Cell and Developmental Biology Commons^™

Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao

Pharmaceutical Sciences (PhD) Dissertations

A significant problem faced in oncology is the lack of chemotherapeutic agents that are tumor site-specific, resulting in reduced therapeutic efficacy and unintended infliction of harm to surrounding healthy tissues and cells that often lead to serious side effects. Current strategies being explored to circumvent this issue aim to refine delivery of  chemotherapeutic agents specifically to tumor sites, which may be achieved via conjugation of these agents to biomarker-specific ligands. This forms the foundation of ligand-targeted drug delivery. Among different breast cancers, treatment of the triple-negative breast cancer (TNBC) subtype has been particularly challenging, largely due to the absence of …

Investigating The Presence Of Amyloid In The C. Elegans Germline And Embryos, Sereen M. El Jamal

Biochemistry and Molecular Biology

Amyloids, insoluble protein aggregates of cross ß-sheet structure, are commonly associated with amyloidosis diseases. However, more recent studies support that some amyloids serve essential functions evolutionarily conserved across several taxa, particularly in reproduction. The nematode Caenorhabditis elegans serves as an excellent model organism in reproductive research. Prior to this study, no research has investigated the presence of functional amyloid in the C. elegans reproductive system. We hypothesize that similar to the presence of functional amyloid in the eggshells and epididymides of other organisms, functional amyloid will also be present in the germline and embryos of C. elegans. Using immunostaining, …

Cell Surface Expansion And Tension Regulation: How Cellular Forces Shape Embryonic Development, Samantha A. Pressman, Sophia M. Micale, Bing He

Wetterhahn Science Symposium Posters

Congenital birth deformities often arise during epithelial morphogenesis, displaying the need to understand the mechanisms underlying this process. Cell shape changes that mediate morphogenesis often require cell surface expansion to accommodate shifts in 3D tissue geometry. Our lab has identified Four Wheel Drive (Fwd), a Golgi-localized phosphatidylinositol 4-kinase (PI4K) IIIβ ortholog, as a regulator for cell surface expansion during Drosophila ventral furrow formation, a well-characterized model for epithelial folding. We hypothesize that Fwd and Rab11, a regulator of exocytosis and endocytic recycling, coordinate the trans-Golgi network and recycling endosomes to promote vesicle trafficking. Using live imaging of fluorescently tagged Fwd …

Mitochondria In Local Control Of Programmed Cell Killing & Resilience, Rashna Sharmin

Biology Dissertations - Archive

Specialized cells are commonplace and defined by different compartments. Organelle transport across cell compartments is critical for cell function, as in morphologically complex neurons. Specialized cells can undergo programmed elimination, an essential facet of normal development. My central thesis question asks how intracellular transport of mitochondria, the cell’s energy producers, regulate fated elimination of complex cells. I explored this using the specialized tail-spike cell (TSC) of the roundworm C. elegans. The TSC dies embryonically through the novel ‘tripartite’ developmental killing program, Compartmentalized Cell Elimination (CCE).  In my study, I defined and characterized events at the CCE initiation compartment of the …

Investigation Of Genx Exposure To Pathways Associated With Colorectal Cancer Risk, Emily J. Ferguson

Theses and Dissertations--Toxicology and Cancer Biology

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in drinking water and food sources, resulting in chronic human exposure. Among these compounds, hexafluoropropylene oxide dimer acid (HFPO-DA), commonly known as GenX, has been introduced as a short-chain replacement for legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Although GenX is believed to be a safer alternative, emerging research suggests it can still affect human health.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States, highlighting the need to better understand environmental …

Uncovering The Mechanism Of Reep2-Mediated Emt-Driven Membrane Trafficking In Lung Adenocarcinoma, Kevin Fulp

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking is frequently disrupted during cancer progression, and the underlying mechanisms remain largely unknown. Currently, no effective drugs target dysregulated membrane trafficking for cancer treatment. Recent evidence has demonstrated that epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma (LUAD) employs a membrane trafficking program to coordinate cancer cell invasion and immunosuppression. To further dissect the pro-tumorigenic membrane trafficking program, we initiated an in vivo CRISPRi screen to assess more than 2,000 membrane trafficking-related genes in a syngeneic mouse LUAD model. We identified REEP2, an endoplasmic reticulum (ER) shaping protein, as a novel regulator of EMT-driven membrane trafficking. High REEP2 expression is …

Reep2-Driven Pro-Metastatic Secretion Promotes Lung Cancer Progression, Oluwafunminiyi E. Obaleye

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking plays a critical role in cellular function and is frequently dysregulated in cancer to promote metastasis. In lung adenocarcinoma (LUAD), the epithelial-to-mesenchymal transition (EMT) activating transcription factor, ZEB1, drives a pro-metastatic membrane trafficking program; however, the underlying molecular mechanisms remain poorly understood. Using a CRISPR interference (CRISPRi) in vivo screen of 2,099 membrane trafficking regulators in a syngeneic mouse model of EMT-driven LUAD, we identified REEP2 — an endoplasmic reticulum (ER) shaping protein — as a critical regulator of tumor progression. REEP2 mRNA expression correlates with poor prognosis, EMT signatures, and an immunosuppressive tumor microenvironment in LUAD patients. …

Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler

MUSC Theses and Dissertations

Diabetes Mellitus (DM) affects 13.9% of men and 14.3% of women worldwide, a total of approximately 828 million people. Patients with diabetes are at risk of several complications including diabetic nephropathy (DN) and metabolic-associated steatohepatitis (MASH). These diseases eventually lead to end stage kidney disease (ESKD) and liver failure requiring dialysis and organ transplantation. In addition, diabetes exacerbates disease severity of autosomal dominant polycystic kidney disease (ADPKD), the most common potentially lethal genetic disease to affect humans with a prevalence of 1 in 500-1000. Therefore, a therapeutic approach that can attenuate organ damage and restore function in patients with DM, …

The Impact Of The Different Vdac Isoforms On Hbv Replication And Hbx Localization, Cody Mcumber

MUSC Theses and Dissertations

Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma worldwide. Despite the availability of a preventative vaccine, there are approximately 254 million people living with a chronic HBV infection. There are 9 known HBV genotypes, each with their own clinical impacts and manifestation in infected patients. HBx is the only regulatory protein encoded by the HBV genome and is required for efficient viral replication. HBx has many effects in infected hepatocytes besides known effects on HBV replication, such as localization to the mitochondria. HBx is also known to have impacts on mitochondrial membrane potential, mitochondrial permeability …

Generating A Gfp Reporter Via Crispr To Visualize Ssa4 Export, Aara Khairollahi, Rebecca Adams

SPARK Symposium Presentations

In eukaryotic cells, the transport of mRNA from the nucleus to the cytoplasm is a very regulated process controlled by nuclear pore complexes (NPCs). During stress conditions, such as heat shock, most mRNA export is inhibited in Saccharomyces cerevisiae, yet the transcript for SSA4, a gene responsible for refolding denatured essential proteins, is exported. The mechanism behind this selective export remains unknown. To investigate this, we used CRISPR-Cas9 to generate a reporter strain in which the SSA4 open reading frame was replaced or inserted with green fluorescent protein (GFP). This reporter is designed to produce GFP only under conditions that …

Exploring The Synergistic Effects Of Cisplatin And Curcumin In Osteosarcoma Cells, Ellis Stafford, Alexa Cabral, Andrea Florian Ph.D., Reese Nagy

SPARK Symposium Presentations

Osteosarcoma (OS) is a highly aggressive bone cancer characterized by rapid metastasis, which drastically reduces patient survival rates from 70% in localized cases to 30% upon metastasis. Current treatments combining chemotherapy with cisplatin and surgical intervention are often ineffective against metastatic OS and are associated with significant side effects. Cisplatin targets cancer cells by binding to DNA, disrupting transcription and replication, and inducing apoptosis. To address the challenges associated with current treatments, this study investigates the potential of combining cisplatin with curcumin, the bioactive compound derived from turmeric, as a novel therapeutic approach. Curcumin has shown anticancer properties by inducing …

Proteome-Based Identification And Validation Of Nxpe3 In Childhood Acute Lymphoblastic Leukaemia, Najia Tabassum, Yamna Khurshid, Basir Syed, Aftab Ahmad, Sadia Muhammad, Rehan Imad, Talat Mirza

Pharmacy Faculty Articles and Research

Background: Childhood acute lymphoblastic leukaemia (cALL) tends to metastasize to central nervous system. Treatment with antileukemic agents against CNS leukaemia is an essential component for cure in ALL. Hence, it is essential to identify biomarkers for CNS infiltration. Proteomics, supported by mass spectrometry, is the platform for exploring biomarkers in various biological samples, contributing to translational research. Objectives: This study aimed to identify the plasma proteome profile of children across different risk groups of cALL. Neurexophilin and PC-esterase family, member 3 (NXPE3), was validated. The protein-protein interactions (PPI) of NXPE3 were evaluated with bioinformatics analyses. Methods: Plasma …

Fluorescent Protein Imaging Approaches Uncover Dynamic Subcellular Distribution Of Core Clock Proteins In Neurospora Crassa, Ziyan Wang

Dartmouth College Ph.D Dissertations

Circadian clocks are endogenous self-sustained timekeeping systems that allow organisms to anticipate and adapt to daily environmental cycles. Found in diverse forms of life, these molecular clocks regulate the expression of ~ 40% of the genome in animals, fungi, and plants. In animals and fungi, circadian oscillators are built on transcription-translation feedback loops (TTFLs), in which positive regulators drive the expression of negative regulators which, once synthesized and imported into the nucleus, inhibit their own activators. This precisely regulated negative feedback incorporates multiple steps of delays that are essential for generating ~24-hour rhythms. Through these mechanisms, circadian clocks temporally coordinate …

Crispr Transgenic Clytia Hemisphaerica As A Vector For Toxin Delivery In A Zebrafish Melanoma Model, Theodore G. Paz

Theses, Dissertations and Culminating Projects

The jellyfish Clytia hemisphaerica has the potential to be used in cancer therapies with the discovery of potential active toxin target regions to be modified for use. The program Venomix is a Uniprot-based database that was utilized in this experiment to generate likely flagged hit regions using Clytia hemisphaerica CDS files run against its database of terrestrial toxins (Furuno et al., 2003; Macrander et al., 2018). By themselves they are indeterminate as to whether they are active toxin region hits (Macrander et al., 2018). With further analysis such as toxin homology in closely related, annotated marine taxa and accounting for …

Effect Of Mid-Range Ultraviolet Light On Avian Embryonic Development, Keelie Hughes

Biology Theses

While it is a known fact that specific environmental conditions must be met to ensure proper embryonic development, the impact of changes in this delicate balance is unclear. Ultraviolet (UV) light has a narrow range of effectiveness in mature tissue, where too little can hinder molecular signaling and too much can cause damage to genetic material. This study exposed in ovo chicken embryos in the preliminary stages of development to mid-range UV radiation to examine developing embryo and tissue morphology using anthropometric methods and comparing proliferative cells among embryos exposed to varying doses of UV light. Additionally, quantitative polymerase chain …

Characterization Of The Effects Of Atp On Primary Brainstem Glial Cells, Donovan J. Aardema Faigh

Graduate Theses/Dissertations

Migraine and temporomandibular joint disorder (TMD) are debilitating orofacial pain disorders that negatively impact one’s quality of life. These disorders are characterized by elevated levels of adenosine triphosphate (ATP) and activation of central nervous system glial cells that promote and maintain central sensitization and enhance pain signaling in response to inflammatory stimuli. The goal of my study was to characterize the effects of the pro-inflammatory signaling molecule adenosine triphosphate (ATP) on intracellular calcium levels, mRNA levels, and protein expression in astrocytes, microglia, and oligodendrocytes to better understand the role of ATP in promoting central sensitization. To address this goal, primary …

The Effect Of Sex On A-To-I Editing In Skeletal Muscle During Inflammation, Skyler Lee

Graduate Theses/Dissertations

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional mechanism mediated by ADAR enzymes that can alter RNA sequence, protein function, and gene regulation. Because ADAR1 is upregulated during inflammation and plays a critical role in innate immunity, previous studies investigated the effects of acute inflammation on RNA editing in male and female mice. Lipopolysaccharide (LPS) was used to induce inflammation, and RNA editing levels were examined in the heart, brain, and skeletal muscle. While editing levels in the heart and brain remained unchanged, skeletal muscle exhibited tissue- and sex-specific differences in editing. In this thesis, LPS treatment affected selective editing, increasing …

Bpa: Effects Of The "Plastic Era", Bianca G. Pietrangeli

Student Work

Infographic review of sources of BPA and its impacts on human health with a focus on osteoporosis.

Forecasting Lung Cancer Burden Using Multicenter Real-World Data, Omer Aydin, Levent Korkmaz, Aybeyan Selim, Murat Kuzlu, Ferhat Ozgur Catak, Huseyin Kusetogullari, Umit Cali

Engineering Technology Faculty Publications

Background – Lung cancer continues to place a significant clinical and operational burden on healthcare infrastructure and systems. While essential epidemiological data can be obtained from population-based registries, these systems often fail to provide information on long-term follow-up and healthcare utilization dynamics. Real-world data collected from healthcare institutions offer valuable insights; however, in-depth and careful analysis is necessary to distinguish true diagnostic trends from changes in service utilization and access.

Objectives – The primary objective of this study is to characterize and forecast the prevalence of lung cancer diagnoses at the specified hospitals for future years. The study aims to …

A Sweet Spot For Chemotherapy: The Influence Of Insulin And Glucagon On Oxaliplatin Sensitivity In Colorectal Cancer Cells, Daniella Cohen, Andrea Florian

SPARK Symposium Presentations

There is a well-established relationship between cellular metabolism, cancer progression, and treatment response. Metabolic hormones such as insulin and glucagon regulate pathways involved in cell growth, survival, and stress responses and have been linked to tumor development and chemotherapy sensitivity. Understanding how metabolic signaling influences cancer treatment may provide insight into factors that affect therapeutic outcomes. This study aims to investigate how insulin and glucagon affect the susceptibility of colorectal cancer cells (CRC) to the chemotherapeutic agent oxaliplatin. CRC cells were treated with insulin or glucagon and exposed to varying concentrations of oxaliplatin. Cell viability was measured to evaluate treatment …