Medicine and Health Sciences Commons^™

Herbivore Identity And Species Richness Shape Fruit Chemical And Quality Responses To Foliar Herbivory, Xavier Ozowara, Taylor M. Sloey, Susan R. Whitehead

Biological Sciences Faculty Publications

The cascading consequences of foliar herbivory on fruit chemistry and quality remain relatively underexplored, with most existing studies focusing on the effects of only one or two attackers. In this study, we examine how increasing herbivore species richness during foliar herbivory alters strawberry (Fragaria × ananassa Duch) fruit quality and phenolic chemistry. We conducted a greenhouse experiment with single species feeding and different combinations of feeding by three generalist lepidopteran species: Spodoptera frugiperda, Heliothis virescens, Helicoverpa zea. Species fed on leaves for 72 h as fruits ripened, and fully ripe fruits were harvested 72 h after …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ticks secrete several molecules, including lipocalins, in their saliva during blood feeding on a vertebrate host. In this study, we provide novel evidence on the role of Ornithodoros turicata americanus tick lipocalin (Otlip) in modulating cytokine expression and in triggering apoptosis in mammalian macrophages and keratinocytes. The cytokine array analysis revealed significantly increased secretion of insulin-like growth factor-binding protein 3 (IGFBP3) from murine macrophage cell line upon treatment with recombinant Otlip protein (rGST-Otlip) when compared to the secretion noted from cells treated with a control protein (rGST). Similar observation with cytokine protein array analysis was noted when murine macrophages were …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …

Optimal Control Analysis Of Malaria Transmission In The Presence Of Insecticide Resistance And Climate Variability In Kenya, Lorna Chepkemoi, Titus Okello Orwa, Samuel Mwalili, Rachel Waema Mbogo, Steeven Belvinos Affognon, Daisy Salifu, Henri E.Z. Tonnang

All Peer-Reviewed Publications

Malaria remains a major public health concern in Kenya, where changing climatic conditions, insecticide resistance, and mosquito behavioral adaptations continue to challenge control efforts. This study develops and analyzes a climate-sensitive malaria transmission model that incorporates mosquito behavior, insecticide resistance, and vector–human ecological dynamics to identify optimal control strategies for the Kenyan context. The model’s well-posedness was established, the basic reproduction number (R0) computed using the next-generation matrix method, and the stability of equilibrium points assessed. Spatial analysis of R0 was performed using temperature and rainfall raster data to map transmission risk across Kenya under varying insecticide use scenarios. Results …

Genomic Determinants Of Response And Resistance To Pirtobrutinib In Relapsed/Refractory Chronic Lymphocytic Leukemia, Jennifer R Brown, Bastien Nguyen, Sai Prasad Desikan, Helen Won, Shady I Tantawy, Samuel C Mcneely, Narasimha Marella, Hetal S Randeria, Lauren M Hanson, Andrew Parker, Salomé Calado Botelho, Jennifer A Woyach, Krish Patel, Constantine S Tam, Toby A Eyre, Chan Y Cheah, Nirav N Shah, Paolo Ghia, Wojciech Jurczak, Minna Balbas, Binoj Nair, Paolo Abada, Chunxiao Wang, Denise Wang, Lindsey E Roeker, Varsha Gandhi, William G Wierda

Faculty, Staff and Student Publications

Pirtobrutinib, a noncovalent, reversible Bruton tyrosine kinase inhibitor (BTKi), demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), resistant to covalent BTKi (cBTKi). We analyzed genomic correlations with response and resistance to pirtobrutinib in relapsed/refractory (R/R) patients with CLL pretreated with cBTKi enrolled in the phase 1/2 BRUIN trial. DNA sequencing was performed on peripheral blood mononuclear cells at baseline, on treatment, and at progressive disease (PD). Common alterations at baseline included mutations in BTK (43%), TP53 (38%), SF3B1 (25%), NOTCH1 (23%), ATM (19%), XPO1 (11%), PLCG2 (9%), BCL2 (8%), and 17p deletion (28%). Common baseline BTK mutations included C481S …

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Organized Sports-Based Interventions And Motor Outcomes In Children Diagnosed With Autism Spectrum Disorder: A Systematic Review, Kailash Ram, Maeren Hill, Caitlyn Stewart, Kaitlin P. Hardy Md, Sonia Khurana

Rehabilitation Sciences Faculty Publications

Aim

To evaluate the effectiveness of organized sports-based interventions on motor outcomes in children with autism spectrum disorder (ASD).

Method

Four databases were searched from inception to November 2025 for randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) reporting motor outcomes of organized sports-based interventions in children with ASD. Risk of bias was evaluated using ROB-2 (Cochrane Risk of Bias Tool, Version Two) for RCTs and ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) for NRCTs.

Results

Eleven studies (six RCTs, five NRCTs) were included and categorized as martial arts (n = 5), aquatic training (n = …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Uncertainty-Guided Test-Time Optimization For Personalizing Segmentation Models In Longitudinal Medical Imaging, Jaehee Chun, Austin Castelo, Mckell Woodland, Caleb O'Connor, Mais Al Taie, Mohamed Eltaher, Aashish Gupta, Bilel Daoud, Shanli Ding, Jeddy Bennett, Anirban Maitra, Matthew A Firpo, Kimberly Kirkwood, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Background: Accurate and consistent image segmentation across longitudinal scans is essential in many clinical applications, including surveillance, treatment monitoring, and adaptive interventions. While personalized model adaptation using patient-specific prior scans has shown promise, current approaches typically rely on fixed training durations and lack mechanisms to determine optimal stopping points on a per-patient basis, particularly in the absence of validation labels.

Purpose: We propose an uncertainty-guided test-time optimization (TTO) framework that dynamically adjusts the personalization duration for each patient using a validation-free stopping criterion based on predictive uncertainty.

Methods: Our framework personalizes a generalized segmentation model using patient-specific prior imaging and …

Contralateral Breast Cancer After Radiotherapy And Hormone Therapy In Two Cohorts Of Us Breast Cancer Survivors, Lene H S Veiga, Gretchen L Gierach, Susan A Smith, Rebecca M Howell, Matthew M Mille, Monjoy Saha, Rochelle E Curtis, Cody Ramin, Clara Bodelon, Heather Spencer Feigelson, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Jacqueline B Vo, Choonsik Lee, Amy Berrington De Gonzalez

Faculty, Staff and Student Publications

Background: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

Methods: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use.

Results: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); SEER cohort (n = 244,834) included 10,470 cases (72% ER+). Among women with ER+ …

Host Modulation Therapy In Periodontitis: From Established Therapies To Emerging Technologies, Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, Simon Young, Chun-Teh Lee

Faculty, Staff and Student Publications

Periodontitis is a biofilm-induced chronic inflammatory disease, characterized by gingival inflammation and alveolar bone loss. According to a national survey, approximately half of the U.S. adults are affected by periodontal disease. To effectively prevent and treat periodontitis, it is essential to address its underlying causes. The primary etiological factors include polymicrobial synergy and dysbiosis of the oral microbiota, and a dysregulated immune response. The standard therapeutic approach, mechanical removal of biofilm through debridement, sometimes demonstrates limited efficacy, particularly in cases of severe periodontitis, which may require adjunctive or additional therapy. Emerging evidence indicates that periodontal tissue destruction is initiated by …

Single-Cell Transciptomic Analysis Reveals Age-Related Remodeling Of Brain Endothelial Cells, Hai Duc Nguyen, Summer Siddiqui, Diana G. Bohannon, Robert V. Blair, Hong-Wen Deng, Alexandre Prat, Woong-Ki Kim

Microbiology & Molecular Cell Biology Faculty Publications

Blood–brain barrier (BBB) integrity naturally declines with age. Brain endothelial cells (ECs) and pericytes (PCs) form the BBB, and aging impairs tight junctions, likely via altered PC-to-EC signaling. However, the molecular mechanisms underlying this impairment remain unclear. Using single-cell RNA sequencing, we profiled 68,316 brain ECs expressing 15,564 genes from young and old mice. Unsupervised clustering and annotation revealed five distinct EC subtypes—Capillary EC1, Capillary EC2, Arterial EC, Venous EC1, and Venous EC2—defined by marker genes Mfsd2a, Plvap, Bmx, Nr2f2, and Vcam1, respectively. Aging shifted EC subtype distribution, with reduced Capillary EC1 (45% vs. 57%) and increased Arterial …

Dietitian-Led Nutrition Care Across The Cellular Therapy Continuum Supports Weight And Strength Recovery, Ashley Pagano Ms, Rdn, Ldn, Samantha Okerson Rdn, Erin Levine Rd, Cso, Ldn, Deanna Yerg Ms, Rdn, Ldn

Clinical Nutrition Service

No abstract provided.

High-Osmolality Medication Exposure And Length Of Stay In Icu Patients With Rectal Tubes, Kimberly Cephas Ms, Rdn, Ldn, Rachel Geosits Ms, Rdn, Cnsc, Ldn, Matthew Fair Pharmd, Hope Kincaid Mph, Cph, Alison Sutter Mph

Clinical Nutrition Service

No abstract provided.

A Systematic Review And Meta-Analysis Of Mosquito Arboviral Infections Detected Through Xenosurveillance In Africa: A Focus On West Nile, Rift Valley Fever, And Chikungunya Virus Infections, Mxolisi Mgongoma, Armanda Bastos, Abel Ramoelo, David P. Tchouassi

All Peer-Reviewed Publications

This systematic review and meta-analysis comprehensively evaluated the mosquito arboviral infections with West Nile virus (WNV), Rift Valley fever virus (RVFV), and chikungunya virus (CHIV), detected through xenosurveillance, reported in mosquito vectors across Africa in the last 25 years (2000–2024). The study analysed xenosurveillance data from 45 studies conducted with over 115,000 mosquito specimens, and incorporated moderator analyses to assess the influence of trap type, seasonality, regional location, settlement type, and screening methods on virus detection rates. The estimated pooled prevalence of WNV was 1.18% (95% CI: 0.60–3.43%), with higher rates observed in Culex quinquefasciatus and Culex pipiens, particularly in …

Privacy-Preserving Federated Learning With Optimized Ensemble Weighting And Knowledge Distillation For Covid-19 Detection From Non-Iid Medical Imaging Data, Richard Annan, Hong Qin, Robert Newman, Madhuri Siddula, Letu Qingge

Computer Science Faculty Publications

Medical imaging enables rapid and accurate diagnosis of COVID-19, with CT scans proving especially effective. However, data privacy concerns limit collaborative model development across hospitals. To address this issue, we introduce a novel federated learning framework. It is referred to as Independent Knowledge Distillation with post-Ensemble Federated Learning (IKDEFL). Differential Privacy (DP) is integrated into the framework to improve privacy guarantees. Three DP mechanisms are evaluated. These include Fixed Gaussian, Gaussian Adaptive, and Tree Adaptive. The evaluation has been conducted on heterogeneous and Non-Independent and Identically Distributed (Non-IID) datasets. These datasets reflect real-world hospital scenarios. Results show that IKDEFL significantly …

Attention-Based Multi-Omics Fusion For Drug Synergy Prediction, Kusal Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Drug combination therapy in disease management gained popularity in the last few decades. Computational modeling of such combinations is an active area of research in the drug discovery domain. While earlier approaches solely emphasized on the structural features of participating drugs for designing synergistic models, they lack other crucial factors directly linked with drug administration - omics expressions. As differential omics expression is a downstream consequence of the administered drug combinations, utilizing such expressions while designing synergistic models promises robust and dynamic modeling. In this work, we propose SynergyLM that fuses multi-omics features with drug embeddings to build an omics-aware …

Chromnet: A Multi-Task Learning Framework For Cross-Cell Type Prediction Of 3d Chromatin Interactions Using Epigenetic Signals, Bin Wang, Shaokai Wang, Liqing Ding, Hongdong Li, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

The 3D organization of chromatin plays a fundamental role in gene regulation, cellular function, and disease mechanisms. However, current experimental techniques, such as Hi-C, remain costly and labor-intensive, limiting their application in large-scale and disease-related studies. To address this challenge, ChromNet is presented, a multi-task learning framework that integrates epigenetic signals across diverse cell types to enable high-precision prediction of chromatin architecture. By incorporating noise perturbation and auxiliary classification tasks, ChromNet improves the identification of topologically associating domains (TADs) and cell-type-specific chromatin structures, demonstrating superior generalization performance. Notably, ChromNet accurately predicts chromatin interactions in acute myeloid leukemia (AML) samples by …

Fumigant Toxicity Of Essential Oils From Chemotypes Of Curry Tree (Murraya Koenigii) Against Adult African Malaria Mosquito (Anopheles Gambiae Sensu Stricto), Clarence M. Mang’Era, Fathiya M. Khamis, Ahmed Hassanali, Paul O. Mireji

All Peer-Reviewed Publications

The toxicity of fumigant formulations of essential oils (EOs) from curry tree (Murraya koenigii (L.) Spreng (Rutaceae)) against African malaria adult mosquito (Anopheles gambiae sensu stricto (Giles, 1902) (Diptera: Culicidae: Culicini)) was evaluated to identify most effective chemotype of the curry tree against the mosquitoes. Ninety-two compounds (91.78%–96.47% coverage) in the EO profiles were identified, among which EO isolated from curry tree chemotype from Kibwezi was most toxic. This chemotype had a median lethal dose (LD50) of 3.6 × 10⁻³ mg/cm³ (95% CI: 2.70–4.58) and a lethal time (Ti50) of 1.91 ± 0.086 h (p < 0.001). The equivalent LD50 of EOs of chemotypes from Mombasa, Makindu, and Malindi in Kenya was 4.9 × 10⁻³, 6.6 …

A Comprehensive Overview Of Neurophysiological Correlates Of Cognitive Impairment In Amyotrophic Lateral Sclerosis, Seyyed Bahram Borgheai, Brie E. Achorn, Alyssa H. Zisk, Sarah M. Hosni, Karl E. G. Richter, Frank S. Menniti, Yalda Shahriari

Computer Science Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the gradual loss of motor control, typically resulting in paralysis and death within 3 to 5 years of diagnosis. ALS shares neuropathological and genetic associations with fronto-temporal dementia (FTD), a neurodegenerative condition primarily impacting cognitive functions. These two conditions are increasingly viewed as manifestations of a single molecular disease process that affects distinct brain systems, impacting motor neuronal pathways in ALS and fronto-cortical functions in FTD. However, this simple dichotomy belies the complexity of these conditions. In particular, patients with primary motor ALS can also experience significant cognitive …

Roles Of Cytokines In Modulating Trypanosoma Brucei Rhodesiense Infection Outcomes In Vervet Monkeys, Clarah Jebet, John Kibuthu Thuita, Daniel Masiga, Benedict Owino Orindi, John Oidho, Mark C. Field, Enock Matovu, Vincent Owino Adung’A

All Peer-Reviewed Publications

Introduction:

Human African trypanosomiasis (HAT), caused by Trypanosoma brucei rhodesiense, is categorized as acute due to rapid disease progression but presents varying clinical outcomes. Although the mechanisms underpinning differential clinical progression are poorly understood, both host and parasite factors are implicated. Therefore, we sought to elucidate roles of primate host factors in mediating varying T. b. rhodesiense infection outcomes.

Methods:

Here, we assessed the roles of selected host cytokines in disease progression using a tsetse-mediated infection in a non-human primate (NHP) vervet monkey model that closely mimics HAT and natural infection. We quantified eight cytokines, including TNF-α, IFN-γ, IL-10, IL-6, …

Nanoparticle Carriers Enhance The Prophylactic Antiviral Effects Of Dsrna In Vitro And Ex Vivo, Shayne Oberhoffner, Stephanie Dewitte-Orr, Starla Richardson, Leah Haile, Dominique Daniels, Erin Cooper, Aizah Ijaz, Janet Velasquez Perez, Mathilde Peruzzi, Bertrand Collet, Paul Craig, Kristof Jenik

Theses and Dissertations (Comprehensive)

Aquaculture now outpaces traditional capture fisheries as the world population and demand for sustainable protein sources increases. Wild and farmed species are increasingly susceptible to pathogen spread as global temperatures rise and stocking densities increase. Despite the devastating losses experienced by aquaculture due to viral infections, there remain few effective prophylactic antiviral therapeutics. Long double-stranded (ds)RNA is a uniquely viral molecule produced by nearly all viruses during their replication cycle, and its detection by salmonids like rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytsha) leads to the establishment of a defensive antiviral state. Previous in vitro studies demonstrated a …

Taylorkan-Vit: Parameter-Efficient Vision Transformers For Medical Image Classification, Kaniz Fatema, Dr. Emad Mohammed, Dr. Sukhjit Singh Sehra

Theses and Dissertations (Comprehensive)

Effective and interpretable classification of medical images remains a critical challenge in computer-aided diagnosis, particularly in data-scarce and resource-constrained clinical settings where traditional deep learning models prove impractical. This study addresses the fundamental barrier to Vision Transformer adoption in medical imaging—massive parameter counts and data requirements—through a systematic two-phase methodology. Phase 1 evaluates three spline-based Kolmogorov–Arnold Network (KAN) variants to identify the optimal nonlinear approximation function for parameter-efficient medical image classification: SBTAYLOR-KAN (B-splines with Taylor series), SBRBF-KAN (B-splines with Radial Basis Functions), and SBWAVELET-KAN (B-splines with Morlet wavelets). Comprehensive experiments across brain MRI, chest X-rays, and tuberculosis datasets—without any image …

Investigating The Immunostimulatory Potential Of Dsrna-Silk Nanoparticle Complexes In Melanoma, Samuel J. Peters

Theses and Dissertations (Comprehensive)

The rate of resistance to immune checkpoint inhibitor treatment in metastatic melanoma is quite high, with an overall rate of 70%. Melanoma achieves these high rates of resistance by suppressing the immune response in the tumour microenvironment (TME), making them immunologically “cold”. The type 1 interferon response could be leveraged to initiate immune responses in melanoma, making their “cold” TMEs “warm” again. Double-stranded ribonucleic acids (dsRNAs) are potent activators of an innate immune response; however, they are susceptible to degradation by nucleases present in the body and need a carrier. Silk nanoparticles (SNPs) are an ideal drug-delivery platform as they …

Photo And Spatial Control Of Rna Structures And Functions: Exploring Positional Effects And Photo-Responsiveness Of Azobenzene Modified Nucleotides, Jinxi Du

Electronic Theses & Dissertations (2024 - present)

RNA molecules perform many important biological functions by forming complex three-dimensional structures stabilized by base pairing, tertiary interactions, and metal ion coordination. Because RNA function depends strongly on its structure, methods that allow reversible control of RNA conformation and activity are important for understanding RNA behavior and for potential therapeutic applications. However, achieving reversible and site-specific control of RNA structure, especially at the single-nucleotide level, remains challenging. In this dissertation, I developed and applied azobenzene-modified nucleotides as a chemical tool to enable optical and spatial control of RNA structure and function.

The first part of this dissertation focuses on establishing …

Bioinformatic Identification And Analysis Of Shared Splicing Errors In Myotonic Dystrophy Type (Dm1) And Fuchs' Endothelial Corneal Dystrophy (Fecd), Carter I. Wilkins

Electronic Theses & Dissertations (2024 - present)

Myotonic dystrophy type 1 (DM1) is an autosomal dominant form of muscular dystrophy, and it is the most common form of adult-onset muscular dystrophy. The disease is the result of CTG trinucleotide repeats (TNR) in the 3’UTR of the dystrophia myotonica protein kinase (DMPK) gene. This produces toxic RNA hairpin structures by CUG repeat expansions that sequester proteins–most relevantly muscleblind-like 1 (MBNL)–that regulate alternative RNA splicing. The missplicing of a wide variety of genes results in the symptoms such as myotonia (rigidity of the muscles), atrophy, and cardiac failure.

Fuchs’ Endothelial Corneal Dystrophy (FECD) is characterized by progressive loss and …

Development And Applications Of Fluorescence Microscopy Protocol To Investigate Borrelia Burgdorferi Immune Interactions In The Skin, Rebecca V. Landry

Electronic Theses & Dissertations (2024 - present)

The skin is an immunological organ that acts as the hosts’ first line of defense against infectious agents. Infectious disease vectors like ticks breach this barrier by feeding on hosts, transmitting pathogens like Borrelia burgdorferi in the process. Uncleared infection with B. burgdorferi causes Lyme disease, the most prevalent vector-borne disease in the United States. Previous research has explained many elements of Lyme disease pathogenesis and immunity including the dissemination of the spirochete, innate immune cells performing phagocytosis, the production of antibodies by the humoral response, and the impact of prophylactic treatment with monoclonal antibodies. A remaining gap in the …

Combating Antibiotic Resistance With Plasmid-Dependent Phages, Rhiannon T. Mariano

Electronic Theses & Dissertations (2024 - present)

The alarming rise of carbapenem-resistant bacteria poses an urgent global health threat, driven in large part by the horizontal spread of carbapenemase-encoding plasmids (Ma et al., 2023). These plasmids are often highly mobile and transmissible, enabling rapid dissemination of resistance genes across diverse bacterial populations. Their mobility is largely mediated by conjugation, a process dependent on the formation of pili, which serve as physical bridges for plasmid transfer between cells (Murray et al. 2022; San Millan and MacLean 2017; Virolle et al. 2020). Beyond their role in gene exchange, these pili also act as entry points for a unique class …