Biochemistry, Biophysics, and Structural Biology Commons^™

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 …

Fgf Signaling Is Necessary For Newt Lens Regeneration, Leo Alexander Napoleon

Honors Theses and Capstones

The Iberian ribbed newt Pleurodeles waltl can regenerate the lens by transdifferentiating iris pigmented epithelial (IPE) cells into lens epithelial cells (LECs), but the mechanism by which this occurs remains largely uncharacterized. We aim to mechanistically show an early and critical role for FGF signaling by using small molecules to inhibit FGF receptors and observe the histological and intracellular effects. Two inhibitors were found to completely stall lens regeneration. Cell cycle analysis revealed decreased DNA synthesis and uniformly low but unchanged entry to mitosis under signaling inhibition by staining for EdU incorporation and phospho-histone H3 (pH3), respectively. Western blot revealed …

Generating A Gfp Reporter Via Crispr To Visualize Ssa4 Export, Aara Khairollahi, Rebecca Adams

SPARK Symposium Presentations

In eukaryotic cells, the transport of mRNA from the nucleus to the cytoplasm is a very regulated process controlled by nuclear pore complexes (NPCs). During stress conditions, such as heat shock, most mRNA export is inhibited in Saccharomyces cerevisiae, yet the transcript for SSA4, a gene responsible for refolding denatured essential proteins, is exported. The mechanism behind this selective export remains unknown. To investigate this, we used CRISPR-Cas9 to generate a reporter strain in which the SSA4 open reading frame was replaced or inserted with green fluorescent protein (GFP). This reporter is designed to produce GFP only under conditions that …

Cell Type-Specific Fatty Acid Signalling And Its Sex Dependence, Emeline Masterson

Graduate Studies Theses and Dissertations 2026

Dietary fat is a highly palatable, energy-dense nutrient whose oral detection powerfully shapes ingestion patterns and metabolic outcomes. Despite clear behavioral and physiological evidence that fat can evoke distinct taste signals, the cellular and molecular mechanisms underlying its transduction remain poorly understood. A critical gap exists in our understanding of the cell-type-specific molecular pathways and how these signals are modulated by hormonal status. This dissertation delineates estrogen-dependent plasticity in FA transduction within the peripheral taste system, revealing coordinated, sex and cell-type-specific modulation of these pathways. To understand the missing mechanisms, FA-evoked responses were compared in Type II cells from wild-type …

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 …

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 …

Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff

Biomedical Sciences Theses & Dissertations

Glioblastoma (GB), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), cholangiocarcinoma, and chondrosarcoma (CS) cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme exhibits transformation of alpha-ketoglutarate (αKG) into the oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers. Mitochondrial-mediated transfer between cancer cells and recipient cells is a significant event that impacts the physiology of the receiving cell, specifically the epigenetic landscape. Previous experiments indicating increased DNA methylation in mesenchymal stem cells exposed to IDH1 or IDH2 conditioned medium underscore the potential role of D2HG to alter methylation states. Additionally, the presence of …

A Molecular Mechanism Of Epithelial To Mesenchymal Transition (Emt): An Evidence Based Lesson Applying Molecular Biology Through The Lens Of Cancer, Sophie Hasson, Melissa Rowland-Goldsmith

Open Educational Resources

This lesson aims to strengthen students’ critical thinking and molecular biology data analysis skills as well as their understanding of concepts related to the hallmark of cancer: tissue invasion and metastasis. Students begin by learning about the invasion of cancer cells, Epithelial-Mesenchymal Transition (EMT), and an important protein involved in EMT: E-cadherin. They then apply molecular biology knowledge to analyze data from multiple papers to infer the relationship between Snail and E-cadherin in different types of cancers. Next, they continue to interpret data from many papers to determine that a repressor transcription factor is present during EMT in cancer cells …

Analysis Of Mct-1 Expression In Mouse Neural Retina In Response To Chronic Inflammation, Ian W. Ronson

PANDION: The Osprey Journal of Research and Ideas

Chronic inflammation is a current public health concern as it is linked to the etiology and symptoms of numerous diseases, for example diabetic retinopathy (DR). In the case of DR, inflammation leads to dysregulation of the blood retina barrier causing retinal hemorrhage and macular edema leading ultimately to irreversible vision loss. MCT-1 is critical for the survival of photoreceptor cells because MCT-1 forms protein complexes with Basigin, a cell-cell adhesion protein, that enables Müller glial cells to efficiently provide lactate as a high energy fuel source. Previous studies have shown chronic inflammation reduces Basigin expression in the retina and that …

Investigating The Role Of Early Growth Response 1 (Egr1) Gene In Riluzole-Induced Apoptosis In Osteosarcoma, Syeda Maryam Azeem

Dissertations, Theses, and Capstone Projects

Osteosarcoma is a rare but aggressive bone malignancy most commonly affecting adolescents and young adults (AYA). With 5-year survival rate stagnating over the last four decades despite the advancements in multi-modal therapy, drug repurposing offers a rapid path to new osteosarcoma treatments. Recent studies suggest that Riluzole, a drug approved for amyotrophic lateral sclerosis (ALS), may be repurposed for osteosarcoma treatment due to its ability to slow tumor progression and induce apoptosis. Previously, we have shown that Riluzole increases reactive oxygen species (ROS), activating c-Abl, which phosphorylates YAP in the nucleus. YAP then forms a complex with p73 to enhance …

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

Mechanistic Insights Into The Neuroprotective Effects Of The Antidepressant Agomelatine In Alzheimer's Disease, Grace Terry

Dissertations, Theses, and Capstone Projects

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that has limited treatment options and no cure. AD is characterized by robust pathology including extracellular amyloid beta plaques, intracellular neurofibrillary tangles, neuronal and synaptic loss, neuroinflammation, and brain atrophy. AD presents with cognitive decline and memory loss but only years after neuropathology has started to accumulate. This robust pathology has made AD difficult to treat and highlights the need for therapeutics that modulate multiple pathways. Agomelatine (AGO) was selected by a high-throughput machine learning drug repurposing algorithm by our collaborator Dr. Lie Xie (Hunter College Dept. of Comp. Sci.) as having …

Centrosomal And Non-Centrosomal Microtubule Networks Coordinate To Drive Nuclear Dynamics In Developing Epithelium, Rashmi Budhathoki

Electronic Theses and Dissertations

The morphogenesis of developing tissues relies on extensive cellular rearrangements in shape, position, and identity. A key process in reshaping tissues is cell intercalation-driven elongation, where epithelial cells align and intercalate along a common axis. Typically, analyses focus on how peripheral cortical forces influence cell shape changes. Less attention is given to how inhomogeneities in internal structures, particularly the nucleus, impact cell shaping. Here, we examine how pulsed contractile and extension dynamics interact with the nucleus in elongating Drosophila embryos. Our data show that tightly packed nuclei in apical layers hinder tissue remodeling/oscillatory behaviors. We identify two mechanisms for resolving …

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells

Electronic Theses and Dissertations

Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

Assessing The Impact Of Pll And Ple Concentrations And Aging On Protein Condensates Formation Via Llps, Nabil Harche

Theses, Dissertations and Culminating Projects

Protein droplets, also referred to as condensates, are membrane-less organelles formed through a biophysical process known as liquid-liquid phase separation (LLPS). These structures play an indispensable role in a wide range of cellular functions, including compartmentalizing biochemical reactions, regulating gene expression, and responding to cellular stress. Unlike traditional membrane-bound organelles, these condensates form dynamically and reversibly within the cytoplasm or nucleus, without the need for lipid membranes. The formation of these protein droplets is affected by several physicochemical factors, including pH, temperature, ionic strength, concentration of biomolecules, and specific molecular interactions such as electrostatics and hydrophobic forces. LLPS results in …

Role Of Cellular Proteins In The Regulation Of Herpes Simplex Virus Type 1 Gene Expression And Dna Replication, Joseph R. Heath

Electronic Theses and Dissertations

Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen that infects the majority of the human population. To facilitate infection, this virus relies on a combination of host and viral factors. Previous studies have revealed a number of host proteins that associate with the HSV-1 genome throughout infection but their putative role(s) in this process remain undefined. This study aims to examine two such proteins to determine their contributions to HSV-1 gene expression and DNA replication. The first of these factors is Ints3, a subunit of the Integrator complex. This protein complex functions in transcription regulation, and Ints3 …

Bifunctional Fusion Protein Pdl1sfv/Micae For Cancer Immunothearpy, Junyi Li

All Dissertations

Cancer immunotherapy has highlighted the importance of immune checkpoint blockade and innate immune cell engagement in battling tumor-mediated immune suppression in the past few decades. However, with cancer development, advanced tumors are often found to develop resistance towards single-target immunotherapy due to the complexity of the immunosuppressive mechanisms within the tumor microenvironment (TME). To address this, we developed a novel bifunctional fusion protein, PDL1sFv/MICAe, which combines the tumor-targeting capability of an anti-PDL1 single-chain variable fragment (sFv) with the NK cells immunostimulatory properties of the MICA extracellular domain.

In vitro functional assays revealed that PDL1sFv/MICAe significantly enhanced cytotoxicity towards natural killer …

The Influence Of Myocardin Effector Genes On The Tgf-Beta Smad3 Signaling Pathway In Human Pleural Mesothelial Cells, Hema Chandra Hrushi Dusharla

Biotechnology Theses

Pleural Fibrosis (PF) involves excessive extracellular matrix (ECM) deposition, mainly by myofibroblasts, leading to pleural thickening and impaired lung function. Pleural mesothelial cells (PMCs) contribute via mesothelial and mesenchymal transition (MesoMT), triggered by cytokines like TGF-β. Our lab identified Myocardin (MyoCD), a transcriptional co-activator of cardiac and smooth muscle, is a master regulator of pleural fibrosis through interactions with serum response factor (SRF) and Smad2/3 transcription factors which initiate fibrosis signaling. RNA sequencing and qPCR analysis revealed that silencing MyoCD decreased the expression of CTNNB1, MDFI, and Tspan2. MDFI emerged as a potent candidate, as this gene affecting the expression …

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …

Carbon Monoxide Releasing Polymeric Micelles, Riya Joshi

Electronic Theses and Dissertations

Carbon monoxide (CO), traditionally known as a toxic gas, has emerged as a potential therapeutic agent due to its cytoprotective, anti-inflammatory, and vasodilatory properties. This study explores the development of CO-releasing polymeric micelles as a controlled delivery system for biomedical applications. Using ring-opening metathesis polymerization (ROMP), we synthesized diblock copolymers incorporating CO-releasing moiety diphenylcyclopropenone (DPCP) with hydrophilic polyethylene glycol (PEG) to enhance solubility and stability of the overall CO releasing system. Dynamic light scattering (DLS) and electron microscopy (EM) confirmed the formation of well-defined micelles, while fluorescence assays demonstrated efficient CO release with the use of Iridium photocatalyst under 470 …

The Anticancer Activity Of Novel Chromene Derivatives Against Colorectal Cancer Cells, Rym Magramane

Thesis/ Dissertation Defenses

Colorectal cancer (CRC) stands as the third most common cancer globally, accounting for nearly 10% of all newly diagnosed cancer cases. In the UAE, CRC was ranked as the third most frequently diagnosed malignancy, and the leading cause of cancer-associated deaths in 2023. Standard CRC treatment strategies include surgical resection, chemotherapy, immunotherapy, targeted therapy, or a combination of all, depending on the cancer stage and molecular profile. Despite these interventions, disease recurrence is experienced by a considerable number of cancer patients. Hence, there is an urgent need to develop novel alternative treatments to overcome poor prognosis. Recently, cancer research has …

Investigating A Link Between Dna Repair And Dna Replication In Escherichia Coli Using A Bacterial Two-Hybrid System, Lo Cooper

University Honors Theses

Cells rely on nucleotide excision repair (NER) to remove bulky DNA lesions, such as those caused by UV light. In Escherichia coli, NER involves the UvrABC complex, and includes two main pathways, global genomic repair and transcription-coupled repair (TCR). While TCR, which preferentially removes lesions that block RNA polymerase on the transcribed strand of active genes, is well studied, less is known about whether a similar coupling between repair proteins and replisomes blocked by damaged DNA exists. Such a process has been suggested by a high throughput interactome study, using the replisome subunit HolC as bait and the damage …

Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is an irreversible and devastating neurodegenerative disease characterized by progressive synaptic, dendritic, glial, and neuronal loss, collectively leading to impairments in learning, memory, and deterioration of cognitive and behavioral functions. AD is the most common form of dementia accounting for 60-80% of all cases. AD affects approximately 7 million Americans and is the 6th leading cause of death in the US. Furthermore, by 2050, the US is projected to spend over $1.1 trillion on AD-related treatments. Pathological hallmarks of AD include beta-amyloid (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), and chronic neuroinflammation, which can promote and exacerbate both …

Drivers And Mechanisms Of Golgi Fragmentation As A Modulator Of Disease, Amanda Macke

Theses & Dissertations

The Golgi apparatus plays a pivotal role in post-translational modification, trafficking, and secretion of proteins, ensuring proper cellular function. As a result, its fragmentation has been implicated in multiple pathological conditions, including alcohol-induced liver injury and prostate cancer (PCa). Despite its known impact on cellular homeostasis, the molecular mechanisms governing Golgi fragmentation remain to be clarified. Additionally, we have only just begun to understand the vast consequences of Golgi disorganization on disease progression.

This dissertation investigates the drivers and mechanisms of Golgi fragmentation, with a focus on its role as a modulator of disease. Using both in vitro and in …

Exploring Intracellular Signaling Responses To Ks18, A Potent Mcl-1 Inhibitor, In Multiple Myeloma, Emily Nelson, Omar S Al-Odat, Dhruti A. Brahmbhatt, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Kumar Pandey

Rowan-Virtua Research Day

Multiple myeloma (MM), a cancer of plasma B cells, is a hematological malignancy in which patients inevitably relapse and develop drug resistance. Mcl-1, a member of the anti-apoptotic subgroup of Bcl-2 family proteins, plays a critical role in the progression of multiple myeloma and contributes significantly to drug resistance. Elevated Mcl-1 expression is observed in approximately 52% of MM patients at diagnosis, increasing to 81% at relapse. Given its driving role in disease progression and therapy resistance, Mcl-1 inhibition has emerged as a promising therapeutic target, prompting ongoing research into the development and clinical evaluation of Mcl-1 inhibitors, particularly for …

Examining The Molecular Mechanisms Of Glucagon-Like Peptide-1 Receptor Agonists In Cancer Cell Biology, Oliver G. Sabet

Honors Scholar Theses

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are synthetic analogs of glucagon-like peptide-1 (GLP-1) used to treat obesity and diabetes by reducing blood glucose levels and appetite. While early rodent studies suggested a link between GLP-1RAs and thyroid cancer pathogenesis, evidence in humans remains inconclusive, with randomized controlled trials not supporting that link. Due to the rapid, widespread use of these drugs, concerns have expanded to other obesity-associated cancers, with conflicting findings on their role in cancer progression. With this contradictory evidence in a novel intersection of obesity medicine and oncology, this literature review aims to summarize current understandings between GLP-1-RAs and …

The Role Of Myosin L In The Survival Of Toxoplasma Gondii And The Importance Of Mlc1 For In Vitro And In Vivo Myosin F Motility, Victoria K. Yi

Honors Scholar Theses

My thesis discusses the work that I have conducted on two myosins in Toxoplasma gondii, which is an obligate intracellular parasite that has chronically infected around 10% of the American population. It causes toxoplasmosis and severe health consequences for individuals with compromised immune systems or when infections occur in utero. However, immunocompetent individuals are asymptomatic or present with subclinical symptoms. In the Heaslip lab, I investigated two myosins in the parasite: Myosin L and Myosin F. MyoL is an uncharacterized motor that localizes at the apical end of the parasite. It was shown to be important for parasite …

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 …