Cell and Developmental Biology Commons^™

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

University Scholar Projects

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Determining Therapeutic Efficacy Of Low-Frequency Ultrasound In Targeting In-Vitro Human Attached Cell Lines With Adjuvant Chemotherapy, Charles Schauer

Renée Crown University Honors Thesis Projects - All

Research in the Fondy laboratory at Syracuse University has shown that in free-moving cancer cell lines, such as leukemia and lymphoma, larger cells are preferentially targeted by ultrasound therapy and have reduced viability as a result. Little time with respect to ultrasound, however, has been dedicated to the study of cell lines such as colorectal carcinoma and glioblastoma, which require connective tissue to grow.

Our research involves the low-frequency ultrasound treatment of attached carcinoma cell lines with adjuvant chemotherapy to evaluate an effective regimen for reducing viability of cancer cells. Prior research with human glioblastoma has shown that cells attached …

Pcr Cloning: New Parameters For Managing Alzheimer’S Dementia, Asra Khan, Rehana Rehman, Saara Ahmad

Department of Biological & Biomedical Sciences

No abstract provided.

Hdac Regulates Transcription At The Outset Of Axolotl Tail Regeneration, S. Randal Voss, Larissa V. Ponomareva, Varun B. Dwaraka, Kaitlin E. Pardue, Nour W. Al Haj Baddar, A. Katherine Rodgers, M. Ryan Woodcock, Qingchao Qiu, Anne Crowner, Dana Blichmann, Shivam Khatri, Jon S. Thorson

Neuroscience Faculty Publications

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited …

The Effects Of Eicosapentaenoic Acid (Epa) And Docosahexaenoic Acid (Dha) On Brown Adipogenesis In Stem Cell Culture, Darynne Dahlem

Animal Science Undergraduate Honors Theses

Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are major maternal dietary supplements due to their positive benefits on neurological tissue growth during the first 12 weeks of gestation. Previous studies show that EPA and DHA inhibit muscle formation but promote adipogenesis. However, no research has addressed the question whether high intake of EPA and DHA affects brown fat development during gestation. The objective of this study was to measure the effect of EPA and DHA supplement on brown adipogenesis and potential pathways related to mitochondrial biosynthesis using fibroblasts as in vitro model. Using Oil-Red-O staining …

Developing A Modern Microbiology Laboratory Manual To Enhance Student Learning, Alexander Yonchak

Senior Honors Projects

My project has been addressing the issue of incorporating recent developments in biosafety and pedagogical approaches for lab-courses into our existing educational curriculum by developing a new, modern lab manual aimed at improving experiential learning for introductory microbiology teaching labs. Through researching the most recent safety regulations, industry standards, & guidelines for such teaching labs, my manual clearly delineates learning outcomes to match the skills expected of undergraduates completing degrees within the life sciences. In addition, the lab manual that I have designed has been modernized to incorporate the most recent recommended safety precautions and is written in a user-friendly …

Phylogenomics And Geometric Morphometrics Define Species Flocks Of Snowtrout (Teleostei: Schizothorax) In The Central Himalayas, Binod Regmi

Graduate Theses and Dissertations

Schizothorax (Snowtrout) is a genus of medium-sized minnows (Cypriniformes) inhabiting glacier-fed streams, rivers, and lakes in the Himalayas. There are more than 30 species of Schizothorax across the region. The speciation and diversity of the Snowtrout in the vast hinterlands of the Himalayan Region has not been fully explored. Three species in Lake Rara, Western Nepal are considered a species flock, comprising endemic ecotypes that are morphologically differentiated and reproductively isolated.

My dissertation research examined the diversity of Schizothorax in the Central Himalayan region and evolutionary relationships among species distributed in the Tibet, Central and Southeast Asia. Chapter I describes …

The Role Of Ppal In The Moss Physcomitrella Patens., Noela M. Botaka

College of Arts & Sciences Senior Theses

Protein prenylation is a post-translational modification that involves the addition of lipid groups to the carboxy end of a target protein and is necessary for protein activity. Prenylation has important roles in the cell: targeting and localizing proteins to subcellular compartments and promoting protein-protein interactions. As a highly conserved process in eukaryotes, prenylation is especially important for plant development. In contrast to other eukaryotes, in which loss of prenylation components can be lethal, in the flowering plant Arabidopsis thaliana and the moss Physcomitrella patens, most are viable. Prior studies have shown that prenylation is involved in ABA hormone responses, …

Human Anatomy And Physiology I: Course Map With Expected Learning Outcomes, Carlos Liachovitzky

Open Educational Resources

This document contains a list with all the Anatomy and Physiology I expected learning outcomes organized by topics, and grouped into ten units: 1. Introduction to A&P: body plan & organization; 2. Introduction to A&P: homeostasis; 3. The chemical level of organization; 4. Levels of organization: the cellular level of organization; 5. Levels of organization: the tissue level of organization; 6. Support and movement: integumentary system; 7. Support and movement: skeletal system & articulations; 8. Support and movement: muscular system; 9. Regulation, integration, and control: nervous system; 10. Regulation, integration, and control: special senses

Each learning outcome is referred to …

Transcriptional Influence Of Retinoic Acid And Its Effects On Angiogenesis Of Murine Salivary Glands., Isaac Feinn

College of Arts & Sciences Senior Theses

Salivary gland hypofunction is a major disorder of salivary glands, and can arise either from diseases such as xerostomia, or from defective epithelial morphogenesis during embryogenesis. Hundreds of thousands of individuals suffer from dry mouth, and there is currently no restorative therapy for these patients. Investigation of salivary gland developmental biology will inform regenerative therapies. Currently it is known that retinoic acid (RA), the biologically active form of Vitamin A, is required for proper development of the salivary gland, but little is known about its cellular mechanism regulating organogenesis. This study sought to analyze salivary gland development in Rdh10 knock …

Attenuated Responses To Inflammatory Cytokines In Mouse Embryonic Stem Cells: Biological Implications And The Molecular Basis, Bohan Chen

Master's Theses

Embryonic stem cells (ESCs) have attracted intense interest due to their great potential for regenerative medicine. However, their immune property is an overlooked but a significant issue that needs to be thoroughly investigated not only to resolve the concern for therapeutic applications but also for further understanding the early stage of organismal development. Recent studies demonstrated that ESCs are deficient in innate immune responses to viral/bacterial infections and inflammatory cytokines. Inflammatory conditions generally inhibit cell proliferation, which could be detrimental to ESCs, since cell proliferation is their dedicated task during early embryogenesis. Thus, I hypothesize that the attenuated innate immunity …

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

Comparative Plasma Proteomics In Muscle Atrophy Induced By Cancer Cachexia And Hindlimb Unloading, Kirsten Rene Dunlap

Graduate Theses and Dissertations

Introduction: Muscle atrophy results from a dysfunction in protein turnover that leads to loss of mass and function and occurs concurrently with multiple pathologies such as cancer and extended bed rest. Atrophy reduces overall quality of life while increasing morbidity and mortality. Currently, efficacious therapeutic interventions to treat and prevent muscle wasting in all its forms are lacking, however if conserved mechanisms can be identified between wasting conditions, this would aid in the development of multipurpose therapeutics to ameliorate this pathology. Purpose: To examine circulating factors present across atrophic pathologies. Methods: 35 male C57BL/6J mice were assigned to hindlimb unloading …

Exploring The Role Of Ptn1 In Ustilago Maydis., Lalu Murali Krishna Vijayakrishna Pillai

Electronic Theses and Dissertations

Signal transduction is a key aspect of biological life. Cell signaling involves a series of biochemical and molecular steps that regulate the normal cellular functions, and any disruption at any of these steps is likely to have substantial impacts on cell physiology. The current study was aimed at the characterization of ptn1 of Ustilago maydis, a basidiomycete fungus. When the U. maydis, ptn1 gene was either deleted or overexpressed, it was found that the deletion of this gene lead to reduced virulence, spore production, and germination rate; effects of the overexpression were more subtle or not discernable. Previous studies …

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 …

An Oxanthroquinone Derivative Disrupts Ras Plasma Membrane Localization And Function By Inhibition Of Acylpeptide Hydrolase And Perturbation Of Sphingomyelin Metabolism, Lingxiao Tan

Dissertations and Theses (Open Access)

Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examined the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalized HRAS and KRAS from the PM with similar potency and disrupted the spatial organization of RAS proteins remaining on the PM. G01 also inhibited recycling of epidermal growth factor receptor and transferrin receptor, but did not impair internalization …

Embryonic Lethality Of Cranial Neural Crest Deletion Of Cdc73, Lilia Shen

Honors Scholar Theses

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a disease characterized by parathyroid tumors, renal cysts or tumors, uterine tumors, and ossifying jaw fibromas. The cause of this syndrome is linked to a tumor suppressor gene called Cdc73, which encodes the protein product parafibromin. The loss of proper expression of Cdc73/parafibromin is implicated in the development of the tumors typical of HPT-JT, although the exact mechanisms of tumorigenesis are unclear. In particular, not much is understood about the development of ossifying fibromas (OF) of the jaw in this syndrome. OF is a benign bone neoplasm that can affect the mandible and …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

Honors Scholar Theses

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Spatial Reorganization Of Histone-Like Nucleoid Structuring Proteins Caused By Silver Nanoparticles, Meaad Alqahtany

Graduate Theses and Dissertations

Silver nanoparticles (AgNPs) and ions (Ag+) can be the new generation of antibiotics due to their antimicrobial effects against bacteria and other microbes. Many studies have shown that AgNPs and suppress the growth of bacteria and damage the cell walls of the microbes; therefore, treating bacterial cells with AgNPs may be a promising method to terminate multi-resistant bacteria. In this work, the effect of AgNPs with two different surface coatings on the spatial reorganization of histone-like nucleoid structuring (H-NS) proteins in Escherichia coli bacteria was investigated using quantitative super-resolution fluorescence microscopy to understand the toxicity and antimicrobial mechanism of AgNPs. …

Do Enallagma Exsulans From Streams And Lakes Show Patterns Of Divergence?, Savannah Rae Graham

Graduate Theses and Dissertations

Divergent selection across heterogenous environments could lead to adaptive divergence in populations resulting in potential local adaption. These populations have phenotypic differences that are fitness related and make native individuals more fit than non-native individuals. My research focuses on a species of damselfly, Enallagma exsulans, to explore local adaptation and morphological differences as a result of divergent selection or plasticity. My first study explored potential local adaptation of wild caught stream and lake E. exsulans using a reciprocal transplant design, a classic approach for this objective. The stream and lake sites chosen were on a small spatial scale allowing for …

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Graduate Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient and …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

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

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 …

Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao

Dissertations, Theses, and Capstone Projects

Many human breast cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. Expression of MDM2 and MDMX occurs in both estrogen receptor α positive (ER+) and triple negative breast cancer (TNBC). We and others have reported that estrogen activated MDM2 strongly promotes proliferation in ER+ T47D breast cancer cells in a p53-independent manner. Whether MDM2 elicits in vivo p53-independent proliferative functions in T47D breast cancer cells has not been determined. Furthermore it has been shown that ectopic expression of MDM2 targets E-Cadherin for degradation thus leading to increased cell migration and invasion. Therefore we assessed the in vivo …

The Molecular Mechanisms Underlying The Cancer Killing Effect Of Interleukin-24, Leah Eshanie Persaud

Dissertations, Theses, and Capstone Projects

Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer

Dissertations and Theses (Open Access)

Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I …

Thiol-Based Misfolding: Linking Redox Balance To Cytosolic Proteostasis, Ford Amy

Dissertations and Theses (Open Access)

The eukaryotic cytosolic proteome is vulnerable to changes in proteostatic and redox balance caused by temperature, pH, oxidants and xenobiotics. Cysteine-containing proteins are especially at risk as the thiol side chain is subject to oxidation, adduction and chelation by thiol-reactive compounds. All of these thiol-modifiers have been demonstrated to induce the heat shock response and recruit protein chaperones to sites of presumed protein aggregation in the budding yeast Saccharomyces cerevisiae. However, endogenous targets of thiol stress toxicity responsible for these outcomes are largely unknown. Furthermore, I hypothesize proteins identified as redox-active are prone to misfolding and aggregation by thiol-specific …

Il-6/Jak1 Drives Pd-L1 Phosphorylation And Glycosylation To Promote Cancer Immune Evasion, Li-Chuan Chan

Dissertations and Theses (Open Access)

Glycosylation of immune receptors and ligands, such as T-cell receptor (TCR), major histocompatibility complex (MHC), and co-inhibitory molecules, regulates immune signaling activation, antigen presentation, and immune surveillance. Recent studies revealed that the glycan structures of co-inhibitory molecules are required for receptor-ligand interaction, a critical feature for activating cancer immune evasion. However, it is unclear how oncogenic signaling initiates glycosylation of co-inhibitory molecules to induce immunosuppression. Here we show interleukin (IL)-6-activated Janus kinase 1 (JAK1) phosphorylates programmed death-ligand 1 (PD-L1)-Tyr112, leading to the recruitment of endoplasmic reticulum (ER)-associated N-glycosyltransferase, STT3A, which catalyzes the glycosylation of PD-L1, contributing to its stability. A …