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Articles 1 - 30 of 496
Full-Text Articles in Molecular Genetics
Gene Therapy Strategies To Enhance Antifungal Immunity In Microgravity, Riley Dienna
Gene Therapy Strategies To Enhance Antifungal Immunity In Microgravity, Riley Dienna
Discovery Day - Daytona Beach
During spaceflight, the immune system of astronauts becomes impaired due to microgravity, resulting in increased susceptibility to infections caused by pathogens such as Candida albicans. One of the most common clinical treatments for aggressive candidiasis is amphotericin B, a polyene antimycotic that targeted ergosterol in the fungal cell membrane and compromised the stability of the membrane. However, due to the chemical similarities between ergosterol and cholesterol, this treatment also affects the somatic cells of patients it is administered to. A novel treatment is therefore required to combat the aggressive fungal infection while minimizing damage to the host’s cells. This project …
Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel
Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel
Dissertations, Theses, and Capstone Projects
Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …
Validation Of A Real-Time Pcr Laboratory Developed Test For The Detection Of Pneumocystis Jirovecii In Bronchoalveolar Lavage Samples, Caitlyn Moon
Honors Scholar Theses
Pneumocystis jirovecii is an opportunistic, host-obligate fungal pathogen responsible for causing P. jirovecii pneumonia (PJP) in humans. PJP is treated with trimethoprim-sulfamethoxazole (TMP-SMX), a strong broad-spectrum antibiotic that carries risk of renal and hepatotoxicity. Therefore, rapid diagnosis or exclusion of PJP is crucial to ensure PJP-positive patients receive effective treatment and PJP-negative patients avoid unnecessary antibiotics. Unlike most microorganisms, P. jirovecii cannot be cultured, presenting complications for the typical methods of diagnosing fungal pathogens. Historically, the gold standard for diagnosis was direct microscopic examination with stains such as methenamine silver and calcofluor white, but this diagnostic technique requires highly skilled …
Quantification Of Mouse Tracheal Epithelial Cell Differentiation With Cilia Defects, Olivia V. Allen
Quantification Of Mouse Tracheal Epithelial Cell Differentiation With Cilia Defects, Olivia V. Allen
Honors Thesis
Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder that affects 1 in every 7,500 live births. PCD results from motile cilia defects, impairing mucociliary clearance and causing chronic respiratory infections. Our lab studies include three PCD mouse lines — bgh (Spef2), nm1054 (Cfap221), and Cfap54gt/gt (Cfap54). Prior transcriptomic data led us to hypothesize that PCD mutant mouse tracheal epithelial cells (MTECs) exhibit reduced differentiation into ciliated cells. MTECs from the trachea of the Wild Type (WT) and the PCD mutant mouse lines were cultured at an Air Liquid Interface (ALI) to start …
Optimizing Itpa R178c Assays Via Hplc, Jared J. Reisnouer, Wally D. Pines
Optimizing Itpa R178c Assays Via Hplc, Jared J. Reisnouer, Wally D. Pines
2026 Symposium
Two of the major nucleotide bases in DNA and RNA (Adenine and Guanine) are derived from the purine Inosine Monophosphate (IMP). IMP may occasionally form the noncanonical nucleotide Inosine Triphosphate (ITP) within the cell and become incorporated into DNA during replication, leading to potentially lethal errors. To combat this, human cells produce the “housekeeping” enzyme Inosine Triphosphatase (ITPA) to revert ITP to IMP. A mutation of this protein that replaces the 178th amino acid Arginine with Cysteine (R178C) is associated with a fatal infantile encephalopathy. Previous assessments of enzyme-substrate binding and catalysis for ITPA variants have been run at a …
Transgenic Plant Cells For The Cost-Effective Production Of Pharmaceutical Proteins, Maria Gambaro
Transgenic Plant Cells For The Cost-Effective Production Of Pharmaceutical Proteins, Maria Gambaro
Create@State
Plant-based systems are becoming an important method for producing pharmaceutical proteins because they can be more cost-effective, and safer compared to traditional production methods which commonly use mammalian cells. This project aims to develop a transgenic plant cell system that can produce a pharmaceutical protein using molecular cloning techniques. A transgenic plant cell has the DNA of another plant integrated into its genome, altering its gene expression to produce different proteins. To begin, a plasmid carrying the gene of interest and the DNA components needed for expression will be designed. The plasmid will then be used to introduce the gene …
Phenol–Chloroform Dna Extraction For Dna Amplification From Personal Items, Aditya Rahman Ernanto, Dinda Amaliyatul Khasanah, Yunita Aldirahayu, Rizki Setiyaningrum, Arya Iswara
Phenol–Chloroform Dna Extraction For Dna Amplification From Personal Items, Aditya Rahman Ernanto, Dinda Amaliyatul Khasanah, Yunita Aldirahayu, Rizki Setiyaningrum, Arya Iswara
Makara Journal of Science
This study examined the feasibility of extracting DNA from various personal items using the phenol–chloroform–isoamyl alcohol (PCIA) method. A towel, collared shirt, toothbrush, shower puff, comb, hair tie, and buccal swabs were analyzed. The quality of the DNA extraction, along with DNA concentration, purity, and suitability for multiplex PCR amplification, were evaluated. The shower puff exhibited the highest DNA concentration (68.35 ng/µL), whereas the collared shirt yielded the lowest (26.43 ng/µL). All samples exhibited good DNA purity (A260 nm/A280 nm ranging from 1.827 to 1.985), emphasizing the potential of this method for forensic analysis. Factors influencing DNA concentration included material …
Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković
Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković
Administration and Staff Articles and Research
Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …
Oral Streptococcus And Vitamin B12 Deficiency In E-Cigarette Users: A Microbial–Nutrient–Neurotransmitter Axis Linking To Mood Disturbances, Maryam Sabah Naser, Ali Jabbar Abd Al-Hussain Alkawaz, Ali Abbas Hashim Almusawi, Ali Jalil Obaid, Hasanain Ayed Mohammed Al-Khafaji, Reihaneh Sabbaghzadeh
Oral Streptococcus And Vitamin B12 Deficiency In E-Cigarette Users: A Microbial–Nutrient–Neurotransmitter Axis Linking To Mood Disturbances, Maryam Sabah Naser, Ali Jabbar Abd Al-Hussain Alkawaz, Ali Abbas Hashim Almusawi, Ali Jalil Obaid, Hasanain Ayed Mohammed Al-Khafaji, Reihaneh Sabbaghzadeh
Karbala International Journal of Modern Science
Background: With the rising popularity of e-cigarettes, questions have emerged regarding their broader influence on oral ecology, nutrient absorption, and psychological health. Disruptions in the oral microbiome may alter vitamin B12 dynamics. This, in turn, may indirectly influence serotonin biosynthesis and mood regulation.
Methods: An observational cross-sectional study involved 150 young adults segregated into groups of 50 each as vapers, smokers, or non-users. Streptococcus sanguinis and vitamin B12 metabolism-related variable statuses methylmalonic acid and holotranscobalamin were quantified in samples, along with inflammatory markers interleukin-6, kynurenine/tryptophan ratio, and serotonin. Statistical techniques, including ANOVA and the Kruskal-Walli’s test, correlation, and serial mediation …
Chronic Alcohol Consumption Enhances The Differentiation Capacity Of Hematopoietic Stem And Progenitor Cells Into Osteoclast Precursors, Hami Hemati, Madison B. Blanton, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi
Chronic Alcohol Consumption Enhances The Differentiation Capacity Of Hematopoietic Stem And Progenitor Cells Into Osteoclast Precursors, Hami Hemati, Madison B. Blanton, Jude Koura, Rupak Khadka, Kathleen A. Grant, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Chronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. In a rhesus macaque model of voluntary ethanol consumption, CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them toward a hyper-inflammatory response. In the present study, those studies were extended to investigate alterations in osteoclast development, which, in postnatal life, differentiate from HSPCs and play a critical role in maintaining bone homeostasis. Spectral flow cytometry revealed a skewing of HSPCs toward granulocyte-monocyte progenitors in the CAC group, consistent with an increased …
Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications To Promote Osteoclastogenesis, Hami Hemati, Brianna M. Doratt, Ilhem Messaoudi
Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications To Promote Osteoclastogenesis, Hami Hemati, Brianna M. Doratt, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Chronic alcohol consumption increases the risk of osteoporosis and fracture by disrupting bone remodeling, in part by enhancing osteoclastogenesis. However, the cellular mechanisms underlying this process remain incompletely defined. We analyzed scRNA-seq data from osteoclasts differentiated in vitro from bone marrow mononuclear cells obtained from macaques following 12 months of chronic ethanol or isocaloric control solution consumption. Module scoring, trajectory inference with generalized additive modeling (tradeSeq), and CellChat-based analyses of intercellular communication were applied to uncover ethanol-induced changes in metabolic reprogramming, lineage progression, and signaling network dynamics. Module scoring indicated metabolic reprogramming toward oxidative phosphorylation, with reduced glycolytic, migratory, and …
Alcohol Consumption Exacerbates High-Fat Diet- Mediated Disruptions In Myelopoiesis And Osteoclastogenesis In Mouse Models Of Metabolic Dysfunction-Associated Liver Diseases, Hami Hemati, Madison B. Blanton, Lauren Rutt, Nicholas Keiran, Rebecca Geron, Florence Lima, Rebecca L. Mccullough, Ilhem Messaoudi
Alcohol Consumption Exacerbates High-Fat Diet- Mediated Disruptions In Myelopoiesis And Osteoclastogenesis In Mouse Models Of Metabolic Dysfunction-Associated Liver Diseases, Hami Hemati, Madison B. Blanton, Lauren Rutt, Nicholas Keiran, Rebecca Geron, Florence Lima, Rebecca L. Mccullough, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Objective: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Alcohol-related Liver Disease (MetALD) exhibit systemic immune abnormalities. Given that such immune dysregulation is closely linked to the skeletal complications frequently observed in MASLD and MetALD, we sought to comprehensively characterize the bone marrow hematopoietic compartment and its link to osteoclastogenesis.
Methods: We utilized bone marrow from mouse models of MASLD (high-fat diet, HFD) and MetALD (high-fat diet plus ethanol, HFD+EtOH), followed by flow cytometric analysis to phenotype hematopoietic stem and progenitor cells (HSPCs), as well as in vitro and in vivo assays to evaluate osteoclastogenesis.
Results: We found that …
Transcriptional Signatures Of Rapid Protection From Sudan Virus Infection By A Single Dose Of A Vesicular Stomatitis Virus-Based Vaccine, Brianna M. Doratt, Sheridan B. Wagner, Delphine C. Malherbe, Gregory T. Smith, Andrea Marzi, Ilhem Messaoudi
Transcriptional Signatures Of Rapid Protection From Sudan Virus Infection By A Single Dose Of A Vesicular Stomatitis Virus-Based Vaccine, Brianna M. Doratt, Sheridan B. Wagner, Delphine C. Malherbe, Gregory T. Smith, Andrea Marzi, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Sudan virus (SUDV) has caused multiple outbreaks of human disease with case fatality rates ranging from 41 to 100%. We have previously shown that a single vaccination with a recombinant vesicular stomatitis virus-based vaccine expressing the SUDV-Gulu glycoprotein (VSV-SUDV) prevented clinical and fatal disease from lethal SUDV challenge in cynomolgus macaques. With the high probability of future outbreaks, it is critical to determine the molecular mechanisms of VSV-SUDV-mediated protection and the ability to impart rapid protection against SUDV infection. In this study, RNA from whole blood samples obtained from nine cynomolgus macaques that were challenged with SUDV-Gulu post-vaccination with either …
Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi
Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Background: The East Palestine, Ohio, train derailment on February 3rd, 2023, resulted in the exposure of residents and the surrounding area to numerous hazardous chemicals, which included known acute irritants and human carcinogens. Despite evacuation and cleanup, both residents and responders reported high occurrences of symptoms associated with exposure in the months following, such as eye, skin, and respiratory irritation, headaches, and fatigue. The long-term health consequences for residents remain uncertain.
Objective: To assess the potential for immune perturbations resulting from the exposure, we performed a broad investigation of circulating immune cells and mediators from residents of East Palestine, OH, …
Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian
Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Immunotherapies have greatly improved outcomes for patients with renal cell carcinoma (RCC), yet response rates remain suboptimal and the factors promoting therapy resistance versus sensitivity are incompletely understood. Currently, no preclinical model of orthotopic renal cancer exists that permits evaluation of tumor antigen–specific (TAS) CD8+ tumor-infiltrating lymphocytes (TILs). To address this deficiency, we developed a mouse renal cancer model that permits tracking of adoptively transferred TAS CD8+ T cells. Renca-LUC tumor cells were transduced to express tumor ERK (tERK), a model antigen expressing a one-amino-acid change from wild-type ERK, resulting in recognition by tERK/H-2Kd-specific DUC Thy1.1 …
Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi
Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …
Glycoprotein-Specific Transcriptional Response Contributes To Differential Vaccine Protection Against Lethal Ebola Virus Infection, Sheridan B. Wagner, Delphine C. Malherbe, Ethan G. Napier, Andrea Marzi, Ilhem Messaoudi
Glycoprotein-Specific Transcriptional Response Contributes To Differential Vaccine Protection Against Lethal Ebola Virus Infection, Sheridan B. Wagner, Delphine C. Malherbe, Ethan G. Napier, Andrea Marzi, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 10 7 PFU to provide broader population protection. Identification …
A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay
A Novel Tyrosine Kinase Axis In Innate Immune Signaling, Santanu Das, Pracheta Sengupta, Manoj Veleeparambil, Saurabh Chattopadhyay
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Tyrosine phosphorylation has emerged as a central regulatory mechanism in innate immunity. Building on our recent studies that Syk and EGFR sequentially phosphorylate TLR9 to fully activate it, we discuss how similar mechanisms operate across other Toll-like receptors and the cytosolic DNA sensor STING. Evidence from complementary systems reveals that receptor and nonreceptor tyrosine kinases, including Src-family kinases, Syk, BTK, and EGFR, form an integrated signaling network that triggers receptor activation, trafficking, and downstream gene expression. Scavenger receptors such as SR-A further drive this kinase cascade by coordinating viral recognition to TLR activation. These observations reveal a novel ‘tyrosine kinase …
Maternal Opioid Use Disorder And Hepatitis C Infection In Pregnancy Reshape The Peripheral Immune Landscape At Term, Brianna M. Doratt, Heather E. True, Sheridan B. Wagner, Delphine C. Malherbe, Zachary M. Reynolds, Cynthia Cockerham, John O'Brien, Ilhem Messaoudi
Maternal Opioid Use Disorder And Hepatitis C Infection In Pregnancy Reshape The Peripheral Immune Landscape At Term, Brianna M. Doratt, Heather E. True, Sheridan B. Wagner, Delphine C. Malherbe, Zachary M. Reynolds, Cynthia Cockerham, John O'Brien, Ilhem Messaoudi
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Background: Pregnancy requires precisely timed immune adaptations to maintain foetal tolerance while enabling timely initiation of labour, a process often conceptualised as the ‘immune clock’ of pregnancy. Disruption of this immune clock contributes to adverse obstetric outcomes. While maternal opioid use disorder (OUD) is a recognised risk factor for poor maternal and neonatal health, its impact on maternal immune landscape at delivery remains poorly understood.
Methods: We analysed peripheral blood collected from pregnant individuals with and without OUD at time of admission for delivery before the onset of active labour. We employed multiparameter flow cytometry, cytokine profiling, and single-cell-RNA sequencing …
Determining Genes Involved In Recovery From Chemotherapy In 4t1, Emt6, And Eo771 Breast Cancer Cells, Akash Jagdeesh, Joseph Landry Ph.D.
Determining Genes Involved In Recovery From Chemotherapy In 4t1, Emt6, And Eo771 Breast Cancer Cells, Akash Jagdeesh, Joseph Landry Ph.D.
UROP Posters
Breast cancer is one of the most common types of cancer, and often has poor prognosis. Traditional treatments for breast cancer include chemotherapy, which involves a chemical attack on all growing cells within the body. However, these treatments are not 100% effective, and patients might experience recurrence in their cancer months or years after achieving remission. Cancer cells can evade chemotherapy through five mechanisms: senescence, quiescence, cytoprotective autophagy, and apoptosis/necroptosis suppression. Prior studies have conducted CRISPR screens and experiments involving inhibition of epigenetic regulators, to alter the regulation of genes that can contribute to breast cancer chemotherapy resistance. This study …
Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi
Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi
Graduate Theses and Dissertations (2019 - present)
During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …
Evaluating The Potential And Limitations Of Nanopore Adaptive Sampling For Targeted Transcriptome Sequencing, Nicole Debruyne, Feng Wang, Yang Xu, Lan Lin
Evaluating The Potential And Limitations Of Nanopore Adaptive Sampling For Targeted Transcriptome Sequencing, Nicole Debruyne, Feng Wang, Yang Xu, Lan Lin
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Long-read RNA sequencing is a powerful technology for transcriptomics, but low throughput and high cost pose challenges. Adaptive sampling, a feature of Oxford Nanopore Technologies, offers real-time enrichment by selectively ejecting non-target molecules. We evaluate adaptive sampling for human transcriptome analysis. Adaptive sampling modestly enriches target transcripts (1.3 × for cDNA sequencing, 1.9 × for direct RNA sequencing) while preserving gene expression and splicing profiles, but is significantly less effective than cDNA hybridization capture. Short read lengths and low sequencing quality limit performance. Adaptive sampling on direct RNA sequencing can boost target yield (~ 20%) within fixed run times, potentially …
Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu
Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu
School of Medicine Faculty Publications
Basal-like breast cancer (BLBC) is a major subtype of triple-negative breast cancer (TNBC), characterized by aggressive behavior, limited treatment options, and poor prognosis. While HER3 overexpression is frequently observed in TNBC and associated with poor outcomes, its subtype-specific expression and therapeutic potential remain unclear. Here, we demonstrated that HER3 signaling is selectively hyperactivated in BLBC compared to claudin-low breast cancer (CLBC) using transcriptomic profiling. Histone deacetylase inhibitors (HDACi), Romidepsin and Panobinostat, exerted potent antitumor effects on BLBC by selectively downregulating HER3 expression. HER3 levels were positively correlated with FOXA1, a key transcriptional activator. Mechanistically, we identified GATA2 and GATA3 as …
Ai-Powered Multi-Omics Integration For Predictive Modeling Of Genotype-Environment-Phenotype Relationships, You Wu
Dissertations, Theses, and Capstone Projects
This dissertation presents a series of machine learning frameworks for modeling genotype–environment–phenotype relationships through integrative predictive modeling of multi-omics data. The work addresses three major axes of biological complexity: modeling biological information transmission cross-levels from genes to proteins to phenotypes, predicting molecular features cross-scale from cells to tissues to organisms, and translating phenotypes cross-species from model systems to humans. Each proposed method also tackles key machine learning (ML) challenges in the biomedical domain, including data scarcity, domain shift, out-of-distribution (OOD) generalization, and hierarchical modeling. Specifically, this dissertation introduces five novel deep learning algorithms: MultiDCP predicts drug-induced transcriptomic and viability responses …
Enhancing Preparedness: A Genetic Study Of Sar-Cov-2 And Other Microbial Public Health Threats In Wastewater From A College Town, Christian N. Hutchinson
Enhancing Preparedness: A Genetic Study Of Sar-Cov-2 And Other Microbial Public Health Threats In Wastewater From A College Town, Christian N. Hutchinson
Master's Theses
Problem
The SARS-CoV-2 (COVID-19) pandemic revealed both the systemic vulnerabilities of our healthcare system as well as the importance of timely, localized data for informing public health responses. Traditional testing approaches were essential but often failed to capture the full extent of viral spread, especially in those with mild or asymptomatic conditions that relied on at home testing. This underreporting hindered effective allocation of resources and made developing effective intervention strategies difficult. We also realized the potential for wastewater surveillance to be applied to tracking antimicrobial resistance gene markers. Taken together, this approach should have important implications for improving public …
Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu
Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu
Mako: NSU Undergraduate Student Journal
Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …
Diagnostic And Clinical Utility Of Oncoscan Microarray And Ngs-Based Sequencing In Pediatric Solid Tumors: Children’S Mercy Hospital’S Experience, Aravindh Nagarajan, Lisa Lansdon, Midhat Farooqi, Lei Zhang, Elena Repnikova
Diagnostic And Clinical Utility Of Oncoscan Microarray And Ngs-Based Sequencing In Pediatric Solid Tumors: Children’S Mercy Hospital’S Experience, Aravindh Nagarajan, Lisa Lansdon, Midhat Farooqi, Lei Zhang, Elena Repnikova
Research Days
This papers attempts to evaluate the diagnostic and clinical utility of microarray-based OS+ in detecting clinically relevant genetic alterations in FFPE solid tumor samples and to compare the yield of somatic mutation detection by WGS/WES in pediatric solid tumors at Children’s Mercy Hospital - Kansas City.
Examining Loss Of Imprint In F1 Hybrid Female Mice Due To X Chromosome Epimutation And The Implications For Autism, Arianna H. Roach
Examining Loss Of Imprint In F1 Hybrid Female Mice Due To X Chromosome Epimutation And The Implications For Autism, Arianna H. Roach
Honors Scholar Theses
Sex biases are prevalent among various neurodevelopmental disorders, with males experiencing them at higher frequencies or severities than females. This male bias is poorly understood, and our lab aims to elucidate this mechanism using our model of transgenerational epigenetic inheritance. Our lab identified the cluster of genes Xlr3b/4b/4c on the X chromosome that are imprinted in the female brain. Preliminary studies suggest that Xlr3 acts as a mediator molecule in our model. Xlr3 knockdown male mice exhibited significant meiocyte loss that can be attributed to Meiotic Sex Chromosome Inactivation. Their female offspring also displayed loss of imprinting of Xlr3 and …
Implications Of Type Iv Pilus Retraction For Dna Uptake By Acinetobacter Baumannii, Yafan Yu
Implications Of Type Iv Pilus Retraction For Dna Uptake By Acinetobacter Baumannii, Yafan Yu
Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–
Horizontal gene transfer (HGT) via natural competence allows bacteria to incorporate extracellular DNA (eDNA) into their genomes, facilitating genetic diversity and adaptation. In Acinetobacter species, natural competence depends on DNA binding and uptake mediated by type IV pili (T4P). T4P are dynamic extracellular filaments composed primarily of the major pilin subunit PilA, along with a few minor subunits. T4P drive a range of cellular functions including twitching motility, biofilm formation, and DNA uptake, with some functions dependent on pilus retraction and others not. However, how Acinetobacter T4P bind DNA and how T4P/eDNA interactions impact biofilm formation remain unclear. Here, I …
Hypoxia Induced Ribosomal Rna Fragmentation Mediated By Rnase L, Vanessa Kristina Pizutelli, Dimitri G Pestov
Hypoxia Induced Ribosomal Rna Fragmentation Mediated By Rnase L, Vanessa Kristina Pizutelli, Dimitri G Pestov
Rowan-Virtua Research Day
Ischemic injury contributes to a range of global pathologies. Ischemia/Reperfusion Injury (IRI) is a paradoxical phenomenon that involves an initial restriction of blood flow followed by a sudden restoration of perfusion. This type of injury takes place in conditions such as myocardial infarction, acute kidney disease, and ischemic stroke and often leads to cellular death. Additionally, IRI exacerbates post-surgical outcomes and plays a role in graft dysfunction and transplant rejection. Despite efforts to develop therapies targeting known IRI pathways, clinical trials have largely been unsuccessful, underscoring the need for alternative mechanisms and biomarkers associated with IRI-induced apoptosis. Reactive oxygen species …