Disease Modeling Commons^™

Novel Approaches For Enhancing Cell Survival And Function In Vivo, Ou Wang

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin …

A Dystrophin Exon‐52 Deleted Miniature Pig Model Of Duchenne Muscular Dystrophy And Evaluation Of Exon Skipping, Yusuke Echigoya, Nhu Trieu, William Duddy, Hong M. Moulton, Haifang Yin, Terence A. Partridge, Eric P. Hoffman, Joe N. Kornegay, Frank A. Rohret, Christopher S. Rogers, Toshifumi Yokota

Genomics and Precision Medicine Faculty Publications

No abstract provided.

Ecology Of Hantaviruses In Rodent Reservoirs And Their Early Innate Immune Responses In Human Model Systems, Evan Peter Williams

Theses and Dissertations (ETD)

The spillover of zoonotic RNA viruses is responsible for a great deal of the disease outbreaks in human populations. These spillover events are set to continue due to anthropogenic and environmental changes that impact the distribution of these viruses. The viruses in the family Hantaviridae are classified as one of these emerging zoonotic RNA viruses. The spillover of the viruses in this family are responsible for two severe human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These viruses are distributed across the globe and are responsible for a large number of human disease cases with …

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations and Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …

Identifying The Molecular Cause Of Extreme Endoplasmic Reticulum Dilation In Pediatric Osteosarcoma And Its Relationship To The Disease, Rachael Wood

Theses and Dissertations (ETD)

Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology …

Modeling, Analysis And Simulation Of Covid-19 Interaction Dynamics Between Local Community In Saudi Arabia And Visiting Sub-Population, Manal Badgaish, Padmanabhan Seshaiyer

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Using Parameter Estimation For Mathematical Model Predicting Pediatric Scd Pain, Quindel Jones

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Advancing Rna Virus Discovery And Biology With Whole Genome Sequencing, Mariah Katherine Taylor

Theses and Dissertations (ETD)

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute …

Simulating Influenza Epidemics With Waning Vaccine Immunity, Chun-Miin Chen, Alia C. Stanciu

Faculty Journal Articles

In this study, we simulate an influenza epidemic that considers the effects of waning immunity by fitting epidemiological models to CDC secondary historical data aggregated on a weekly basis, and derive the transmission rates at which susceptible individuals become infected over the course of the influenza season. Using a system of differential equations, we define four groups of individuals in a population: susceptible, vaccinated, infected, and recovered. We show that a larger number of initially infected individuals might not only bring the influenza season to an end sooner but also reduce the epidemic size. Moreover, any influenza virus that entails …

Epithelial Memory Of Resolved Inflammation Limits Tissue Damage While Promoting Pancreatic Tumorigenesis, I-Lin Ho

Dissertations and Theses (Open Access)

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma. When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS …

Implementation Of Pediatric Adverse Childhood Experiences Screening In Primary Care, Alexzandra Hillyer

Dissertations

Implementation of Pediatric Adverse Childhood Experiences Screening in Primary Care

Problem: Over half of children worldwide have experienced abuse in the past year. In 2012, The American Academy of Pediatrics released a policy statement emphasizing the importance of primary care providers implementing Adverse Childhood Experience (ACE) screening into all well-child examinations.

Methods: This quality improvement project was a descriptive, observational pilot study in which Center for Youth-Well ACE Questionnaire (CYW-ACE-Q) was implemented into a large, metropolitan pediatric primary care clinic. A convenience sample was utilized composed of pediatric patients between the ages of 5 and 18 being seen for a …

Mathematical Modeling, Analysis, And Simulation Of The Covid-19 Pandemic With Behavioral Patterns And Group Mixing, Comfort Ohajunwa, Padmanabhan Seshaiyer

Spora: A Journal of Biomathematics

Due to the rise of COVID-19 cases, many mathematical models have been developed to study the disease dynamics of the virus. However, despite its role in the spread of COVID-19, many SEIR models neglect to account for human behavior. In this project, we develop a novel mathematical modeling framework for studying the impact of mixing patterns and social behavior on the spread of COVID-19. Specifically, we consider two groups, one exhibiting normal behavior who do not reduce their contacts and another exhibiting altered behavior who reduce their contacts by practicing non-pharmaceutical interventions such as social distancing and self-isolation. The dynamics …

Information Needs Of Traditional Medicine Practitioners (Tmps) In Nigeria With A Particular Reference To Alimosho Local Government Of Lagos State, Adeniran Pauline Oghenekaro Mrs.

Library Philosophy and Practice (e-journal)

Information plays a crucial role in modern society. It helps people to develop their knowledge of the world. This knowledge guides them against mistakes leading to effectiveness and efficiency in all aspects of life. This survey aimed to determine the Information needs and sources of Information of Traditional Medicine Practitioners (TMPs) in Nigeria with reference to Alimosho Local Government Area of Lagos State. The study population comprised forty (40) registered traditional medicine practitioners in Alimosho Local Government Area of Lagos State. The questionnaire instrument was used for data collection in which forty (40) copies were administered to the traditional medicine …

Personalized Digital Phenotype Score, Healthcare Management And Intervention Strategies Using Knowledge Enabled Digital Health Framework For Pediatric Asthma, Utkarshani Jaimini, Amit Sheth

Publications

Asthma is a personalized, and multi-trigger respiratory condition which requires continuous monitoring and management of symptoms and medication adherence. We developed kHealth: Knowledge-enabled Digital Healthcare Framework to monitor and manage the asthma symptoms, medication adherence, lung function, daily activity, sleep quality, indoor, and outdoor environmental triggers of pediatric asthma patients. The kHealth framework collects up to 1852 data points per patient per day. It is practically impossible for the clinicians, parents, and the patient to analyze this vast amount of multimodal data collected from the kHealth framework. In this chapter, we describe the personalized scores, clinically relevant asthma categorization using …

Prophylactic Phage Therapy In Infant Rabbits Model Of Cholera, Sadeq Ag Kaabi Asst Prof Dr

Karbala International Journal of Modern Science

A number of 8 phages lytic of V. cholerae O1- biotype-EI-Tor, serotype Inaba were selected for the formulation of a phage cocktail. A phage cocktail composed of 8 phages was prepared and showed 100% inhibition of V. cholerae isolates comparing with a percentage ranged from 0-75% for every single phage in growth inhibition assay. The potential activity of phage cocktail of prophylactic therapy for infant rabbits model of cholera was evaluated through phage retention time and length of phage prophylaxis studies. Results have been showed that phage cocktail was potent in the prevention of development of cholera in infant rabbits …

Identification Of Effectors Of Synergistic Lethality In Candida Albicans-Staphylococcus Aureus Polymicrobial Intra-Abdominal Infection, Olivia Adele Todd

Theses and Dissertations (ETD)

Candida albicans, an opportunistic fungal pathogen, and Staphylococcus aureus, a ubiquitous pathogenic bacterium, are among the most prevalent causes of nosocomial infections and cause severe morbidity and mortality. Moreover, they are frequently coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Relatively little is known about the complex interactions and signaling events that occur between microbes and even less so how microbial “cross-talk” shapes human health and disease.

Using a murine model of polymicrobial intra-abdominal infection (IAI), we have previously shown that coinfection with C. albicans and S. aureus leads to synergistic lethality whereas monomicrobial infection is nonlethal. …

Modeling The Spread Of Covid-19 Over Varied Contact Networks, Ryan L. Solorzano

Master's Theses

When attempting to mitigate the spread of an epidemic without the use of a vaccine, many measures may be made to dampen the spread of the disease such as physically distancing and wearing masks. The implementation of an effective test and quarantine strategy on a population has the potential to make a large impact on the spread of the disease as well. Testing and quarantining strategies become difficult when a portion of the population are asymptomatic spreaders of the disease. Additionally, a study has shown that randomly testing a portion of a population for asymptomatic individuals makes a small impact …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

The Dopamine D3 Receptor Antagonist Vk4-40 Attenuates Morphine-Induced Hyperactivity But Not Cocaine-Induced Hyperactivity In Mice, Desta M. Pulley, Jessica J. Debski, Daniel Manvich

Rowan-Virtua Research Day

In light of the increasing rates of opioid abuse in the US, the search for viable medications to treat opioid abuse disorder (OUD) has become ever more urgent. Opioids exert their abuse-related effects in part by indirectly increasing dopamine (DA) neurotransmission in the mesolimbic system, a dopaminergic projection arising in the ventral tegmental area and terminating in the nucleus accumbens. The DA D3 receptor (D3R), which belongs to the D2 family of dopamine receptors (D2, D3 , D4 receptor subtypes), is highly expressed in these brain regions and has shown strong potential as a pharmacotherapeutic target for the treatment of …

Physiological Response And Tissue Damage Following Different Depths Of Impact In A Rodent Model Of Mild Traumatic Brain Injury, Haven K. Predale, Christopher P. Knapp, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

Mild traumatic brain injury (mTBI) is a serious public health concern that can result in significant neurological and behavioral deficit. mTBI results from impact to the head and can be repetitive in nature, especially in sports and domestic violence cases. Our laboratory studies the effects of repetitive mTBI on risky choice behavior in rodents using a closed-head controlled cortical impact (CH-CCI) model of injury and a well-established probabilistic discounting task that assesses risk-based decision-making behavior. We have recently found that females, but not males, display transient increases in risky choice behavior following three CH-CI’s delivered at 5.5m/s velocity and 2.5 …

Coronary Artery Disease: An Analysis Of Its Biochemical, Physiological, And Sociological Causes And Effects, Alexander Velazquez

Honors Theses

Coronary Artery Disease (CAD) is a serious condition caused by a buildup of plaque in your coronary arteries, the blood vessels that bring oxygen-rich blood to your heart. It disproportionately affects millions of Americans and thousands of Mississippians. This study presents the results of an evaluation of causation factors of CAD, the physiological impact on the body, and the contributing determinants of CAD on Mississippi populations. Data on Mississippi populations were collected using the Center for Population Studies at the University of Mississippi. A multitude of individuals were evaluated when examining the causes and effects of CAD including men, women, …

The Impact Of Prolonged Estrogen Deficiency On Cardiac Hypertrophy Following Chronic Sympathetic Stimulation, Isabelle Krueger

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of death for both men and women in developed countries. Compared to age-matched males, premenopausal women experience lower rates of CVD but this increases after menopause. A central feature in CVD is changes in sympathetic regulation leading to pathological changes such as cardiac hypertrophy characterized by changes in cardiomyocyte size due to overcompensation of the muscle following injury. The goal of this research is to study the effect of prolonged estrogen loss on cardiac hypertrophy following chronic sympathetic stimulation. Female mice were ovariectomized at 10 weeks of age and treated with Isoproterenol to …

Genetic And Functional Analysis Of Rat Mammary Cancer Susceptibility., Emily L Duderstadt

Electronic Theses and Dissertations

Breast cancer genetic susceptibility is modulated by high to low penetrance risk alleles. Population frequencies of high and moderate penetrant predisposing mutations are rare and responsible for a small percentage of population cases. Most genetic variation in breast cancer susceptibility is low penetrance common variants where causal genes and risk-associated mechanisms are largely unknown. Comparative genetics uses animal models to isolate and mechanistically evaluate genetic susceptibility to human disease. Rat strains have different susceptibility phenotypes to chemical-induced carcinogenesis. Selective breeding and genetic linkage analysis using a 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis model have identified Mammary carcinoma susceptibilityquantitative trait loci …

The Effects Of Differences In Vaccination Rates Across Socioeconomic Groups On The Size Of Measles Outbreaks, Elizabeth Hunter, John D. Kelleher

Conference papers

Vaccination rates are often presented at the level of a country or region. However, within those areas there might be geographic or demographic pockets that have higher or lower vaccination rates. We use an agent-based model designed to simulate the spread of measles in Irish towns to examine if the effectiveness of vaccination rates to reduce disease at a population level is sensitive to the uniformity of vaccinations across socioeconomic groups. We find that when vaccinations are not applied evenly across socioeconomic groups we see more outbreaks and outbreaks with larger magnitudes.

Non-Selective Primary Human Tumor Cell Line Generation From Surgical Resections To Be Paired With Flash Frozen And Paraffin Embedded Tissue: Advancements In Democratizing Translational Research Materials To Rural Institutions, Jennifer Hawkins, Rebecca Russell, Logan M. Lawrence, Amrita Valluri, Jessica Wellman, Krista Denning

Marshall Journal of Medicine

Translational cancer research relies on the availability of human patient tissue demonstrating the specific disease process under investigation. Biobanks of human tissue have historically been and remain to date the primary access point for cancer research samples. Biorepositories routinely supply researchers with varying sample types for use in biomedical studies; most commonly formalin-fixed and paraffin-embedded (FFPE) tissue, or fresh snap-frozen tissue. In conjunction with preserved tissue samples, viable tumor cell lines derived from patient tissue have emerged to be a new gold standard in cancer research particularly in drug discovery and functional prognostic assays. Tissue banks providing these samples are …

Predicting Tumor Response To Radiotherapy Based On Estimation Of Non-Treatment Parameters, Yutian Huang, Allison L. Lewis

Spora: A Journal of Biomathematics

Though clinicians can now collect detailed information about a variety of tumor characteristics as a tumor evolves, it remains difficult to predict the efficacy of a given treatment prior to administration. Additionally, the process of data collection may be invasive and expensive. Thus, the creation of a framework for predicting patient response to treatment using only information collected prior to the start of treatment could be invaluable. In this study, we employ ordinary differential equation models for tumor growth and utilize synthetic data from a cellular automaton model for calibration. We investigate which parameters have the most influence upon treatment …

Using A Hybrid Agent-Based And Equation Based Model To Test School Closure Policies During A Measles Outbreak, Elizabeth Hunter, John D. Kelleher

Articles

Background

In order to be prepared for an infectious disease outbreak it is important to know what interventions will or will not have an impact on reducing the outbreak. While some interventions might have a greater effect in mitigating an outbreak, others might only have a minor effect but all interventions will have a cost in implementation. Estimating the effectiveness of an intervention can be done using computational modelling. In particular, comparing the results of model runs with an intervention in place to control runs where no interventions were used can help to determine what interventions will have the greatest …

Modeling Of Covid-19 Utilizing Various Compartmental Models To Predict Infection Rates Throughout Michigan, Colleen M. Staniszewski

Honors Theses

Compartmental modeling is a method of employing math to create a visual representation of a disease interacting with a select population, typically used in epidemiology analyses. This project applies compartmental modeling equations to data collected on the various aspects of COVID-19 in Michigan. Comparing current data to past predictive models, as well as the visual representations that were developed through the various compartmental modeling methods, allows an assessment of the effects of the preventative measures taken by the state, the various rates at which the infection is able to spread, as well as the potential path and spread of the …

Predictive Modeling And Estimation Of The Doubling Time Of Confirmed Cases Of Covid-19 In Niger, Ibrahim Sidi Zakari, Hadiza Galadima

Community & Environmental Health Faculty Publications

Modeling is increasingly used to assess scenarios and make projections on the future course of new coronavirus disease. This allows for better planning of care as well as a relaxation or tightening of the restrictive measures decreed by the government and the health authorities. The data analyzed in this study covers the period from March 19 to June 05, 2020 and allowed predictions of new cases of COVID-19 based on a growth model with a growth rate that changes linearly over time. In addition, we calculated and predicted the doubling time of the number of positive cases in each region …

Long-Term Dynamics Of The Kidney Disease Epidemic Among Hiv-Infected Individuals, Heather Gudaz, Henry A. Ogu, Elissa J. Schwartz

Spora: A Journal of Biomathematics

One of many risks facing HIV+ individuals is the development of kidney dysfunction and end stage kidney disease (ESKD). A differential equation-based mathematical model was developed to assess the impact of antiretroviral therapy on the progression to kidney disease and on reducing mortality due to kidney failure. Analytical and numerical predictions of long-term HIV+ ESKD prevalence show that therapy can lead to either extremely low levels of disease prevalence or increased prevalence, depending on drug efficacy levels and mechanisms of action. Maintenance of HIV+ ESKD prevalence below one individual is possible with sufficient efficacy (e.g., 99%) against the progression from …