Biochemistry, Biophysics, and Structural Biology Commons^™

Development Of Self-Assembled Polymeric Polyplexes For Microrna Delivery: Toward Treatment Of Alcohol-Associated Liver Disease, Marjina Akter Kalpana

Theses & Dissertations

Self-assembled polymeric polyplexes have the potential to serve as an RNA interference (RNAi) delivery platform for the combined inhibition of CXCR4 and miR-155 in the treatment of alcohol-associated liver disease (AALD). A central challenge in RNA delivery is balancing the extracellular stability of polyplexes, cellular uptake, and intracellular release of RNA cargo. We developed polymeric polyplexes using the CXCR4-antagonist polymer PAMD, designed to target CXCR4 on activated hepatic stellate cells (HSCs) and deliver therapeutic miRNA to activated Kupffer cells (KCs) in fibrotic liver. We improved the polyplexes by cholesterol modification of PAMD and by PEGylation of PAMD-Ch. The cholesterol modification …

Evaluating Bmx-001 As A Selective Radioprotector For Healthy Tissue In Pelvic Cancers, Molly Myers

Theses & Dissertations

Pelvic cancers, including rectal, anal, and prostate cancer, are relatively survivable cancers with high five-year survival rates, partially due to the addition of radiation to treatment regimens. Radiation confers excellent tumor control, but also causes damage to surrounding tissue, resulting in both short-term and long-term side effects. In a patient population that is surviving longer after treatment, limiting the impact of side effects is instrumental to improving patient quality of life. Radiation-induced ROS is instrumental in causing these side effects and provides a unique opportunity to protect healthy tissue from damage while sensitizing cancer tissue to treatment, as cancer cells …

Self-Assembling Rna Nanostructures Are Highly Sensitive To Environmental Conditions, Jordan Aposhian, Surya Pratap S. Deopa, Scott Horowitz, Joseph D. Yesselman

Chemistry and Biochemistry: Faculty Scholarship

Recent developments in RNA nanotechnology have led to an increase in the design of specific, higher-order RNA structures, which will ultimately be used in drug delivery and immunomodulation applications. As researchers create RNA nanostructures with the intention of making them a standard tool in molecular biologists' toolkits, further investigation is required into the robustness of RNA designs. Primarily, in what different molecular contexts are the designed and intended nanostructures stable? In this work, we show that RNA nanostructure self-assembly is highly sensitive to environmental conditions by using second-order right-angle light scattering. While a test RNA hexagonal grid nanostructure forms correctly …

Investigating The Role And Mechanism Of Faecalibacterium Prausnitzii In Fatty Acid Metabolism And Obesity Using The Drosophila Melanogaster Model, Jackson Head, Whitley Whitehead

Student Scholar Symposium

The obesity epidemic has increased to enormous numbers with 890 million adults being classified as obese (BMI≥30). Obesity is of extreme concern as it is a comorbidity to coronary heart disease, type-2 diabetes, and cancer. Although obesity has classically been attributed to genetics and lifestyle, there is a growing interest in other factors, including the gut microbiome. Germ-free mice are resistant to weight gain even when placed on a high-calorie diet, establishing that metabolites produced by gut microbiota can dramatically inhibit metabolism. Here, we use Faecalibacterium prausnitzii, which has been previously shown to be reduced in obese individuals; however, …

Indole Improves Outcomes Of Cronobacter Sakazakii Infection In C. Elegans Through Ahr-1, Cayden Durrough

Student Scholar Symposium

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting premature infants. Toll-like receptor 4 (TLR4)-mediated epithelial damage allows microbial translocation, triggering inflammation that can lead to sepsis and death. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, and AhR ligands have been shown to prevent NEC in a mouse model. Indole, an AhR ligand, has been reported to extend the healthspan of C. elegans, and we have shown previously it mitigates poor outcomes in wild-type worms infected with Cronobacter sakazakii (Cs), a bacterial pathogen linked to NEC. We hypothesized that C. elegans must express ahr-1, the ortholog …

Levels Of Beta Catenin With Treatment Of Hd5 In Iec-6 Rat Cells, Audrey Birdwell, Josiah Stafford, Obaid Ashari, Emily Powell, Maryam Gerges, Maryam Mina

Student Scholar Symposium

Human Defensin 5 (HD5) is an antimicrobial peptide present in the small intestine that plays a role in gut homeostasis. We have been investigating the role of HD5 in colon cells, but research shows that HD5 levels in the small and large intestine vary significantly in Crohn's. Previous data from our lab suggests that HD5 leads to a decrease in wound healing and an increase in apoptosis in colon cells, we want to see if the same is true in the small intestine. So, we are investigating the effect of HD5 on expression of β-catenin, a key protein in the …

Understanding The Role Of Hd5 In Colonic Epithelial Cell Death, Maryam M. Gerges, Amanda D. Williams

Student Scholar Symposium

Inflammatory bowel disease (IBD) is an autoimmune disorder where the immune system attacks healthy tissue. IBD can occur in both adults and children, describing Ulcerative Colitis (UC) and Crohn’s Colitis (CC). Our lab studies human alpha defensin 5 (HD5), an antimicrobial peptide that normally maintains small intestinal sterility. However, in CC patients, HD5 is overexpressed in the colon. Preliminary data suggests that HD5 increases colonic cell death. This project aims to determine if HD5 induces apoptosis and its mechanisms. To this end, we will test if the suppression of caspase enzymes with a pan-caspase inhibitor reduces cell death triggered by …

Functionality Of The Ryanodine Receptor Type 1 (Ryr1) In The Development Of Malignant Hyperthermia (Mh), Cesar Medina, Joshua Owens

Student Scholar Symposium

Malignant Hyperthermia (MH) is a rare but potentially lethal pharmacogenetic disorder, affecting roughly 1 in 30,000 children and 1 in 100,000 adults undergoing surgery. MH can be triggered by agents used for general anesthesia. These may include volatile anesthetics such as sevoflurane, isoflurane, desflurane, halothane or depolarizing neuromuscular blockers such as succinylcholine. Upon administration of a trigger, an MH susceptible (MHS) patient can develop a hypermetabolic state during the intraoperative or postoperative periods. If not treated quickly, an MH episode could result in organ dysfunction or death. The primary mechanisms involved in the development of an MH crisis include the …

Elucidating The Effects Of Hd5 On Actc1 Expression In Crohn's Disease, Carolyn Tran, Sohir Abdelnour, Joyce Lawson, Ellis Puscas

Student Scholar Symposium

Approximately 1.6 million Americans currently have Crohn’s Disease (CD), a condition that affects the gastrointestinal (GI) tract, particularly the small intestine, leading to chronic inflammation, abdominal pain, severe diarrhea, and fatigue. Although treatments exist, misdiagnosis remains a challenge due to symptom overlap with other inflammatory bowel diseases (IBD). Previous studies have shown an increase in Human Alpha Defensin (HD5) in Crohn’s Colitis, resulting in slower wound healing closure, increased apoptosis, and potential effects regarding alpha-actin expression. However, its effects in the small intestine remain unclear. Alpha-actin is a cytoskeletal protein that maintains cellular structure through cell migration, tissue remodeling, and …

Have You Had Your Vitamins Today? Development Of An Lc-Ms/Ms Method With A 100% Aqueous Gradient To Simultaneously Measure B Vitamins In Plasma From Study Participants In A “Greens” Nutritional Supplement Clinical Trial, Kennedy Brothers, Abigail Davis, Anna Losher, Yusra Ahmed, Sora Ghanem, Matthew J. Vergne

Student Scholar Symposium

This study assessed the absorption of key micronutrients from the multi-ingredient supplement using a novel developed LC-MS/MS method capable of analyzing B vitamins in a single run.

The study a randomized, double-blind, placebo-controlled crossover trial with 16 healthy participants (8 males, 8 females) to measure plasma nutrient appearance over 8 hours after supplement consumption. Serial blood samples were collected pre-consumption and at specified intervals post-ingestion. The novel LC-MS/MS method simultaneously quantified biotin, nicotinamide, pyridoxine, riboflavin, and thiamin in blood samples.

Results:The LC-MS/MS method had a range of 0.1 ng/mL to 1000 ng/mL and it proved to be robust and …

Structural Basis Of A Class Ii Ribonucleotide Reductase Found If Mycobacterium Tuberculosis, Leah Jacob

Student Scholar Symposium

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health challenge, particularly due to its ability to enter a dormant, drug-tolerant state that enables long-term persistence within the host. Just before dormancy, Mtb replicates its entire genome creating DNA precursors for when the infection reactivates. Ribonucleotide reductases (RNRs) play a critical role in bacterial survival by catalyzing the conversion of ribonucleotides into deoxyribonucleotides, a necessary step for DNA replication and repair. The class II RNR, NrdZ, has been implicated in facilitating Mtb persistence under hypoxic stress conditions, yet its structural and mechanistic function remains largely uncharacterized. …

Unmasking Metals: Icp-Oes Detection Of Toxins In Costume Jewelry, Bailee Kirk, Sierra Beck, Jesse Lampley

Student Scholar Symposium

The presence of toxic trace metals in costume jewelry poses potential health risks and raises environmental concerns. Many inexpensive jewelry items contain harmful elements such as lead, cadmium, nickel, and arsenic, which can cause skin irritation, allergic reactions, and systemic toxicity through prolonged exposure. Regulatory guidelines exist to limit these metals in consumer products, but compliance varies, necessitating continued monitoring. This study utilizes Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) to detect and quantify trace metals in costume jewelry. ICP-OES offers high sensitivity and multi-element analysis capabilities, making it an effective tool for evaluating the composition of complex materials. Jewelry …

Design, Synthesis And Biological Activities Of N-Substituted Phthalimide Derivative, Beaula Mangundah

Honors Theses

Phthalimides are a group of compounds among bicyclic non-aromatic nitrogen heterocycles that have gained recognition for their bioactivity across various fields, notably anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory. This study discusses the synthesis of a novel phthalimide derivative and provides an analysis of its biological activity. It was conducted through a Boric acid Imide synthesis and yielded a successful derivative using hexylamine. The product was evaluated in vitro for antimicrobial, anticoagulant, and anti-inflammatory properties using Kirby-Bauer disk diffusion, clotting time, hemolysis inhibition, and protein denaturation assays. It showed mild anticoagulant and anti-inflammatory activity.

Methods For The Discovery Of Antibodies Toward Junin Virus Utilizing Yeast Surface Display, Jonathon E. Corral

Doctoral Dissertations and Projects

The importance of this study is to perform antibody discovery as a means to derive novel preventative and therapeutic antibody countermeasures against the Junín virus, to alleviate the potential risk of a global pandemic. The purpose of this methodological study was to develop a protocol that utilizes yeast surface display to discover antibodies, from naïve human antibody libraries, that can bind the Junín Virus antigen. The methodology of yeast surface display employs the galactose-inducible GAL1 promoter to synthesize and express antibody proteins bound to the Aga2p and Aga1p and anchored to the cell wall by glycosyl phosphatidylinositol motif (GPI). The …

Geometric And Proximity Based Substrate Targeting By Cullin-Ring Ligases, Jerry Li

UNLV Theses, Dissertations, Professional Papers, and Capstones

Homeostasis, the process of maintaining stable biochemical and biophysical conditions, is a fundamental facet of cellular viability. Biochemical homeostasis is critical to support the biological functions that sustain living organisms. Protein ubiquitylation is one of the primary cellular pathways that regulate protein homeostasis and turnover. Ubiquitylation is initiated through the conjugation of a small globular protein known as ubiquitin, onto a given substrate. There exists a myriad of cellular fates that ubiquitylated proteins may undergo, but the most widely studied pathway is protein degradation, whereby a ubiquitylated protein substrate is shunted to a large macromolecular protease known as the proteasome, …

Deciphering The Crl Code: Novel Mechanisms Of Canonical And Non-Canonical Ubiquitylation, Nicholas Wayne Purser

UNLV Theses, Dissertations, Professional Papers, and Capstones

Protein degradation is a fundamental process required for maintaining cellular homeostasis in eukaryotic organisms. In humans, distinct cell types exhibit unique proteomic landscapes that are dynamically balanced by the continual synthesis and degradation of proteins. The timely removal of damaged, misfolded, or old proteins is essential to permit new protein synthesis and to ensure proper cellular function.

Central to this regulatory network is ubiquitylation, a highly conserved posttranslational modification system that governs protein stability and function across all eukaryotic cells. Through the covalent attachment of ubiquitin molecules to protein substrates, this system modulates a broad range of biological processes, including …

The Dynamic Interplay Between Monovalent Salts And Ribosomal Protein S1 In Regulating Rna G-Quadruplex Structure, Chloe M. Martin

Honors Theses

Many remarkable discoveries, especially in the last decade, have shown scientists just how important RNA is. In this study, the secondary structure of RNA, G-Quadruplexes, is the topic of interest and how they are affected by salts and S1 protein. To obtain the S1 protein it was transformed from E. Coli using a bacterial plasmid. The S1 protein was then purified from the bacteria through the use of many purification methods. The monovalent cationic salts used were LiCl and KCl which have different ionic radii size that contributes to the stability of RNA G-Quadruplexes. This stability was observed and affected …

Structural Basis Of Panx1 Permeation And Positive Modulation By Mefloquine, Yangyang Li, Zheng Ruan, Junuk Lee, Ian Orozco, Edward Zhou, Juan Du, Wei Lü

Department of Biochemistry and Molecular Biology Faculty Papers

Purinergic signaling relies on ATP release through exocytosis and large-pore channels. Large-pore channels permeate both small anions like chloride and large signaling molecules like ATP, but how this broad cargo selectivity is structurally controlled remains elusive. Here we investigate PANX1, a prototypical large-pore channel, and uncover structural plasticity at the extracellular entrance formed by seven tryptophan (W74) residues. The W74 sidechains are flexible, sampling conformations that range from a constricted state permissive only to chloride to a dilated state compatible with ATP. These states are coupled to variable cation-π interactions between W74 and arginine 75 (R75), suggesting a mechanism for …

Book Of Abstracts, Seton Hall University

2025 Augustine Undergraduate Research Symposium

No abstract provided.

Engineered Multifunctional Drug-Loaded Dendrimer Nanoparticles For Glaucoma: Triple Mechanism Via Antioxidant Activity, Iron Chelation, And Enhanced Ocular Transport, Burhan Ates, Ashish Trital, Vimalin Jeyalatha Mani, Lei Xu, Jonathan Kenlee, Nuran Ercal, Hu Yang

Chemistry Faculty Research & Creative Works

In this study, we developed multifunctional nanoparticles based on polyamidoamine (PAMAM) dendrimers functionalized with caffeic acid (CA) and poly (ethylene glycol) maleimide (PEGM) for the topical delivery of hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX). The PAMAM-CA and PAMAM-CA-PEGM conjugates exhibited antioxidant and iron-chelating activities in a dose-dependent manner. BM- and BX-loaded dendrimer nanoparticles produced using a multi-inlet vortex mixer showed uniform spherical morphology (∼80 nm by TEM) and hydrated sizes of ∼135-144 nm by DLS. Both nano formulations demonstrated high cytocompatibility with human corneal epithelial cells and were nonirritant in the HET-CAM assay, with PEGM further improving cytocompatibility. …

You Have To Cut&Walk; Before You Can Cut&Run;: Regulation Of Gene Expression By The Vitamin D Receptor (Vdr) In The Annual Killifish, Austrofundulus Limnaeus, Rosalia Tanori

Dissertations and Theses

The annual killifish, Austrofundulus limnaeus, found in ephemeral ponds in South America, possesses a remarkable ability to survive extended periods without water and oxygen. This ability is associated with developmental dormancy known as diapause. Numerous genetic and environmental factors influence the entry into diapause and tolerance to environmental stress. Among these is vitamin D3 signaling mediated by the vitamin D receptor (VDR), which plays a crucial role in regulating entry into diapause and the continuous development of an embryo in a temperature-dependent manner. Vitamin D3 signaling influences a variety of physiological processes in vertebrates. While extensively characterized in mammalian …

Buffer Vs. Swabs: Efficacy Of Carrier Nucleic Acids In Robotic Extractions, Shawn Cecil

Honors Projects

This study compared the efficiency of two carrier nucleic acid methods, specifically using salmon sperm DNA (spDNA), in robotic solid-phase extractions of cotton swab samples. Robotic extractions reduce processing time and workload but result in substantially lower DNA recovery than manual organic extraction. This research tested 10 µg of spDNA being added to the lysis buffer or pre-treating the swabs with it before DNA was added. Both methods showed a significant increase in recovery compared to extractions with no carrier. In the buffer extractions, recovery ranged from 69.4% to 117.5% and the swabs being pre-treated ranged from 84.2% to 125.8% …

Investigating Factors That Affect Total Ige Antibody Levels Of A Canine Population In Louisville, Ky, Iris N. Gillespie

Undergraduate Theses

Canine atopic dermatitis (CAD) is a genetically predisposed condition that causes inflammatory and pruritic (itchy) skin reactions in response to environmental and food allergens. The main purpose of this study is to determine if there is a correlation between pollen counts and total canine IgE antibody levels of dogs living in Louisville, KY. Additionally, data is analyzed to look for trends documented in previous studies related to the impacts of sex, age, and allergic symptoms on total IgE count. In collaboration with the Downtown Animal Hospital, blood samples were drawn from 16 dogs at one point in February (when pollen …

Grapes Cure Cancer: My First Molecular Docking Analysis Of Resveratrol Binding To Anti-Apoptotic Protein Bcl-2: In Silico, Sydni Ann Kolokoltsev, Vishwas Joshi

Publications and Research

B-cell lymphoma 2 (BCL-2) is an anti-apoptotic protein frequently overexpressed in cancer, enabling tumor cells to evade programmed death. Resveratrol, a grape-derived polyphenol, has reported anticancer properties. Here we performed in silico docking of resveratrol to human BCL-2 using AutoDock Vina. The best-ranked pose exhibited a predicted binding free energy of 8.0 kcal/mol and formed at least one short hydrogen bond (~1.8 Å) with pocket residues. These results support further evaluation of resveratrol as a potential modulator of BCL-2-mediated apoptosis.

Unsaturated Fatty Acid Oil-Based Microdroplets: A Promising Novel Class Of Microdroplets, Ramiz S. Alejilat

Seton Hall University Dissertations and Theses (ETDs)

Droplet-based microfluidics has rapidly advanced numerous fields, including chemistry, biology, materials science, medicine, food science, and cosmetics. In these systems, fluorocarbon oil combined with fluorinated surfactants is the preferred medium for fluid encapsulation, offering exceptional stability and biocompatibility essential for sensitive biological and chemical processes. However, growing concerns about the environmental and biological risks associated with fluorinated chemicals have prompted a search for alternatives.

This study is the first to explore the use of unsaturated fatty acids derived from emu oil for microdroplet formation. We characterized droplet formation based on flow rates and the presence non-fluorinated surfactant at a certain …

The Triangular Interaction Between Dietary Polyphenols, Gut Microbiota, And Metabolic Syndrome, Emily Bayliss

Senior Honors Theses

Type 2 diabetes mellitus (T2DM) is a growing global health concern characterized by peripheral insulin resistance as well as impaired insulin secretion from pancreatic β-cells. Emerging evidence suggests that the gut microbiome, specifically gut dysbiosis, an imbalance in the gut microbiome, is a critical modulator of the pathophysiology of T2DM. Dietary polyphenols, a diverse group of bioactive compounds that are abundant in plant-based foods, have recently gained attention for their potential to attenuate metabolic disorders through their antioxidant and anti-inflammatory properties as well as through modulating the composition and activity of gut microbes, thereby attenuating dysbiosis. However, the diabetic state …

Evaluating The Effectiveness Of An Air Purification System In Reducing Bacterial Chondronecrosis With Osteomyelitis Lameness In Broiler Chickens, Abdulaziz Ali Alqahtani

Graduate Theses and Dissertations

Bacterial chondronecrosis with osteomyelitis (BCO) is the primary cause of lameness in commercial broiler production and has a profound impact on animal welfare and cost-effectiveness. The purpose of this experiment was to examine the effect of an air purification system on mitigating BCO lameness in broiler chickens. One thousand eight hundred broiler chicks were reared in two side-by-side research barns. Eight air filtration units were installed in one building, and none in the other. Treatment groups in both houses included positive control birds on wire flooring to induce BCO, as well as negative control, feed additive, vaccination, and a combination …

Engineered An Ultrasmall Curcumin Oral Nanoformulation Restores Intestinal Integrity And Gut Microbiota Dysbiosis, Vivek Sharma, Prateeksha Prateeksha, Balwant Paliya, Sateesh Gupta, Sarvendra Singh, Anand Anunay, Sushil Agrahari, Shailendra Singh, Chandana Rao, Saroj Barik, Brahma Singh

Department of Biochemistry and Molecular Biology Faculty Papers

Antibiotic therapy for bacterial infections often disrupts gut microbiota (GM) and intestinal integrity, inducing chronic inflammation and inflammatory bowel diseases. An effective therapeutic intervention is urgently needed to alleviate the aforementioned adverse effects of antibiotics. Curcumin (CUR) reveals great potential to restore intestinal integrity and GM dysbiosis due to its strong antiinflammatory and prebiotic effects. However, the weak solubility and stability of CUR result in limited bioavailability and a short half-life, which restricts its clinical uses. An ultra-small CUR oral nanoformulation was created using a carboxylated galactomannan (cGM), facilitated by hydrogen bonding between the phenolic hydroxyl groups of CUR and …

Development Of Novel Small Molecule Therapeutics For Myotonic Dystrophy, Xhesika Azis

Biological Sciences

Myotonic Dystrophy type 1 (DM1) results from expanded CUG repeat RNA that sequesters MBNL proteins and disrupts alternative splicing. Small molecules that bind toxic repeat RNA and release MBNL proteins represent a promising therapeutic strategy. This thesis examines newly synthesized modified polycyclic compounds (MPCs) engineered to target CUG RNA with enhanced specificity and efficacy. Through Suzuki–Miyaura coupling and benzoquinone-mediated cyclization, MPC03 was synthesized and characterized by NMR and LC–MS.

The biological activity of these compounds was assessed in DM1 patient-derived myotubes and fibroblasts. MPC03 consistently produced dose-dependent rescue of multiple MBNL-regulated exons, restoring splicing patterns toward those observed in healthy …

Blood-Based Clinical Markers For Early Dementia Detection: Insights From Ad-Detect-Cohort, Benard Aliwa, Jasmit Shah, Olivera Nesic Taylor,, Samuel Nguku, Juzar Hooker, Dilraj Sokhi, Sylvia Mbugua, Litha Musili, Rachel Maina, Harrison Kaleli, Levi Muyela, Anne Njoki Gitere, Anne Nyambura, Zul Merali, Karen Blackmon, Chinedu Momoh

Brain and Mind Institute

Background: Over 55 million people worldwide live with dementia, with more than60% residing in low- and middle-income countries. Alzheimer’s disease, the mostcommon form of dementia, accounts for 60–70% of cases. Early and accurate diagnosisremains a global challenge, necessitating novel approaches to mitigate the diseaseburden. Biomarkers hold significant promise in improving diagnostic accuracy andpredicting disease progression. Validated biomarkers for the preclinical stages ofdementia are crucial for advancing diagnosis and therapeutic strategies. We aimedto identify potential clinical markers for early dementia detection and assess theirpredictive accuracy in identifying high-risk individuals.

Method: We analyzed blood samples from dementia cases (n = 30) and …