Cell and Developmental Biology Commons^™

Antioxidant Potential Of A Non-Heme Iron Complex: Mitigating H2O2-Induced Cellular Damage, Magy A. Mekhail, David M. Freire, Cameron Bowers, Grant Elam, Nora Del Bosque, Hannah K. Pyle, Sarah K. Dunn, Spencer Lanyon, Timothy J. Hubin, Giridhar Akkaraju, Kayla N. Green

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Iron complexes with antioxidant activity have garnered significant interest for both general and medical applications, yet few studies have yielded functional nonheme iron-based mimics for H₂O₂ mitigation in aqueous environments. Here, we investigate water-soluble nonheme iron complexes derived from 12-membered pyridinophanes (^CF₃PyN₃, PyN₃, ^NMe₂PyN₃, and Py₂N₂) to evaluate the impact of ligand scaffolds on H₂O₂ decomposition activity both in vitro and in a cellular model. Speciation and kinetic analyses reveal that both electronic and geometric modulation of the macrocyclic …

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …

Metal Oxide Nanoparticle‑Integrated Phema Hydrogels: Morphology, Chemical Properties, And Biological Interaction, Venkateswar Rao, Collin Cox, Brandon Clark, Arushi Rai, Erick S. Vasquez-Guardado, Madhuri Kango-Singh, Soubantika Palchoudhury

Chemical and Materials Engineering Faculty Publications

Hydrogels offer attractive matrices for incorporating inorganic metal oxide nanoparticles (NPs) to generate multifunctional hybrid materials, but challenges remain in scalable synthesis and correlating their properties to bio-interaction. Therefore, we report the synthesis and characterization of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels, and pHEMA hydrogels encapsulating iron oxide or zinc oxide NPs, using a modified free-radical polymerization. Dose-dependent survivorship studies on Drosophila melanogaster revealed that both NP-embedded hydrogels are tolerated over a wide dose range (e.g., 50–200 mg), although ZnO NP-gels exhibit lower survivorship at some concentrations due to their inherent composition and a wider size distribution of iron oxide NPs.

Structure-Based Discovery Of Malate Dehydrogenase Inhibitors With Efficacy Against C. Parvum Oocysts, Ankita Bharatbhai Kheni

Biochemistry and Molecular Biology

Cryptosporidium parvum, the etiological agent of Cryptosporidiosis (diarrheal illness) represents a significant global health burden, particularly affecting immunodeficient and pediatric populations. Since the parasite has a highly reduced mitochondrion and relies on glycolysis, enzymes such as C. parvum malate dehydrogenase (CpMDH), which are believed to be indispensable for parasite viability due to their pivotal roles in NAD⁺ regeneration and redox balance, remain largely unexplored as therapeutic targets. The present study employed a multifaceted experimental and computational strategy to evaluate the inhibitory activity of two lead-like and drug-like small molecules, referred to as compound 1.8 and compound 1.5, against the cofactor …

Decorin Promotes Nascent Proteoglycan Retention In Cartilage Matrix By Strengthening Collagen Ii-Aggrecan Integration, Thomas Li, Gabriela Canziani, Yuchen Liu, Neil Patel, Biao Han, Mingyue Fan, Annie Porter, Bryan Kwok, Chao Wang, Qing Li, David E. Birk, Renato V. Iozzo, Irwin M. Chaiken, X. Lucas Lu, Robert L. Mauck, Lin Han

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cartilage extracellular matrix (ECM), a hydrated collagen II-aggrecan composite, undergoes dynamic turnover during both normal homeostasis and disease-associated remodeling. This study elucidates a crucial role for decorin in promoting the retention and stability of nascent aggrecan within this matrix. By applying bio-orthogonal click-labeling, we demonstrate that loss of decorin accelerates the release of nascent aggrecan under both physiological and inflammatory conditions, without affecting its preferential localization to the pericellular matrix. Conversely, supplementation with exogenous decorin mitigates inflammation-induced loss of nascent aggrecan, supporting its potential as a therapeutic target. At the molecular level, decorin exhibits strong binding affinity for aggrecan, and …

Uncovering Dkk1 As A Therapeutically Relevant Target In Aggressive Er+ Breast Cancer Using A Novel Antiestrogen, Kristen Young

Dissertations

Over 70 percent of breast cancers are estrogen receptor-positive (ERα+), meaning that the hormone estrogen drives tumor growth. Although first-line targeted therapies that directly block ERα from hormone-dependent pathologies are initially effective, almost half of patients ultimately progress. These patients show high mutational rates to the ESR1 gene that encodes for ERα. A hotspot missense tyrosine to serine mutation at position 537 (Y537S) initiates hormone-independent, allele-specific transcriptional programs that increase metastasis. While next-generation ERα-targeted therapies show promise, benefits are often limited compared to standard-of-care. Understanding the mechanisms of action used by the Y537S ESR1 breast cancer cells to evade therapeutic …

Loss Of Mct1 Mediated Lactate Uptake Causes Delayed Endplate Maturation And Intervertebral Disc Degeneration, Maria Tsingas, Konstantinos Tsingas, Mei Smyers, Wujuan Zhang, Aaron R. Goldman, Eulisa Lawrence, John A. Collins, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

During skeletal growth, it is thought that the lactate secreted by the glycolytic nucleus pulposus (NP) cells exits the intervertebral disc into circulation via endplates. Our current studies challenge this long-held notion. Mice with early postnatal, endplate, and annulus fibrosus-specific deletion of lactate importer, MCT1, exhibited disc degeneration characterized by NP cell loss and pronounced endplate structural changes. Using metabolic and transcriptomic approaches, we demonstrate that MCT1 loss inhibits endplate chondrocyte differentiation and that lactate serves both as a crucial TCA metabolite and promotes protein and histone lactylation and gene expression. These findings suggest that during skeletal growth, NP-derived lactate …

Profiling Nucleolin Phosphorylation During Dna Damage Response And Cell Cycle Arrest, Hanjun Jeon

Dissertations, Theses, and Capstone Projects

This dissertation examines site-specific and global phosphorylation dynamics of nucleolin (NCL) in response to DNA damage and cell-cycle perturbations. By combining phospho-specific immunoblotting with Phos-tag SDS-PAGE analysis, distinct phosphorylation patterns were identified across experimental conditions. The results define reproducible, condition-dependent phosphorylation states of NCL and provide a framework for studying its regulation under cellular stress.

Routine Transfusion Of Rh(D)-Positive Rbcs To Rh(D)-Negative Patients Designated As Do Not Resuscitate Conserves Rh(D)-Negative Red Blood Cell Inventory, Julie Katz Karp, Jovanna Everetts, Juliana Guarente, Angelica Vivero, Tiffany Bohr, Mary Harach

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: A minority of blood donors are Rh(D)-negative, and Rh(D)-negative red blood cell (RBC) products are often overutilized. As such, Rh(D)-negative RBCs may be difficult to maintain in blood bank inventory.

Study design and methods: We changed our blood bank laboratory policy to approve non-alloimmunized Rh(D)-negative patients to receive Rh(D)-positive RBCs for routine transfusion under defined criteria. Those criteria included Rh(D)-negative males (all ages) and females (aged >50 years) who were designated as do not resuscitate (DNR), either with or without intubation, in the electronic medical record.

Results: From August 15, 2024 through August 15, 2025, a total of 204 …

Is Trimethylamine N-Oxide A Friend, Foe, Or Hormetic Agent In Patients With Parkinson’S Disease: A Focused Review Of One Microbial Metabolite, Abraham B. Alton

Student Works

This review synthesizes recent literature examining trimethylamine N-oxide (TMAO) synthesis and its potential role in Parkinson’s Disease (PD) pathology. An increase in TMAO plasma and CSF concentration is associated with PD progression and severity. TMAO biosynthesis is a two-step process. First, precursors including carnitine and choline are converted to trimethylamine (TMA) by gut microbes. Second, TMAO is oxidized to TMAO in the liver. Once absorbed into circulation TMAO crosses the blood brain barrier and may influence PD disease pathology by increasing neuroinflammation and astrocyte activation and damaging the cerebral lymphatic system. These mechanisms may contribute to the cognitive and motor …

Mitochondria-Er Contact Sites (Mercs) In The Cell Cycle: Molecular Architecture And Functional Remodeling Across Cellular States, Eduardo Silva-Pavez, Bruno Torres-Gonzalez, Michelle Sotomayor, Benjamín Cartes-Saavedra, Dorian V. Ziegler, Yessia Hidalgo-Fadic, Ulises Ahumada-Castro

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria–endoplasmic reticulum (ER) contact sites (MERCS) are nanoscopic, dynamic platforms integrating metabolism, signaling, and stress responses to regulate cell fate. These nanoscopic interfaces remodel continuously to meet the demands of proliferating, quiescent, and senescent cells. We synthesize evidence that MERCS actively coordinate local Ca2+ signaling, non-vesicular lipid transfer, and proteostasis to shape mitochondrial function and cellular homeostasis. We discuss how MERCS architecture changes across the cell cycle and during arrest, distinguishing adaptive from maladaptive remodeling, and consider therapeutic potential in aging and age-related disease.

The Impact Of Tgfβ Conditioning And Socs3 Expression On Cytokine Signal Transduction And Inflammatory Gene Expression In Fibroblasts, Morgan Anderson-Crannage

NYMC Student Theses and Dissertations

Inflammation is a major driver in many aspects of recessive dystrophic epidermolysis bullosa (RDEB) pathology, including impaired wound healing, fibrosis, and potentially cutaneous squamous cell carcinoma development. Fibroblasts, as key stromal cells in the dermis, are responsible for orchestrating inflammatory responses through the secretion of cytokines and chemokines upon stimulation with IL-1α or IL-6. Suppressor of Cytokine Signaling 3 (SOCS3) functions as a negative feedback regulator of cytokine signaling and has emerged as a key modulator of inflammatory responses in immune cells and fibroblasts. Transforming Growth Factor Beta (TGFβ), a known driver of fibrosis in RDEB, has been implicated in …

In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel

Biological Sciences Theses and Dissertations

One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …

Characterizing A Potential Cbp/P300 Histone Acetyltransferase Homolog In Tardigrade Germline Specification And Development, Brittney Michelle Hartshorn

Honors Projects

Germline specification is a fundamental process that ensures the proper development of germ cells. Germline specification occurs either through germ cell determinants maternally inherited through the mechanism of preformation or through induction, where cell interaction and epigenetic modifications direct specification. Determining how these mechanisms evolved and diverged remains an important question in developmental biology. Despite research on germline regulation in model organisms such as Caenorhabditis elegans or Drosophila melanogaster, such regulation remains poorly understood in many other animal groups. Tardigrades are an emerging model system for investigating developmental mechanisms due to their phylogenetic placement and experimentally tractable embryos. CBP/P300 is …

Mllt1 Is Required To Maintain B-Lymphopoiesis, Janani Prakash

Dissertations

MLLT1 (also named ENL) is an epigenetic reader protein that binds to crotonylated or acetylated lysine residues of histone 3 through its N-terminal YEATS domain. Positive and negative regulatory complexes compete for binding to C-terminal MLLT1, and promote transcription elongation (SEC, Super elongation complex; DOT1L) or transcriptional repression (PRC1, Polycomb repressive complex 1). MLLT1 was initially identified as a chromosomal translocation partner to MLL(KMT2A) in a subset of MLL-rearranged leukemias. MLL-ENL fusion protein causes both lymphoid (predominantly B-ALL) and mixed lineage leukemias. MLLT1 has been implicated in leukemic stem cell survival in MLL-rearranged cell lines but its role in normal …

Potential Innate And Adaptive Roles Played By Γδ T Cells In A Bacterial Immunization Model, Lee Anne Talbot

Seton Hall University Dissertations and Theses (ETDs)

Francisella tularensis is a highly infectious intracellular bacterium and the causative agent of tularemia, with pulmonary infection resulting in severe disease and high mortality if untreated. While protective immunity to F. tularensis has been largely attributed to CD4⁺ T cell–mediated IFN-γ responses, the contribution of γδ T cells to mucosal immunity and vaccine-induced protection remains poorly defined. The objective of this study was to characterize the role of γδ T cells during primary pulmonary infection with F. tularensis live vaccine strain (LVS) and following intranasal immunization with inactivated F. tularensis (iFt) prior to LVS challenge.

Using a murine intranasal infection …

P300/Cbp Inhibition With Inobrodib In Combination With Gilteritinib And Venetoclax Targets Leukemia Stem Cells In Epigenetic Mutant Aml, Melanie L. Goetz, Jennifer S. Romer-Seibert, Amanda M. Versace, Scott Kogan, Chetan Jeurkar, Robert L. Bowman, Nigel Brooks, Kris Frese, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and …

Junctional Actin As A Mechanical Hub For Supracellular Actomyosin Force Transmission During Apical Constriction, Jasneet Brar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Apical constriction is a conserved morphogenetic mechanism that drives epithelial folding during development. During ventral furrow formation in Drosophila melanogaster, contractile actomyosin networks generate forces that reduce apical cell area resulting in tissue invagination. For these cell-scale forces to produce coordinated tissue-scale changes, contractile networks must be mechanically integrated across neighboring cells. Although adherens junctions are known to mediate this coupling, it is unclear how junctions are integrated into cortical actin cytoskeleton, which directly determines cell, and consequently tissue, shape. This thesis tests the hypothesis that supracellular actomyosin organization during apical constriction depends on distinct adherens junction based mechanical couplings: …

Thrombin-Induced Myofibroblast Differentiation Is Regulated By Myocardin And Novel Effector Genes In Ipf Fibroblasts, Christiana Okeke

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by fibroblast activation, excessive extracellular matrix (ECM) deposition, and irreversible respiratory decline. In this study, we investigated the role of myocardin and its downstream effectors, RGS5, DLGAP5, and TAGLN, in thrombin-induced myofibroblast differentiation and ECM remodeling using primary human IPF fibroblasts. Myocardin knockdown significantly attenuated thrombin-induced expression of profibrotic genes, including FN1, COL1A1, PAI-1, ACTA2, and CNN1, as well as the novel effectors RGS5, DLGAP5, and TAGLN, confirming myocardin as a central regulator of fibrotic signaling. Silencing RGS5 produced minimal effects on gene and protein expression despite minor downward …

The Dynamics Of Synchrony On Replicating Biological Populations, Montse Torres Garcia, Kevin Mcgoff, Francis Motta, Breschine Cummins, Steve Haase

Biology and Medicine Through Mathematics Conference

No abstract provided.