Disease Modeling Commons^™

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Personalizing Intermittent Fasting: The Role Of Microbiome Diversity And Fiber Intake In Shaping Health Outcomes, Jana Gjini, Robin Moore, Venkateswar Venkataraman

Rowan-Virtua Research Day

BACKGROUND: Intermittent fasting (IF) has been linked to improved metabolic health, reduced inflammation, and increased longevity in animal models. These effects are thought to be mediated through changes in the gut microbiome. Murine studies consistently show that IF enhances microbial diversity and promotes beneficial species like Lactobacillus and Bifidobacterium, improving metabolic profiles and gut barrier function. However, human studies reveal inconsistent results, suggesting that individual-level factors such as baseline microbiome composition and fiber intake may influence response to IF.

HYPOTHESIS: Baseline gut microbiome diversity and habitual dietary fiber intake modulate the metabolic and inflammatory benefits of intermittent fasting in humans. …

Identifying Novel Molecular Targets To Induce Ferroptosis In Drug-Tolerant Cancer Cells Through Computational Modeling, Haris J. Rana

Biological Sciences Undergraduate Honors Theses

Ferroptosis is an iron-dependent, reactive oxygen species (ROS)-driven form of regulated cell death in which the cell membrane is degraded by lipid peroxidation. It is regulated by multiple enzymes, such as glutathione peroxidase 4 (GPX4), which prevents membrane degradation by reducing lipid peroxides and protecting cells from oxidative damage. When inhibitors like RSL3 target GPX4, lipid peroxides build up, and toxic ROS compromises membrane integrity. Traditional anticancer treatments, such as most chemotherapies, aim to eliminate tumor cells by damaging DNA and triggering apoptosis. However, resistance to apoptosis is a “hallmark of cancer,” often resulting in treatment failure. As a distinct …

Effects Of The Non-Stimulant Norepinephrine Reuptake Inhibitor, Atomoxetine, On Cognitive Flexibility In Healthy Adult Long-Evans Rats, Noah A. Ivak, Samantha Walkow, Christopher Knapp, Eleni Papadopoulos, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua Research Day

Executive function is the control of multiple higher order cognitive processes that include attention, working memory, and cognitive flexibility. Cognitive flexibility is the ability to shift behavioral strategies

in response to changing environmental demands and task complexity. This cognitive modality is often impaired in many neuropsychiatric disorders like attention deficit hyperactivity disorder (ADHD). Deficits in cognitive flexibility are associated with dysregulation of the catecholamines, norepinephrine (NE) and dopamine (DA) within the prefrontal cortex (PFC). Atomoxetine (ATX), a non-stimulant NE reuptake inhibitor, elevates levels of NE and DA in the PFC by inhibiting the norepinephrine transporter (NET). ATX is used to …

Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro

Rowan-Virtua Research Day

Melanoma is the fifth most common cancer among American adults, with significant morbidity and mortality at 5 years remaining >60% for patients with stage IV disease. The malignancy is due to the transformation of melanocytes, with one of the major risk factors being ultraviolet light exposure. Although as many as one in five human cancers have been linked to chronic inflammation, the role of inflammatory signals in melanoma growth and metastasis remains poorly understood.

Tumor necrosis factor (TNF)-transgenic (TNFtg) mice are a well-established model of chronic systemic inflammation, with involvement of joints and other organ systems. To assess the effect …

Effects Of Social Isolation On Cecum Opioid Receptor Expression And Affective Behavior, Jordan Riser, John Tkaczynski, Nicole Shellenbarger, Maya Patel, Daniel Chandler, Daniel Manvich

Rowan-Virtua Research Day

BACKGROUND

Psychological stress can induce gastrointestinal symptoms and exacerbate existing gastrointestinal disorders, indicating an interaction between the central and enteric nervous systems. Central nervous system activation of opioid receptors stimulates sympathetic outflow to the enteric nervous system, delaying motility and reducing gastrointestinal secretions, producing a similar clinical presentation to IBS.

HYPOTHESIS

We hypothesize that social isolation induces anxiety states, disrupting homeostatic noradrenergic activity in the brain and gut, leading to neurophysiological changes in the cecum characterized by altered expression of opioid receptors.

METHODS

Sprague-Dawley rats were housed in either group (control) or socially isolated conditions. Affective behavior was assessed using …

Advancing Research On Retinitis Pigmentosa: An Investigation Of Natural History, Visual System Plasticity, And Mutation-Independent Treatment., Cecilia A. Attaway

Electronic Theses and Dissertations

Retinitis Pigmentosa (RP) is an inherited retinal disease characterized by rod and then cone photoreceptor degeneration. ~25% of cases are caused by a genetic mutation that results in autosomal dominant RP (adRP). There has been a lack of exploration of the progression of degeneration in adRP models. In Chapter Two, I examined visual acuity (VA) changes, retinal structure, and function from early to late-stage disease in a murine P23H Rho ‘knock-in’ mouse model (Rho^P23H/+), the most common form of adRP in North America. To establish a natural history, I evaluated behavioral VA, using the visual water task, …

Effects Of Social Isolation On Locus Coeruleus Opioid Receptor Expression And Affective Behavior, John Tkaczynski, Jordan Riser, Maya Patel, Nicole Shellenbarger, Jin Park, Daniel Manvich, Daniel J Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Social isolation is a stressor that impairs homeostatic neuroendocrine functions and is associated with the development of several mood disorders characterized by persistent negative affect. Persistent feelings of loneliness have been growing public health concerns for several years and were greatly exacerbated by the onset of the COVID-19 pandemic. The problem has grown so severe the U.S. Surgeon General recently declared loneliness to be an epidemic health concern that is associated with poor mental and somatic health outcomes. Therefore, identifying mechanisms of neuroadaptation that contribute to the development of persistent negative affect is a critical step in the identifying better …

Bloom: Behavioral Learning And Outcome Observation In Microbes, Sean Sarwar Haque, Luke Compton Wharton, Ming Lin, Razvan Voicu

Symposium of Student Scholars

Understanding how pathogens respond to physical changes in their environment is crucial for developing effective treatments and preventative measures. Current research often relies on static models or experimental data that either fail to capture the dynamic interactions within cellular environments or are not generalizable to other types of pathogens. This project aims to address this gap by creating a comprehensive cell simulation that models pathogens and their response to chemical, physical, and physiological changes. The proposed solution is a simulation that integrates biological data and computational modeling to replicate the behavior of pathogens in real time as they are affected …

Arrhythmogenic Right Ventricular Cardiomyopathy: A Comprehensive Review, Taha Shaikh, Darren Nguyen, Jasmine Dugal, Michael Dicaro, Brianna Yee, Nazanin Houshmand, Kachon Lei, Ali Namazi

Department of Internal Medicine Faculty Research

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by structural abnormalities, arrhythmias, and a spectrum of genetic and clinical manifestations. Clinically, ARVC is structurally distinguished by right ventricular dilation due to increased adiposity and fibrosis in the ventricular walls, and it manifests as cardiac arrhythmias ranging from non-sustained ventricular tachycardia to sudden cardiac death. Its prevalence has been estimated to range from 1 in every 1000 to 5000 people, with its large range being attributed to the variability in genetic penetrance from asymptomatic to significant burden. It is even suggested that the prevalence is underestimated, as the presence of genotypic mutations …

Estimating Per-Infection Cost And Burden For Dengue And Zika As A Function Of Antibody-Dependent Enhancement, Christopher M. Kribs

Mathematics Faculty Publications - Archive

The complex immune interactions produced by the tetravalent dengue vaccine Dengvaxia have foregrounded the important role of antibody-dependent enhancement (ADE) in dengue infection. Some evidence exists that ADE may extend beyond the four dengue serotypes to Zika, a closely related flavivirus transmitted by the same mosquito species as dengue, and may also account for the increased severity of some cases. Estimates of the public health impact of dengue vaccination may then need to include its effects on the transmission of Zika in addition to dengue. This study gathers primary references to build estimates of per-case economic cost and disease burden …

Opioid Tolerance And Withdrawal In The Mouse Colon, James Fune

Theses and Dissertations

Constipation is a major clinical obstacle associated with opioids, prompting patients to discontinue treatment due to pain, discomfort, and psychosocial stressors. Moreover, chronic users become tolerant to the analgesic effects of opioids, but not to their constipating effects. Upon cessation of long-term treatment, serious diarrhea–among other somatic signs of withdrawal–may ensue. These symptoms become a driving factor for relapse, causing patients to restart opioid treatment. In this study, we aim to understand mechanisms that contribute to opioid tolerance and withdrawal in the colon. Previous findings suggest that constipation occurs partly due to the colon’s lack of tolerance to opioids’ inhibitory …

Lrtm Left-Right Transition Matrices For Molecular Interaction Prediction, Kaitlin Zheng, Guihua Duan, Mengyun Yang, Wei Wu, Yao-Hang Li, Jianxin Wang

Computer Science Faculty Publications

Molecular interactions are central to most biological processes. The discovery and identification of potential associations between molecules can provide insights into biological exploration, diagnostic and therapeutic interventions, and drug development. So far many relevant computational methods have been proposed, but most of them are usually limited to specific domains and rely on complex preprocessing procedures, which restricts the models’ ability to be applied to other tasks. Therefore, it remains a challenge to explore a generalized approach to accurately predicting potential associations. In this study, We propose Left-Right Transition Matrices (LRTM) for molecular interaction prediction. From the perspective on the diffusion …

The Diseased Extracellular Matrix In Chronic Obstructive Pulmonary Disease Modeling, Leigh-Ann M. Antczak

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the world, with an increasing prevalence as the world’s population ages. In the distal regions of the lungs, COPD is characterized by progressive emphysema due to an imbalance of proteases that continuously degrade essential extracellular matrix (ECM) proteins within the alveolar walls, causing fatal tissue impairment. This dissertation examines the unique properties of this diseased lung ECM in two parts: (1) As a key constituent in inflammatory signaling that leads to increased inflammation and progression of COPD, and (2) as a tool in three-dimensional (3D) in …

Enhancing The Accuracy Of Image Classification For Degenerative Brain Diseases With Cnn Ensemble Models Using Mel-Spectrograms, Sang-Ha Sung, Michael Pokojovy, Do-Young Kang, Woo-Yong Bae, Yeon-Jae Hong, Sangjin Kim

Mathematics & Statistics Faculty Publications

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are prevalent neurodegenerative disorders among the elderly, leading to cognitive decline and motor impairments. As the population ages, the prevalence of these neurodegenerative disorders is increasing, providing motivation for active research in this area. However, most studies are conducted using brain imaging, with relatively few studies utilizing voice data. Using voice data offers advantages in accessibility compared to brain imaging analysis. This study introduces a novel ensemble-based classification model that utilizes Mel spectrograms and Convolutional Neural Networks (CNNs) to distinguish between healthy individuals (NM), AD, and PD patients. A total of 700 voice …

Determining Essential Regulatory Factors In Extravillous-Trophoblast Differentiation And Splice Variants Associated With The Development Of Preeclampsia, Brandt Hugh Beck

Electronic Theses & Dissertations (2024 - present)

Preeclampsia is a common condition affecting mothers across the world. Rates for preeclampsia have been rising in the past years due to factors such as obesity and diabetes. Since this condition has been more prevalent, a better understanding of the factors surrounding the preeclamptic state are needed. Core cell types and biological functions of placenta development are known but the cause behind the preeclamptic environment is not well understood. This research aims to investigate the potential causes behind preeclampsia by first reviewing Extravillous-Trophoblast differentiation factors in the context of differential gene expression and alternative splicing then evaluate towards preeclamptic tissue. …

Mathematical Modelling Of Disease Outbreak, Favour Christian, Matthew Molloy

SURE Journal: Science Undergraduate Research Experience Journal

Establishing a model framework for more research necessitates a thorough understanding of the causes, distribution, prevalence, and evolution of infectious illnesses. The main mathematical concept used in this modelling simulation is ordinary differential equations (ODEs). The purpose of this study was to investigate the significance of the many criteria linked to a zombie virus spread. The zombie framework provides an accessible and relatively simple representation of the nature of infectious disease spread, allowing for tractable assumptions and the development of more complex situations.

The models are designed around a zombie outbreak in which the zombie virus is spread through a …

Early Ctdna Kinetics As A Dynamic Biomarker Of Cancer Treatment Response, Aaron Li, Emil Lou, Kevin Leder, Jasmine Foo

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum

Dissertations, Theses, and Capstone Projects

Approximately 99.6% of potential Alzheimer’s drugs fail, thus developing successful drugs is a high priority. The failure at developing successful drugs relates to the complex nature of the disease itself. Many components act together to trigger a cascade that ultimately results in neurodegeneration and cognitive dysfunction associated with the disease. In building a multiplex model of Alzheimer’s it is important to understand its specific biological mechanisms. One of these key pathological mechanisms is neuroinflammation. Understanding the pathways involved in neuroinflammation in Alzheimer’s is an urgent need, as it poses a promising avenue for future effective therapeutics. Specifically, as many investigational …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

Modeling The Effect Of Human Behavior On Disease Transmission, Katie Yan

Rose-Hulman Undergraduate Mathematics Journal

Many infectious disease models build upon the classic Susceptible-Infected-Recovered (SIR) model, a compartmental system that is used to simulate disease transmission in a population. The SIR model focuses on the transmission of disease but rarely includes behavioral or informational components that explore how disease perception influences transmission. In this paper, we propose a six-compartment behavioral SIR model that further segments the classic SIR system based on knowledge of information about the disease, and we explore how sharing information affects disease transmission. We designate two states as aware and unaware based on whether the relevant information is known by the population. …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

Deciphering The Contribution Of Microglia To Neurodegeneration In Friedreich's Ataxia, Sydney N. Gillette

Master's Theses

Friedreich's ataxia (FRDA) is the most prevalent inherited ataxia, affecting one in every 50,000 individuals in the United States. This hereditary condition is caused by an abnormal GAA trinucleotide repeat expansion within the first intron of the frataxin gene resulting in decreased levels of the frataxin protein (FXN). Insufficient cellular frataxin levels results in iron accumulation, increased reactive oxygen species production and mitochondrial dysfunction. Tissues most heavily impacted are those most dependent on oxidative phosphorylation as an energy source and include the nervous system and muscle tissue. This is evident in the clinical phenotype which includes muscle weakness, ataxia, neurodegeneration …

Blunt Cerebrovascular Injury (Bcvi): Universal Cta Neck Screening At Level 2 Trauma Center, Tamine Gogel

Doctor of Nursing Practice Projects

Blunt Cerebrovascular Injury (BCVI) refers to injuries to the vessels supplying blood to the brain, primarily carotid and vertebral arteries, and can result from trauma, resulting in stroke by vessel dissection, thrombus formation, embolization, and hemorrhage. Timely identification is crucial for effective intervention and improved outcomes. This doctoral project proposes the implementation of universal screening using Computed Tomography Angiography (CTA) of the neck during initial workup for blunt force trauma at a Level II ACS-verified trauma center. The primary objective is to mitigate potential delays in diagnosing and treating BCVI, thereby reducing the likelihood of complications. Patients ≥ 15 years …

Modeling Fast Information And Slow(Er) Disease Spreading: A Geometric Analysis, Iulia Martina Bulai, Mattia Sensi, Sara Sottile

Biology and Medicine Through Mathematics Conference

No abstract provided.

Assessing The Impact And Cost-Effectiveness Of Covid-19 Testing In Adult Social Care Homes In England, Siyu Chen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Dual-Domain Clustering Of Spatiotemporal Infectious Disease Data, Samuel R. Thornton, Erin C.S. Acquesta, Patrick D. Finley, Mansoor A. Haider

Biology and Medicine Through Mathematics Conference

No abstract provided.

Information Feedback Delays Within Epidemic Models And Their Effect On Model Dynamics., Maria K. Bouka, Christopher Strickland Dr

Biology and Medicine Through Mathematics Conference

No abstract provided.

Statistical Approaches For The Early Detection Of Colorectal Cancer Using Longitudinal Biomarkers, Emily Berry

Statistical Science Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States [45]. CRC is believed to advance from adenomatous polyps creating a unique opportunity for both early detection and cancer prevention [4, 23]. Like other diseases, CRC screening reduces mortality by detecting cancer at earlier, more treatable stages; however, it can also reduce incidence through the removal of precancerous lesions [4]. As a result, screening is recommended for average-risk adults ≥ 45 years of age and includes a variety of tests [4, 12]. Despite alternate screening options, colonoscopy capacity is often cited as a barrier to …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …