Cell and Developmental Biology Commons^™

Potential Role Of A Ruthenium-Based Compound Ru-Im In The Treatment Of Triple Negative Breast Cancer, Rachele Rameau

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive and heterogeneous molecular subtype of breast cancer that has limited available treatments. The organometallic cationic ruthenium derivative Ru-IM was found to be highly water soluble, was differentially toxic for breast cancer cells and tumors, and was involved in the pI3K/AKT/mTOR pathway. However, a full understanding of genetic and epigenetic factors that can be part of regulatory mechanisms of Ru-IM is yet to be determined. Epigenetic assays including DNA methylation, histone acetylation and histone deacetylation were performed with the half inhibitory concentration (IC50) values of Ru-IM. Bisulfite sequencing of untreated and treated MDA-MB-231 …

Retinal Precursor Cell Enriched Multiomic And Pseudo-Time Analysis Of Developing And Reprogrammed Photoreceptors, Brendon M. Patierno

Dissertations, Theses, and Capstone Projects

The vertebrate retina is a complex tissue made up of seven major cell subtypes which during development must differentiate and localize into a highly organized structure. These neuronal cells do not regenerate if damaged or diseased, and the progressive deterioration of cone photoreceptor cells is the leading cause of age related blindness. Currently there are no cures for this disease, but one promising therapeutic avenue is cell transplantation research. If we can further elucidate the gene regulatory networks that define cone cell development, this knowledge could be applied to the generation of healthy cone cells in clinically relevant models.

The …

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

Mechanistic Insights Into The Neuroprotective Effects Of The Antidepressant Agomelatine In Alzheimer's Disease, Grace Terry

Dissertations, Theses, and Capstone Projects

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that has limited treatment options and no cure. AD is characterized by robust pathology including extracellular amyloid beta plaques, intracellular neurofibrillary tangles, neuronal and synaptic loss, neuroinflammation, and brain atrophy. AD presents with cognitive decline and memory loss but only years after neuropathology has started to accumulate. This robust pathology has made AD difficult to treat and highlights the need for therapeutics that modulate multiple pathways. Agomelatine (AGO) was selected by a high-throughput machine learning drug repurposing algorithm by our collaborator Dr. Lie Xie (Hunter College Dept. of Comp. Sci.) as having …

Bmp Signaling Co-Regulation Of Immune Response And Lipid Metabolism, Katerina K. Yamamoto

Dissertations, Theses, and Capstone Projects

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-β) family, initially identified for their roles in development and differentiation across animal species. They are now increasingly recognized for their roles in physiology and infectious disease. In the nematode Caenorhabditis elegans, the BMP ligand DBL-1 controls fat metabolism and immune response, in addition to its roles in body size regulation and development. DBL-1 regulates classical aspects of innate immunity, including the induction of anti-microbial peptides. We theorized that BMP-dependent regulation of fat metabolism could also promote resilience against microbial pathogens. We found that …

Investigating The Role Of Early Growth Response 1 (Egr1) Gene In Riluzole-Induced Apoptosis In Osteosarcoma, Syeda Maryam Azeem

Dissertations, Theses, and Capstone Projects

Osteosarcoma is a rare but aggressive bone malignancy most commonly affecting adolescents and young adults (AYA). With 5-year survival rate stagnating over the last four decades despite the advancements in multi-modal therapy, drug repurposing offers a rapid path to new osteosarcoma treatments. Recent studies suggest that Riluzole, a drug approved for amyotrophic lateral sclerosis (ALS), may be repurposed for osteosarcoma treatment due to its ability to slow tumor progression and induce apoptosis. Previously, we have shown that Riluzole increases reactive oxygen species (ROS), activating c-Abl, which phosphorylates YAP in the nucleus. YAP then forms a complex with p73 to enhance …

Co-Culture 3d Model For Breast Cancer, Anh Duc Nguyen

Research from the Berry Summer Thesis Institute, 2025

The ability to replicate the tumor microenvironment using 3D models have allowed researchers to study the tumors in vitro closer to their in vivo counterparts without the drawbacks of those models. The 3D co-culture model is an improved version of the 3D monoculture model, capable of replicating the tumor microenvironment, letting researchers study cancer response mechanism, tumor metastases, drug resistance, simulate cell-cell interactions, etc., in breast cancer. The models can be classified into four classes based on their formation method and content, all of which have different advantages and disadvantages.

Heterogeneity Of Molecular Subtypes In Multifocal And Multicentric Breast Cancer, Anna M. Schmitz

Research from the Berry Summer Thesis Institute, 2025

Multifocal and multicentric breast cancers (MMBC), commonly referred to as multiple synchronous ipsilateral breast cancers, are heterogeneous diseases. There is a high degree of diversity between and within the tumors of a MMBC-bearing patient. Tumor heterogeneity can describe multiple features, such as morphological and molecular profiles. Knowledge about a patient's tumor heterogeneity can be used to determine a prognosis and treatment plan. However, transferring our growing knowledge of heterogeneity in MMBC into a clinical setting remains a challenge due to the large degree of diversity between tumor microenvironments and the cancer cells that tumors are composed of. This review article …

Centrosomal And Non-Centrosomal Microtubule Networks Coordinate To Drive Nuclear Dynamics In Developing Epithelium, Rashmi Budhathoki

Electronic Theses and Dissertations

The morphogenesis of developing tissues relies on extensive cellular rearrangements in shape, position, and identity. A key process in reshaping tissues is cell intercalation-driven elongation, where epithelial cells align and intercalate along a common axis. Typically, analyses focus on how peripheral cortical forces influence cell shape changes. Less attention is given to how inhomogeneities in internal structures, particularly the nucleus, impact cell shaping. Here, we examine how pulsed contractile and extension dynamics interact with the nucleus in elongating Drosophila embryos. Our data show that tightly packed nuclei in apical layers hinder tissue remodeling/oscillatory behaviors. We identify two mechanisms for resolving …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

3d Bioprinting On Electrospun Nanofibrous Scaffolds To Fabricate Myocardial Patches, Muthu Parkkavi S

Theses and Dissertations

Tissue-engineered three-dimensional (3D) myocardial patches offer superior and innovative treatment strategy for myocardial infarction (MI). Among the various scaffold fabrication techniques, electrospinning and 3D bioprinting have received great attention due to their ability to recreate native cardiac tissue mimetic characteristics. Despite several advantages, electrospun nanofibers have limitations in cell delivery due to random cell seeding, while bioprinting faces challenges in creating hydrogel constructs with ideal mechanical properties capable of supporting cardiac contraction/relaxation cycle. Hence in this work, hybrid myocardial patches were developed by converging electrospinning and bioprinting techniques.

Electrospinning of PLCL:PEOz (B73, 7:3 blend of poly-L-lactide-co-ε-caprolactone (PLCL) and polyethyl oxazoline …

Role Of Stabilin-1 Expressing Macrophages In Colorectal Liver Metastasis, Jampa L. Gurung

Theses & Dissertations

Colorectal cancer (CRC) is the 2nd most common cause of cancer-related mortality, primarily due to its spread to distant organs. Colorectal liver metastasis (CRLM) is the foremost form of CRC spread due to the anatomical link between the liver and intestine. Despite advancements in diagnostic tools and adjuvant therapies, the survival rate of CRLM remains low, indicating the significant need to identify targetable mechanisms. Stabilin-1 (STAB1), a scavenger receptor expressed on tumor-associated macrophages, has been linked to tumorigenesis and poor outcomes in various cancers. However, the role of STAB1 in CRLM is not known. Here, we investigated the role of …

Kinase Suppressor Of Ras 2 Regulates Energy Balance And Tumor Initiation, Dianna H. Huisman

Theses & Dissertations

Kinase Suppressor of Ras 2 (KSR2) is a scaffold that facilitates Raf-MEK-ERK signaling and is expressed in the brain, pituitary, and adrenal gland. Here, we demonstrate that KSR2 functions in the adult brain to maintain organismal energy balance and in small-cell lung carcinoma (SCLC) to promote self-renewal and clonogenicity. Disruption of KSR2 in adult mice results in hyperphagia, obesity, reduced metabolic rate, and altered activity. Using spatial transcriptomics, we identify regions of the brain associated with regulation of feeding and energy expenditure with altered gene expression following KSR2 disruption. These findings reveal regions of interest in which targeted KSR2 disruption …

Claudin-1-Mediated Signaling And Therapy Resistance In Colorectal Cancer: From Mechanism To Translation, Mark W. Primeaux

Theses & Dissertations

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with metastatic cases showing poor response to chemotherapy due to both intrinsic and acquired therapy resistance. Claudin-1 (CLDN1), a tight junction protein, is overexpressed and mislocalized outside of tight junctions in CRC, where it contributes to an aggressive, metastatic phenotype. Although this causal relationship has been well established, the mechanisms by which CLDN1 promotes tumor progression were unclear due to its lack of intrinsic enzymatic activity. This dissertation investigates the molecular mechanisms through which CLDN1 drives oncogenic signaling, its role in therapy resistance, and its translational potential as both a …

Protocol For Vibratome Sectioning, Immunofluorescence, And S-Phase Labeling Of Inner Ear Organoids, Jiayi Wu, Stefan Heller, Maggie S. Matern

Biology Faculty Publications

Inner ear organoids represent a potentially inexhaustible source of otic tissues, including sensory hair cells and supporting cells, for in vitro manipulation. Here, we present a protocol for labeling S-phase entry of cells in inner ear organoids using 5-ethynyl-2′-deoxyuridine (EdU), followed by fixation and vibratome sectioning. Nuclear EdU is then detected alongside protein markers of interest via immunofluorescence. This workflow enables the visualization of cell and tissue morphologies within developing organoids and assessment of how different manipulations affect cell proliferation.

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge

MUSC Theses and Dissertations

In pancreatic ductal adenocarcinoma (PDAC), ~95% of cases harbor an activating KRAS mutation. The most common KRAS mutations in PDAC are KRAS^G12D (42%), KRAS^G12V (31%), and KRAS^G12R (15%). Patients harboring KRAS^G12R mutations have increased overall survival compared to those with KRAS^G12D/V-mutations. While KRAS^G12D/Vare common in all KRAS-mutant cancers, KRAS^G12Ris only common in PDAC.

KRAS^G12R is unable to activate the lipid kinase PIK3CA, a KRAS effector that is important for tumorigenesis in murine models. To investigate the tumorigenic potential of KRAS^G12R and the mechanisms that enable this mutation …

Applying Transcriptomics For Technology Development And Conservation In North American Marine Organisms, Cory Von Eiff

Dissertations

RNA biology is a rapidly expanding field, with many avenues of discovery among marine organisms. In this study, we analyze both mollusks and sawfish. First, we perform an evaluation of sRNA biogenesis pathways throughout Mollusca, with emphasis on the easter oyster, Crassostrea virginica. Understanding these molecules prescribes RNAi-based gene silencing approaches, benefiting genetic investigation and biotechnology. Similar to other animal groups, mollusks have conserved microRNAs (miRNAs), with some shared with ecdysozoans and deuterostomes; however, there is no evidence of an endogenous small interfering RNA (siRNA) pathway. These results suggest that long double-stranded RNA (dsRNA)-based RNAi is not appropriate for gene …

Adiponectin-Regulated Macrophage Responses In Aspergillus Fumigatus Infection: Mechanisms Of Uptake And Killing, Sri Harshini Goli

All-Inclusive List of Electronic Theses and Dissertations

Invasive aspergillosis (IA), caused by Aspergillus fumigatus, is a life-threatening infection in immunocompromised individuals, necessitating novel host-directed therapies. Macrophages are pivotal in antifungal defense, yet their function can be dysregulated; the influence of the adipokine adiponectin (APN) on this process is not fully understood. This thesis investigated the role of APN signaling in alveolar macrophage (AM) and bone marrow-derived macrophage (BMDM) responses to A. fumigatus and assessed the therapeutic potential of the APN receptor agonist, AdipoRon. Initial studies revealed that genetic deficiency in APN or its receptors renders AMs intrinsically pro-inflammatory and significantly impaired fungicidal activity against A. fumigatus. Subsequent …

Effect Of Moderate Decrease In Contractility On Epithelial Cell-Cell Contacts Under External Stretch, Saika Sharmin

Mechanical & Aerospace Engineering Theses & Dissertations

Epithelial tissues are characterized by extensive cell–cell contacts and often subject to stretch during normal function. Cell-cell contact adhesion strength maintains mechanical continuity from cell to cell. Mechanical forces exerted by cells via actomyosin contractility are known to strengthen cell-cell adhesions to a certain extent. While it is known that a large decrease in contractility causes cell-cell contact rupture due to weakened adhesions, it is unclear how a moderate reduction in contractility affects cell-cell junction stability. Here, we studied how a moderate inhibition of non-muscle myosin II (NMII) affects the integrity of epithelial cell-cell contacts, especially when subject to the …

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

Assessing The Impact Of Pll And Ple Concentrations And Aging On Protein Condensates Formation Via Llps, Nabil Harche

Theses, Dissertations and Culminating Projects

Protein droplets, also referred to as condensates, are membrane-less organelles formed through a biophysical process known as liquid-liquid phase separation (LLPS). These structures play an indispensable role in a wide range of cellular functions, including compartmentalizing biochemical reactions, regulating gene expression, and responding to cellular stress. Unlike traditional membrane-bound organelles, these condensates form dynamically and reversibly within the cytoplasm or nucleus, without the need for lipid membranes. The formation of these protein droplets is affected by several physicochemical factors, including pH, temperature, ionic strength, concentration of biomolecules, and specific molecular interactions such as electrostatics and hydrophobic forces. LLPS results in …

Regulation Of Icer Degradation And Its Role In Melanoma, Justin Wheelan

Theses, Dissertations and Culminating Projects

Melanoma is the deadliest form of skin cancer, with 100,640 new cases and 8,290 deaths estimated in the United States in 2024. While targeted therapies and immunotherapy have improved patient outcomes, resistance remains a major challenge, necessitating new therapeutic approaches. Approximately 50% of melanomas harbor BRAFⱽ⁶⁰⁰ᴱ mutations, leading to constitutive MAPK pathway activation. Targeted small molecule therapies such as BRAF and MEK inhibitors are available and initially reduce tumor burden, however resistance frequently occurs, likely through many pathways including compensatory activation of cAMP signaling. ICER (Inducible cAMP Early Repressor), a transcriptional repressor of CREB-mediated gene expression, is absent in melanoma …

3,5-Dihydroxy-4-Isopropylstilbene (Tapinarof) Is A Partial Aryl Hydrocarbon Receptor Agonist In Fish, Conner A. Dicks

All Theses

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that is essential in regulating development, immune homeostasis, and drug and xenobiotic metabolism. Activation of the AHR by specific ligands results in its translocation to the nucleus where it induces a myriad of gene products, including cytochrome P450 (CYP) drug metabolizing enzymes (e.g., CYP1A1) and other components of the chemical defensome, as well as inflammatory control. Interestingly, the AHR can bind a wide variety of endogenous and xenobiotic ligands which are able to induce unique downstream effects dependent on cell type, inflammatory context, and ligand stability. The AHR is …

Crevice Corrosion Mechanisms Of Cocrmo Alloys In Orthopedic Implants: Retrieval Analysis, Nano-Tribocorrosion And Cellular Responses, Hwaran Lee

All Dissertations

Mechanically assisted corrosion and non-mechanically (chemically) driven corrosion in modular junctions of orthopedic implants using cobalt-chromium-molybdenum (CoCrMo) alloys remain clinical concerns and may contribute to implant failure. The underlying corrosion mechanisms are not yet fully understood, leaving a critical research gap. We hypothesized that corrosion in modular junctions may be driven by aggressive local environments, including fretting, metal ion release (cobalt ion, Co²⁺), low pH and reactive oxygen species (ROS). This dissertation aims to (1) analyze corrosion modes and potential causes in modular junctions; (2) identify chemically driven corrosion modes on CoCrMo alloys using simulated inflammatory modular taper …

Analysis Of An Ethanol Sensitive Bmp-Nkx2.3-Fgf Signaling Pathway In Pouch Morphogenesis., Hieu Dai Le Vo

Electronic Theses and Dissertations

Craniofacial malformations lie at the heart of Fetal Alcohol Spectrum Disorders (FASD). While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Bone Morphogenetic Protein (Bmp) signaling pathway dependent pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3 and Fibroblast Growth Factor (Fgf) signaling, may mediate the impact of ethanol on Bmp mutants. Here, I …

Integrating Bulk And Single-Cell Transcriptomics To Investigate Intratumor Heterogeneity, Shuai Guo

Dissertations and Theses (Open Access)

Cancers are heterogeneous mixtures of tumor and surrounding cells, where each component comprises multiple distinct sub-types and/or states. Understanding the cell-type-specific contributions is critical for advancing cancer biology, yet high-throughput expression profiles from tumor tissues only represent combined signals from all diverse cellular sources. Bulk deconvolution with single-cell/nucleus (sc/sn) RNA-seq data has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns, yet the technological discrepancy across sequencing platforms limits accuracy.

To systematically evaluate the impact of platform discrepancies on bulk deconvolution, we first generated a benchmark dataset of 24 healthy retinas with paired bulk and …

Clonal Phenotype Mapping Reveals Genomic Alterations Underlying Tumor Immunosuppression During Immunotherapy, Er-Yen Yen

Dissertations and Theses (Open Access)

Tumors are dynamic ecosystems that evolve under selective pressures, shaping their ability to either elicit or evade immune responses. In pancreatic ductal adenocarcinoma (PDAC), where immunotherapy has yet to become an effective treatment option, we investigated the role of intratumoral heterogeneity in influencing immune interactions. Using orthotopic clonal replica tumors, we tracked clonal dynamics in response to anti-PD1 therapy and found that while treatment had limited impact on overall tumor volume, it induced profound shifts in clonal composition. Spatial lineage analysis of treatment-naïve tumors revealed that clones with distinct immunotherapy sensitivities occupy unique tumor microenvironments, a pattern that remained stable …

The Role Of Cleavage And Polyadenylation Spcific Factor 6 (Cpsf6) In Hematopoiesis, Fengxi Ye

Dissertations and Theses (Open Access)

Cleavage and polyadenylation specific factor 6 (Cpsf6) translocation is frequently reported in APLL, which is Acute Promyelocytic Leukemia (APL)-like acute myeloid leukemia (AML) and other types of blood diseases associated with abnormal hematopoiesis. CPSF6 is a subunit of the Cleavage Factor I mammalian (CFIm) complex, which regulates post-transcriptional alternative polyadenylation (APA) of pre-mRNAs. Previous research indicated that Cpsf6 plays an essential role in alternative polyadenylation, development, and tumorigenesis. However, the role of Cpsf6 in hematopoiesis is unknown. Given its roles in APA, development and cancer, we hypothesize that Cpsf6 plays a critical role in hematopoiesis and that its …

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …