Biochemistry, Biophysics, and Structural Biology Commons^™

Impact Of Tumor Cell Expressed Cd38 On Metastasis And Immune Evasion In Breast Cancer, Tanvi Visal

Dissertations and Theses (Open Access)

Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype. The epithelial-to-mesenchymal transition (EMT) of cancer cells is a key feature of the metastatic cascade and is not a binary process but often generates malignant cells with both epithelial (E) and mesenchymal (M) traits known as hybrid EM cells. Recent studies highlight the enhanced metastatic potential of the hybrid EM cells. However, molecular insights and targetable vulnerabilities within hybrid EM remain elusive. We discovered that hybrid EM murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid …

The Extracellular Domains Of The Ampa, Kainate, And Orphan Delta Receptor Regulate Channel Gating In Distinct Ways, Cuauhtemoc Ulises Gonzalez

Dissertations and Theses (Open Access)

The ionotropic glutamate receptors are ligand-gated cationic channels essential for neuroplasticity and neurological functions such as learning, memory, behavior, cognition, and motor coordination. Mutations in these channels are linked to various disorders including autism, ataxia, and epilepsy, making them compelling pharmacological targets. Within this family, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptor mediate their function through fast glutamate-gated ionotropic activity, which needs precise structural changes to perform properly. While Cryo-EM structures have provided snap shots of these proteins, questions remain regarding the dynamics across conformations and individual roles of the extracellular amino-terminal and agonist binding domain in dictating function. …

Overcoming Resistance To Cdk4/6-Targeted Therapy Using Jak2/Stat3 Inhibitor In Triple-Negative Breast Cancer, Chuling Zhuang

Dissertations and Theses (Open Access)

Breast cancer is the most common type of cancer diagnosed in women, with nearly 30% of cases becoming metastatic accounting for over 90% of breast cancer-related deaths. Among different breast cancer subtypes, triple-negative breast cancer (TNBC) has the worst prognosis and the highest propensity to metastasize. However, TNBC patients have limited treatment options due to their lack of actionable drug targets while therapeutic resistances result in high rates of recurrence and metastasis. Cyclin-dependent kinase 4 and 6 (CDK4/6) are major cell cycle regulators that control G1 to S phase transition and aberrant hyperactivation of the CDK4/6 pathway results in uncontrolled …

Role Of Mir-4732-3p In Breast Cancer Brain Metastasis And Brain Metastatic Tumor Microenvironment, Munazza Samar Khan

Dissertations and Theses (Open Access)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. MiR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal …

Investigating Metabolic And Mitochondrial Adaptations Triggered By Blood Flow During The Endothelial-To-Hematopoietic Transition, Paulina Horton

Dissertations and Theses (Open Access)

Hematopoietic stem cell (HSC) transplant is the standard of care for many hematologic diseases. However, many patients cannot benefit from this potentially curative treatment because they cannot find a suitable donor, contributing to a high level of unmet need. Recently, bona fide HSCs capable of robust engraftment and differentiation have been generated from iPSCs utilizing wall shear stress (WSS) to help promote HSC generation. However, the mechanisms through which WSS regulates hematopoiesis remain poorly understood. Scientists, therefore, continue to look for the mechanotransduction pathways that promote hematopoiesis, and key answers may lie in examining the role of extrinsic factors that …

Leveraging Natural Variation In Yeast To Understand Susceptibility Differences In Parkinson’S Disease, Julio Andres Molina Pineda

Graduate Theses and Dissertations

Parkinson’s Disease (PD) is a neurodegenerative disorder that causes countless suffering around the world. Both forms, familial and sporadic, have been associated with the misfolding and cytotoxicity of α-synuclein, an otherwise non-pathogenic protein suspected to have various roles in the normal maintenance of the central nervous system. Model organisms have emerged as great vessels to uncover the cellular and molecular mechanisms that shape α-syn biology, and great strides have been made to understand it. Yet, it is still unclear why some individuals are affected by α-syn toxicity, while others not so much. Since it’s extremely complicated to study and probe …

Evolutionarily Conserved Functions Of The Gene Frazzled In Midline Axon Guidance In Drosophila Melanogaster And Tribolium Castaneum., Piyasi Ghosh

Graduate Theses and Dissertations

Axon guidance in bilaterians is often controlled by various signaling pathways in the nervous system, which determine the fate of the axons if they cross the midline or not. One such pathway involved is the ligand-receptor pair Netrin (Net) and Frazzled (Fra), which is also known as the attractive pathway that promotes midline crossing axons in insects and other bilaterians. Orthologs of the pathway ligand Netrins and their receptors Frazzled [Fra] in insects and Deleted in Colorectal cancer [DCC] in vertebrates are widely conserved in bilaterians. How well these regulatory roles of the protein are conserved is poorly understood. In …

Bacterial Chondronecrosis With Osteomyelitis In Broiler Chickens: Experimental Lameness And Additive Probiotic Treatments, Amanda Anthney

Graduate Theses and Dissertations

With the global population already surpassing 8.2 billion and expected to reach 9.7 billion by 2050, the poultry industry has seen a surge in demand due to its unmatched efficiency and affordability for consumers across the globe. Selective breeding and quality nutrition developments since the industry's commercialization have allowed producers to grow broilers up to 7 pounds by market age. While this extraordinarily efficient process has allowed quality poultry products to be available worldwide, the modern-day broiler has developed a multitude of musculoskeletal issues. Due to the lack of integral skeletal development to match the rapid production of muscle tissue, …

Intraspecific Genetic Variation In Green Salamanders (Aneides Aeneus) At Bays Mountain Park, Brianna Drake

Electronic Theses and Dissertations

Accurate taxonomy is crucial for conserving vulnerable cryptic species like the green salamander (Aneides aeneus) in the Southern Appalachian Mountains. Prior studies identified three distinct lineages within the A. aeneus complex: Northern Appalachians, Southern Appalachians, and Blue-Ridge Escarpment. One previously collected sample indicated green salamanders in northeast Tennessee fit within the Northern lineage. The present study uses molecular data of A. aeneus at Bays Mountain Park (BMP) in Kingsport, Tennessee, to determine where the BMP population fits within these lineages. It was hypothesized that individuals from BMP belong in the northern lineage. Tail tips were collected from thirty-four …

Transcription Factor Y- Box Binding Protein 1 (Ybx1) Enhances Sorafenib Resistance And Tumorigenic Capacities In Hepatocellular Carcinoma (Hcc), Dennis Kwabiah

Theses and Dissertations

Hepatocellular carcinoma (HCC) is the most common liver cancer, with early-stage cases potentially benefiting from surgical treatments like liver transplantation and hepatectomy. However, advanced HCC stages have poor prognosis due to resistance to therapies, especially sorafenib, a tyrosine kinase inhibitor approved for late-stage HCC. Despite its clinical use, sorafenib has limited efficacy in prolonging survival, and the mechanisms of resistance remain unclear. Analysis of The Cancer Genome Atlas (TCGA) HCC dataset shows elevated Y-box binding protein 1 (YBX1) expression in HCC tumors compared to normal liver tissues. Previous studies have indicated that YBX1 is involved in drug resistance in various …

Investigation Into Mycorrhizae Associated With Native Venus' Flytrap Root Tissue, Anna Carnaggio

Electronic Theses and Dissertations

Dionaea muscipula, a plant commonly known as the Venus' flytrap, is found native to the southeast corner of North Carolina and the northeast corner of South Carolina. Several populations of native Venus' flytraps are known to exist in the nutrient-poor peat bog conditions in and around Lewis Ocean Bay Heritage Preserve (LOBHP) in Northeastern South Carolina. Anthropogenic pressures in Horry County, specifically surrounding LOBHP, have resulted in a loss of habitat for several native and endangered species. As a result, conservation efforts are focused on relocating native Venus' flytraps into adjacent habitats to ensure survival. This is only a temporary …

Amyloid Aggregation And Mitigation, Zhenzhen Zhang

All Dissertations

The buildup of protein in tissues and organs plays a major role in unfunctional several serious diseases, including Alzheimer’s disease, Parkinson’s disease, and Type 2 diabetes, each tied to specific proteins that form harmful amyloid deposits. Amyloid aggregation typically follows a sigmoidal kinetic curve, beginning with a slow lag phase, followed by rapid fibril growth, and eventually reaching a plateau where mature, stable fibrils are formed. However, the early stage of aggregation remains particularly difficult to capture experimentally due to the highly dynamic nature and low abundance of small oligomeric species. In this dissertation, we employed discrete molecular dynamics (DMD) …

Structure Disorder And Magnetic Behavior Of An Olivine-Type Cathode Material, Hamida Hassan, Madalynn Marshall

Symposium of Student Scholars

Our research investigates the structure disorder and magnetic behavior of Li(Mn,Fe)PO₄, an olivine-type material relevant for lithium-ion battery applications. Using single-crystal neutron diffraction at Oak Ridge National Laboratory, we precisely determined Mn and Fe occupancy, revealing a 56% Fe and 44% Mn distribution at the atomic 4c site within the Pnma space group. Additionally, we observed significant lithium site vacancies (78% occupied), influencing the material's electrochemical and magnetic properties. The varying Mn/Fe ratio affected spin reorientation transitions, shifting from antiferromagnetic alignment along the a-axis to the b-axis. Our findings provide crucial insights for optimizing olivine-based cathodes, enhancing energy …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Cloning The Yersinia Enterocolitica Alkaline Phosphatase For An Affinity Chromatography Ligand, Flavio E. Arellano

ATU Scholars Symposium

Alkaline phosphatase (ALP) is an enzyme responsible for the dephosphorylation of extra-cytoplasmic molecules. Conversion to a neutral molecule enhances their ability to pass through cell membranes. When microbes such as Yersinia enterocolitica are ingested, they are exposed to large changes in pH level. These changes range from ~pH6.5 in the oral cavity to pH 2 in the stomach and pH 8 in the mid-intestine. The ability of microorganisms to survive this change in pH it largely dependent on their ability to change which proteins are expressed at differing pH levels or their ability to modify those proteins to meet the …

Glycosylation Of Serine/Threonine-Rich Intrinsically Disordered Regions Of Membrane-Associated Proteins In Streptococci., Mohammad M Rahman, Svetlana Zamakhaeva, Jeffrey S. Rush, Catherine T Chaton, Cameron W Kenner, Yin Mon Hla, Ho-Ching Tiffany Tsui, Vladimir N Uversky, Malcolm E Winkler, Konstantin V Korotkov, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

Proteins harboring intrinsically disordered regions (IDRs) lacking stable secondary or tertiary structures are abundant across the three domains of life. These regions have not been systematically studied in prokaryotes. Here, our genome-wide analysis identifies extracytoplasmic serine/threonine-rich IDRs in several biologically important membrane-associated proteins in streptococci. We demonstrate that these IDRs are glycosylated with glucose by glycosyltransferases GtrB and PgtC2 in Streptococcus pyogenes and Streptococcus pneumoniae, and with N-acetylgalactosamine by a Pgf-dependent mechanism in Streptococcus mutans. The absence of glycosylation leads to a defect in biofilm formation under ethanol-stressed conditions in S. mutans. We link this phenotype to the C-terminal IDR …

The Chemistry Of Decomposition: The Mechanisms To Decay The Human Body, Lydia J. Buxa

Senior Honors Theses

Taphonomic analysis separates decomposition into four major stages: fresh, early decomposition, advanced decomposition, and skeletonization. It is easy to demarcate the observable changes to the body, but it is far more difficult to know what underlying biochemical processes are occurring. Fresh decomposition begins with algor mortis, livor mortis, and rigor mortis, which sets the stage for the major workforces of decomposition: autolysis and putrefaction. The external signs of decomposition appear in early decomposition, which can be attributed to the breakdown of proteins, lipids, carbohydrates, and nucleic acids. This also leads to major changes in the moisture levels during advanced decomposition, …

Metabolic And Microbial Crossroads: Sodium-Glucose Cotransporter-2 Inhibitors And Urinary Tract Infections In (Asian) Diabetes Care, Rob E. Carpenter

Human Resource Development Faculty Publications and Presentations

The global rise of type 2 diabetes, particularly in Asian populations, has led to widespread adoption of sodium-glucose cotransporter-2 (SGLT2) inhibitors for glycemic control. While effective, these agents elevate the risk of urinary tract infections (UTIs) by inducing glycosuria, which creates a nutrient-rich environment that favors uropathogen growth. Asian individuals may be disproportionately vulnerable to SGLT2 inhibitor–associated UTIs due to a confluence of factors, including lower body mass index, increased visceral adiposity, congenital urinary tract anomalies, and genetic polymorphisms that impair uroepithelial integrity and immunity. This review integrates emerging evidence on the molecular, anatomical, and immunometabolic mechanisms that underlie infection …

Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) offer targeted drug delivery of potent cytotoxic payloads, minimizing systemic toxicity. However, the stability of the linker is integral to ensure that there is minimal off-target payload release and little systemic toxicity. This study analyzes the physical and biological stability of our new legumain-cleavable vs traditional cathepsin-cleavable antibody-drug conjugates (ADCs), with a focus on hydrophobicity, thermal stability, aggregation, and biological payload release. Our findings indicate that decreased hydrophobicity of the legumain-cleavable ADCs compared to cathepsin-cleavable ADCs is correlated with decreased aggregation (predicting lower uptake by liver macrophages and therefore slower clearance and less systemic toxicity) and lower …

Exploring The Role Of Azoreductase Enzymes In Drug Metabolism: Implications For Personalized Medicine, Najoude Claude, Robert Ghergurovich

Chemistry & Biochemistry Student Scholarship

Najoude Claude ’26, Biology major

Robert Ghergurovich ’26, Biochemistry major

Faculty mentor: Dr. Tyler Stack, Chemistry and Biochemistry

The gut microbiome hosts trillions of microorganisms that metabolize xenobiotics such as drugs and food dyes. Individual differences lead to variable drug metabolism. We studied two azoreductases: E. coli’s P41407 and Alistipes sp. CHKCL003’s A0A143XFE8. Enzyme P41407 acted on methyl red and ethyl red, while A0A143XFE8 acted on these and also on phenol blue, HMND, and sunset yellow. We propose these enzymes function as quinone reductases, requiring a quinone-like intermediate. Three synthesized compounds confirmed similar kinetics. In conclusion, these insights significantly advance …

Discovery, Purification And Annotation Of Four Novel Mycobacteriophages In New England, Mason Krawczynski

Chemistry & Biochemistry Student Scholarship

Mason Krawczynski ’26, Biology and Psychology major

Faculty mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Mycobacteriophages are viruses that infect bacteria of the Mycobacterium genus. Several thousand mycobacteriophages have been discovered, isolated, and characterized to advance the current understanding of their genomic diversity. The mycobacterium phage selection proves valuable, as they have a broad host range and potential for therapeutic application to treat pathogenic and antibiotic-resistant mycobacteria, such as Mycobacterium tuberculosis, the causative agent of tuberculosis infection. Kraw was isolated from a soil sample collected in Oaks Bluff, Massachusetts, on the island of Martha’s Vineyard in July 2023. FairyPath, Calvinny, …

Tools For Harnessing Atropisomerism In 1-Aryl-Β-Carbolines, Cristina Díaz, Malaquias Loiza, Josef Crenshaw, Brian Ladino, Elizabeth Perda, Alma Martinez, Joseph Mazzucca, John Stathoulopoulos

Chemistry & Biochemistry Student Scholarship

Cristina Díaz ’25, Chemistry major

Malaquias Loiza ’26, Biochemistry major

Josef Crenshaw ’28, Biochemistry major

Brian Ladino ’28, Biochemistry major

Elizabeth Perda ’26, Biochemistry major

Alma Martinez ’26, Biochemistry major

Joseph Mazzucca ’25, Biochemistry major

John Stathoulopoulos ’26, Chemistry major

Faculty mentor: Dr. Seann Mulcahy, Chemistry and Biochemistry

Axially chiral molecules with high barriers to rotation are becoming increasingly more prominent in drug discovery, chemical biology, and materials science. We have shown that 1-aryl-β-carbolines exhibit high configurationally stability, with barriers to rotation greater than 30 kcal/mol and have recently disclosed an asymmetric synthesis of these molecules. In this presentation, we …

Discovery, Purification And Annotation Of A Novel Mycobacteriophage Discovered On The Providence College Campus, Jenna Greene

Chemistry & Biochemistry Student Scholarship

Jenna Greene ’26, Biochemistry major

Faculty mentor: Dr. Kathleen Cornely, Chemistry and Biochemistry

Bacteriophages—viruses that infect bacteria—offer a promising alternative to antibiotics in the face of rising antibiotic resistance. In this project, I isolated a novel phage from a soil sample collected in front of Raymond Dining Hall at Providence College. Using Mycobacterium smegmatis as the host, the sample underwent multiple rounds of purification until a single phage, named GMonster (a nod to my family nickname, “Greene Monster”), was isolated. GMonster was submitted to the PhagesDB database and confirmed through sequencing to belong to the A1 cluster—the first of its …

Exploring An Electron-Rich Iron Tricarbonyl Complex Containing An Α-Diimine Ligand, Joseph Maher

Chemistry & Biochemistry Student Scholarship

Joseph Maher ’25, Chemistry major

Faculty mentor: Dr. Maria Carroll, Chemistry and Biochemistry

The combustion of fossil fuels increases atmospheric CO2, making hydrogen a promising cleaner energy alternative. Pt has been able to facilitate this reaction efficiently, however, it is expensive and scarce. Fe has shown promise in facilitating 2-electron transfers when bound to redox-active ligands. Reacting the redox-active CyDABMe with benzylidene acetone iron tricarbonyl (bdaFe(CO)3) forms Fe[CyDABMe](CO)3, with vCO values ~10 cm-1 lower than FeArDABMe(CO)3, indicating increased electron density. The reduction potential of CyDABMe was probed using Zn[CyDABMe]Cl2, showing a reduction at 200 mV more negative than Zn[ArDABMe]Cl2. X-ray …

Effects Of Hyperglycemia In Cognition And Sex, Erin E. Mcdonald

Senior Honors Theses

An empirical study tested the effects of Type 1 Diabetes (T1D) on cognitive function in a hyperglycemic mouse model. Strong correlations between mental illnesses, such as major depressive disorder, neuropathologies like Alzheimer’s disease, and diabetes suggest comorbid pathology. Considering the prevalence of both T1D and cognitive decline within the general population, the findings were relevant and aimed to identify early signs of cognitive decline in diabetic patients. Behavioral tests and immunohistochemical staining were utilized to determine the cognitive function of the mice, revealing decline or deterioration caused by hyperglycemia. Data gathered from the hyperglycemic or control mice were analyzed based …

Developing An Unfolding-Incorporated Coarse-Grained Polymer Model For Fibrinogen To Study The Mechanical Behaviour, Vivek Sharma, Poulomi Sadhukhan

Northeast Journal of Complex Systems (NEJCS)

Fibrinogen is a protein found in blood that forms Fibrin polymer network to build a clot during wound healing process when there is a cut in the blood vessel. The fibrin fiber is highly stretchable and shows a complex mechanical properties. The fibrin monomer, Fibrinogen, has a very complex structure which is responsible for its unusual elastic behaviour. In this work, we focus on mechanism of unfolding of D-domain of Fibrinogen, and study its effect in the mechanical behaviour. We develop a coarse-grained (CG) bead-spring model for Fibrinogen which captures the unfolding of folded D-domains along with other necessary structural …

Trenching And Compost Sustain Grain Yield Increases Over Nine Years On Deep Sands But At A Cost, David J.M. Hall, Tom J. Edwards

Grain and Other Field Crops Research Articles

Context. Crops grown on deep sands on the south coast of WA are limited by soil physical and chemical properties including compaction and poor nutrition. Aims. Crops grown on deep sands on the south coast of Western Australia are limited by soil physical and chemical properties including compaction and poor nutrition. Our aim was to determine what effects deep-placed organic amendments have on soil properties and crop production in a deep sand and whether such amendments are profitable. Methods. A long-term field trial was conducted over nine years (2015–2023) to investigate soil amendments including lime (0 and …

Neuronal Cftr: A Study Of Subcellular Localization And Interactions With Implications For A Role In Synaptic Transmission, Brandon J. Leviskas

LSU Doctoral Dissertations

Protein-protein interactions vary among cell types and the localization of these interactions help to define protein function. The function of cystic fibrosis transmembrane conductance regulator (CFTR) is well established in the context of epithelial tissue due to the debilitating effects of its mutations that cause the disease cystic fibrosis. While in neurons a role has been established in our lab for CFTR in the regulation of cytosolic Cl- in retinal amacrine cells (ACs). This research sets out to learn if CFTR has a synaptic role. Exploring this potential role, localization of CFTR was examined using fluorescent and immunogold labeled transmission …

Antioxidant Properties Of Phytochemicals In Watercress And Mint Extracts In Serum Albumin, Perla Tovar

Undergraduate Research Conference

Hypothesis: Phytochemicals present in mint and watercress help stabilize protein under oxidative stress. Main Objective: Analyze the interaction of HSA with different phytochemicals present in mint extract.

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …