Cell and Developmental Biology Commons^™

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 …

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.

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 …

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 …

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 …

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 …

A Toi Rna Editing In Three Members Of The Microbotryum Violaceum Fungal Complext And Characterization Of Adar Genes Of Microbotryum Superbum., Shikhi Baruri

Electronic Theses and Dissertations

A-to-I RNA editing is a process that occurs post-transcriptionally. Through this process, adenosine (A) is replaced by inosine (I) in RNAs by adenosine deaminase enzymes that act on the single-stranded RNA. These enzymes, also known as ADARs, act on RNA. The translation and splicing mechanisms subsequently interpret inosine as guanosine (G), which effectively alters genetic information. This kind of RNA alteration can cause both nonsynonymous and synonymous changes in codon, which may have an impact on protein function. A group of over 89 basidiomycete fungal species known as the Microbotryum violaceum complex infects a similarly large group of plant host …

Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells

Electronic Theses and Dissertations

Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …

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 …

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 …

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 …

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 …

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 …

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 …