Preclinical Animal Modeling To Investigate Redox-Mediated Molecular Dysfunction In Traumatic Brain Injury, Brandon Z. Mcdonald

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Impacts associated with traumatic brain injury (TBI) induce a multitude of neurological morbidities mediated by a spread of biochemical dysfunction. Redox stress is a significant contributor to TBI pathophysiology and several redox stress markers have substantial evidence to support their role in diagnosing preclinical and clinical TBI. However, there is a critical need to verify their translational utility through correlations with behavioral, imaging, and molecular modalities. In chapter two, we examined the therapeutic efficacy of an antioxidant treatment (NPC3) using a controlled cortical impact (CCI) mouse model of TBI. NPC3 alleviated glial expression and reactivity while influencing the expression of …

Probing The Roles Of Connexin 43 Hemichannels In A Mouse Model Of Alzheimer's Disease, Madison Treasure-Areno

All Graduate Theses and Dissertations, Fall 2023 to Present

Alzheimer’s disease is a progressive disorder involving neuronal death and cognitive decline, such as memory loss and changes in personality. One feature of the disease is buildup of abnormal protein called amyloid-beta in the brain. Amyloid-beta may activate support cells called astrocytes, triggering them to release large amounts of chemicals, possibly harming nearby cells. This study set out to examine the roles of the channels on astrocytes involved in releasing these chemicals, called connexin 43 hemichannels. Using a mouse model of Alzheimer’s disease, this study blocked the hemichannels using the drug Tonabersat, and measured spatial learning and memory in a …

Evidence-Based Practice In Speech-Language Pathology: Creating Effective Therapy Materials, Avalee Dunkley

Undergraduate Honors Capstone Projects

Evidence-based practice is a fairly new topic in speech-language pathology, gaining traction among professionals in the field in the last twenty years. Evidence-based practice is the integration of high-quality research, patient cultural and social values, and clinician expertise to treat a patient. Patients are more likely to progress when these three factors are combined. This paper explores four areas of speech-language pathology that are commonly treated in school-aged children: speech sound disorders, language disorders, social communication disorders, and the use of augmentative and alternative communication. Each section gives a summary of the disorder and how the disorder can be treated …

Establishing Caenorhabditis Elegans As A Platform For Bioaccumulation And Selectivity Screening Of Anthelmintic Compounds, Jiarui Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

To address the cuticular barrier in anthelmintic discovery, this study establishes a bifurcated framework in Caenorhabditis elegans. First, HPLC-based quantification of 14 PIM inhibitors revealed that cuticular penetrance is primarily dictated by phylogenetic lineage (Clade V) rather than ecological niche. Specifically, C. elegans demonstrated a significant pharmacokinetic correlation with the hookworm Ancylostoma ceylanicum (Clade V) but not the whipworm Trichuris muris (Clade I), validating it as a superior surrogate model for hookworm bioaccumulation. Within this small molecule inhibitor library, SGI-12was identified as a lead candidate with superior potency against C. elegans and bioaccumulation. Second, target validation using a C. …

Recommendations For Sharing Cardiovascular Implantable Electronic Device Data With Patients Based On Clinician Interviews, Carly Daley, Jonathan Shirazi, Tina Allmandinger, Mindy Flanagan, Stephanie Pruitt, Hung-Yeh Lin, Victor P. Cornet, Jeanne Carroll, Yi Rong Tan, Tammy Toscos, Michael Mirro

Health Services and Informatics Research

BACKGROUND Cardiovascular implantable electronic devices (CIEDs) capture an abundance of data that requires specific medical knowledge to interpret. Currently, there are no clear recommenda tions for sharing clinically meaningful CIED data with patients from the abundance of data in CIED remote monitoring reports.

OBJECTIVE The objectives of this study were to explore clinicians’ perceptions of clinical care gaps related to CIED data that could be improved through patient access to data and to generate recom mendations for sharing CIED data with patients.

METHODS In this institutional review board-exempt, 2-phase sequential qualitative study, 42 semi-structured phone interviews were conducted with 32 …

Factors Affecting Pedestrian-Vehicle Conflicts: An Empirical Analysis, Christo D. Jamo

Honors Scholar Theses

The number of pedestrian deaths increased by 78% between 2009 and 2023, while other motor vehicle crash deaths increased by 13% in the same period [1]. To identify potential pedestrian safety measures, this study analyzed the effects of location-based demographics, pedestrian phasing type, and other physical infrastructure and behavior variables on the probability of pedestrian-vehicle conflicts at signalized intersections, which is a surrogate measure of crash risk. Data were collected from 55 intersections in Connecticut, and the pedestrian-vehicle interactions were classified by severity based on the Swedish Traffic Conflict Technique: undisturbed passage, potential conflict, minor conflict, or serious conflict. Because …

Play To Win: A Randomized Controlled Trial To Assess The Effects Of Play-Based Training On Upper Extremity Function In Children With Hemiplegia, Vivian London

Honors Scholar Theses

Hemiplegia, or paralysis of one side of the body, is the primary symptom of unilateral cerebral palsy, a subtype of cerebral palsy, the most common movement disorder in children. Standard of care is regular physical and occupational therapy to improve performance in bimanual activities, but conventional therapy can be expensive and draining for caregivers and children, so a need exists for a novel intervention that can take place at home and that is economical for families while being engaging for children. This thesis reports data from a subset of ten children seen as part of a randomized controlled clinical trial …

The Development Of A Crispr-Based Calibrated Functional Assay For Classifying Pathogenicity Of Msh2 And Msh6 Variants In Lynch Syndrome, Olivia N. Amodeo

Honors Scholar Theses

Lynch syndrome is a hereditary disease caused by the inheritance of a mismatch repair gene variant. Individuals with this condition are predisposed to cancer development, most commonly colorectal cancer. Current guidelines for variant classification are based on numerous evidence categories, including functional evidence. However, many novel clinical variants are not well characterized, and evidence is difficult to obtain if functional assays are not calibrated.

To address this, our lab created a calibrated functional assay that calculates an odds of pathogenicity score for MSH2 and MSH6 gene variants that can be used as evidence for classifying variants of uncertain significance. This …

Cultural Adaptation Of A Single Session Acceptance And Commitment Therapy Guide For College Students In Uganda, Miriam Mukasa Kasozi

All Graduate Theses and Dissertations, Fall 2023 to Present

Mental health problems such as depression, anxiety, and stress are common among Ugandan university students and can make it difficult for them to succeed in school or maintain well-being. However, many students do not have access to professional mental health care. Digital self-help programs can make support more available, especially when they are designed to fit the local culture and context. This project examined how an online program called ACT Guide Lite, which teaches skills from Acceptance and Commitment Therapy (ACT), could be adapted for use with Ugandan college students. Students and other university community members first completed the program …

Dyadic Agreement In And Task Correlates To A Measurement Of Conversational Success, Samantha Budge

All Graduate Theses and Dissertations, Fall 2023 to Present

Successful conversation matters for social connection, wellbeing, and quality of life, but people do not always agree on whether a conversation was successful, even when they participated in the same interaction. Conversation is also commonly measured through task success, even though it’s unclear how task success correlates to how successful a conversation feels. This study examined how conversational success is experienced by different conversation partners and whether feeling successful in a conversation is related to how well a task is completed.

Participants took part in a structured conversational task and then rated their own conversational experience using a self-report questionnaire …

Mechanisms Of Synergy Between Nanosecond Pulsed Electric Field (Nspef) And Cold Atmospheric Pressure Plasma Discharge (Cap) In Pancreatic Cancer: The Role Of Ros-Mediated Oxidative Stress And Apoptosis, Zobia Minhas

Biomedical Sciences Theses & Dissertations

Pancreatic ductal adenocarcinoma is a highly lethal malignancy characterized by poor prognosis and resistance to conventional therapies. Novel treatment strategies are needed to overcome this resistance. Non-thermal physical modalities, including nanosecond pulsed electric field (nsPEF) and cold atmospheric pressure plasma discharge (CAP), have emerged as potential anticancer approaches; however, the mechanisms underlying their combined effects remain unclear.

This study evaluated whether nsPEF enhances CAP-induced cytotoxicity and investigated the associated molecular mechanisms using the murine Pan02 pancreatic cancer cell line. Cell viability was assessed by WST-1 metabolic activity assays and electric cell–substrate impedance sensing (ECIS). Intracellular reactive oxygen species (ROS) were …

University Student Mental Health: Service Utilization, Equity Gaps, And Strategies To Improve Access, Richard Mutua Kilonzo

Electronic Theses and Dissertations

Student mental health and access to care are pressing concerns in higher education. This study assesses mental health outcomes and access to campus mental health services at East Tennessee State University. Survey data from the 2023–2024 Healthy Minds Study were analyzed to report the prevalence of depression, anxiety, and suicidal ideation across the student population. The study evaluates disparities in these outcomes and barriers to care across student groups, with particular attention to equity-impacted students, especially sexual and gender minority students.

Findings indicate widespread psychological distress alongside persistent barriers, including long wait times, limited-service availability, and stigma-related concerns. These barriers …

Ligand-Based Pharmacophore Modeling And Structure-Based Virtual Screening For Identifying Potential Therapeutic Agents Targeting The Sars-Cov-2 Spike Protein-Ace2 Receptor Interaction, Timoteo Delgado-Maldonado, Gilberto Vargas-Salas, Debasish Bandyopadhyay, Adriana Moreno-Rodriguez, Eyra Ortiz-Pérez, Gildardo Rivera-Sanchez

School of Integrative Biological & Chemical Sciences Faculty Publications

Coronavirus disease (COVID-19) remains a global health concern due to its high mortality and morbidity. In this study, we combined ligand-based pharmacophore modeling (LBPM) with structure-based virtual screening (SBVS) to identify novel inhibitors targeting the SARS-CoV-2 spike protein. Ligands from the MolPort database were screened via docking and molecular dynamics simulations at the receptor-binding domain (RBD). Four compounds showed promising docking scores (-8.7 to -6.4 kcal/mol) and dynamic stability (root mean square deviation < 5 Å). In vitro assays confirmed that compounds C3 (IC50 = 0.03 µM) and C4 (IC50 = 10.4 µM) effectively inhibited spike-ACE2 binding with low cytotoxicity (CC50 > 100 µM). These findings show the efficacy of the LBPM technique and highlight 1H-pyrazol-5-ol derivatives as potential building blocks for developing new antiviral agents against SARS-CoV-2.

How Are Women Dealing With Polycystic Ovary Syndrome?, Adrianna A. Brown

Electronic Theses, Projects, and Dissertations

Background and Aims: PCOS is one of the leading multisystem conditions among women of reproductive age. Dietary changes may help improve outcomes associated with PCOS and its comorbidities. While a lower carbohydrate, moderate protein diet is often recommended, those with PCOS often use temporary diets or dietary supplements instead of or in addition to prescription medications due to dissatisfaction with their treatment options. Additionally, studies examining the usefulness of supplements and their effects on PCOS symptoms are lacking. This study explored the prevalence of use of temporary diets, prescription medications, and dietary supplements among women with PCOS.

Methods: An anonymous …

Effects Of A Passive Assistive Hamstring Device On Overground Running Kinematics And Hamstring Activation., Quinn Castner

All Theses

Hamstring strain injuries are among the most common and recurring injuries in sports, occurring most often during the terminal swing phase of gait. Despite progress in rehabilitation, the incidence of injury has only increased, suggesting a need for a novel intervention. We designed a passive, assistive, wearable device with two specific criteria in mind: to offload the hamstrings during running, and do so without hindering normal kinematic patterns. The device consists of an adjustable elastic band anchored proximally at the waist and distally just above the ankle joint center. It stretches and shortens with the hamstrings, providing passive hip extension …

Fluorescence-Based Quantification Of Hepatic Ldl Uptake And Donor Hepatocyte Engraftment Using Atto 700–Labeled Ldl, Victor Agustin Cortes Flores

All Theses

Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) that increases the risk of premature atherosclerotic cardiovascular disease. In severe FH, including low-density lipoprotein receptor (LDLR), hepatic LDL clearance is profoundly impaired and many lipid lowering treatment strategies have limited effectiveness. Current advances in ex vivo CRISPR–Cas9 hepatocyte gene editing in vivo and ex vivo approaches for treatment of FH are under development.

However, a central barrier to translation is the ability to quantitatively measure the percentage of healthy gen edited hepatocytes in the liver while simultaneously assessing functional hepatic LDL handling. This thesis establishes …

Technical Development, Optimization, And Clinical Implementation Of Quantitative Magnetic Resonance Imaging Methods For Radiation Oncology, Lucas Mccullum

Dissertations and Theses (Open Access)

Magnetic resonance imaging (MRI) has gradually grown more important in the field of radiation oncology. This paradigm shift has grown from initial experiments with MRI of cancerous lesions in the early 1970s, to the integration of MRI images for radiation therapy treatment planning (i.e., MRI-Simulation) in the early 1980s, to the combined MRI linear accelerator (MR-Linac) becoming commercially available in 2018 which can simultaneously image a tumor and treat it with radiation. However, due to its novelty in radiation oncology, its full potential for the integration of quantitative MRI-based biomarkers has yet to be fully realized.

Therefore, this dissertation will …

An Integrated Framework For Early Detection And Transmissibility Assessment Of Emerging Variants In Wastewater, Xingwen Chen, Tin Phan, Wei Lin Lee, Katie Clark, Steven F Rhode, Samantha Brozak, Bruce Pell, Tsultrim Palden, Mats Leifels, Anna Gitter, Yang Kuang, Stefan Wuertz, Janelle Thompson, Kristina D Mena, Eric J Alm, Fuqing Wu

Faculty, Staff and Student Publications

Tracking the emergence of new viral variants is critical for epidemic preparedness, but remains challenging because variants typically circulate at low prevalence during the early phase of outbreaks. Here, we present an integrated framework that combines sensitive variant detection in wastewater with quantitative assessment of transmissibility through dynamic epidemic modeling. Using the SARS-CoV-2 Omicron variant as a proof of concept, we developed a novel nested allele-specific RT-qPCR assay (NAS-PCR) that achieved a thousand-fold increase in sensitivity compared with allele-specific RT-qPCR (limit of detection: 0.5 copies/μl). NAS-PCR detected Omicron in wastewater samples from the Greater Boston area starting in September 2021, …

Associations Of Blood Biomarkers Of Glial Cell Dysfunction And Neuronal Injury With Future Cognitive Decline And Incident Dementia, Srishti Shrestha, Xiaoqian Zhu, B Gwen Windham, Kevin J Sullivan, Priya Palta, Rebecca F Gottesman, Russell P Tracy, Clifford R Jack, Petrice M Cogswell, Prashanthi Vemuri, Sudha Seshadri, Thomas H Mosley, Michael E Griswold, Myriam Fornage

Faculty, Staff and Student Publications

Introduction: Prospective studies of blood-based biomarkers reflecting pathogenic processes, other than Alzheimer-specific pathologies, that contribute to dementia in diverse cohorts are lacking.

Methods: We jointly fitted linear mixed-effect models and proportional hazards models to examine associations of midlife glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL-40), soluble cluster of differentiation-14 (sCD14), neurofilament light chain (NfL), total tau (t-tau), and ubiquitin C-terminal hydrolase L1 (UCHL1) levels in serum (collected in 1993 to 1995) with cognitive decline and incident dementia (ascertained over 29 years through 2022) in the community-based Atherosclerosis Risk in Communities Study. sCD14 and YKL-40 were measured in 3082 …

A Bilingual Ai-Based Chatbot For Nutrition Education In A Food Is Medicine Intervention For High-Risk Pregnant Women: Design And Development Study, Lorena Macias-Navarro, Nalini Ranjit, Gregory W Bounds, Brendon A Providence, Yesmeena Shmaitelly, Naomi M Tice, Shreela V Sharma

Faculty, Staff and Student Publications

Background: Conversational agents (artificial intelligence [AI]-based chatbots) offer a novel approach to health interventions by providing personalized, adaptive interactions that improve over time based on user engagement. In nutrition education, given the wide variation in knowledge, skills, and abilities across participants, AI-based chatbots have the potential to enhance accessibility, engagement, and behavior change. Food is Medicine (FIM) interventions, which aim to improve food security and diet quality among multicultural, at-risk populations, often face challenges related to sustained engagement and use.

Objective: This paper describes the design, development, and iterative refinement of a bilingual AI-driven nutrition chatbot integrated into an FIM …

In-Vitro Testing Of Light Wavelength To Detect Clots In Neonatal Extracorporeal Membrane Oxygenation Circuitry, Amanda Holmes

Dissertations and Theses (Open Access)

Background: Neonates requiring extracorporeal membrane oxygenation (ECMO) are at high risk for thrombotic complications, which contribute substantially to morbidity and mortality. Current circuit surveillance methods rely on intermittent visual inspection and indirect laboratory markers, both of which often detect thrombosis only after clinically significant progression. Optical approaches offer a non-invasive alternative for earlier clot visualization, yet the influence of illumination wavelength on detection performance under realistic ECMO conditions remains incompletely characterized.

Methods: This study evaluated wavelength-dependent clot detection performance in a controlled in-vitro neonatal ECMO circuit model using a portable imaging prototype designed to emulate bedside workflow. Twelve independent ECMO …

Towards Dementia-Inclusive Digital Text-Based Health Information: A Multi-Method Investigation Of Cognitive And Affective Accessibility, Margi Engineer

All Dissertations

This dissertation examines the accessibility, readability, emotional tone, and trustworthiness of digital, text‑based dementia information and investigates how older adults with and without dementia cognitively and affectively engage with such content. It further explores the potential of generative AI to improve dementia information delivery through the development of a domain‑specific retrieval‑augmented generation (RAG) large language model (LLM) chatbot designed to deliver accessible, stigma‑free information. The dissertation comprises four studies using complementary quantitative and qualitative methods. Study I conducts a large‑scale content analysis of 300 medical articles, 35 websites, and 50 blogs, applying readability metrics, LIWC‑based linguistic and sentiment analysis, and …

Neurointerventional Advances In 2025, Amol Mehta, Sunil A Sheth, Ashutosh P Jadhav

Faculty, Staff and Student Publications

No abstract provided.

Computational Modeling Meets 3d Bioprinting: Emerging Synergies In Cardiovascular Disease Modeling, Tanmay Mukherjee, Mehdi Salar Amoli, Sarah Rezapourdamanab, Lama Rita El Shammas, Martin L Tomov, Emilio A Mendiola, Vahid Serpooshan, Reza Avazmohammadi

Faculty, Staff and Student Publications

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, underscoring the need for improved strategies in diagnosis, treatment, and disease modeling. Traditional in vitro models often fall short in replicating human CV physiology, prompting efforts to advance cardiac tissue engineering and computational modeling. Among these, three-dimensional (3D) bioprinting has emerged as a transformative tool, enabling the creation of biomimetic CV constructs that more faithfully replicate native tissue structure and function. However, challenges persist in achieving appropriate mechanical properties and long-term performance of engineered CV constructs. Computational modeling offers powerful solutions to assist with these challenges, providing predictive insights into …

Role Of Allied Health Professions In Falls Prevention For Community-Dwelling Older Adults: A Scoping Review, Amy Lawton, Nicholas Tripodi, Rebecca Wospil, Breanna M. Wright, Hylton B. Menz, Suzanne Martin, Daniel R. Bonanno, Corey Linton, Andisheh Bastani, Andrew Ross, Rees Thomas, Daniel Corcoran, Timothy Mcnamara, Danielle Baxter, Brett Vaughan, Rebecca Lane, Jack Feehan

Research outputs 2022 to 2026

Objective: Falls among community-dwelling older adults are prevalent and have serious individual, societal and economic consequences. Allied health professionals provide key falls prevention interventions yet their representation in current clinical practice guidelines is inconsistent. Increased recognition of allied health roles and delivering context-specific guidelines for falls care could help to address workforce gaps and optimise care approaches. This scoping review explored the roles of the allied health professions in falls prevention screening, assessment and intervention for community-dwelling older adults. Design: Scoping review, using the Joanna Briggs Institute methodology for scoping reviews. Data sources: PubMed, CINAHL, Scopus, Cochrane, Web of Science …

Most-Favored-Nation Benchmarking Versus Value-Based Contracting: Institutional Fit Of Pharmaceutical Pricing Tools In The United States, Canada, And The United Kingdom, Kola Adegoke, Olajide Alfred Durojaye, Abimbola Adegoke, Adeyinka Adegoke

Health & Biomedical Sciences Faculty Publications

Background: Soaring drug prices pose a significant obstacle to affordable and equitable access to medicines in high-income healthcare systems. This study compares two leading reform tool families, Most Favored Nation (MFN)/international reference pricing (IRP) and value-based contracting (VBC), across the United States, Canada, and the United Kingdom, with attention to cost containment, value-linked incentive design, equity of access, and implementation feasibility. U.S. policy developments (CMS Innovation Center’s GENEROUS, GLOBE, and GUARD models) extend international benchmark-based design options beyond the 2020 MFN rule.

Methods: Guided by institutional and governance theories, we conducted a structured comparative policy analysis using a four-dimensional trade-off …

Factors Influencing Patient Recall For Follow-Up In The Multi-Stage Deployment Of Medical Intelligent Screening Systems, Wenjie Chen

Dissertations and Theses Collection (Open Access)

With the deep integration of artificial intelligence (AI) technology in the healthcare sector, intelligent screening systems have achieved significant breakthroughs in predictive accuracy; however, they commonly face a management challenge in clinical implementation: accurate early warnings but limited patient recall. To address this ineffective technological empowerment issue in practice, this study proposes a theoretical framework featuringbidirectional interactions between "technological empowerment" and"relational empowerment" based on empowerment theory to systematicallyinvestigate the dynamic evolution mechanisms and boundary conditions of patient recall willingness under multi-stage, cross-departmental deployment of medical intelligent screening systems. Using a leading municipal hospital as the primary experimental setting, the study …

Ai-Powered Insights In Pediatric Nephrology: Current Applications And Future Opportunities., Arwa Nada, Yamen Ahmed, Jieji Hu, Darcy K. Weidemann, Gregory H. Gorman, Eva Glenn Lecea, Ibrahim A. Sandokji, Stephen Cha, Stella Shin, Salar Bani-Hani, Sai Sudha Mannemuddhu, Rebecca L. Ruebner, Aadil Kakajiwala, Rupesh Raina, Roshan George, Rim Elchaki, Michael L. Moritz, The American Society Of Pediatric Nephrology Quality Improvement And Artificial Intelligence (Aspn Qi/Ai) Interest Group

Manuscripts, Articles, Book Chapters and Other Papers

Artificial intelligence (AI) is rapidly emerging as a transformative force in pediatric nephrology, enabling improvements in diagnostic accuracy, therapeutic precision, and operational workflows. By integrating diverse datasets-including patient histories, genomics, imaging, and longitudinal clinical records-AI-driven tools can detect subtle kidney anomalies, predict acute kidney injury, and forecast disease progression. Deep learning models, for instance, have demonstrated the potential to enhance ultrasound interpretations, refine kidney biopsy assessments, and streamline pathology evaluations. Coupled with robust decision support systems, these innovations also optimize medication dosing and dialysis regimens, ultimately improving patient outcomes. AI-powered chatbots hold promise for improving patient engagement and adherence, while …

Development Of Low-Cost Triaxial Force Sensor For Measurement Of Human-Exoskeleton Interaction Forces, Hamdan Khan Sarvathullah

All Theses

Contemporary research suggests that shear force is a major contributor to discomfort and pressure injury. However, the variation of shear forces during human-exoskeleton interaction dynamics is a highly unexplored field. The high cost of commercial triaxial force sensors may be a major factor in the notable lack of research in this field. Therefore, in this paper, we present a low-cost, 3D-printed triaxial force sensor designed specifically to measure the triaxial interaction forces between an exoskeleton and its user. The triaxial force sensor uses Carbon-Black/Silicone Rubber (CB/SR) strings to measure shear forces, whereas the normal force is measured with a Force …

Mif-Cd74 Signaling Drives Immune Modulation In Medulloblastoma, Benjamin Draper, Zhen You, Dean Thompson, Xu Guo, Alaide Morcavallo, Diego Chillon Pino, Carlos Lorenzo Gido Nery, Sumana Shrestha, Chantelle E Bowers, Courtney Himsworth, Alberto Delaidelli, Bethany Remeniuk, Sonia Morlando, Brandon Wade, Freya Gordon, Yara Sanchez-Corrales, Bei Hopkins, Natalie Monteiro, Darren Locke, Miao Liu, Jacob Torrejon Diaz, Kevin Greenslade, Barbara Martins Da Costa, Karen Barker, Colin Kwok, Olumide Ogunbiyi, Anya Fletcher, Stacey Richardson, Carlos Custodia, Rafael Roque, Thomas Jackson, Regan Barfoot, Sergi Castellano, Rebecca M Hill, Olivier Saulnier, Thomas S Jacques, Michael D Taylor, Claudia C Faria, Olivier Ayrault, Poul H Sorensen, John Anderson, Louis Chesler, L Frank Huang, Steven C Clifford, Laura K Donovan

Faculty, Staff and Students Publications

Background: Relapsed medulloblastoma remains a significant therapeutic challenge as it is near universally fatal. The tumor microenvironment of medulloblastoma plays a critical role in tumor progression, influencing tumor growth, immune evasion, and therapeutic resistance. We hypothesized that defining tumor-immune interactions in diagnostic and relapsed medulloblastoma may uncover mechanisms of immune evasion and identify novel therapeutic targets.

Methods: We analyzed paired primary and recurrent RNA-sequencing data from 140 medulloblastoma patients to profile immune cell composition and validate spatial relationships within the TME. To identify key tumor-immune interactions, we developed a novel algorithm to detect receptor-ligand pairs using single-cell RNA-sequencing data. These …