Cell and Developmental Biology Commons^™

The Gut-Liver Axis Regulates Pulmonary Inflammation After Intoxication And Burn Injury, Michael M. Chen

Dissertations

The increasing prevalence of binge drinking and its high association with traumatic injury warrant further investigation into the mechanisms underlying the worsened clinical outcomes associated with this combined injury. Existing literature suggests the liver is at the center of the postburn systemic response with crosstalk between the intestinal microbiome and the liver playing an important role after injury. There is a paucity in the literature, however, regarding the role of the gut-liver axis in the common clinical scenario of burns preceded by alcohol intoxication. Previous studies in our laboratory demonstrated intoxication potentiates postburn hepatic damage and IL-6 production in a …

Development Of Circadian Oscillators In Neurosphere Cultures During Adult Neurogenesis, Astha Malik, Roudabeh J. Jamasbi, Roman V. Kondratov, Michael Eric Geusz

Biological Sciences Faculty Publications

Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ), a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in …

Regulation Of The Gαi - G-Protein Regulatory (Gpr) Module And The Biological Function Of Gpr-Containing Proteins In Chemokine Signal Processing Of Primary Leukocytes, William Gene Robichaux Iii

MUSC Theses and Dissertations

Activators of G-protein Signaling (AGS) proteins modulate G-protein signaling in diverse and unexpected ways and have functional roles in numerous physiological systems. The functions of AGS proteins in the immune system, where Gαi-coupled chemokine receptors are predominantly involved in dynamic signaling events, are poorly understood. The Group II AGS proteins AGS3 and AGS4 express multiple G-protein regulatory (GPR) motifs, each of which dock GDP-bound Gαi/o/t subunits and effectively compete with Gβγ for binding. This unique ability positions these proteins to modulate downstream signaling of Gαi and Gβγ, thus promoting signal diversity from seven-transmembrane receptors (7TMR). However, regulatory mechanisms and functional …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …

The Influence Of Matrix Stiffness On Extracellular Matrix Protein Expression In 3d Encapsulated Mammary Fibroblasts, Kathryn Woods

PCOM Biomedical Studies Student Scholarship

A disease that transcends all races is breast cancer, the second leading cause of death among women with cancer. One factor, which participates in breast tumor progression, is the extracellular matrix (ECM), an acellular, protein-rich entity, which drives several cell, processes shown to promote tumorigenesis. Specifically, abnormal expression patterns and cross-linking of matrix fibers induces a more dense tissue structure, which has been reported to drive breast cancer progression. Alterations in ECM expression and cross-linking are in part due to carcinoma-associated fibroblasts (CAFs), activated fibroblasts which deposit copious ECM in the breast tumor environment. The goal of this study is …

Histological And Immunohistochemical Analyses Used To Study Craniosynostosis In Pediatric Patients, Palvir Kaur Baadh

Williams Honors College, Honors Research Projects

Craniosynostosis is a condition in which one or more of the sutures of the skull grow together (fuse) earlier than normal in infants. Sutures are large gaps located at the bony plates or joints of the head. Craniosynostosis causes the skull to expand and grow in the direction of any normal open suture, creating craniofacial complications, such as drooping eyelids and abnormal intracranial pressure, head shape, or brain morphology. This premature fusion or ossification of sutures affects approximately 300-500 live births in 1,000,000 (Kolpakova-Hart et al., 2008) with considerable variation in phenotype, depending on which suture(s) is involved. Corrective …

The Significance Of Crispr/Cas9-Directed Cul3 Knockout On Human Colorectal Cancer Cells, Zoe A. Lautz

Departmental Honors Projects

Cancer, the second leading cause of death in the US, is caused by mutations in select genes that alter cellular function leading to uncontrolled proliferation. Understanding the specific genes that drive cancer can lead to the generation of novel cancer therapies. To identify novel genes that drive cancer in the colon (CRC), lungs, and ovaries in mice, Starr et al. employed a transposon-based insertional mutagenesis system. One of the genes identified, APC, is mutated in 70-80% of human CRCs. CUL3, suspected to be a general driver gene, was discovered in the lung cancer screen. CUL3 was analyzed for its role …

Effect Of Adjuvant And Neoadjuvant Anti-Telomerase With Anthracycline Based Chemotherapy On Triple Negative Breast Cancer Cells, Luke T. Pardy

Student Summer Scholars Manuscripts

Breast cancer is the second leading cause of cancer related death in women in the US. In addition, 20% of all breast cancer cases in the U.S. are from the subtype known as Triple-Negative Breast Cancer (TNBC), which is the most aggressive and invasive form of the disease. This type of breast cancer has the worst prognosis, a decreased survival rate, and no targeted therapy. Over the decades, interest in pre- (Neoadjuvant) and post- (Adjuvant) chemotherapy treatments, in the management of TNBC has increased. Therefore, we evaluated the Adjuvant and Neoadjuvant effects of anti-telomerases (BIBR 1532 and GV6) with anthracycline-based …

High-Throughput Screening Of Age-Related Changes In Caenorhabditis Elegans, Neil Copes

USF Tampa Graduate Theses and Dissertations

This project was developed to identify novel methods for high-throughput culturing and screening of C. elegans to investigate age-related metabolic changes and to survey the proteomic and metabolomic factors associated with age-related changes. To accomplish these goals we developed a novel way to grow C. elegans in liquid culture in 96-well microplates for several weeks without suffering significant fluid loss due to evaporation and without needing to shake or unseal the plates for aeration. We also developed methods for assaying the total volume of live C. elegans in microplate cultures using a fluorescence microplate reader and for performing RNAi experiments …

Strategies For Preventing Age And Neurodegenerative Disease-Associated Mitochondrial Dysfunction, Vedad Delic

USF Tampa Graduate Theses and Dissertations

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal …

Genomic Aberrations At The 3q And 14q Loci: Investigation Of Key Players In Ovarian And Renal Cancer Biology, Punashi Dutta

USF Tampa Graduate Theses and Dissertations

Genomic aberrations are primary contributors to the pathophysiology of cancer [11]. Dysregulated expression of genes located within these aberrations are important predictors of chemoresistance, disease prognosis, and patient outcome [12]. This dissertation is focused on understanding the regulation and/or functions of specific genes located at dysregulated genomic regions such as 3q26 and 14q32 in the biology of ovarian and renal cancer, respectively.

Serous epithelial ovarian cancer (EOC) manifest amplification at the 3q26.2 locus [2], an observation consistent with the cancer genome atlas (TCGA) [13]. The most amplified gene in this region is EVI1 which has been extensively studied in hematological …

The Effects Of Supplemented Metabolites On Lifespan And Stress Response Pathways In Caenorhabditis Elegans, Clare B. Edwards

USF Tampa Graduate Theses and Dissertations

Understanding how metabolites contribute to anaplerosis, antioxidant effects, and hormetic pathways during aging is fundamental to creating supplements and dietary habits that may decrease age-associated disease and decline, thus improving the quality of life in old age. In order to uncover metabolic pathways that delay aging, the effects of large sets of metabolites associated with mitochondrial function on lifespan were investigated.

Malate, the tricarboxylic acid (TCA) cycle metabolite, increased lifespan and thermotolerance in C. elegans. Addition of fumarate and succinate also extended lifespan and all three metabolites activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced …

Targeting T-Bet For Prevention Of Graft-Versus-Host Disease And Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation, Jianing Fu

USF Tampa Graduate Theses and Dissertations

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. On the other hand, antigen-presenting cells (APCs) are essential for allogeneic T-cell priming and the development of GVHD. The T-box transcription factor T-bet is a master regulator for IFN-γ production and Th1 differentiation. T-bet also regulates the functions of APCs including dendritic cells (DCs) and …

What Are The Possible Causes For Autism Spectrum Disorder?, Rochel Preiserowicz

The Science Journal of the Lander College of Arts and Sciences

Ever since the mid 1980’s when Autism Spectrum Disorder (ASD) started to become increasingly prevalent, researchers have been trying to find a possible cause for it. Autism Spectrum Disorder is a developmental disorder that manifests itself in children who are between 18-30 months old. People with autism have reduced social skills, and they have a difficult time communicating verbally and non-verbally. Autism is diagnosed through a questionnaire and other instruments that allow psychologists, psychiatrists, speech therapists, neurologists and many other doctors to determine if a child has a form of ASD. There are many theories about what causes autism. It …

Unraveling The Genetic Mechanisms Involved In The Evolution And Development Of The Thoracic Appendages In Insects, Victor Medved

Wayne State University Dissertations

Insects display the greatest amount of structural and functional variation among animal groups, particularly in regard to their appendage morphology. These differences can range from the diverse pigmentation patterns between fore- and hindwings to changes in the size and shape of legs. The greatly enlarged jumping hind leg in crickets and grasshoppers is one of the best known illustrations of such diversity, representing a unique feature for the entire order of these insects (Orthoptera). Previous work from our lab has shown that the homeotic gene Ultrabithorax (Ubx) plays a key role in the enlargement of hind legs not only in …

Hrd1 Partners In Endoplasmic Reticulum-Associated Degradation, Aaron Alexander Burr

Wayne State University Dissertations

Protein Quality Control (PQC) comprises cellular pathways that regulate the turnover of short-lived, misfolded proteins. A main component of PQC is Endoplasmic Reticulum (ER)-Associated Degradation (ERAD), which controls the degradation of proteins synthesized in the ER. Aberrations in ERAD have been linked to malignancies such as sarcomas, breast, and pancreatic carcinomas, as well as neurodegenerative disease. The machinery in this system is complex and while significant progress has been made to understand ERAD, it is not clear how the different components come together, or how they are regulated. HRD1 is a resident ubiquitin ligase that has been proposed as a …

Soy Isoflavones Mediate Radioprotection Of Normal Lung Tissue By Modulating The Radiation-Induced Inflammatory Response, Lisa Marie Abernathy

Wayne State University Dissertations

Radiation-induced lung injury (RILI) is caused by an early inflammatory process triggered by damage to lung parenchyma, epithelial cells, vascular endothelial cells and stroma. Initially, oxidative injuries after radiation induce altered expression of pro-inflammatory cytokines. Infiltrating inflammatory cells are stimulated and activated, producing additional mediators, resulting in a cytokine cascade. The expansion and perpetual activation of inflammatory cells, as well as lung parenchyma, lead to clinical pneumonitis. Activated cells produce molecular mediators and growth factors that affect the proliferation and gene expression of lung fibroblasts. This process leads to increased collagen synthesis and deposition, eventually leading to the development of …

Adipocyte-Induced Inflammation In Prostate Tumor Progression In Bone: Role Of Cxcr2 And Osteopontin, Aimalie Lynnette Hardaway

Wayne State University Dissertations

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men. Evidence suggests that age and obesity, conditions associated with adipocyte accumulation in the bone marrow, are linked to increased risk of developing PCa and progressing to metastatic disease. Studies presented in this dissertation were based on the hypothesis that metastatic progression in bone is a result of a cooperative effort between bone marrow adipocytes, macrophages, osteoclasts, and PCa cells. We specifically focused on two adipocyte-supplied chemokines, CXCL1 and CXCL2, and bone marrow macrophage-secreted osteopontin as key drivers of pro-inflammatory environment in the bone marrow and important …

Expression And Characterization Of Ecm14, A Metallocarboxypeptidase From Saccharomyces Cerevisiae, Matthew James Schott

Master's Theses

Metallocarboxypeptidases are found in most organisms and function in the digestion and maturation of proteins. Ecm14 is a putative metallocarboxypeptidase found in the yeast Saccharomyces cerevisiae vacuole. The function of Ecm14 as an enzyme has been unclear due to the presence of active site amino acids not typically found in metallocarboxypeptidases, suggesting either no enzymatic activity or a unique mechanism. In order to investigate the enzymatic mechanism of Ecm14, expression of histidine-tagged Ecm14 protein was attempted in human HEK293T cell culture, S. cerevisiae, and baculovirus expression systems. No expression was detected in HEK293T cells in preliminary experiments. Expression in the …