Disease Modeling Commons^™

The Epigenetic Effects Of Prenatal Diabetes On The Developing Vascular System- A Gsea Analysis, Daniel I. Telles Orellana

SPARK Symposium Presentations

Prenatal diabetes is a critical medical condition that extensively affects neonatal patients and their families. Numerous previous studies have suggested impairments in vascular development, size, and diversification; however, the molecular and gene regulatory mechanisms underlying these effects remain poorly understood. Understanding these mechanisms is essential for identifying potential therapeutic targets and improving treatment strategies. This study combined experimental zebrafish phenotypic analysis with re-analysis of publicly available RNA-seq data to investigate the effects of elevated glucose on embryonic vascular development. Zebrafish (Danio rerio) embryos were exposed to increasing glucose concentrations (1–3%) during early developmental stages. High glucose exposure showed …

Stimulation Of The Medial Septum Diagonal Band Of Broca Rescues Learning And Memory Deficits In Fmr1 Ko Mice, Mohamed Ouardouz, Amanda E Hernan, J. Matthew Mahoney, Rodney C Scott

SKMC Student Presentations and Publications

Fragile X Syndrome (FXS), the most common inherited cause of intellectual disability and a leading monogenic cause of autism, arises from the loss of Fragile X Messenger Ribonucleoprotein (Fmr protein), leading to synaptic and cognitive dysfunction. Here, we demonstrate that the frequency-specific electrical stimulation of the medial septum/diagonal band of Broca (MSDB) can restore cognitive and synaptic impairments in Fmr1 knockout mice, a validated model of FXS. Thirty minutes of 35 Hz MSDB stimulation significantly improved subsequent recognition memory, sociability, spatial learning, and fear memory, with recognition memory enhancements persisting for up to 7 days after daily 30 min …

Oropharyngeal Syphilis Presenting As Tongue Based Ulcer With Lymphadenopathy, Serena F. Pu, Kevin J. Carlson, Jonathan R. Mark, Benjamin J. Rubinstein

Department of Otolaryngology (ENT) Faculty Publications

Within the aerodigestive tract, syphilis presents with varied signs and symptoms, some of which may mimic malignancy or other disease processes. We present the case of a 29-year-old man with otalgia and odynophagia who was found on physical examination and office laryngoscopy to have a 4-cm ulcerative mass of the tongue base and cervical lymphadenopathy. While planning for tissue diagnosis, the patient’s serologies revealed positive treponemal antibody testing and elevated rapid plasma reagin (RPR) titers, confirming syphilitic infection, likely representing secondary syphilis. While awaiting operative biopsy, the patient received intramuscular penicillin with complete resolution of the mass and symptoms, and …

Paneugenesis: A Regenerative Systems Hypothesis For Advancing Health Promotion, Craig M. Becker, Leslie Hoglund, Beth Chaney, Joseph G. L. Lee, Michael Stellefson, Alex Davis

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Despite major advances in health promotion science, dominant approaches remain largely prevention-and risk-reduction-oriented. The prevailing orientation creates a substantial opportunity to advance generative, system-design strategies that intentionally produce well-being rather than merely prevent disease. This article proposes paneugenesis as a regenerative systems framework and a testable theoretical model for the intentional creation of net-positive outcomes, thereby extending health promotion beyond its traditional pathogenic emphasis. Paneugenesis integrates systems science, salutogenesis, behavioral science, complexity theory, and quality management principles into a unified four-function process: operationalizing idealized outcomes, identifying key precursors, optimizing processes, and continually plotting progress through feedback mechanisms. The central hypothesis …

A Scoping Review To Conceptualize Social Privilege For Studying Patients' Health Outcomes And Health Disparities, Elizabeth A. Brown, Priyanka Patel, Esther May B. Sarino, Vladimir Markovic, Carles Muntaner

Health Behavior, Policy & Management Faculty Publications

Background

The continued reliance on single-category self-reported demographic data (e.g., race/ethnicity) reflects conceptual limitations that hinder the study and understanding of health outcomes research. There is a pressing need for more precise measures of social privilege that conceptualize privilege and oppression while enabling the examination of their effects on health outcomes in the United States (US) healthcare system.

Objective

The purpose of this scoping review was to review the literature, determine how researchers have measured aspects of privilege and oppression, and develop a conceptual framework to study patients' social privilege in the US healthcare system and public health research.

Methods …

The Crucial Role Of Machine Learning Models In Predicting Current Childhood Asthma: Model Comparison, Calibration, And Shap-Based Interpretation, Aditya Chakraborty, A. K.M. Raquibul Bashar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background: Asthma is one of the most prominent chronic diseases in children and one of the most challenging ailments to diagnose in infants and preschoolers in the United States. Predictive models can be instrumental in improving early diagnosis, personalized treatment strategies, and disease progression. By utilizing nationalized data, this study focuses on building and comparing high-performing analytical predictive models based on the relevant risk factors and identifying the most influential predictors.

Methods: We analyzed cross-sectional BRFSS Asthma Call-Back Survey data (2011-2020; N = 9,813) and randomly split participants into training and testing sets. An XGBoost model (hyperparameters tuned via grid …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …

Facial Analytics Based On A Coordinate Extrapolation System (Zface) For Morphometric Phenotyping Of Developing Zebrafish, Lorena Maili, Oscar E Ruiz, Philip H Kahan, Frankie Chiu, Stephen T Larson, S Shahrukh Hashmi, Jacqueline T Hecht, George T Eisenhoffer

Faculty, Staff and Student Publications

Facial development requires a complex and coordinated series of cellular events that, when perturbed, can lead to structural birth defects. A quantitative approach to quickly assess morphological changes could address how genetic or environmental inputs lead to differences in facial shape and promote malformations. Here, we report on a method to rapidly analyze craniofacial development in zebrafish embryos using facial analytics based on a coordinate extrapolation system, termed zFACE. Confocal images capture facial structures and morphometric data are quantified based on anatomical landmarks present during development. The quantitative morphometric data can detect phenotypic variation and inform on changes in facial …

A Look Into The Physiological Impacts Of Childhood Cancers And Modeling Of Tumor Growth Rate, Erica Steiner, Kimberly Hansen, Marissa Stanton

Honors Program: Senior Projects (Public)

Cancer is one of the deadliest diseases present in the world. Children have different reactions to diseases and treatments; thus, it is important to study those reactions specifically in children. Knowing how children are impacted by these factors can be helpful in diagnosis and treatment of cancer. I performed this study by researching the different types of cancer I was interested in and using MATLAB to code for and simulate a growth curve of a brain tumor. I found that there are many different physiological impacts of different cancers in children. As for the modeling, I was able to get …

Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow …

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …

Marineepi: A Gui-Based Matlab Toolbox To Simulate Marine Pathogen Transmission, Gorka Bidegain, Tal Ben-Horin, Eric N. Powell, John M. Klinck, Eileen E. Hofmann

CCPO Publications

The Graphical User Interface (GUI) MarineEpi is presented as a Matlab toolbox for easily (i) constructing disease transmission models for different marine host-pathogen systems, (ii) running simulations by specifying initial conditions and model parameters, and (iii) interpreting the resulting time series of the host and pathogen population dynamics. MarineEpi users can generate models for systems in which pathogen transmission occurs through contact with infected individuals (SI), contact with dead infected individuals (SID), contact with environmental pathogens released by infected individuals (SIP), and contact with environmental pathogens released by dead infected individuals (SIPD). MarineEpi is a freely available GUI that provides …

Heart Disease Prediction Using Stacking Model With Balancing Techniques And Dimensionality Reduction, Ayesha Noor, Nadeem Javaid, Nabil Alrajeh, Babar Mansoor, Ali Khaqan, Safdar Hussain Bouk

School of Cybersecurity Faculty Publications

Heart disease is a serious worldwide health issue with wide-reaching effects. Since heart disease is one of the leading causes of mortality worldwide, early detection is crucial. Emerging technologies like Machine Learning (ML) are currently being actively used by the biomedical, healthcare, and health prediction industries. PaRSEL, a new stacking model is proposed in this research, that combines four classifiers, Passive Aggressive Classifier (PAC), Ridge Classifier (RC), Stochastic Gradient Descent Classifier (SGDC), and eXtreme Gradient Boosting (XGBoost), at the base layer, and LogitBoost is deployed for the final predictions at the meta layer. The imbalanced and irrelevant features in the …

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 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 …

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. …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

University Scholar Projects

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

Honors Scholar Theses

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …