Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Vulnerability And Adaptation Of Neocortical Neuron Subtypes In Models Of Concussive Traumatic Brain Injury And Multiple Sclerosis, Alan C. Harris Jr.

Theses and Dissertations

The pathognomonic sequela of traumatic brain injury is traumatic axonal injury, the

burden of which correlates with less favorable outcomes. Elucidation of

the intrinsic variables that endow delineated neuronal subgroups and microanatomical domains with outsized vulnerability to injury represents a critical domain of inquiry toward the successful translation of disease-modifying therapeutics. To this end, we studied mild traumatic brain injury (mTBI) within the central fluid percussion model to examine the consequences of mTBI on the morphology and functional integrity of the axon initial segment (AIS) and the relative contributions to network homeostasis mediated by distinct populations of inhibitory interneurons. One …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Crosstalk Between Hippo And Rb Tumour Suppressor Pathways In Ovarian Cancer, Fatmata Sesay

Theses and Dissertations

The cell cycle is a highly regulated process that ensures the timely and accurate division of cells. Events of the normal cell cycle fall under two categories - positive and negative regulatory mechanisms. The first category, positive regulatory machinery, includes active protein complexes of cyclins in association with their partnering cyclin-dependent kinases (cyclin/CDK), which mediate series of phosphorylation events that relay a cell cycle progression from one stage to the next. The second category, the negative regulatory mechanisms, include the checkpoint controls consisting of the retinoblastoma (RB) family of proteins, some of which can form a transcriptional repressor complex DREAM. …

Analysis Of Single Cell Rna-Seq Data Revealed Interferon Gamma Signaling Alteration In Severe Covid Patients, Ahmed Elbaz

Theses and Dissertations

Background: SARS-COV2 virus detected in December 2019, and was considered a pandemic in March 2020 by the WHO. Symptoms range from asymptomatic to life threatening ones. Studying cell-cell interactions in patients' blood samples may lead to novel diagnosis and treatment approaches.

Aim: This study aims to analyze single-cell RNA sequencing data to identify differences in cell-cell communications between healthy and COVID patients and differentially expressed T-cells genes that contributed to immune system antiviral activity.

Materials and methods: Single-Cell RNA sequencing data from seven COVID patients and five healthy individuals were collected from (GEO accession GSE155673). Cell types were identified and …

A Novel Review Of Heat Shock Protein 110 Kda: A Basis For Research And Continued Experimentation Through Biochemical Analysis, Crist W. Cuffee

Theses and Dissertations

Heat shock protein 110 kDa, Hsp110, is a distinct cellular protector, different in form and function from Hsp70, a close relative of Hsp110. Functioning primarily as a holdase or in tandem with other molecular chaperones, a review of current accomplishments elucidates the uniqueness of this protein and the continued mysteries that surrounds it. Found only in eukaryotes, Hsp110 has been linked to many diseases, ranging from parasitic infection to neurodegenerative disorders. While still lacking, studies of this protein have provided much in the realm of speculation on the mechanisms behind Hsp110s’ contribution to different pathologies. This review will serve as …

The Role Of Interleukin-18 In Myocardial Ischemia/Reperfusion, Yogesh Dhakal

Theses and Dissertations

Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity for cardiovascular diseases (CVDs) in the western world. While mortality rates for AMI has reduced in the last 20 years due to advancements in clinical interventions, patients who have an AMI are significantly more likely to develop heart failure (HF) in the following years. Reperfusion of the ischemic tissue is a necessary procedure to restore blood delivery to cardiomyocytes, minimize myocardial dysfunction, and reduce infarct size. Still, the step of reperfusion itself induces myocardial damage in a phenomenon known as reperfusion injury. Considering that the degree of myocardial …

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …

Characterization Of The Novel Interaction Between Neisseria Gonorrhoeae Tdfj And Its Human Ligand S100a7, Stavros Maurakis

Theses and Dissertations

Neisseria gonorrhoeae is an obligate human pathogen that causes the common STI gonorrhea, which presents a growing threat to global health. The WHO estimated 78 million new cases of gonorrhea worldwide in 2017, with estimates of 820,000 new cases in the United States alone according to the CDC. High-frequency phase and antigenic variation inherent in N. gonorrhoeae, coupled with its natural ability to rapidly acquire and stably integrate antimicrobial resistance factors into its genome, have culminated in an infection against which there is no effective vaccine, and for which the list of viable therapeutic options is quickly shrinking. Moreover, no …

The Role Of Tumor And Tumor Microenvironment On Breast Cancer-Associated Adipocyte Plasticity, Janina V. Pearce

Theses and Dissertations

Cancer-associated cachexia is a condition defined by a sustained net-negative energy imbalance. Although the different types of adipose tissue – white, beige, and brown – have been implicated in contributing to cancer-associated cachexia, the mechanisms of these maladaptive changes and their impact on whole-body energy expenditure have not been fully elucidated. Using breast cancer as our model, we demonstrate white adipose tissue browning in murine and human breast cancer; furthermore, we demonstrate that this effect is extremely localized and takes place early in tumor progression. We utilized in vitro cell culture techniques and demonstrate that cancer secreted factors and cross-talk …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Role Of Mir-489 In Her2 Positive Breast Cancer, Yogin Patel

Theses and Dissertations

Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several micro RNAs (miRs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRs dysregulated in HER2-positive breast cancer cells. Molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenicity and tumor growth in xenograft mice. Mechanistically, …

Role Of Cox2 In Cellular Senescence, Mingxiao Feng

Theses and Dissertations

The survivors of childhood cancers are often associated with adverse late effects including hypoplasia, fatigue, and infertility, which are characteristics of aging. However, the underlying mechanisms of the late effects of chemotherapy are still elusive. We have found that transgenic cyclooxygenase-2 (COX2) expression causes premature aging phenotypes. Since COX2 expression is highly induced by various chemotherapeutic agents, we further investigated the possible link between COX2 and the late effects of chemotherapy. Treatment of juvenile wild-type mice with doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, resulted in premature aging phenotypes and escalated cellular senescence level in various tissues. We found that tissue …

Radioactive Contamination Of Natural Biological Systems: Oxidative Balance And Genetic Stability, Daniel Einor

Theses and Dissertations

The global demand for nuclear energy grows, and so do the risks of an accidental release of nuclear products into the environment. Therefore, understanding the health and ecological effects of contamination by radionuclides should be of great interest for biomedical specialists and the public. Empirical studies unequivocally show that high doses of ionizing radiation (IR) shift the redox-balance of many biological systems and increase the rates of genetic errors. However, the effects of chronic low doses of radiation vary significantly between tissues and between species. The present dissertation comprises the results of experimental and meta-analytical research of a variety of …

Environmental Relationships And Predator-Prey Interactions Within The Snapper-Grouper Complex In The Southeastern U.S. Atlantic – Implications For Fisheries Management, Dawn M. Glasgow

Theses and Dissertations

Stock assessments indicate many valuable fish species are declining, or are considered overfished and/or are undergoing overfishing. Fisheries scientists and managers in the southeastern U.S. typically have utilized a single-species approach, and relied on catch per unit effort data derived from fishery-independent surveys to determine indices of abundance for economically important reef fish. However, catchability for these surveys vary for many reasons including environmental and predator-prey relationships. This research was developed to elucidate environmental influences on reef fish assemblages and distribution of reef-associated marine predators, and examine predator-prey dynamics that may influence relative abundance of large predators based on chevron …

Applications Of Multimedia Resources Developed As Part Of The Virtual Cell Animation Collection In Undergraduate Introductory Biology, Eric Edward Goff

Theses and Dissertations

Calls for reform in undergraduate STEM education have arisen from an increased need for well-trained biology graduates in the future scientific workforce. To address this need, many institutions have focused on a pedagogical restructuring of instructional practices to promote deeper conceptual understanding of core biological concepts. This study investigates the implementation of multimedia resources as a possible reliable supplement to undergraduate introductory biology and aims to provide empirical evidence on the instructional best practices of their use. As a central part of this study, we focus on one specific multimedia package, the Virtual Cell Animation Collection, due to its developmental …

Modulation Of Pkr Activity During Hiv Infection And Cellular Stress By Pact And Trbp, Evelyn E. Chukwurah

Theses and Dissertations

A crucial component of the cellular response to stress is the attenuation of protein synthesis to allow the cell to dedicate resources for the restoration of homeostasis or towards the induction of apoptotic cell death in case the stressors overwhelm the cell. This process is itself regulated by one of the four eIF2α kinases of which PKR (Protein Kinase R) is responsible for inhibiting general translation during viral infection, oxidative stress, ER stress, heat shock or serum withdrawal.

During viral infection, PKR is transcriptionally induced by interferon but remains latent until it interacts with dsRNA. This interaction induces a conformational …

Cannabinoid-Mediated Epigenetic Regulation Of Immune Functions, Jessica Margaret Sido

Theses and Dissertations

The cannabinoid system consisting of exogenous and endogenous ligands as well as dedicated receptors has been proposed to play a regulatory role in immune functions. The exogenous cannabinoid Δ9-tetrahydrocannabinol (THC), one of the most widely studied marijuana derivatives, has been associated with multiple anti-inflammatory properties over the years. The majority of THC research has centered on the shift from Th1 to Th2 responses however, the complexity of inflammation has since increased. Recent studies have revealed that epigenome, Th cell subsets, and immunoregulatory cell induction, are all known to impact inflammation. In the current research, we have attempted to look holistically …

Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli

Theses and Dissertations

Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …

Gliotoxin Production In Aspergillus Fumigatus, Susan Musyimi

Theses and Dissertations

Aspergillus fumigalus is a ubiquitous fungus that causes an infection called aspergillosis in immune-compromised surgery patients (Latge, 2001, 384; Bok et al. 2006). Aspergillosis cases have increased in the past decade due to the increasing number of patients undergoing immunosuppressive therapy and receiving organ transplants (Bok et al. 2006). Although there is still disagreement as to the causative agent of the symptoms accompanying aspergillosis, many scientists suspect that the compound, gliotoxin, plays a major role, hi this study, we compared the amounts of gliotoxin produced from clinical and environmental isolates of A. fumigatus. We hypothesized that the amount of gliotoxin …