Cell and Developmental Biology Commons^™

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.

The Effects Of Cinnamaldehyde On Tetrahymena Thermophila, Sydney Kurland

Publications and Research

In addition to their common use as spices in cooking and baking, cinnamon plants, Cinnamomum zeylanicum and Cinnamomum cassia for example, have long been used in herbal remedies worldwide. Cinnamon contains many vital oils and active compounds including cinnamaldehyde (CMD). Numerous studies looking at potential therapeutic effects of cinnamon have demonstrated its antioxidant, anti-inflammatory, and antimicrobial properties (1, 2, 3).   Therefore, it is important to continue studying the efficacy, benefits, and mechanisms of action of cinnamon and CMD to have a complete understanding of its full potential. Tetrahymena thermophila is a ciliated protozoan commonly used as a model organism to …

Phosphate-Mediated Regulation Of Intracellular Calcium Dynamics, Huma Shahzad, Mohammed S. Razzaque

School of Medicine Publications

Phosphate (Pi) and calcium (Ca2+) are essential mineral ions that play coordinated roles in maintaining normal cellular functions. While various steps of calcium signaling are well characterized, emerging evidence suggests the critical role of both intracellular and extra cellular phosphate in regulating intracellular Ca2+. In the cytoplasm, phosphate influences ATP production and organelle calcium buffering and influences the activity of calcium pumps, such as sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and the plasma membrane Ca2+-ATPase (PMCA). Extracellular phosphate, taken up via sodium-dependent phosphate transporters, triggers signaling cascades that affect the processes of calcium influx, storage, and release. Additionally, high extracellular phosphate levels …

The Risk Of Bpa In B Lymphocyte-Mediated Autoimmunity, Mario J. Palacios

Senior Honors Theses

Autoimmune disorders disproportionately affect females, a bias largely attributed to estrogen's modulation of B lymphocyte development and tolerance. Bisphenol A (BPA), a common plastic monomer, shows estrogenic activity and acts as an endocrine disruptor and epigenetic modifier. This thesis examines how BPA may increase autoimmune risk by mimicking estrogen such that it can excite estrogen receptors which rescue autoreactive B lymphocytes from apoptosis. While direct research linking BPA to B lymphocyte-mediated autoimmunity is limited, understanding BPA’s course of action in B lymphocytes is critical for addressing the rising prevalence of autoimmune diseases and its possible link to the increased and …

Synthesis Of A Nicotine-Like Backbone Ligand For Binding Evaluation At Plk-1 Pbd, Carter Johnson

Undergraduate University Honors Capstones

Cancer is a significant problem and requires continued research, as it remains one of the leading causes of death worldwide (Ramos, 2021). This capstone explores the synthesis and preliminary evaluation of a nicotine-type compound as a potential cancer-curing agent targeting the PLK-1 PBD protein using fluorescence polarization. The hypothesis is that a specific ligand may contribute to cancer research. This project also reviews cancer management methods while illustrating the discovery of chemical drugs used in chemotherapy. The project involves synthesizing and testing 3-((1-methylpyrrolidin-2-yl)methoxy)-1-alkylpyridin-1-ium, known as Compound C, to determine whether it can function as a potential cancer management agent. The …

Nanoparticle-Based Therapy For Peripheral Artery Disease: Evaluation Of Collagen Reduction And Fibrosis Mitigation In Ischemic Tissue, Tresha Nguyen

2026 Spring Honors Capstones Projects

Peripheral Artery Disease (PAD) is characterized by reduced blood flow, ischemic injury, and fibrosis, which collectively impair tissue function. Current treatment strategies are limited in their ability to target fibrotic tissue and restore normal function effectively. This study evaluates the therapeutic potential of drug-loaded nanoparticles to reduce fibrosis in ischemic tissue. Nanoparticles were synthesized and characterized for in vivo application. Tissue samples from experimental groups, including saline control, blank nanoparticles, free drug, and drug-loaded nanoparticles, were analyzed using Masson’s Trichrome staining to quantify collagen deposition. Histological images were processed using image analysis software to determine the percentage of collagen area. …

Cell Cycle Inhibition: Illudin S And Its Effects On Cdk2 In Ewing Sarcoma, Stephanie Diez, Natalie Flores, Alexandria Hernandez, Viviana Palacios, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcomas are aggressive round cell mesenchymal neoplasmas that have a high occurrence in children and young adults. CDK2 is a protein that is involved in the G1 phase of the cell cycle, which promotes the transition to the S phase. CDK2 kinase activation is mainly observed in the G1/S-phase transition.3 CDK2 binds to Cyclin proteins is responsible for entry and progression, thereby leading to maximal apoptosis activity in the S-phase. Illudin S is a drug that has been known to target cancer-specific cells, such as leukemia. Illudin S, in general are a cytotoxic metabolite that comes from plants, specifically …

Yap1 Knockdown And Panobinostat Treatment Increase Apoptotic Response And Decrease Gene Expression In Ewing Sarcoma Cells, Luna Collazo-Garcia, Alejandra Favela Santos, Madeline Torres-Salazar, Isabella Toscano, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma (EWS) is considered to be one of the most aggressive pediatric malignancies, often characterized by its dysregulated gene expression driven by oncogenic fusion proteins. The Hippo signaling effector Yes-associated protein 1 (YAP1) has been known in promoting cell proliferation, survival, and therapeutic resistance in multiple cancers. However, its role in Ewing sarcoma response to treatment remains unclear. This study investigated whether YAP1 knockdown enhances the sensitivity of Ewing sarcoma cells to the histone deacetylase inhibitor Panobinostat. Ewing sarcoma, ES8, cells were transfected with a YAP1-targeting siRNA (siYAP1) or a non-targeting control (siControl) and treated with DMSO, 0.1 μM, …

Everolimus Treatment Combined With Akt1 Knockdown Increased Apoptosis And Decreased Cell Proliferation In Ewing Sarcoma Cells, Arisha Arif, Alfie Barcenez, Sophia Ruter, Nicole Vanegas-Riddick, Terry Jo Shackleford

Cell and Molecular Methods

The purpose of this study is to use the gene AKT1, due to the interest in AKT1’s role in cancer cell proliferation, and the drug Everolimus, to determine if combined targeted therapy works as a more efficient therapeutic approach. Ewing Sarcoma has been connected to chromosomal translocations and is most common in pediatric patients. It is most often treated with chemotherapy and local treatments. It may be connected to the gene AKT1 due to how it regulates cell metabolism, growth, and proliferation. The gene mTOR is similarly connected to cell metabolism and proliferation, and is inhibited by the drug Everolimus. …

Sirna Knockdown Of Rptor Reduces Rptor Expression, Increases Brd4 Expression, And Alters Proliferation And Apoptosis In Ewing's Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Olivia, Liam Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a highly aggressive cancer that primarily affects children and young adults. Although treatment options exist, many patients do not respond effectively, showing the need for improved targeted therapies. RPTOR is a key in mTORC1 complex which regulates cell growth, proliferation, and survival. LY2874455 is a selective pan-FGFR inhibitor that targets growth factor signaling pathways involved in tumor progression, and FGFR signaling interacts with pathways such as mTOR, making it a potential target for combination therapies. We hypothesized that silencing RPTOR in Ewing sarcoma cells would disrupt mTOR signaling and alter expression of genes linked to cell survival …

Everolimus And Sirna-Mediated Mtor Inhibition Reduces Proliferation And Promotes Apoptosis In Ewing Sarcoma Cells, Dylan Calvert, Malorie Martinez, Alexa Miner, Ellis Quiroga, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is an aggressive pediatric bone cancer characterized by rapid cell proliferation and poor prognosis, making the identification of therapeutic targets critical. One of  the mechanistic targets is rapamycin (mTOR) signaling pathway, which is critical for regulating cell growth, proliferation, and survival. Abnormal activation of the mTOR signaling pathway has been linked to the progression of ES, as it drives uncontrolled cell growth and apoptosis resistance. Because mTOR represents a promising therapeutic target for ES treatment, we hypothesized that inhibiting mTOR activity through an siRNA-mediated knockdown or through Everolimus drug treatment, would reduce cell proliferation and promote ES …

Role Of Kif4a In The Fxa-Induced Phenotypic Modulation Of Pleural Mesothelial Cells, Sudishna Khanal

Biotechnology Theses

Pleural injuries can disrupt the organization of the pleural surface, leading to pleural remodeling and fibrosis (PF), characterized by the proliferation of myofibroblasts expressing alpha-smooth muscle actin (α-SMA) and the deposition of extracellular matrix proteins, primarily due to the mesenchymal transition of pleural mesothelial cells (PMCs) (MesoMT). It is well established that various external stimuli, such as TGF-β, thrombin, and factor Xa (FXa), induce MesoMT. Our laboratory found that myocardin, a transcriptional co-activator, was dramatically up-regulated during MesoMT, and that gene silencing of myocardin (MyoCD) diminished MesoMT. RNA sequencing data showed that FXa activated a set of genes not upregulated …

Bax Activation Through The N-Terminal Bh3-Like Domains Of Vdac1 And Vdac2, Autumn A. Peters

Honors Theses

Voltage-dependent anion channels (VDACs) are central to mitochondrial function by mediating metabolite diffusion across the mitochondrial outer membrane (MOM). Two isoforms­­­­­­­­­­­,­­­­­­­­­­­­­­­­­­­­­­­­­­­­ VDACs 1 and 2, are also implicated in apoptosis based on interactions with Bcl-2 family proteins that control this process, including Bax and Bcl-xL. Activation of the pro-apoptotic protein Bax by interaction with ‘BH3-only’ proteins, such as Bim or Bid, induces MOM permeabilization to signal apoptosis, yet accumulating evidence indicates VDACs 1 and 2 may also affect Bax. We discovered that the VDAC N-terminal domains contain high sequence similarity to the conserved BH3 domains within Bcl-2 family members that …

A Conserved Role For Cyclin C In Regulated Cell Death Across Yeast And Humans, Samar Emami, David Stieg, Daniel Smethurst, Justin Bauer, Randy Strich

Rowan-Virtua Research Day

Background: Programmed cell death (PCD) is a tightly regulated process that maintains tissue homeostasis and eliminates damaged, infected, or malignant cells. A key regulator of this process is Cyclin C (CCNC), which functions as a component of the mediator complex to regulate gene transcription. During cellular stress, CCNC translocates from the nucleus to the mitochondria, where it associates with Dnm1 to promote mitochondrial fragmentation and  apoptosis.

Objective: This study aimed to unravel conservation of CCNC’s function between yeast and humans by investigating whether human CCNC can induce apoptosis in yeast and whether it does so through interaction with …