Hemic and Lymphatic Diseases Commons^™

Orchestrated Architecture Dismantling: Borrelia Burgdorferi’S Coordinated Destruction Of Adaptive Immune Responses, Craig A. Land

Electronic Theses and Dissertations

Borrelia burgdorferi represents the most prevalent vector-borne bacteria in North America, affecting ~476,000 Americans annually yet persisting despite robust immune responses. This project reveals spirochetes target adaptive immunity through coordinated lymphatic colonization and precision immune dysregulation.

Using comparative host models (C57BL/6 vs. reservoir Peromyscus leucopus), we demonstrate lymph node colonization within 48-hours, with spirochetes exploiting LYVE-1-positive lymphatic structures as dissemination highways while avoiding the interior of follicular regions. Critically, we identify targeted CD4+ T-cell elimination in germinal center border zones at 21-DPI, precisely when these cells should be coordinating protective immunity. Concurrent upregulation of inhibitory receptor CD32b creates molecular …

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Implementation Of Lymphedema Education Toolkit For Nurse Coordinators, Heather Gee

Master's Projects and Capstones

Problem: Lymphedema is a chronic condition that develops secondary to cancer treatments such as chemotherapy, radiation, and surgical removal of affected lymph nodes. This swelling in patient’s limbs can cause discomfort and limit mobility, however lymphedema is often not detected until later stages, delaying treatment and patient education.

Context: This quality improvement project was conducted at Hospital S Women’s Cancer Center, an outpatient center specializing in advanced treatments for breast and gynecological cancers. This center has a multidisciplinary team focusing on both the medical and surgical aspects of oncology treatment.

Interventions: An evidence-based lymphedema education toolkit was created for nurse …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Step Squad Bundle In Older Adults With Multiple Myeloma Hospitalized For An Autologous Stem Cell Transplant, Nadya Panjwani

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: Multiple Myeloma (MM) is a hematological malignancy with demographic disparities. MM is a debilitating cancer mainly affecting older adults, with 66% over the age of 70. Additionally, 33% of older patients with MM are frail with weakness, fatigue, slow gait, weight loss, and malnutrition.

PICOTS: The purpose of this Doctor of Nursing (DNP) scholarly project is to implement an evidence-based practice (EBP) change consisting of a Step Squad Bundle that will identify frailty in older patients with MM hospitalized for an Autologous Stem Cell Transplant (ASCT) to reduce morbidity and mortality and increase the chances of a quality of …

Developing Toolkit For Adults With Autism Spectrum Disorder In An Oncology Outpatient Clinic, Brittany J. Johnson Dnp, Fnp-C

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Autistic adults are at higher risk of being diagnosed with co-occurring health conditions, and yet they are a vulnerable group for disparities in access and outcomes. One of the key barriers to better outcomes is poor patient-provider communication. This study the use of AASPIRE’s AHAT communication toolkit as a channel between healthcare workers and autistic adults to facilitate their appointments within the outpatient oncology department, as well as assessing healthcare providers’ knowledge and self-efficacy in caring for the patients. Sixteen healthcare providers (12 registered nurses and four patient care assistants) completed pre and post intervention surveys and utilized the AHAT …

Real-World Pharmacological Anticoagulation And Clinical Outcomes Of Venous Thromboembolism In Adults With Sickle Cell Disease, Ming Chen

Theses and Dissertations (ETD)

Sickle cell disease (SCD) is an inherited disease characterized by sickle-shaped red blood cells that can slow or block blood flow. It affects about 100,000 people in the United States, and occurs more commonly in people of African descent. SCD is considered as a hypercoagulable state and venous thromboembolism (VTE) is a serious disease-specific complication. However, there have been limited real-world studies on VTE in SCD patients. This work aims to provide a comprehensive assessment of the risk factors and treatment of VTE in adults with SCD by using longitudinal real-world data. First, a retrospective cohort study on 30-day readmission …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations and Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Improving Lymphedema Self-Management And Screening In Newly Diagnosed Breast Cancer Clients Through The Use Of A Self-Management Lymphedema Toolkit, Kescia Gray

Doctor of Nursing Practice (DNP) Manuscripts

Background and Significance: With breast cancer effecting women at much younger ages and modern treatments prolonging the life span, survivors are at increased risk of developing breast cancer-related lymphedema (BCRL), a chronic, progressive condition that can cause disability.

Purpose: The purpose of the project was to determine the level of knowledge and awareness of BCRL in newly diagnosed breast cancer clients; and to provided education on self-care after treatment, using of a self-management lymphedema toolkit (SMLT), to decrease risks of treatment-related lymphedema, improve self-efficacy, and enhance quality of life (QOL).

Methods: Newly diagnosed breast cancer clients (N=10) from the Breast …

Genomic Characterization Of Sickle Cell Mouse Models For Therapeutic Genome Editing Applications, Kaitly Jensen Woodard

Theses and Dissertations (ETD)

Sickle cell disease (SCD) is caused by a mutation of the β-globin gene (HBB), resulting in abnormal hemoglobin molecules that polymerize when deoxygenated, forming “sickle” shaped red blood cells (RBCs). Sickle RBCs lead to anemia, multi-organ damage and pain crises, beginning the first year of life. The onset of symptoms coincides with the developmental switch of β-like globin gene expression from fetal stage γ-globin to adult stage β-globin, resulting in a shift from fetal hemoglobin (HbF, α2γ2) to adult hemoglobin (HbA, α2β2). Some individuals harbor rare genetic variants in the extended β-globin gene cluster that cause constitutively elevated postnatal HbF, …

Genetic Mechanisms Of Transcriptional Regulation In Childhood Acute Lymphoblastic Leukemia, Xujie Zhao

Theses and Dissertations (ETD)

Introduction. Advances in genomic profiling and sequencing studies have identified germline and somatic variations that are associated with childhood ALL, improving our understanding of the genetic basis of childhood acute lymphoblastic leukemia (ALL). Recent genome-wide association studies (GWAS) have identified germline genetic variations of ARID5B and, more recently, IGF2BP1 that are associated with susceptibility to ALL. Genome-wide sequencing studies also discovered a new ALL subtype characterized of ZNF384-mediated chromosomal translocations, providing new insights into genetic heterogeneity in childhood ALL. However, the underlying mechanism by which these genetic variants contribute to the transcriptional regulatory circuitries of ALL is still poorly understood. …

The Heme-Regulated Inhibitor Pathway Modulates Susceptibility Of Poor Prognosis B-Lineage Acute Leukemia To Bh3-Mimetics, Kaitlyn Hill Smith

Theses and Dissertations (ETD)

Anti-apoptotic MCL1 is one of the most frequently amplified genes in human cancers and its elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The anti-malarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Do Needle Exchange Programs Cause More Harm To Injection Drug Users And Compromise The Safety Of The Communities In Which They Are In Place?, Amber L. Payne

Theses, Dissertations and Capstones

Needle Exchange Programs (NEP) are put in place in regions in the US, where illegal injectable drug use is prevalent, in order to decrease the amount of blood borne diseases by at least 10%, such as Hepatitis C and Human Immunodeficiency Virus (HIV), being spread throughout the drug-using community. People and Healthcare Professionals in these communities have questioned if NEPs have caused more harm to the drug users and if they have compromised public safety due to incorrect disposal of syringes.

During a study in 2011, the spread of blood borne diseases in areas where NEPs were present, decreased among …

The Epigenetic Effects Of Omega-3 Fatty Acids In Diffuse Large B-Cell Lymphoma, Tanner Jeffrey Bakhshi

Theses, Dissertations and Capstones

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. It is an aggressive cancer, with 50-70% of patients diagnosed at an advanced stage and 30-50% of patients not cured by chemoimmunotherapy. DLBCL is almost always caused by genetic damage sustained during the germinal center (GC) reaction. The mechanisms that govern the GC reaction bear a striking resemblance to those that drive DLBCL. Genomic studies have shown that some of its most common mutations occur in genes that encode epigenetic modifiers, including the lysine (histone) acetyltransferases CREBBP and p300. These mutations prevent the acetylation of multiple histone residues, …

Effects Of The Needle Exchange Program Implemented In West Virginia, Amber Graves, Anthony B. Uriarte, Katherine Duty

Theses, Dissertations and Capstones

Introduction: West Virginia has had a recent spike in infectious diseases such as HIV and hepatitis due to increased rates of injectable drug use. The rising costs associated with such diseases have been a cause for concern in the sector of healthcare and public health. In the state, the exchanging of dirty needles has resulted in the spread of bloodborne pathogens, however, the implementation of needle exchange programs has sought to decrease the rates of infection, improve health outcomes, and lower healthcare costs. However, there is a question as to the effectiveness of such programs.

Purpose of Study: …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

The Interleukin-12 Family Of Cytokines And Receptor Signaling In Graft-Versus-Host Disease, David Bastian

MUSC Theses and Dissertations

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective means by which to treat a wide variety of diseases resulting from dysfunctional hematopoiesis due to a potent anti-tumor response known as the graft-versus-tumor (GVT) effect after chemotherapy and/or irradiation. The necessity of donor T cells to mediate GVT is offset by the consequential development of graft-versus-host disease (GVHD); a leading cause of mortality among allo- HCT recipients. The IL-12 family of cytokines signals through Janus Kinase 2 (JAK2) and is comprised of IL-12, IL-23, IL-27, IL-35 and IL-39. IL-12 (p35+p40) and IL-23 (p19+p40) have well documented proinflammatory functions responsible for …

Accounting For The Uncertainty Due To Chemicals Below The Detection Limit In Mixture Analysis, Paul M. Hargarten

Theses and Dissertations

Humans are exposed to multiple chemicals every day. Epidemiological studies have shown that chemical mixtures are associated with cancers, allergies, neurodevelopmental disorders, and other adverse health effects. To assess these associations, investigators are increasingly using chemical mixture approaches like weighted quantile sum (WQS) regression. In these studies, the research objectives are to determine whether a mixture of correlated chemicals is associated with an adverse health outcome and to identify the important chemicals. However, as experimental equipment measures each exposure to a chemical-specific detection limit, the exposures are unknown between zero and the detection limit. Indeed, the number of exposures below …

Role Of Rac1-Pak Pathway In Aggressive B-Cell Lymphoma, Tian Tian

Theses & Dissertations

Aggressive B-cell lymphomas are diverse group of neoplasms that arise at different stages of B-cell development and by various mechanisms of neoplastic transformation. Aggressive B-cell lymphomas include many types, subtypes and variants of diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL) and B lymphoblastic lymphoma. The treatment of patients with aggressive B-cell lymphomas remains a clinical challenge. Conventional chemotherapeutic regimens, mainly based on the CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) combination, obtain a relatively high number of complete or partial clinical responses (20-80%), but the tumor relapses in most patients, who will die of the disease. …

Dual Therapy Treatment Of Pediatric Acute Lymphoblastic Leukemia With Blinotumomab And A Standard Chemotherapy Regimen, Tori I. Scheffler

Selected Honors Theses

Leukemia is the number one cancer affecting children in the nation, with acute lymphoblastic leukemia being the most prevalent classification.1 While new and innovative treatment protocols have greatly increased the success rate of primary cancer patients, those who face relapse receive a much more dismal prognosis. Recent studies have shown that patients who relapse quite frequently have developed drug-resistant clones of the original cancer cells, leading to a need for various secondary treatment options. The drug-resistance is due to clonal mutations that take place within the cancer cell, most often because of an outside pressure or stress within the environment …

Experiential Learning In Dietetics: Can Diabetes Camp Make A Difference?, Mallory Jean Mount

Theses, Dissertations and Capstones

This longitudinal qualitative case study explored the knowledge, perceptions, confidence, and empathy gained by dietetics students during experiential learning at a residential diabetes camp. Qualitative research methods were used to explore and understand participants’ experience of hands-on involvement with type one diabetes, and what they learned at camp that cannot be learned in a classroom. Data were collected over two years at Camp Kno-Koma, the diabetes camp of West Virginia. This study suggests that experiential learning at diabetes camp can make an important contribution to the overall education of dietetics students. One year of experiential learning was beneficial to participating …

The Right Vasopressor At The Right Time Does Early Use Of Vasopressors Decrease Morbidity And Mortality In Septic Shock, Michael Kittok

Theses and Graduate Projects

Sepsis and septic shock is a disease process that carries a high mortality rate and is responsible for a large portion of healthcare expenditures in the United States. The Surviving Sepsis Campaign has been working to decrease the mortality of sepsis since 2001. Their mission is two-fold; providing evidence based guidelines to help direct treatment, and raising awareness to healthcare providers and patients about sepsis. A main goal in treating sepsis is to reverse the hypoperfused state by giving crystalloid fluids and administering vasopressors, specifically norepinephrine, after patients have received adequate fluids. Would modifying this treatment by giving a combination …

Barriers That Prevent Initial Prescription Of Hydroxyurea In Sickle Cell Disease, Harini Halaharvi

Theses and Graduate Projects

Sickle cell disease (SCD) is one of the most common inherited red blood cell disorders, affecting millions of people worldwide. According to CDC, SCD affects approximately 100,000 Americans and is most prominent in people with ancestry from sub-Saharan Africa, Spanish- speaking regions in the Western Hemisphere (South America, the Caribbean, and Central America), Saudi Arabia, India, and Mediterranean countries such as Turkey, Greece, and Italy. 1 out of every 365 black or African-American and 1 out of every 16,300 Hispanic-American children are born with SCD.1 Approximately 6,000 Latin Americans are born with SCD annually in both US and Latin American …

Physical Activity Guidelines In Patients With Hemophilia: Benefits, Barriers, And Recommendations, Chelsea Johnson

Theses and Graduate Projects

Hemophilia describes a group of genetic disorders that lead to the dysfunction of proteins involved in the clotting cascade.1 These proteins, also known as coagulation factors, are required to form clots and ultimately cessate bleeding. Although there are three distinct forms of congenital hemophilia (hemophilia A, hemophilia B, and hemophilia C), the affected proteins (factor VIII, factor IX, and factor XI, respectively), are within the same pathway leading to the formation of a clot. In condensed terms, each of these factors play a role in the ultimate activation of thrombin, which activates fibrinogen to form a fibrin clot and solidify …