Disease Modeling Commons^™

Unraveling The Role Of Gjb3 In Lung Adenocarcinoma, Swathi M. Priyanka

Theses & Dissertations

Lung cancer stands as a leading cause of cancer-related mortality worldwide, with small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) comprising its primary categories. NSCLC, representing nearly 85% of cases, exhibits a 5-year survival rate of less than 21%. Among NSCLC subtypes, lung adenocarcinoma (LUAD) prevails as the most common, followed by squamous cell carcinoma and large cell carcinoma. Gap junctions are crucial for intercellular communication and cellular homeostasis maintenance, demonstrate altered expression patterns in various diseases, including cancer. Gap junction beta 3 (GJB3 or Connexin31) exhibits significant expression in both preclinical and clinical LUAD samples, prompting investigation into …

Interactions Between Repetitive Mild Traumatic Brain Injury And Methylphenidate Administration On Catecholamine Transporter Protein Levels Within The Rodent Prefrontal Cortex, Anna Abrimian, Eleni Papadopoulos, Christopher P. Knapp, J. Loweth, Barry Waterhouse, Rachel Navarra

Rowan-Virtua Research Day

It is theorized that low concentrations of dopamine (DA) and norepinephrine (NE) within in the prefrontal cortex (PFC) following traumatic brain injury (TBI) leads to increased risky behavior. Our lab has shown that repeated mild TBI (rmTBI) sex-differentially increases risky behavior in a rodent model. Methylphenidate (MPH) is a psychostimulant drug used to treat symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), also driven by a hypo-catecholaminergic PFC. MPH elevates catecholamine levels by blocking DA and NE transporters, DAT and NET. While the potential of psychostimulants to treat post-TBI symptoms have been explored, the effects of sub-chronic MPH on transporter levels following …

Identifying Chewing Alterations In A Parkinsonian Model, Nicholas Zanghi, Taylor Good, Shivam Patel, Francois Gould

Rowan-Virtua Research Day

Patients suffering from Parkinson’s Disease will typically experience a range of motor and nonmotor symptoms. Characteristic signs of Parkinson’s include pill-rolling tremor, stooped posture, and shuffling gate. Patients with this disease can also develop oropharyngeal dysfunction, which can disable patients from meeting their physiologic needs. Understanding this disability and the changes in mastication kinematics can lead to potential future treatment. Our study induced Parkinson’s in rats with rotenone injections. Their jaw kinematics were identified through fluoroscopy of radio-opaque beads implanted into different areas of their jaws. The Parkinson’s induction altered mastication significantly with an increase in anterior/posterior range of motion …

Fos Expression In Lateral Hypothalamus/Perifornical Area Is Correlated With Psychosocial Stress-Induced Cocaine-Seeking Behavior In A Sex-Specific Manner, Milena Sudarikov, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Daniel F. Manvich

Rowan-Virtua Research Day

Cocaine Use Disorder persists as a significant public health concern in the United States. Recent epidemiological data indicate that rates of cocaine-involved overdose deaths are rising, and treatment of Cocaine Use Disorder is challenging due to a lack of FDA-approved medications to help patients achieve abstinence and avoid relapse. Stress can precipitate cocaine craving and trigger relapse episodes, however the underlying neural circuitry by which stressors drive cocaine seeking is not completely understood. Our laboratory has recently identified the potential involvement of the rostrolateral aspect of the periaqueductal gray (rlPAG) in psychosocial stress-induced cocaine-seeking behavior using a rodent model of …

A Preliminary Report On The Role Of Lipoxin A4 In Reinstating The Blood-Brain Barrier Integrity In A Rodent Model Of Acute Inflammation With Impaired Cerebrovasculature, Minjal Patel, Shruti Varshney, Ananya Nethikunta, George G. Godsey, Mary C. Kosciuk, Ana Rodriguez, Bernd Spur, Kingsley Yin, Randel L. Swanson, Venkat Venkataraman, Robert G. Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB) is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs). SPMs are known to inhibit immune response through inhibition of cellular infiltration, downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Hence, LXs are recognized as “breaking signals” in the inflammatory process. One form of LXs, Lipoxin A4 (LXA4) …

Efficacy Of Psilocybin In The Treatment Of Substance And Alcohol Use Disorders, Hanna Brancaccio

Rowan-Virtua Research Day

Introduction: Substance use disorder (SUD) and alcohol use disorder (AUD) are major public health crises, affecting millions of Americans. Current treatment options include behavioral therapies and medications. In this review, we explored psilocybin’s efficacy in treating SUD and AUD.

Methods: Key terms were used to search databases to identify articles that addressed psilocybin in the treatment of SUD. Included in the review were indexed, peer-reviewed, primary sources that were published within the last 10 years. Excluded studies were non-peer reviewed, not relevant to the thesis, and did not have an English translation.

Results: The psychodynamic antidepressant effects of psilocybin mark …

The Effects Of Circadian Misalignment On Astrocyte Morphology In The Nucleus Tractus Solitarius, Kush C. Patel, Mina Shenouda, Diana Martinez

Rowan-Virtua Research Day

Circadian misalignment, as experienced by shift workers, was found to increase the number of astrocytes in the nucleus tractus solitarius (nTS) - a brain region crucial for autonomic control of blood pressure. Sprague Dawley rats subjected to a 6-hour light-dark phase delay every 2 days to simulate shift work exhibited a significant increase in astrocyte cell bodies compared to control rats, both at 9am and 9pm timepoints. The increase in astrocytes may lead to greater glutamate uptake, reducing extracellular glutamate levels in the nTS. Decreased glutamatergic neurotransmission in this region has been linked to the development of hypertension. These findings …

Effect Of Dosage On Severity Of Dysphagia In A Toxicological Rat Model Of Parkinson's Disease, Shivam Patel, Taylor Good, Nicholas Zanghi, Francois Gould

Rowan-Virtua Research Day

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg …

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

Intra-Accumbens Microinfusion Of The Dopamine D3 Receptor Partial Agonist (±)Vk4-40 Does Not Affect Basal Locomotion In Mice, Yeonwoo Sim, Nicole M. Hinds, Amy Hauck Newman, Daniel F. Manvich

Rowan-Virtua Research Day

The opioid epidemic remains a pressing public health crisis, prompting the search for alternative pharmacotherapies for Opioid Use Disorder (OUD). This study explores the potential of the dopamine D3 receptor (D3R) partial agonist, (±)VK4-40, as a novel treatment option. We investigated the impact of intra-nucleus accumbens (NAc) microinfusion of VK4-40 on basal locomotion in mice. Results indicate that VK4-40 did not significantly alter basal locomotion, suggesting that its therapeutic effects may not be mediated through disruptions in generalized motor function. Future research will focus on elucidating the neuropharmacological mechanisms underlying VK4-40's therapeutic actions and exploring its effects on psychostimulant-induced hyperlocomotion. …

Exploring The Neuroprotective Effects Of Cannabinoids On Oxygen Glucose Deprived Neurons In An In-Vitro Model Of Stroke, Bhavya Chatragadda, Emily Potts, Hang Ma, Navindra Seeram, Claudia Fallini

Senior Honors Projects

Stroke is a leading cause of long-term disability and decreased mobility worldwide. During stroke, neuronal damage results from both the initial oxygen-glucose deprivation and the increase in excitotoxicity and oxidative stress after restoration of blood flow, a phase called Ischemia-Reperfusion Injury (IRI). Reducing the impact of these processes could result in better outcomes for post-stroke patients by preventing excessive neuronal death. Many natural compounds derived from the Cannabis Sativa plant have been tested for neuroprotective effects due to their potential antioxidant properties. We hypothesized that neurons treated with cannabinoids immediately after experiencing an acute ischemic event will have an overall …

Code For Care: Hypertension Prediction In Women Aged 18-39 Years, Kruti Sheth

Electronic Theses, Projects, and Dissertations

The longstanding prevalence of hypertension, often undiagnosed, poses significant risks of severe chronic and cardiovascular complications if left untreated. This study investigated the causes and underlying risks of hypertension in females aged between 18-39 years. The research questions were: (Q1.) What factors affect the occurrence of hypertension in females aged 18-39 years? (Q2.) What machine learning algorithms are suited for effectively predicting hypertension? (Q3.) How can SHAP values be leveraged to analyze the factors from model outputs? The findings are: (Q1.) Performing Feature selection using binary classification Logistic regression algorithm reveals an array of 30 most influential factors at an …

Modeling An Infection Outbreak With Quarantine: The Sibkr Model, Mikenna Dew, Amanda Langosch, Theadora Baker-Wallerstein

Rose-Hulman Undergraduate Mathematics Journal

Influenza is a respiratory infection that places a substantial burden in the world population each year. In this project, we study and interpret a data set from a flu outbreak in a British boarding school in 1978 with mathematical modeling. First, we propose a generalization of the SIR model based on the quarantine measure in place and establish the long-time behavior of the model. By analyzing the model mathematically, we determine the analytic formulas of the basic reproduction number, the long-time limit of solutions, and the maximum number of infection population. Moreover, we estimate the parameters of the model based …

Nanoparticles For Applications In Specific Diagnostics And Precision Medicine, Naxhije Berisha

Dissertations, Theses, and Capstone Projects

Heterogeneity is common in the expression of cancer and treatment response. Precision medicine enables healthcare providers to tailor medical care to an individual's distinct genetic and environmental makeup. This customization has the potential to result in more efficient treatments while minimizing side effects. We believe that by studying the interface of nanotechnology and cancer medicine we can elucidate innovative solutions that address the challenges of disease heterogeneity. This includes advancements in drug delivery, formulations development, and diagnostic sensing. We highlight three studies that use nanotechnology for applications in precision medicine. In Chapter 2, we highlight design optimization of drug formulations …

A Tale Of Two Viruses: Why Smallpox Was Eradicated And Polio Persists, Katherine G. Mcgough, Erin N. Bodine

Spora: A Journal of Biomathematics

The smallpox and poliomyelitis (polio) viruses were, at a time, one of the largest threats to global public health killing millions until global eradication campaigns were put into effect. Vaccination led to the eradication of smallpox and the elimination of polio for most of the world. However, polio continues to persist at endemic levels in Pakistan and Afghanistan. We developed ODE models of smallpox and polio to explore differences in transmission dynamics and determine if the underlying biology has made poliomyelitis more difficult to eradicate. Our model analysis shows there are multiple factors which should allow polio to have a …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Role Of Myocardin Effector Genes On The Progression Of Cytoskeletal Remodeling And Phenotype Switching Of Hpmcs, Kasumi Sato

Biotechnology Theses

Pleural fibrosis (PF) is characterized by thickening of the pleura around the lungs due to mesothelial cells transitioning into myofibroblasts. Our research delved into the role of Myocardin (MYOCD) in this transition, revealing Twinfilin 1 (TWF1) and Leiomodin 1 (LMOD1) as significant genes influenced by MYOCD. In our investigation, we explored how TWF1 and LMOD1 impact cytoskeletal changes in human pleural mesothelial cells (HPMCs) induced by Transforming growth factor beta (TGF-β). Knocking down TWF1 resulted in reduced expression of Calponin 1 and alpha-Smooth Muscle Actin (α-SMA), while LMOD1 knock-down suppressed α-SMA expression. Inhibition of TWF1 hindered stress fiber formation but …

When Brain Meets Artificial Intelligence, Lu Zhang

Computer Science and Engineering Dissertations - Archive

When we review the history of development of artificial intelligence (AI), we will find that brain science plays a pivotal role in fostering breakthroughs in AI, such as artificial neural networks (ANNs). Today, AI has made remarkable strides, particularly with the emergence of large language models (LLMs), surpassing expectations and achieving human-level performance in certain tasks. Nonetheless, an insurmountable gap remains between AI and human intelligence. It is urgent to establish a bridge between brain science and AI, promoting their mutual enhancement and collaborations. This involve establishing connections from brain science to AI (brain-inspired AI), and reversely, from AI to …

Employing A Machine Learning Approach In Precision Oncology To Predict Pik3ca Functional Status And Identify Phenocopying Variants Of Deleterious Pik3ca Mutations, Javier Castillo

CMC Senior Theses

The following proposal describes a modular machine learning approach that detects malfunctioning genes and pathways in cancer using the transcriptome of cancer patients. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. Applied to the PI3K/AKT/mTOR pathway, this method can be used to predict PIK3CA functional status and identify phenocopying variants of deleterious PIK3CA mutations. The classifier will do this by integrating RNA-seq, copy number, and mutation data from tumors to determine the functional status of PIK3CA using a set of learned gene-specific weights. The classifier will then be …

Impacts Of Climate Change On Vector-Borne Disease Burden In The United States: Exploring The Epidemiological Evidence, Leah V. Loetman

Honors Theses

Climate change models predict shifts in vector-borne diseases (VBDs) around the world, including in the United States. However, to my knowledge there has yet to be a comprehensive descriptive epidemiological study examining prevalence, geographic distribution, and trends for all tick- and mosquito-borne diseases in the United States. I compiled data from the U.S. Centers for Disease Control (CDC), which publishes yearly case numbers for 17 vector-borne diseases. However, these publications depend on a scattered framework of state regulations regarding disease reporting. I compiled data from the CDC to determine the current geographic distribution, prevalence, and trends of tick- and mosquito-borne …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Human Cell Modeling Of Cdkl5-Deficiency Disorder With Patient-Derived Organoids And Hd-Mea, Alyssa Paynton

Cal Poly Humboldt theses and projects

CDKL5 deficiency disorder (CDD) is an X-linked disorder that leads to severe cognitive impairments as well as infantile epilepsy. The only FDA approved therapy helps to reduce seizure frequency, however there are currently no cures approved. While murine models have proven useful in characterizing CDD, there are limitations due to differences in brain structure and development across species that may lead to the reported lack of spontaneous seizures in the mouse, a hallmark in humans affected by this disorder. By the utilization of patient-specific iPSCs generated into cerebral organoids, a more comprehensive and in-depth analysis into rare neurological disorders, such …

Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks

Electronic Theses & Dissertations (2024 - present)

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expression of expanded CUG (CUG^exp) repeat RNA from the myotonic dystrophy protein kinase (DMPK) gene. This CUG^exp repeat RNA’s gain-of-function mechanism leads to the sequestration of muscleblind-like (MBNL) proteins, resulting in widespread alternative splicing dysregulation across tissues. Despite significant research, there are currently no approved therapeutics targeting the underlying causes of DM1. This dissertation explores the development and optimization of a novel class of small molecules, Modified Polycyclic Compounds (MPCs), designed to address splicing dysregulation in DM1. MPCs were designed from previously published …

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …

Regulation Of Mirnas In Obesity And Diabetes, Eva Maher, Ava O'Meara, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Introduction: The prevalence of obesity and obesity-related secondary disorders has increased dramatically in recent years. Dysregulated microRNA (miRNA) expression has been linked to the development of obesity and its associated disorders. Adipose derived stem cells (ADSCs) are promising cell models of obesity, obesity-related inflammation and diabetes. Furthermore, miRNA expression profiles have emerged as promising targets for the novel treatment of diseases such as obesity. In order to enhance miRNA-based therapies, the miRNA expression profile of obesity and its related disorders must be monitored to further understand the underlying mechanisms of obesity and to identify novel targets.

Aim: The aim of …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Ethanol Dysregulates Sirt1-Mediated Lipogenic Signaling Pathways Through Α4*-Nicotinic Acetylcholine Receptors In Hepatocytes., Caitlin Christina Wilkerson

Electronic Theses and Dissertations

Alcohol-associated liver disease (ALD) is a broad spectrum of diseases ranging from steatosis to severe hepatic cirrhosis, none of which have any FDA approved therapies. Downregulation of hepatic Sirtuin 1 (Sirt1) activity by ethanol has been shown to lead to an upregulation of the pro-lipogenic gene targets under its jurisdiction, resulting in increased lipogenesis and triglyceride accumulation. It was hypothesized that ethanol acts on α4*-nicotinic acetylcholine receptors (α4*-nAChRs) in hepatocytes to decrease Sirt1 expression, which ultimately dysregulates lipid metabolic homeostasis. Ethanol’s effects were investigated in cultured AML12 hepatocytes and in WT primary mouse hepatocytes acutely exposed to ethanol. Consistent with …

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …

An Ode Model For Investigating The Sleep-Pain Relationship In Sickle Cell Disease, Quindel Jones, Angela Reynolds, Rebecca Segal, Reginald Mcgee

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.