Molecular Biology Commons^™

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) causes severe respiratory tract infections in all cohorts, but especially in vulnerable groups such as children, older adults, and the immunocompromised. The matrix (M) protein of HMPV, like the M proteins of other members of the Mononegavirales order, is involved in virus assembly and budding. However, other functions of the HMPV M protein have yet to be elucidated. To investigate these various functions of the M protein, we used a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense agent designed to block translation of the M gene to reduce M expression during infection. Treatment with varying concentrations of an …

Antiestrogens As Bone Protective Therapeutics For Estrogen Receptor-Positive Breast Cancer In The Presence Of Osteoporosis, Faith E. Parker, Emily K. Zboril, David C. Boyd, Rachel Myrick, J. Chuck Harrell

Undergraduate Research Posters

Breast cancer (BC) is one of the most significant causes of mortality among women and the second leading cause of cancer death in women. The estrogen receptor (ER) is a key oncogenic driver in the majority of breast cancer. ER+ BC is the most common molecular subtype of BC. Management of ER+ breast cancer varies depending on menopausal status. For premenopausal women, the goal is to suppress estradiol production from the ovaries with surgical oophorectomy and/or aromatase inhibitors. In postmenopausal women, endocrine therapy (ET) serves to suppress estradiol production from sources other than the ovaries. During the menopausal transition, estradiol …

Patterns Of Ovarian And Gonadotropin Hormones In Emerging Adult Oral Contraceptive Users, Summer Mcormond

Undergraduate Research Posters

Oral contraceptives (OCs) are often initiated during adolescence and emerging adulthood, a period of continued maturation of the hypothalamic–pituitary–gonadal (HPG) axis. Because hormonal exposure during this window may shape emotional, biological, and reproductive outcomes, it is important to understand the specific formulations young women take and the hormonal profiles these formulations produce. This study characterizes OC formulation features and measured hormone levels in young adult OC users (n = 30).

Ethinyl estradiol (EE) doses ranged from 0.01–0.035 mg (mean = 0.022 mg), with 70% using ≤0.02 mg. Pill regimens included 21/7 packs (83%), 24/4 packs (10%), and 84/7 regimens (3%). …

The Geminivirus Al2 Protein Interacts With Host Proteins Involved In The Plant Antiviral Response, Pheobean Atieno Odongo

Graduate Research Theses & Dissertations

Geminiviruses are economically important plant DNA viruses infecting a broad range of plant species and causing devastating crop diseases, resulting in up to 100% crop loss. As a result of these heavy losses on food and cash crops, these viruses represent a new threat to global food security and sustainability. In this research, I use Tomato golden mosaic virus (TGMV) to study host-virus relationships with an overall goal of developing sustainable and eco-friendly crop resistance. TGMV belongs to the Geminivirus subgroup, Begomovirus, that is characterized by a split genome consisting of two single-stranded circular DNAs. The TGMV genome encodes proteins …

Role Of The Osaa Transcription Factor Gene In Development, Secondary Metabolism And Virulence In The Mycotoxigenic Fungus Aspergillus Flavus, Farzana Ehetasum Hossain

Graduate Research Theses & Dissertations

Aspergillus flavus colonizes oil-seed crops, contaminating them with aflatoxins; highly carcinogenic mycotoxins that cause severe health and economic losses. Genetic studies may reveal new targets for effective control strategies. Here, we characterized a putative WOPR transcription factor gene, osaA, in A. flavus. Our results revealed that osaA regulates conidiation and sclerotial formation. Importantly, deletion of osaA reduces aflatoxin B1 production, while, unexpectedly, transcriptome analysis indicated upregulation of aflatoxin biosynthetic genes, suggesting post-transcriptional or cofactor-mediated regulation. Cyclopiazonic acid production also decreased in the absence of osaA. In addition, the osaA mutant exhibited upregulation of genes in the imizoquin and aspirochlorine clusters. …

Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode

Graduate Studies Theses and Dissertations 2026

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with therapeutic resistance continuing to limit the effectiveness of current treatments. Three complementary studies were conducted to identify therapeutic vulnerabilities and evaluate novel combination strategies in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC).  First, dual inhibition of fibroblast growth factor receptor 4 (FGFR4) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling was investigated in PDAC models. A combination of targeted drug treatments reduced viability, clonogenic survival, migration, and suppressed signaling pathways involved in translational control. This supported a functional interaction between FGFR4 and PI3K-mTOR co-activation in …

The Biosynthesis Of The Natural Product N-Nitroglycine, Gabriel Padilla

Graduate Studies Theses and Dissertations 2026

N-Nitroglycine (NNG) is a nitramine [R(R′)N–NO2; R′=H or alkyl] natural product (NP) produced by certain actinomycetes, such as Streptomyces noursei. At the beginning of this project, the biosynthesis of this NP was unknown. The goal was to determine how NNG and its nitramine moiety are enzymatically formed. This could lead to the discovery of novel nitramine NPs with diverse applications as well as alternative/green synthesis of nitramine explosives. This work begins by examining diverse biochemical N–N bond formation strategies. Nitrogen cycle enzymes, nitration of NPs, kutzneride biosynthesis, the aspartate/nitrosuccinate superfamily, hydrazinoacetic acid (HAA) biosynthesis, and streptozocin biosynthesis are among the …

The Importance Of The Proline Residue In The Ldiapa Motif Of Cholera Toxin, Akash Bharathan

Honors Undergraduate Theses

Cholera is currently on its seventh global pandemic, disproportionately affecting developing countries. Vibrio cholerae, the bacterial etiologic agent, is able to cause infection by adhering to intestinal epithelial cells and secreting cholera toxin (CT), an AB-type exotoxin that dysregulates signaling pathways. Previous research by the Teter lab has shown that Hsp90, a host cytosolic chaperone, is required for CT to enter the cytosol where it produces toxic effects. Hsp90 binds to CT at two specific motifs, RPPDEI and LDIAPA. The prolines in the RPPDEI motif are essential for binding, but the proline in the LDIAPA has yet to be …

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 …

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. …

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 …