Enhanced Meropenem Activity And Stability Following Load In Polyvinyl Alcohol Nanofiber Scaffolds With Sitagliptin As Quorum Sensing Inhibitor On Pseudomonas Aeruginosa, Samar A. Salim, Abdelrhman Mohsen, Mohamed Emara, Taghrid Elmahdy

Nanotechnology Research Centre

Background The increasing resistance of bacteria to conventional antibiotics poses a significant health challenge. Innovative strategies, such as combining antibiotics with agents like quorum sensing inhibitors (QSIs), have been developed to combat this issue. QSIs enhance antibiotic efficacy without inhibiting bacterial growth, minimizing the risk of resistance. Aims Evaluate the combined effect of Sitagliptin (STG) as a QSI with Meropenem (MER), fabricate drug-loaded Polyvinyl Alcohol (PVA) nanofibers, and investigate their antimicrobial activity against standard Pseudomonas aeruginosa (PAO1) and carbapenem-resistant P. aeruginosa (CRPA). Methods The combinatorial effect was assessed using a checkerboard assay. PVA/STG, PVA/MER, and PVA/STG/ MER nanofibers were fabricated …

Proteogenomic Characterization Unveils Biomarkers Associated With Chemoresistance In Muscle-Invasive Bladder Cancer, Matthew V Holt, Yongchao Dou, Meggie N Young, Alexander B Saltzman, Meenakshi Anurag, Jonathan T Lei, Antrix Jain, Mei Leng, Beom-Jun Kim, Lacey E Dobrolecki, Stefanie F Faucher, Sara Savage, Chenwei Wang, Zhiao Shi, Hugo Villanueva, Karoline Kremers, Kyle D Drinnon, Patricia D Castro, Michael M Ittmann, Mehak Mehboob Khatani, Sung Han Kim, Matthew J Ellis, Bing Zhang, Anna Malovannaya, Seth P Lerner

Faculty, Staff and Students Publications

To explore potential chemoresistance mechanisms and identify therapeutic opportunities in muscle-invasive bladder cancer (MIBC), we conduct comprehensive proteogenomic characterization of 46 pre- and 14 post-treatment MIBC tumors incorporating genomics, transcriptomics, proteomics, and phosphoproteomics. Multi-omics clustering not only recapitulated established molecular subtypes but also revealed subtypes associated with chemotherapy sensitivity. Protein isoform level analysis identifies protein abundance of a short isoform of ATAD1 and RAF family proteins as biomarkers of chemosensitivity. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive …

Biogenic Calcite Precipitation For Coastal Sand Stabilization: A Synergistic Approach Using Marine Bacteria And Natural Fibers, Aparna Gs

Theses and Dissertations

Coastal erosion, driven by natural forces such as waves, tides, winds, and currents and further intensified by anthropogenic activities like urbanization, climate change, and coastal infrastructure development, poses a significant threat to shoreline stability. Conventional erosion control methods, including jetties, embankments, and artificial reefs, often face limitations in sustainability and effectiveness. In this context, microbially induced calcite precipitation (MICP) has emerged as a promising ecofriendly solution for ground stabilization.

The present study investigates the potential of an indigenous ureolytic marine bacterium, Bacillus sp. N₉, isolated from the coastal sediments of Nagapattinam, Tamil Nadu, for coastal sand stabilization. The strain was …

Sox2 Regulates Foregut Squamous Epithelial Homeostasis And Is Lost During Barrett’S Esophagus Development, Ramon U Jin, Yuanwei Xu, T Mamie Lih, Yang-Zhe Huang, Toni M Nittolo, Blake E Sells, Olivia M Dres, Jean S Wang, Qing K Li, Hui Zhang, Jason C Mills

Faculty, Staff and Students Publications

Esophageal adenocarcinoma is increasingly prevalent and is thought to arise from Barrett's esophagus (BE), a metaplastic condition in which chronic acid and bile reflux transforms the esophageal squamous epithelium into a gastric-intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We developed a human BE organoid biobank that recapitulates BE's molecular heterogeneity. Bulk and single-cell transcriptomics, supported by patient tissue analysis, revealed that BE differentiation reflects a balance between SOX2 (foregut/esophageal) and CDX2 (hindgut/intestinal) transcription factors. Using squamous-specific inducible Sox2-KO (Krt5CreER/+ Sox2Δ/Δ ROSA26tdTomato/+) mice, we observed increased basal proliferation, reduced squamous differentiation, and expanded metaplastic glands at …

Hot Spring Associated Infectious Diseases In The Great Basin And Southwest, Matthew Bentz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Like all bodies of freshwater, natural hot springs can harbor pathogenic microorganisms that carry the threat of infectious disease. The unique chemistry, increased temperature, and popularity for bathing may alter the risk profile of hot springs compared to other natural bodies of water. Despite this risk, the role of hot springs as a reservoir for infectious diseases remains understudied, particularly within the context of regional public health. Nevada and the Great Basin/Southwest have increasingly promoted hot springs for the purposes of tourism, and they share a strong link to the cultural heritage of the region. The unknown risk profile and …

Co-Targeting Bcl-Xl With Mcl-1 Induces Lethal Mitochondrial Dysfunction In Diffuse Mesothelioma, Yuan Xu, Cristian G Medina, Deborah R Surman, Lacey E Dobrolecki, Monica Vilchis, Maheshwari Ramineni, Susan G Hilsenbeck, Yanming Li, Naren Li, Siqi Wu, Jaylon C Aggison, Xi Chen, Yi Zhu, Ying H Shen, R Taylor Ripley

Faculty, Staff and Students Publications

Diffuse mesothelioma (DM) is a rare but highly aggressive and treatment resistant neoplasm with low survival rates. Effective therapeutic strategies are limited, and resistance to treatment is a major obstacle. Myeloid Cell Leukemia (MCL)-1 and B-cell leukemia (BCL)-xL are anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins that block cell-intrinsic apoptosis through interactions on the mitochondrial outer membrane which contribute to therapeutic resistance.

We investigated whether B-cell homology domain (BH)-3 profiles were consistent between intra-patient fresh tumor sample, patient-derived cells (PDC), and patient-derived xenografts (PDX) by BH3 profiling; we observed striking consistency which enabled cross model comparisons. Next, we co-targeted BCL-xl …

Stabilized And Unstabilized Sampling Methods Result In Differential Fecal 16s Rrna Microbial Sequencing Results, Christopher E. Stamper, Andrew J. Hoisington, Joseph C. Ellis, Christopher A. Lowry, Lisa A. Brenner

Faculty Publications

Over the past decade, studies have been conducted to increase the understanding of associations between the fecal microbiome and human health. In conjunction, researchers have investigated the effects of study design, methods, molecular processing, and sequencing techniques. However, a lack of standardization of fecal sample collection methodology has introduced heterogeneity in sequencing results. Sources of variability include sample collection methods, storage temperatures, and transport times. Here we present 16S rRNA gene amplicon sequencing results from two sample collection methods (unstabilized sterile swab and stabilized OmniGene Gut Kits) collected from the same fecal specimens. The paired samples were collected either at …

Effect Of Histidine Tag On The Enzymatic Activity Of Pseudolysin And Its Interaction With The Streptomyces Metalloprotease Inhibitor (Smpi) Protein, Adewale Adeboye Adewole

Electronic Theses and Dissertations

Pseudolysin (PLN) protein is a major virulent factor in Pseudomonas aeruginosa infection. PLN belongs to the family of zinc-dependent metalloproteases. It is naturally inhibited by a smaller protein called streptomyces metalloprotease inhibitor (SMPI), secreted by Streptomyces nigrescens. Previous and current studies demonstrate that the interaction between PLN and SMPI offers unique mechanistic insights for drug development against infections caused by P. aeruginosa. This study investigated the effect of N-terminal Histidine (His) tag on the enzymatic activity of PLN and its interaction with SMPI. His-tagged PLN and SMPI proteins were expressed in bacteria and purified by affinity chromatography …

Post-Drought Growth Recovery Of Tea (Camellia Sinensis) Under Different Techniques And Doses Of Biofertilizer Applications, Nabila Ragil Wiharti, Intan Ratna Dewi Anjarsari, Yudithia Maxiselly

Jurnal Kultivasi

Drought stress is a major limiting factor affecting the growth, yield, and quality of tea (Camellia sinensis). The present study aimed to analyze the success of post-drought growth recovery of tea in response to different techniques and doses of biofertilizer applications. Field experiments were conducted from January to August 2024 in the experimental garden of the Research Institute for Tea and Cinchona, Gambung Blok A8, Bandung. This work was arranged in a split-plot design, consisting of a main plot with two biofertilizer application techniques (foliar feeding and soil drenching) and subplots with four levels of biofertilizer dosage (control (B1), 15 …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Adiponectin-Regulated Macrophage Responses In Aspergillus Fumigatus Infection: Mechanisms Of Uptake And Killing, Sri Harshini Goli

All-Inclusive List of Electronic Theses and Dissertations

Invasive aspergillosis (IA), caused by Aspergillus fumigatus, is a life-threatening infection in immunocompromised individuals, necessitating novel host-directed therapies. Macrophages are pivotal in antifungal defense, yet their function can be dysregulated; the influence of the adipokine adiponectin (APN) on this process is not fully understood. This thesis investigated the role of APN signaling in alveolar macrophage (AM) and bone marrow-derived macrophage (BMDM) responses to A. fumigatus and assessed the therapeutic potential of the APN receptor agonist, AdipoRon. Initial studies revealed that genetic deficiency in APN or its receptors renders AMs intrinsically pro-inflammatory and significantly impaired fungicidal activity against A. fumigatus. Subsequent …

In Vitro Assessment Of The Antihistomonal Activity Of Methyl Jasmonate And Jasmonic Acid, Mckayla B. Williams

Poultry Science Undergraduate Honors Theses

Histomonas meleagridis is a protozoan parasite and the causative agent of histomonosis in gallinaceous birds. There are currently no approved prevention or treatment options available for histomonosis control in the United States. Mortality in affected turkey flocks can exceed 80% which highlights the urgent need for research investigating novel strategies to mitigate histomonosis in the field. The objective of this study was to evaluate the in vitro antihistomonal and antibacterial effects of of methyl jasmonate (MeJA) and jasmonic acid (JA), two plant-derived compounds, in a xenic culture of H. meleagridis. Assays were conducted using cultured H. meleagridis (PHL strain) treated …

Microbial Guardians Of The Savannah: Unraveling The Gut Microbiome For African Carnivore Conservation, Laura E. Peirson

All NMU Master's Theses

Non-invasive fecal sampling is essential for wildlife gut microbiome (GMB) research, yet field conditions often limit preservation options. I compared gut bacterial communities in paired fecal samples preserved in stabilization tubes and air-dried in paper bags collected from anesthetized African lions (Panthera leo) and spotted hyenas (Crocuta crocuta) in Etosha National Park, Namibia. Additional opportunistic samples from carnivore kill sites were also analyzed. No significant differences in alpha or beta diversity were detected between preserved and dried samples, although bacterial beta diversity differed between preserved and opportunistic samples (PERMANOVA). Core bacterial communities remained consistent across sample …

Determining The Impact Of Surface Roughness On Disinfection Efficacy Of Commercial Products Against Pseudomonas Aeruginosa And Staphylococcus Aureus Wet Surface Biofilms, Kayley Stallings

All Theses

Biofilms are resistant to many stressors including disinfectant treatments. Disinfection may be further complicated by biofilms formed on damaged surfaces, as the damaged parts provide bacteria a better place to attach and grow. To better understand the risks, a new method to standardize surface scratching, to emulate worn surfaces via surface roughness changes was developed. These surfaces were used to grow biofilms with an adapted standardized EPA method to determine disinfection efficacy differences on scratched and non-scratched high-density polyethylene (HDPE) and stainless steel (SS) coupons treated with commercial disinfectants [hypochlorite (CL)-based, hydrogen peroxide (HP)-based, and quaternary ammonium (QA)-based]. Post-80 grit …

A Toi Rna Editing In Three Members Of The Microbotryum Violaceum Fungal Complext And Characterization Of Adar Genes Of Microbotryum Superbum., Shikhi Baruri

Electronic Theses and Dissertations

A-to-I RNA editing is a process that occurs post-transcriptionally. Through this process, adenosine (A) is replaced by inosine (I) in RNAs by adenosine deaminase enzymes that act on the single-stranded RNA. These enzymes, also known as ADARs, act on RNA. The translation and splicing mechanisms subsequently interpret inosine as guanosine (G), which effectively alters genetic information. This kind of RNA alteration can cause both nonsynonymous and synonymous changes in codon, which may have an impact on protein function. A group of over 89 basidiomycete fungal species known as the Microbotryum violaceum complex infects a similarly large group of plant host …

Long-Chain Fatty Acids Promote Candida Albicans Gut Colonization By Restructuring The Fungal Cell Surface, Musfirat Shubaita

Dissertations and Theses (Open Access)

Long-chain fatty acids promote Candida albicans gut colonization by restructuring the fungal cell surface

Musfirat Shubaita, BS

Advisory Professor: J. Christian Perez, Ph.D.

The yeast Candida albicans is a facultative anaerobe residing in the human digestive tract. Although fungal genetic determinants of mammalian host colonization have been identified, little is known about signals and molecules in the intestinal environment that influence C. albicans proliferation. Previously unpublished data from the Perez lab showed that oleic acid, one of the most abundant long-chain fatty acids in nature, promotes C. albicans colonization of the murine intestine. The goal of this research is to …

Microbial Metabolite Regulation Of Microglial Ahr Signaling In Alzheimer’S Disease, Ghalya E. Alrousan

Dissertations and Theses (Open Access)

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaque accumulation, neuroinflammation, and cognitive decline. Recent evidence suggests that systemic factors, particularly the gut microbiota and its metabolites, play a significant role in shaping brain immune responses, including microglial activation. However, the mechanisms linking gut dysbiosis to microglial dysfunction in AD are poorly understood. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor responsive to tryptophan metabolites, has recently gained attention as a key regulator of neuroinflammation and microglial function. I hypothesize that the loss of beneficial microbial AHR ligands, specifically indole derivatives, during aging and AD …

Nerve-To-Cancer Transfer Of Mitochondria During Cancer Metastasis, Gregory Hoover, Shila Gilbert, Olivia Curley, Clémence Obellianne, Mike T Lin, William Hixson, Terry W Pierce, Joel F Andrews, Mikhail F Alexeyev, Yi Ding, Ping Bu, Fariba Behbod, Daniel Medina, Jeffrey T Chang, Gustavo Ayala, Simon Grelet

Faculty, Staff and Students Publications

The nervous system has a pivotal role in cancer biology, and pathological investigations have linked intratumoural nerve density to metastasis1. However, the precise impact of cancer-associated neurons and the communication channels at the nerve–cancer interface remain poorly understood. Previous cancer denervation models in rodents and humans have highlighted robust cancer dependency on nerves, but the underlying mechanisms that drive nerve-mediated cancer aggressivity remain unknown2,3. Here we show that cancer-associated neurons enhance cancer metabolic plasticity by transferring mitochondria to cancer cells. Breast cancer denervation and nerve–cancer coculture models confirmed that neurons significantly improve tumour energetics. …

Distribution, Roles And Environmental Drivers Of Bacterial Communities In The Chesapeake And Delaware Bays, Mir Alvee Ahmed

All Dissertations

In this dissertation, water samples from the Chesapeake and Delaware Bay estuaries were analyzed to see how estuarine environmental gradients drive distributions, functional potential, growth estimates and gene expressions of bacteria. To answer this, the abundant and versatile taxa– Rhodobacterales and Actinobacteriota, along with broader particle-attached (PA) vs. free-living (FL) bacterial assemblages of these Bays were analyzed using a multifaceted ‘omics approach.

The PA fraction, differing from the FL in taxonomy, distribution, functional potential and estimated growth rates across salinities, and bays harbored genes degrading complex aggregates, and surface attachment. The FL counterpart presented genes involved in nutrient uptake …

Orchestrated Architecture Dismantling: Borrelia Burgdorferi’S Coordinated Destruction Of Adaptive Immune Responses, Craig A. Land

Electronic Theses and Dissertations

Borrelia burgdorferi represents the most prevalent vector-borne bacteria in North America, affecting ~476,000 Americans annually yet persisting despite robust immune responses. This project reveals spirochetes target adaptive immunity through coordinated lymphatic colonization and precision immune dysregulation.

Using comparative host models (C57BL/6 vs. reservoir Peromyscus leucopus), we demonstrate lymph node colonization within 48-hours, with spirochetes exploiting LYVE-1-positive lymphatic structures as dissemination highways while avoiding the interior of follicular regions. Critically, we identify targeted CD4+ T-cell elimination in germinal center border zones at 21-DPI, precisely when these cells should be coordinating protective immunity. Concurrent upregulation of inhibitory receptor CD32b creates molecular …

Low-Dose Metformin Requires Brain Rap1 For Its Antidiabetic Action, Hsiao-Yun Lin, Weisheng Lu, Yanlin He, Yukiko Fu, Kentaro Kaneko, Peimeng Huang, Ana B De La Puente-Gomez, Chunmei Wang, Yongjie Yang, Feng Li, Yong Xu, Makoto Fukuda

Faculty, Staff and Students Publications

Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specific Rap1 knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons …

Advanced Analytical Biosensing For Cancer Detection And Neural Diagnostics Using Tapered Optical Fiber (Tof), Protonic, And High Throughput Microplate –Based Technologie, Bayan Hassan Alharbi

Chemistry & Biochemistry Theses & Dissertations

This dissertation investigates the development and application of advanced biosensing technologies to enhance early disease detection, neurological diagnostics, and bioactive compound evaluation. The research spans four key areas. First, it introduces tapered optical fiber (TOF)-based plasmonic biosensors for the non-invasive detection of prostate cancer, demonstrating high sensitivity and specificity compared to conventional diagnostic methods.

Second, it explores the use of fluorescent biosensors to test the Transmembrane Electrostatically Localized Proton (TELP) theory, shedding light on the role of localized protons in neuronal signaling and energy transfer. Third, the work presents a high-throughput, microplate-based biosensing platform for analyzing mitochondrial function under nanosecond …

The Inside Scoop: Elucidating The Three-Way Relationship Between Schistosoma Mansoni, The Gut, And Vaccines, Mariam A. Mhanna

Biomedical Sciences Theses & Dissertations

Schistosomiasis is a neglected tropical disease that affects over 250 million people worldwide. This blood fluke infection burdens communities and areas with limited to no access to clean fresh water. When a host is exposed to cercariae, the infectious agent, in a body of water, it matures in the host’s circulation into adult female and male worms. Copulated adult worms migrate to the mesentery, in the case of Schistosoma mansoni, and produce eggs that can cross the intestinal barrier and get excreted in the feces to continue the lifecycle. The effects of S. mansoni infection on the host …

Microbial And Ecophysiological Indices Of Agricultural Soils As Affected By Different Farming Practices In Tropical Monsoon Climate, Gulshan Ara Begum, Sajal Roy, Nasrin Chowdhury

Journal of Environmental Science and Sustainable Development

Organic farming is increasingly promoted as a sustainable alternative to conventional agriculture due to its positive effects on soil microbial dynamics, a critical component of ecosystem functioning. However, empirical comparisons of microbial responses across these systems are scarce. Therefore, we conducted a study to assess the various microbial indices of soils taken from distinct crop fields (e.g., brinjal, chilli, tomato, bean, and fallow lands) managed under both conventional and organic farming techniques. Composite soil samples from surface layer (0–15 cm) were collected in a completely random way from Bandarban upazila of Bangladesh (22°11'24.0"N 92°09'00.0"E, organic fields; 22°10'12.0"N 92°09'36.0"E, conventional fields). …

Single-Cell Transcriptomics Reveals Biomarker Heterogeneity Linked To Cdk4/6 Inhibitor Resistance In Breast Cancer Cell Lines, Ilenia Migliaccio, Martina Bonechi, Dario Romagnoli, Giulia Boccalini, Francesca Galardi, Cristina Guarducci, Agostina Nardone, Rachel Schiff, Laura Biganzoli, Luca Malorni, Matteo Benelli

Faculty, Staff and Students Publications

Cyclin dependent kinases 4 and 6 inhibitors have brought great improvements in the treatment of luminal breast cancer, but resistance is a major clinical hurdle. Multiple biomarkers of resistance have been proposed, but none is currently utilized in clinical practice. By performing single-cell RNA sequencing of seven palbociclib-naïve luminal breast cancer cell lines and palbociclib-resistant derivatives, we show that established biomarkers and pathways related to CDK4/6i resistance present marked intra- and inter- cell-line heterogeneity. Transcriptional features of resistance could be already observed in naïve cells correlating with levels of sensitivity (IC50) to palbociclib. Resistant derivatives showed transcriptional clusters that significantly …

In Silico Prediction Of Cytotoxic T-Cell Epitopes From Helicobacter Pylori Virulence Factors Using An Immunoinformatics Approach, Demy Valerie Chacon, Kiana Alika Co, Daphne Noreen Enriquez, Aubrey Love Labarda, Reanne Eden Manongsong, Edward Kevin B. Bragais

Biology Faculty Publications

Background: Helicobacter pylori infects approximately half of the global population, leading to gastric and duodenal ulcers. Despite the availability of antibiotics, challenges such as patient reluctance, high treatment costs, and antibiotic resistance limit their effectiveness, making vaccination a promising alternative. This study used immunoinformatics to identify candidate epitopes for a multiepitope vaccine construct against H. pylori.

Material and methods: The protein variability server was utilized for conservation analysis. The epitopes were screened for antigenicity, allergenicity, toxicity, cross-reactivity, and population coverage. Selected epitopes were docked with their corresponding human leukocyte antigen (HLA) alleles, and thermodynamic quantities were determined. Five virulence …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Dietary Lipids Induce Ppard And Bcl6 To Repress Macrophage Il-23 Induction After Intestinal Injury And Lps Exposure, Ashleigh M Gil, Daniel F Zegarra-Ruiz, Wan-Jung Wu, Kendra Norwood, Adrien Assie, Buck S Samuel, Angela M Major, Gretchen E Diehl, Andrea A Hill Mcalester

Faculty, Staff and Students Publications

Unresolved tissue damage is a common feature of Inflammatory Bowel Disease (IBD) that facilitates disease progression. Here, we showed that high animal fat diets (HFD), an environmental risk factor associated with IBD pathogenesis, suppress intestinal macrophage production of critical tissue repair responses after damage. This includes reduced IL-23 production, which drives downstream production of IL-22, which is needed for barrier repair. Indicating that dietary lipids interfere with responses to microbial molecules needed to induce barrier protective functions, we found oleic acid could directly suppress macrophage Il23a induction after lipopolysaccharide (LPS) treatment. Deleting the lipid transporter CD36 on macrophages restored the …

Utilizing The Combinatory Power Of Chemotherapeutic Compounds In Triple Negative Breast Cancer Cells, Matthew I. Hyder

Biology Summer Fellows

Breast cancer is the leading cause of cancer-related deaths among women worldwide and the second most common cause of cancer deaths in women in the United States. Genetic variants that increase the risk of breast cancer include mutations in the breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2). Apoptosis, or programmed cell death, is a natural process that helps the body remove aged cells. However, in cancer, deregulated apoptotic signaling—especially the activation of anti-apoptotic mechanisms—enables cancer cells to evade this process, leading to uncontrolled proliferation, tumor survival, therapeutic resistance, and cancer recurrence. Most anti-cancer drugs function as chemotherapeutic …