Cell and Developmental Biology Commons^™

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

Harnessing The Immunomodulatory Potential Of Radiofrequency Ablation To Improve Therapeutic Outcomes In Pancreatic Ductal Adenocarcinoma, Bhumi Maniyar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) continues to rank among the most lethal cancers with poor prognosis. PDAC is characterized by a thick desmoplastic stroma, severe immunological suppression, and resistance tostandard treatments. The need for innovative therapeutic approaches is highlighted by the tumor microenvironment's (TME) critical role in promoting disease development and reducing the effectiveness oftreatment. A promising locoregional treatment that can induce tumor necrosis and modify the TME is endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA). However, there is still minimal understanding around its wider impact on stromal remodeling and immunological activation. This study investigates the immunomodulatory effects of RFA combined with neoadjuvant …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …

Cloning The Yersinia Enterocolitica Alkaline Phosphatase For An Affinity Chromatography Ligand, Flavio E. Arellano

ATU Scholars Symposium

Alkaline phosphatase (ALP) is an enzyme responsible for the dephosphorylation of extra-cytoplasmic molecules. Conversion to a neutral molecule enhances their ability to pass through cell membranes. When microbes such as Yersinia enterocolitica are ingested, they are exposed to large changes in pH level. These changes range from ~pH6.5 in the oral cavity to pH 2 in the stomach and pH 8 in the mid-intestine. The ability of microorganisms to survive this change in pH it largely dependent on their ability to change which proteins are expressed at differing pH levels or their ability to modify those proteins to meet the …

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Andrea Feria, Nyla Walbrook, Anisa Turaeva, Rebecca Spokony

Publications and Research

Crystal cells, a subset of Drosophila melanogaster hemocytes, are important for melanization, a crucial immune response. While the genetic regulation of crystal cell develop remains incompletely understood, this study investigates the functions of five candidate genes: ACXB, ACXA, Gp210, CG4390, and Cyp4s3; identidied through previous genome-wide association studies. Using the Gal4/UAS system along with RNA interference (RNAi), we exclusively knocked down each gene in third instar larvae and quantified crystal cell populations following heat shock-induced melanization. Our results imply that the knockdown of ACXB and ACXA significantly increased crystal cell counts in both sexes, suggesting these genes either act as …

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Genetic Analysis Of Methionine Restriction-Associated Mitochondrial Unfolded Protein Response Signaling., Josh D. Dodge

Biology Dissertations - Archive

The lifespan of an organism is dictated by various genetic and environmental factors. One such determinant is the health of mitochondria which are organelles that mediate various critical cell functions including a significant role in generating the vast supply of cellular energy. Indeed, the gradual decline of mitochondrial function is believed to be a hallmark and possible cause of aging. Paradoxically, mild mitochondrial dysfunction early in life extends lifespan in various model organisms. Cells use diverse approaches to promote mitochondrial homeostasis, including the transcriptional reprogramming of cells by mitochondrial unfolded protein response (UPRmt) to mitigate mitochondrial stress. Consistently, UPRmt activation …

Mctr3 Mitigates Cigarette Smoke-Induced Pulmonary Inflammation And Damage, Yu Par Aung Myo

Theses and Dissertations

Smoking is deleterious to our lungs and can precipitate in a multitude of diseases, including chronic obstructive pulmonary disease (COPD). COPD is primarily caused by smoking cigarettes and is a major public health issue. Current therapies only treat symptoms without halting or reversing disease progression, thus highlighting a large unmet need to develop new therapies. We address this gap by investigating maresin conjugate in tissue regeneration 3 (MCTR3) which is a newly discovered specialized pro-resoling mediator (SPM) that has the novel property of promoting tissue repair and regeneration in addition to being anti-inflammatory and pro-resolving. For the first time, we …

Functional Analysis Of Ligand Binding Domain 2 Of Outer Surface Protein C Of Borreliella Burgdorferi, Gavin Z. Chambers

Theses and Dissertations

Lyme disease, caused by the spirochete Borreliella burgdorferi, is the most common vector-borne infection in North America. A critical determinant of early mammalian infection is outer surface protein C (OspC), a highly variable lipoprotein that is indispensable for spirochete survival but whose precise function remains unresolved. OspC has been proposed to mediate diverse roles, including complement evasion, adhesion, tissue dissemination, and antiphagocytic activity, supporting the view that it is a multifunctional virulence factor. Structural studies have identified two putative ligand-binding domains (LBD1 and LBD2), with LBD2 forming a solvent-exposed crown at the membrane-distal end of the OspC dimer.

To …

Physical Ablative Methods And Cancer Cell Death: Implications For Immunity And Therapies, Alessandra Rossi, Claudia Muratori

Bioelectrics Publications

Surgery has traditionally been a cornerstone in cancer treatment, yet its feasibility can be limited by factors such as tumor location and patient health conditions. When surgery is not viable, thermal and pulsed electric field (PEF)-based ablation technologies offer valuable alternatives. Emerging evidence suggests that these approaches not only target tumors effectively but also stimulate antitumor immune responses. In this review, we begin by examining the distinctive features of hyperthermic treatments (radiofrequency and microwave ablation), cryoablation, and PEF-technologies. Subsequently, we discuss the mechanisms of cell death, stress responses, and release of danger signals triggered by these diverse ablation technologies. Finally, …

The Impact Of Maternal Environmental Exposures On The Immune Landscape Of The Maternal-Fetal Interface, Heather E. True

Theses and Dissertations--Pharmacy

Maternal environmental exposures and inflammation are known to impact fetal development in utero as well as increase the risk for chronic diseases later in life. Therefore, it is essential that we understand how the maternal environment alters placental structure and immune function.

Therefore, we isolated fetal (chorionic villous) tissues from the placentas of healthy pregnant participants (control) and those with inflammatory conditions, including SARS-COV-2 infection, pregravid obesity, and opioid use disorder. Isolated placental leukocytes were subjected to a series of assays to uncover the phenotypic, functional, and transcriptional (single-cell RNA-sequencing) landscape of placental immune cells. Additional placental tissues were subjected …

The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry

Graduate Theses/Dissertations

HIV-1 is the virus that causes acquired immunodeficiency syndrome (AIDS), and currently, there is no cure once an individual is infected. The development of new drugs targeting HIV-1 replication steps is essential for keeping viral loads low or undetectable to prevent further transmission. An attractive replication step for new drug targets is viral capsid uncoating, where the virus loses the protein structure encapsulating the genome. The exact mechanism of capsid uncoating is unknown; however, several host-factors may be involved including protein SPTBN1. Recent studies have shown a significant decrease in viral infectivity when SPTBN1 is knocked down, yet its role …

Leukocyte Infiltration Profiles At The Site Of Intradermal Injection Of Silikon-1000 In Scleroderma-Prone Ucd200/206 And Healthy White Leghorn Chickens, Katee L. Johnson, Jossie M. Santamaria, Chrysta N. Beck, Gisela F. Erf

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Intradermal injections of silicone-based fillers for the face and body may cause chronic inflammation and fibrotic reactions in some individuals. Chickens from the UCD 200/206 White Leghorn (WL) line spontaneously develop a fibrotic autoimmune disease known as scleroderma/systemic sclerosis (SSc). Using the SSc-prone UCD and healthy WL chickens, a longitudinal study was conducted to examine the cellular inflammatory responses to intradermal (i.d.) injections of sterile SILIKON-1000. Specifically, the pulp (a skin derivative) of growing feathers (GFs) was i.d. injected with sterile SILIKON-1000 or phosphate-buffered saline (PBS) as injection control (8 and 3 birds/line, respectively; 10 µL/GF; 20 GFs/bird). Two GFs …

Comparing Multivalent Cross-Linked Sodium Alginate/ Montmorillonite Beads Containing Curcumin Or Cayenne Pepper As Drug Carriers And Their Antimicrobial Resistance, Shionainn Traynor, Shubham Sharma

SURE Journal: Science Undergraduate Research Experience Journal

The aim of the following work was to investigate and compare curcumin and cayenne pepper in microbeads composed of sodium alginate (SA) crosslinked with montmorillonite (MMT) to act as drug carriers and their antimicrobial resistance. The microbeads were prepared through ion-exchange in multivalent solutions of CaCl₂, MgCl₂ and AlCl₃. The microbeads were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray analysis (EDX) and the time required for intercalation of curcumin and cayenne pepper with MMT. Simulated intestinal fluid (pH 7.3) and gastric fluid (pH 1.2) at 37°C were used for comparison in swelling studies. …

Editorial - Sure Journal Vol 6, Anne M. Friel, Eva Campion, Sinead Loughran

SURE Journal: Science Undergraduate Research Experience Journal

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Testing Vivo-Morpholino Mediated Gene Knockdown Of Stat6, Spi1b, And Hnf4Α In Adult Threespine Stickleback, Stella Dipippo

Honors Scholar Theses

The fibrotic immune response to the cestode parasite, Schistocephalus solidus, varies among threespine stickleback populations. Fibrosis suppresses parasite growth but has costly effects on the fish. Previous genomic studies in stickleback have suggested potential roles of Spi1b, STAT6, and HNF4α in modulating fibrosis severity, but there is presently no evidence for this in-vivo. We used antisense vivo-morpholino oligonucleotides (MOs) to attempt to knockdown the expression of each gene in the liver, spleen, and intestine of adult stickleback. Vivo-MOs have been proven effective in other species of teleost fish, as well as in mice and humans, but …

Lack Of Inflammatory Response In Mouse Embryonic Cells To Listeria Infection, Damilola Oyebode

Master's Theses

Approximately 1 in 5 pregnancies in the United States results in miscarriage, with a significant percentage of these losses attributed to failed implantation due to immunological challenges encountered by the early embryo. Recent research has shown that key cell types within mouse blastocysts, including embryonic stem cells (ESCs) and trophoblast stem cells (TSCs), exhibit remarkable resilience against the cytotoxic effects associated with viral infections and embryotoxic cytokines, such as TNFα and IFNγ, both of which are known to hinder blastocyst development. However, the immune properties of the preimplantation stage embryo, specifically the blastocyst, remain poorly understood. Using mouse cell model, …

Timigp: A Computational Framework To Determine The Tumor Immune Microenvironment Associated With Prognosis And Immunotherapy Response, Chenyang Li

Dissertations and Theses (Open Access)

Accumulating evidence has suggested that the tumor immune microenvironment (TIME) drastically impacts cancer patients’ clinical outcomes, including prognosis and immunotherapy response. However, understanding TIME remains challenging due to its complexity and heterogeneity. In this dissertation, we introduce TimiGP (Tumor Immune Microenvironment Illustration based on Gene Pairs), a computational framework designed to address this challenge. Leveraging single-cell RNA-seq (scRNA-seq) and bulk gene expression data alongside clinical information, TimiGP constructs a cell-cell interaction network that elucidates the relationship between immune cell function and relevant clinical outcomes, such as prognosis and treatment response. With immunological insights, these cell-cell interactions also facilitate the development …

Differential Responses Of Human Neutrophils To Legionella Species., Hannah E. Hanford

Electronic Theses and Dissertations

Legionella species are Gram-negative facultative intracellular bacterial pathogens commonly found in freshwater or soil environments where they survive and replicate within their natural protozoan hosts. Humans serve as an accidental host for Legionella species after inhalation of contaminated aerosolized water droplets or soil particles enabling the bacteria to enter the lungs, infect alveolar macrophages, and result in severe pneumonia. Evasion of degradation and proliferation within alveolar macrophages by Legionella species and manifestation of “Legionnaires’ disease” is dependent on the Dot/Icm type IV secretion system (T4SS). The T4SS apparatus is a needle-like channel for translocation of over ~350 effector proteins, depending …

The Role Of Ganglioside Gd2 And Gd3 Synthase (St8sia1) In The Regulation Of Immune Suppression In Breast Cancer, Bolutyfe Oderinde

Dissertations and Theses (Open Access)

Gangliosides are acidic glycosphingolipids involved in cell adhesion, proliferation, and modulation of signal transduction pathways. It has been reported that tumor-shed gangliosides influence the activity of immune cells including macrophages, NK cells, and T cells. GD3 synthase (GD3S) is the key enzyme that regulates the biosynthesis of the b and c series gangliosides, particularly GD3 and GD2, and studies have shown that GD3S is upregulated in most tumors and plays a role in tumor progression. Similarly, we have previously found GD3S to be significantly upregulated in GD2+ breast cancer stem cells (BCSC) compared to GD2- cells, and the knockdown of …

Electric Potential Energy Optimized 3d Radial Sampling Trajectories For Mri, Christopher Huynh, Datta Singh Goolaub, Christopher K Macgowan

Faculty, Staff and Students Publications

A novel method for creating “golden” 3D center-out radial MRI sampling trajectories was developed and analyzed. This method, called ELECTRO (ELECTRic potential energy Optimized), uses repulsive forces to minimize electric potential energy. An objective function , the electric potential energies of all subsets of consecutive readouts in a 3D radial trajectory, and its reduced form were minimized using a multi-stage optimization strategy. A metric called normalized mean nearest neighbor angular distance (NMNA) was proposed for describing distributions of points on a sphere. ELECTRO and other relevant golden trajectories were compared in silico using NMNA and point spread function analysis. Consecutive …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death, Elizabeth Schmitz

Theses & Dissertations

The primary goal of most anti-cancer therapy is to eradicate neoplastic cells. Simultaneously, neoplastic cell death is the first step of the cancer-immunity cycle, which starts with the release of antigens from cancer cells and ends with T-cell directed killing of cancer cells, in addition to long-standing memory to tumor antigens encountered. Immunogenic damage-associated-molecular patterns (DAMPs) are endogenous cell molecules repurposed in times of insurmountable cell stress (e.g., CALR, ATP, HMGB1) to facilitate communication between dying cells and adaptive immune cells, acting as adjuvants for the cancer-immunity cycle, in a cellular fate termed immunogenic cell death (ICD). It …

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …