Medical Molecular Biology Commons^™

Platelet Gαz Regulates Ovarian Tumor Growth And Mediates The Effects Of Chronic Stress, María G. Torres Carrizalez

Dissertations and Theses (Open Access)

Ovarian cancer is the most aggressive gynecologic cancer, with 12,450 estimated deaths in 2026. Elevated platelet counts are commonly observed in patients with ovarian cancer and are associated with enhanced tumor growth and poor prognosis. Patients with ovarian cancer are frequently exposed to elevated levels of stress, which has been correlated with accelerated disease progression and increased mortality. Interestingly, the platelet Gαz protein is activated by epinephrine through the α2A-adrenergic receptor, suggesting a potential mechanistic link between stress signaling and platelet-driven tumor progression. To investigate this, I evaluated the role of platelet Gαz in ovarian cancer using control (Gz^{fl/fl …}

Exploring The Role Of Hes4 During Retroviral Infection, Raphael Opoku

Graduate Studies Theses and Dissertations 2026

Human immunodeficiency virus (HIV) infection disrupts immune homeostasis and impairs antiviral defenses, partly by compromising natural killer (NK) cell activity, with simian immunodeficiency virus (SIV) infection in rhesus macaques serving as a valuable model to investigate these mechanisms. This research examines the regulatory role of HES4 and its isoforms in NK cell function during retroviral infection, with particular focus on how Notch signaling–dependent regulation of HES4 shapes NK effector responses. HES4, a downstream effector of the Notch signaling pathway, encodes transcriptional repressors central to immune cell differentiation, yet its contribution to NK cell biology remains poorly understood. Using molecular and …

Identifying Novel Fibrotic Mechanisms Underlying Treatment-Resistant Lower Urinary Tract Dysfunction, Quentin Darcy

Graduate Doctoral Dissertations

ABSTRACT

IDENTIFYING NOVEL FIBROTIC MECHANISMS UNDERLYING TREATMENT-RESISTANT LOWER URINARY TRACT DYSFUNCTION

August 2025

Quentin D’Arcy, B.S., University of Massachusetts Amherst

Ph.D., University of Massachusetts Boston

Directed by Dr. Jill Macoska

Lower urinary tract dysfunction (LUTD) is a common, age-related disease that affects millions of men over the age of 50. Current treatment for this and other related prostate diseases concentrate on decreasing benign prostate growth and relaxing smooth muscle contractions to alleviate urinary voiding symptoms. However, up to 45% of patients with LUTD are treatment-resistant and require surgical intervention to resolve prostate issues. By focusing on the contribution of inflammation-derived …

Targeting Prmt5 In Inflammation And Cancer: A Nexus Of Endotoxin Signaling, Antigen Presentation And Immune Evasion., Jimmy James Msemo

Theses and Dissertations--Medical Sciences

Protein Arginine Methyltransferase 5 (PRMT5) is a member of PRMT family that controls both intrinsic and extrinsic oncogenic processes [1]. Protein arginine methyltransferase 5 (PRMT5) is a type II methyltransferase that exerts widespread influence over gene expression, splicing, DNA repair, and immune regulation through symmetric dimethylation of arginine residues on histone and non-histone proteins [2]. The addition of methyl groups induces gene silencing through producing dictatorial histone marks like H2AR3ne2s, H3R8me2s and H4R3mes [3], which act as epigenetic repressive marks on gene promoters. In non-histone proteins, PRMT5 can methylate and regulate transcription factor proteins such as p53, E2F1, and p65, …

Limiting H1n1 Replication Via The Dsrnai Pathway Using Sequence-Specific Ldsrna, Shawn Marie Sharon Carr, Stephanie Dewitte-Orr

Theses and Dissertations (Comprehensive)

The seasonal influenza virus causes a common respiratory illness that can be life threatening to the immunocompromised, the very young, and the elderly. The current strategies for avoiding a serious influenza virus infection are good hygiene practices and the annual influenza vaccine. Unfortunately, last year’s influenza virus vaccine effectiveness ranged between 32-60% for children and adolescents and 46-54% for adults. These low efficacy rates are due to the vaccine often targeting hemagglutinin, a highly variable surface protein. This thesis seeks to create a prophylactic treatment via the RNA interference (RNAi) response that targets the virus’s conserved genes that are integral …

5-Fluorouracil Induced Oxidative Stress Is Variable Across Triple Negative Breast Cancer Cell Lines, Rachel L. Walker

Departmental Honors & Graduate Capstone Projects

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with treatment limited to chemotherapy. However, not all patient tumors respond to chemotherapy. The variable cytotoxic effects of chemotherapies may be due to how cancer cells regulate reactive oxygen species (ROS). In this study, we examined two mouse breast cancer cell lines: 4T1 and EO771, vary when treated with hydrogen peroxide (H2O2) and 5-Fluorouracil (5FU), known ROS-inducing substances. In 4T1 cells H2O2 increased oxidized DNA but caused minimal cell death. While in EO771 cells that same amount of H2O2 caused complete apoptosis. Cell number, ROS, and cell death showed …

Exploring New Frontiers In Space Medicine: Unprecedented Detailed Mapping Of Human Biology During Spaceflight, Laura Ioana Patras, Nadia Houerbi, Jankeun Kim

FRONTIERS UNBOUND: Exploring Extreme Environments

No abstract provided.

Adaptative Survival Of Aspergillus Fumigatus To Echinocandins Arises From Cell Wall Remodeling Beyond Β−1,3-Glucan Synthesis Inhibition, Malitha C. Dickwella Widanage, Isha Gautam, Daipayan Sarkar, Frederic Mentink-Vigier, Josh V. Vermaas, Shi You Ding, Andrew S. Lipton, Thierry Fontaine, Jean Paul Latgé, Ping Wang, Tuo Wang

School of Graduate Studies Faculty Publications

Antifungal echinocandins inhibit the biosynthesis of β−1,3-glucan, a major and essential polysaccharide component of the fungal cell wall. However, the efficacy of echinocandins against the pathogen Aspergillus fumigatus is limited. Here, we use solid-state nuclear magnetic resonance (ssNMR) and other techniques to show that echinocandins induce dynamic changes in the assembly of mobile and rigid polymers within the A. fumigatus cell wall. The reduction of β−1,3-glucan induced by echinocandins is accompanied by a concurrent increase in levels of chitin, chitosan, and highly polymorphic α−1,3-glucans, whose physical association with chitin maintains cell wall integrity and modulates water permeability. The rearrangement of …

Serine Deamination By Human Serine Racemase Synergizes With Antibiotics To Curtail The Replication Of Chlamydia Trachomatis, Patricia D. Mott, Arnold H. Zea, Jamiya Lewis, Oygul Mirzalieva, Ashok A. Aiyar

School of Medicine Faculty Publications

The obligate intracellular bacterium, Chlamydia trachomatis, has evolved to depend on its human host for many metabolites, including most amino acids and three of the four nucleotides. Given this, it is not surprising that depletion of a single amino acid in the host cell growth medium blocks chlamydial replication. Paradoxically, supra-normal levels of some amino acids also block productive replication of Chlamydia. Here, we have determined how elevated serine levels, generated by exogenous supplementation, impede chlamydial inclusion development and reduce the generation of infectious progeny. Our findings reveal that human serine racemase, which is broadly expressed in multiple tissues, potentiates …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Lncrna Impact On Regorafenib Resistance In Colorectal Cancer, Ricardo Pequeno Bracho, Kyle Doxtater, Dennis Kwabiah, Yamile Abuchard Anaya, Sophia Leslie, Mohammad Shabir Hussain, Manish Tripathi

Research Symposium

Cancer metastasis is one of the deadliest aspects of the disease, with about 90% of all cancer-related deaths due to its development at different sites within the body. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States, with 40-50% of all patients developing metastasis at some point during their fight with the disease. With the approval of Regorafenib for treating metastatic colorectal cancer, steps have been taken to combat metastasis in colorectal cancer. A vital aspect of the development of metastasis is the development of resistance to first-line chemotherapy. Regorafenib is an oral small-molecule …

Editorial: Reviews And Advances In The Molecular Mechanisms Of Breast Cancer, A. Redfern, V. Agarwal, Suresh Alahari

School of Medicine Faculty Publications

No abstract provided.

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson

Electronic Theses & Dissertations (2024 - present)

Fibrosis is of significant concern to the medical community as numerous disease processes are characterized by progressive fibrosis leading to organ damage. We begin the process of examining the mechanism of fibrosis to salivary gland hypofunction and briefly consider Sjögren’s Disease (SjD). Method: We employed single-cell RNA sequencing data from a reversible mouse salivary gland injury model and from NOD/ShiLtJ mice, a model of secondary SjD. We performed treatment comparisons with the help of Seurat dotplots and UMAPS. Using differential gene expression analysis and the publicly available R packages: clusterProfiler, WikiPathways and Cytoscape, we identified the processes and pathways …

Enhanced Cd19 Activity In B Cells Contributes To Immunodeficiency In Mice Deficient In The Icf Syndrome Gene Zbtb24, Zhengzhou Ying, Swanand Hardikar, Joshua B Plummer, Tewfik Hamidi, Bin Liu, Jianjun Shen, Kevin M Mcbride, Taiping Chen

Faculty, Staff and Student Publications

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody deficiency. It is caused by mutations in DNMT3B, ZBTB24, CDCA7, or HELLS. While progress has been made in elucidating the roles of these genes in regulating DNA methylation, little is known about the pathogenesis of the life-threatening hypogammaglobulinemia phenotype. Here, we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with ICF syndrome. Specifically, Vav-Cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels …

Investigating The Role Of Maternal Adiposity On Human Breast Milk And Preterm Infant Stool Short Chain Fatty Acid And Microbiome Profiles, Kristy L. Thomas

Electronic Theses and Dissertations

Preterm birth is the number one cause of death in neonates, accounting for 35% of neonatal mortality. The preterm birth rate in the U.S. in 2021 was 10.5%, disproportionally affected by race and ethnicity. Obese women have an increased risk of preterm pregnancy, and if delivered before 37 weeks of gestation, the offspring have higher rates of complications that extend from the neonatal period into life-long metabolic and immune adverse outcomes. In the early months after delivery, preterm infants have higher rates of adverse health outcomes than term infants, including infections, extrauterine growth restrictions, respiratory, metabolic, and neurological complications, necrotizing …

Mir-146a Inhibits Ovarian Tumor Growth In Vivo Via Targeting Immunosuppressive Neutrophils And Enhancing Cd8+ T Cell Infiltration, Rui Chen, Elaina Coleborn, Chintan Bhavsar, Yue Wang, Louisa Alim, Michelle A Tran, Sharat Atluri, Kiefer Wong, Jae-Jun Shim, Siddharth Adityan, Ju-Seog Lee, Willem W Overwijk, Raymond Steptoe, Da Yang, Sherry Y Wu

Faculty, Staff and Student Publications

Immunotherapies have emerged as promising strategies for cancer treatment. However, existing immunotherapies have poor activity in high-grade serous ovarian cancer (HGSC) due to the immunosuppressive tumor microenvironment and the associated low tumoral CD8+ T cell (CTL) infiltration. Through multiple lines of evidence, including integrative analyses of human HGSC tumors, we have identified miR-146a as a master regulator of CTL infiltration in HGSC. Tumoral miR-146a expression is positively correlated with anti-cancer immune signatures in human HGSC tumors, and delivery of miR-146a to tumors resulted in significant reduction in tumor growth in both ID8-p53−/− and IG10 murine HGSC models. Increasing miR-146a expression …

Functional Impact Of Ethyl-Β-D-Glucuronide On Mycobacterium Tuberculosis Stimulated Lung Macrophages, Charles Inaku

Biotechnology Theses

Chronic alcohol abuse has been shown to alter immune defense mechanisms in humans and mice which makes the host susceptible to infections, including Mycobacterium tuberculosis (Mtb) infection. However, limited information is available on the mechanisms involved in alcohol-mediated host immune system dysfunction.

In this study, we determined the effects of ethyl-β-d-glucuronide (EtG), an alcohol-derived metabolite, on immune response of mice lung macrophages. We measured cytokine and chemokine production by gamma-irradiated mtb (γ-mtb) stimulated mice lung macrophages in the presence or absence of EtG. We also determined the effect of EtG on the metabolic state of γ-mtb stimulated mice lung macrophages. …

Investigating Novel Chemotherapeutics Against The Parasite Toxoplasma Gondii, Braydon Dreher

Theses/Capstones/Creative Projects

Toxoplasma gondii, an intracellular protozoan, is a globally prevalent parasite due to the infectivity of T. gondii with nearly 2.5 billion people affected worldwide. Toxoplasma gondii can cause toxoplasmosis, which is a disease acquired through the consumption of undercooked meat or found in the feces of felines, and often leads to profound neuropathology and potentially death. Currently, acute toxoplasmosis is treated with pyrimethamine and sulfadiazine, which is a combination of an antiprotozoal and a sulfonamide. This combination of drugs directly targets the acute stage of infection but has failed to eliminate or impact the chronic carriage of bradyzoites while …

A Review Of Staphylococcus Aureus Pathogenesis, Global Impact, And The Rise Of Antibiotic-Resistant Clones, Anders Kleinbeck

Honors Scholar Theses

Staphylococcus aureus is a pathogen of grave concern to global public health. The pathogen has shown an unrivaled propensity to obtain resistance to nearly every antibiotic drug approved and prescribed for its treatment. This review will provide an overview of the history and evolution of S. aureus, including an analysis of its transition from the nosocomial setting to the community and the factors contributing to the species’ innate pathogenicity. This paper will also discuss the molecular mechanisms by which resistance to a wide range of popular antibiotic substances was obtained and will provide insight into the evolutionary patterns exhibited by …

The Mechanisms Of Mitochondrial Dysfunction In T Cell Aging During Chronic Viral Infection, Madison B. Schank

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections induce a myriad of disturbances to CD4 T cell functions, including mitochondrial compromise, excessive inflammation, increased telomeric DNA damage and attrition, cellular exhaustion and senescence, and accelerated aging. In this dissertation, the mechanisms underlying metabolic failure, accelerated aging, and cellular dysfunctions were evaluated in CD4 T cells from healthy subjects (HS) treated with a telomere-targeting drug (KML001) or HCV-infected individuals or people living with HIV (PLHIV) compared to HS. We observed that KML001-induced telomere injury resulted in mitochondrial swelling and decreased mitochondrial membrane potential, cellular respiration, mitochondrial DNA (mtDNA) copy …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Attenuation Of Relapsing Fever Neuroborreliosis In Mice By Il-17a Blockade, Meihui Cheng, Jingwen Xu, Kaiyun Ding, Jing Zhang, Wei Lu, Jiansheng Liu, Jiahong Gao, Kishore R Alugupalli, Hongqi Liu

Department of Microbiology and Immunology Faculty Papers

Relapsing fever due to Borrelia hermsiiis characterized by recurrent bacteremia episodes. However, infection of B. hermsii, if not treated early, can spread to various organs including the central nervous system (CNS). CNS disease manifestations are commonly referred to as relapsing fever neuroborreliosis (RFNB). In the mouse model of B. hermsiiinfection, we have previously shown that the development of RFNB requires innate immune cells as well as T cells. Here, we found that prior to the onset of RFNB, an increase in the systemic proinflammatory cytokine response followed by sustained levels of IP-10 concurrent with the CNS disease phase. RNA sequencing …

Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication …

Molecular Pathogenesis Of A Novel Subgroup Of Peripheral T-Cell Lymphomas, Jiayu Yu

Theses & Dissertations

Peripheral T-cell Lymphoma (PTCL) consists of numerous distinct disease entities. With the current diagnostic criteria over a third of the cases cannot be further classified and are called "not otherwise specified" (PTCL-NOS). Using gene expression profiling (GEP) of tumors, we identified two novels PTCL-NOS molecular subgroups either characterized by high expression of GATA3 (33%), which is associated with Th2 cell differentiation, or high expression of TBX21 (49%) which regulates Th1 cell maturation. Therefore, stratifying patients for diagnosis and identifying the underlying genetic basis to improve clinical therapy becomes critical to prognosis.

First, we performed DNA copy number analysis by using …

Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

Therapeutic Potential Of Trp Channels In The Targeting Of Rheumatoid Arthritis Synovial Fibroblasts, Brittany Isabella Schwam

Theses and Dissertations (ETD)

Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the synovium, articular cartilage, and bone within a joint, but it is a unique form of arthritis wherein effects are systemic. The cause of this autoimmune disease remains unknown, but there are many environmental and genetic factors that play into susceptibility. Research is still far from drug-free remission despite great advancements over the past few decades. The majority of therapies developed rely on immunosuppressant or immunomodulator molecules and come with risk of infection, high costs, and toxic, uncontrolled side effects. Those diagnosed maintain a significant unmet need for targeted therapies.

There …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

Graduate Theses/Dissertations

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …