Disease Modeling Commons^™

Establishment Of An In Vivo Streptozotocin-Induced Type 1 Diabetes Model Recapitulating Early Brain And Retinal Fibrosis, Kia Bourdot, Lucy Dawson, Igor Kuzin, Arturo Bravo Nuevo, Zeus Antonello

Cooper Rowan Medical Journal

INTRODUCTION: Diabetes has risen to one of the top American public health concerns. The hyperglycemic state of chronic diabetes leads to microvascular and macrovascular changes that predispose patients to delayed wound healing and organ fibrosis. The validation of models to specifically detect early, quantifiable fibrotic changes seen in the diabetic state is of fundamental importance for understanding the diabetic pathophysiology and exploring earlier management options. Here, we investigated if we could detect early signs of internal fibrosis in a streptozotocin (STZ) diabetic mouse model by quantifying α-SMA expression in various organs using flow cytometry.

METHODS: We used a low-dose STZ-induced …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …

Species Data And Vector Modeling: Evaluating Datasets For Improved Models Of Ixodes Ricinus Tick Distribution In Europe Under A Changing Climate, Steven Jones

Electronic Theses and Dissertations

To increase capacity for monitoring and surveillance of tick-borne diseases, publicly available tick distribution and climate change datasets are required to create accurate predictive distribution models. It is difficult, however, to assess model accuracy and utility when using incomplete datasets.  The more recent development of comprehensive tick databases for Europe and availability of climate change scenarios from multiple IPCC Assessment Reports allows for improved modeling efforts. Multiple tick datasets were combined and three climate change projections were compared by predicting current and future distributions of Ixodes ricinus ticks in Europe using the MaxEnt species distribution model. Overall, much of Europe …

Physics-Informed Neural Networks For Informed Vaccine Distribution In Heterogeneously Mixed Populations, Alvan Arulandu, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Humanizing Mathematical Biology Research And Education, Carrie Diaz Eaton, Ognyan Simeonov

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Effect Of Vaccine Misinformation On Disease Spread, Anthony Delegge, Yina Wang

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Stochastic Models Of Zoonotic Avian Influenza With Multiple Hosts, Environmental Transmission, And Migration In The Natural Reservoir, Kaia Smith

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Modeling The Effects Of Media Awareness On Sars-Cov-2 Transmission In Georgia, Eric Numfor

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

An Agent-Based Model Of Environmental Transmission Of Clostridioides Difficile In Healthcare Settings, Max Lewis, Laila Mahrat, Cara Sulyok, Brittany Stephenson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Ischaemic Hepatitis (Ih): Modeling Outcome Based On Ih Patients' Attributes, Madison Utterback, Christiana Beard

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

An Agent-Based Model Of Covid-19 Transmission At Lewis University, Austin Kind, Brittany Stephenson Phd

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Cost Analysis Of Implementing An Exercise Program For Fall And Fracture Prevention In Older Adults On Proton Pump Inhibitor Therapy, Thomas Adam Wichelmann, Nhan Dang, David H. Kruchko, Sufyan Abdulmujeeb, Eli D. Ehrenpreis

Journal of Patient-Centered Research and Reviews

Purpose: Falls have significant financial impact. Proton pump inhibitor (PPI) therapy is associated with an increased risk of falls and fractures. Exercise programs have been shown to decrease risk of falls in the elderly population and are recommended by the U.S. Preventive Services Task Force for patients over age 65 to reduce falls. Our study aimed to explore the potential financial benefit of implementing three different Centers for Disease Control and Prevention-recommended exercise-based interventions for fall prevention (Tai Chi, Stepping On, and Otago Exercise Program) in ≥ 65-year-old patients on PPI therapy.

Methods: A Markov model was developed to predict …

Patient-Specific Genome-Scale Metabolic Models For Individualized Predictions Of Liver Disease, Alexandra Manchel, Jan B. Hoek, Ramon Bataller, Radhakrishnan Mahadevan, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The prevalence of liver disease is steadily increasing, coupled with the limited availability of therapeutic treatments. Recent literature points to metabolic reprogramming as a key feature of liver failure. Hence, we sought to uncover the metabolic pathways and mechanisms associated with liver disease and acute liver failure. We generated patient-specific genome scale metabolic models by integrating RNA-seq data from patient liver samples with a generalized human metabolic model. Flux balance analysis simulations showed a distinct separation of non-alcohol associated and alcohol-associated disease states. Our analysis suggests that the alcohol associated liver has an increased flux through nucleotide and glycerophospholipid metabolic …

Effects Of Dietary Ω-3 Polyunsaturated Fatty Acids (N-3 Pufa) In Light Sensitivity Of Retinas Of Mice Models To Prevent Retinal Damage, Aaron Eugene Rice

Longitudinal Scholar's Project

Light-induced retinal degeneration (LIRD) causes photoreceptor cell death in albino mice after exposure to high intensity light for a set period of time (6-24 hours). This causes retinal photoreceptor cell death through apoptosis. From several previous studies, Dr. Mandal’s lab concluded that de novo biosynthesis of ceramide mediates photoreceptor cell death in a LIRD model. Previous studies in Dr. Mandal’s lab has shown that mouse models with higher endogenous ω-3 Polyunsaturated Fatty Acids (n-3 PUFA) generates less ceramide upon neuronal injury and prevent neurodegeneration (Mol Neurobio 2021). There are currently not many available effective therapies for retinal degeneration in humans …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

University Scholar Projects

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

Honors Scholar Theses

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations and Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

How Environmental Change Will Impact Mosquito-Borne Diseases, Arsal Khan

Master's Projects and Capstones

Mosquitos, the most lethal species throughout human history, are the most prevalent source of vector-borne diseases and therefore a major global health burden. Mosquito-borne disease incidence is expected to shift with environmental change. These changes can be predicted using species distribution models. With the wide variety of methods used for models, consensus for improving accuracy and comparability is needed. A comparative analysis of three recent modeling approaches revealed that integrating modeling techniques compensates for trade-offs associated with a singular approach. An area that represents a critical gap in our ability to predict mosquito behavior in response to changing climate factors, …

Multi-Strain Epidemic Model With Infected Vaccinated And Re-Infected Recovered Population: Application To Covid-19 Pandemic, Olusegun Michael Otunuga

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Effect Of Prep Uptake And Adherence On The Spread Of Hiv In The Presence Of Casual And Long-Term Partnerships, Sylvia J. Gutowska, Katharine Gurski, Kathleen Hoffman

Biology and Medicine Through Mathematics Conference

No abstract provided.

Dynamics Of The Climax And Attack Communities In Cystic Fibrosis, Peter Uhl

Biology and Medicine Through Mathematics Conference

No abstract provided.

Building An Artificial Intelligence Framework For Hypertension Diagnosis: A Use Case Of The Problem List Curation, Ketemwabi Yves Shamavu

Theses & Dissertations

Hypertension is the world's leading factor in cardiovascular disease. Forty-seven percent or close to one in two Americans aged 18 and older are affected. It predicts approximately a thousand deaths per day. Based on recent statistics from the Centers for Disease Control and Prevention, one in three patients with hypertension does not know they are hypertensive. Seventy-five percent of hypertensive patients have uncontrolled hypertension - meaning that they are not treated to target. While there is extensive literature on hypertension diagnosis and management, there is an apparent gap in understanding and acknowledging that a person is hypertensive. Moreover, blood pressure …

An Application Of Differential Mathematical Modeling Techniques To Study The Ongoing Rabies Epizootic In China, Christopher Turner

Electronic Theses and Dissertations

Rabies remains a global public health issue with a wide variety of neurological symptoms such as confusion, slight paralysis, hypersalivation, and hydrophobia. Rabies is usually fatal once symptoms appear. Many species are reservoirs for rabies, such as foxes, racoons, and wild dogs, which in turn can transmit the disease to humans, leading to complex transmission chains. There is a long latent period of rabies, between 1 to 3 months after infection, which further complicates control efforts. Mathematical modeling is a valuable tool in the study of infectious disease outbreaks and there have been many models applied to rabies outbreaks. However, …

A Rat Experimental Model For Investigation Of The Effect Of Diabetes On Submandibular Salivary Glands Treated With Epidermal Growth Factor, Mahmoud Bakr, Mohamed Shamel, Sara Abdelwahed, Mahmoud Al Ankily

Dentistry

BACKGROUND: Despite the plethora of research around the negative effects of diabetes on different body organs, this topic still attracts a lot of attention to find potential remedies that could counteract or reverse the damaging effect of diabetes.AIM: In this study, we developed a reliable experimental rat model that can be used for the investigation of the ability of epidermal growth factor (EFG) in restoring the normal architecture of oral tissues after being damaged by diabetes.METHODS: Eighty adult male albino rats (average weight ±220 gm) were used in the current study. Twenty rats served as control and received no treatment. …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Neuronal Activity Within The Ventral Tegmental Area Is Correlated With Cocaine-Seeking Behavior In Male, But Not Female, Rats, Colton D. Spencer, Nicole M. Hinds, Ireneusz D. Wojtas, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

The objective of this study was to begin to determine the neurobiological underpinnings of psychosocial stress-induced cocaine seeking. Social defeat stress, achieved using the well-established resident-intruder procedure, is an ecologically-valid psychosocial stressor in rodents that may more closely recapitulate those psychosocial experiences that elicit cocaine craving and relapse in human cocaine users. Our laboratory has developed a model of psychosocial stress-induced relapse in rats in which extinguished cocaine seeking is reinstated by re-exposure to a discrete cue that signals impending social defeat stress. We previously reported that an individual rat’s predilection towards the display of active coping behaviors during prior …

Morphine-Induced Hyperactivity Is Attenuated By Intra-Accumbens Administration Of The Highly-Selective Dopamine D3 Receptor Antagonist Vk4-40, Mansi Patel, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

Opioids exert their abuse-related effects by enhancing dopamine (DA) neurotransmission within the brain’s mesolimbic reward system, a neural projection involving DA neurons in the ventral tegmental area (VTA) that project to medium spiny neurons within the nucleus accumbens (NAc). Mu (MOR) are expressed by several populations of GABAergic neurons that tonically inhibit VTA DA neurons. By inhibiting these GABAergic neurons in a MOR-dependent manner, opioids indirectly enhance DA neurotransmission via disinhibition of DAergic neurons. Accumulating evidence indicates that selective pharmacological antagonism of the dopamine D3 receptor (D3R) attenuates the abuse-related effects of several opioids, but the neurobiological mechanisms mediating this …

Alternate Site Pacing And The Impact On Intracellular Calcium Handling During The Post-Extrasystolic Cardiac Cycle, Kent Ozcan, Lawrence Mulligan

Rowan-Virtua Research Day

Objective: Previous work has shown that alternate site (RV apex) results in myocardial dysfunction. With the development of tools to place endocardial pacing leads in locations that create physiological pacing activation, we sought to evaluate how ventricular trans-septal or left ventricular apical placement pacing differs from right atrial pacing. We will evaluate how these chronic pacing modes impact the PR and RF at baseline, 0, and 16 weeks in the canine heart.

Methods: Quantitative analysis will be performed on previously generated data. The data set includes pacing of 15 dogs total (8 with trans-septal leads & 7 with left ventricular …