Cell Biology Commons^™

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 …

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), …

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 …

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.

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 …

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. …

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 …

Identifying The Role Of Human Dna Polymerase Delta During Human Cytomegalovirus Genome Synthesis, Rachel Laree Dansereau

Dartmouth College Master’s Theses

Human cytomegalovirus (HCMV) is a large double stranded DNA virus and member of the Herpesviridae family. Like all herpesviruses, HCMV presents with characteristics of persistent, lifelong infections that transition between lytic and latent states. The replication of the viral genome is traditionally thought to occur by a rolling circle mechanism, but this model is supported by little evidence. It is known that HCMV actively recruits several host proteins to viral replication compartments (RCs), including proteins involved in the DNA damage response (DDR). The exact mechanisms of how these proteins are used and in what ways they help the virus remain …

Analysis Of The Effects Of Astaxanthin On Human Colorectal Cancer Cells, Kara A. Walters

Theses/Capstones/Creative Projects

Astaxanthin (AXT) is an antioxidant carotenoid that is produced by the microalgae Haemococcus pluvialis. This supplement is best known for its potential health benefits including anti-inflammatory, antitumor, immunomodulatory, anticancer and antidiabetic activities. Astaxanthin is marketed as an oral dietary supplement and is widely used in the nutraceutical industry as well as a coloring agent in the food industry. Since Astaxanthin has been increasingly popular as a dietary supplement, cytotoxicity is relevant to consumer exposure. Obtaining the IC50, the concentration that inhibits 50% of cell growth, is important to find how Astaxanthin may interact with cancer, and this can be found …

Morphological Variation Of Lingual Glands In Wild American Alligator (Alligator Mississippiensis) Populations, Benjamin Angalet

Master's Theses

American alligators (Alligator mississippiensis) inhabit diverse aquatic ecosystems including freshwater wetlands, swamps, and estuarine rivers. As apex predators, their physiological resilience has implications for ecosystem stability and long-term conservation. With projected sea-level rise and increasing saltwater intrusion into coastal freshwater habitats, understanding the osmoregulatory capacity of alligators is increasingly important. Unlike marine-tolerant crocodilians such as the saltwater crocodile (Crocodylus porosus), which possess specialized salt-secreting lingual glands in addition to renal and cloacal mechanisms, the morphology and physiological significance of lingual glands in wild American alligators remain poorly understood. This study examined lingual gland morphology and plasma …