation Of Multidrug Efflux Transporter Acrb In Escherichia Coli: Assembly, Degradation And Dynamics, Prasangi Irosha Rajapaksha

Theses and Dissertations--Chemistry

The Resistant Nodulation Division (RND) super family member, tripartite AcrA-AcrB-TolC efflux pump, is a major contributor in conferring multidrug-resistance in Escherichia coli. The structure of the pump complex, and drug translocation by functional rotation mechanism have been widely studied. Despite of all these data, the dynamics of the assembly process of the pump and AcrB during functional rotation in the process of drug efflux remains poorly understood. My thesis focuses on understanding the pump assembly process, dynamics of AcrB in functional rotation mechanism, and also investigate the mechanism of degradation of AcrB facilitated by a C-terminal ssrA tag.

In the …

Developing Synthetic Strategies For Multifaceted Applications Of Stable Gold-Based Complexes, Randall Tyler Mertens

Theses and Dissertations--Chemistry

Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical research and catalytic transformations. Given that auranofin, a gold(I) complex with FDA approval for the treatment of rheumatoid arthritis is used in the clinic, the development of stable gold-based molecules of clinical relevance is urgently needed. Herein are reported, synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented …

Characterization Of Alcohol-Mediated Promotion Of Breast Cancer Stem Cells, Mckenna Below

Master's Theses

Breast cancer is the leading cause of cancer-related death in women globally, and one in eight women will be diagnosed with breast cancer at some point in her life. Alcohol consumption has been linked to increase breast cancer risk and increased risk of tumor recurrence. Understanding the molecular mechanisms of modifiable lifestyle factors such as alcohol consumption will help to lower these risks and design more effective therapeutic approaches. Estrogen Receptor positive (ER+) breast cancer comprises approximately 70% of all breast cancers, and these tumors are effectively targeted by endocrine therapy in the form of estrogen deprivation with aromatase inhibitors, …

Protocadherin-17 Expression And Function In Vertebrate Brain: A Literature Review, Mathea Mcguire

Williams Honors College, Honors Research Projects

For this project, I will be doing a systematic review on protocadherin-17 function in vertebrate brain development and function in the last 10 years. Protocadherins are members of cadherin superfamily. Cadherins are calcium-dependent cell adhesion molecules that are implicated to play crucial roles in the information and maintenance of tissues and organs in vertebrate animals. This review will summarize major findings regarding protocadherin-17 expression and function in major model organisms such as zebrafish and mice, as well as results from human studies. It is hoped that this work will be a valuable source for background knowledge of protocadherin-17 function in …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

Identification Of Effective Senolytic Strategies To Enhance And Prolong Response To Standard-Of-Care Cancer Treatments, Valerie Jean Carpenter

Theses and Dissertations

Senescence is a unique cell state in which cells undergo a prolonged loss of proliferative capacity that is associated with various cytoskeletal, metabolic, and epigenetic alterations. Tumor cells can be induced into senescence by both genotoxic and targeted anti-cancer therapies. While it was long proposed that senescence was irreversible, more recent evidence has demonstrated that tumor cells, in particular those in a state of therapy-induced senescence, are capable of evading the growth arrest and re-entering a proliferative state. Additionally, the accumulation of senescent cells has been shown to contribute to deleterious outcomes, including chemotherapy-related toxicities and disease progression. In light …

Mimicking The Effect Of Prolactin On Stat3/Stat5 Activity In Breast Cancer, Jennifer N. Barbuto, Sarah R. Walker

Honors Theses and Capstones

Signal transducers and activators of transcription (STAT) 3 and 5 are commonly constitutively activated in breast cancer. STAT5 can outcompete STAT3 and reduce cell proliferation and metastasis. STAT5 activation is stimulated by prolactin, a natural hormone that can be harmful at high levels. The aim of this study is to identify some possible previously developed drugs that mimic the effect of prolactin and STAT5 without the added risk in MDA-MB231 breast cancer cells. Using the CLUE database query app and STAT5 up- and downregulation signatures, three drugs (X, K, and M) were chosen based on their similarity in signatures to …

Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne

Articles

Mesenchymal Stem Cells (MSCs) have the ability to differentiate into chondrocytes, the only cellular components of cartilage and are therefore ideal candidates for cartilage and tissue repair technologies. Chondrocytes are surrounded by cartilage-like extracellular matrix (ECM), a complex network rich in glycosaminoglycans, proteoglycans, and collagen, which, together with a multitude of intracellular signalling molecules, trigger the chondrogenesis and allow the chondroprogenitor to acquire the spherical morphology of the chondrocytes. However, although the mechanisms of the differentiation of MSCs have been extensively explored, it has been difficult to provide a holistic picture of the process, in situ. Raman Micro Spectroscopy (RMS) …

Plasma-Treated Solutions (Pts) In Cancer Therapy, Hiromasa Tanaka, Sander Bekeschus, Dayun Yan, Masaru Hori, Michael Keidar, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

Cold physical plasma is a partially ionized gas generating various reactive oxygen and nitrogen species (ROS/RNS) simultaneously. ROS/RNS have therapeutic effects when applied to cells and tissues either directly from the plasma or via exposure to solutions that have been treated beforehand using plasma processes. This review addresses the challenges and opportunities of plasma-treated solutions (PTSs) for cancer treatment. These PTSs include plasma-treated cell culture media in experimental research as well as clinically approved solutions such as saline and Ringer’s lactate, which, in principle, already qualify for testing in therapeutic settings. Several types of cancers were found to succumb to …

Of Pigs And Men: The Best-Laid Plans For Prevention And Control Of Swine Fevers, Jishu Shi, Lihua Wang, David Scott Mcvey

School of Veterinary and Biomedical Sciences: Faculty Publications

John Steinbeck drew the title of his novel “Of Mice and Men” from a line in a Robert Burns poem “To a mouse”: “The best-laid plans of mice and men/Go often awry.” Unlike John Steinbeck who used the title to mirror the characters who were struggling during the Great Depression to the mouse whose nest was accidentally destroyed by the poet (Burns 1785), we chose this line to emphasize that the best-laid plan can go wrong in infectious disease control and prevention. Here, we will discuss the contributing factors behind the global successes and failures in the prevention and control …

Impact Of The Histidine‐Containing Phosphocarrier Protein Hpr On Carbon Metabolism And Virulence In Staphylococcus Aureus, Linda Pätzold, Anne-Christine Brausch, Evelyn-Laura Bielefeld, Lisa Zimmer, Greg A. Somerville, Markus Bischoff, Rosmarie Gaupp

School of Veterinary and Biomedical Sciences: Faculty Publications

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading …