Biochemistry, Biophysics, and Structural Biology Commons^™

Proteomic-Based Strategies To Determine Aberrant Signaling In Cancer, Natasha Chipman Mariano

Dartmouth College Ph.D Dissertations

Proteomics and phosphoproteomics have emerged as powerful tools to elucidate the intricate molecular underpinnings that drive cancer development by quantifying changes in protein and post-translational modification abundances. Throughout my thesis work, I have advanced these techniques to map cancer signaling networks on a global scale. Among breast cancer subtypes, triple-negative (TNBC) remains the most challenging to treat, with poorer clinical outcomes attributed to tumor heterogeneity and yet unidentified, oncogenic driver proteins for therapeutic targeting. To identify potential targeted treatment strategies, we employed mass spectrometry-based quantitative proteomics to analyze 55 formalin-fixed paraffin- embedded TNBC tumor specimens. Unsupervised hierarchical clustering of relative …

Kinetic Control And Trapping In The Supramolecular Polymerization Of M-Terphenyl Bis-Urea Macrocycles, Sophya V. Garashchuk, Gamage Isuri P. Wijesekera, Isabella G. Rushton, Vaibhavi A. Samant, Fahidat A. Gbadamosi, Dr. Md Faizul Islam, Sophya V. Garashchuk, Prof. Dr. Linda S. Shimizu

Faculty Publications

Herein, we examine pathway complexity in the supramolecular polymerization of a novel m-terphenyl bis-urea macrocycle. Designed to induce kinetically metastable states, the macrocycle‘s concentration-dependent aggregation was studied via 1H NMR and IR spectroscopy in THF and CHCl₃. Temperature-dependent UV-Vis spectroscopy in water/THF revealed a cooperative nucleation-growth mechanism, indicated by a shift in λmax to longer wavelengths upon cooling. Morphological studies using DLS, AFM, and SEM demonstrated fibrous aggregate formation. Thermal hysteresis observed in assembly-disassembly cycles indicated kinetically trapped species, with cooling governed by kinetic control and heating by thermodynamic processes. Deviations in ΔH values during cooling, compared to van′t …

How The Biotic And Abiotic Factors In The Belle Forest Cave And Arboretum Soil Dictates Tree Species Prevalence, Amya A. Bingham

SPARK Symposium Presentations

A plethora of factors in the soil impact a plant’s health, including the presence of different biotic and abiotic factors. These include things like temperature, elevation, pH, microbial respiration and the presence of water, clay, loam, silt, sand, nitrogen, potassium, and phosphorus. Different soils will have varying amounts of these, which may dictate what is able to grow in them, and therefore also the surrounding area. This research project explores how the aforementioned biotic and abiotic factors affect the soil at the Belle Forest Cave and Arboretum. Three samples will be taken from four spots along a transect at this …

Dental Disparities: An Analysis Of Dental Caries Risk Factors Promoting Disparities Between Rural And Urban Communities In Nebraska, Nick Lounsbery

Honors Program: Senior Projects (Public)

The prevalence of dental caries in the United States remains a public health concern, as it is one of the most common chronic conditions across people of all ages. Research shows that preventative measures including brushing, fluoridated water, and regular checkups are effective strategies to mitigate tooth decay. However, there appears to be a divide between rural and urban populations, as the presence of dental cavities is significantly greater in remote areas in the State of Nebraska. Research methods used in this analysis included analyzing accredited academic literature to illustrate how cavities form from a biochemical perspective. Research methods also …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

College Of Natural Sciences Newsletter, Spring 2025, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message from Dr. Sen Subramanian
Page 2 Student Spotlights
Page 3 Kaushik honored, Three-Minute Thesis, & Ice Cores revealed
Page 4 Alumni Spotlight
Page 5 Day of Scholars
Page 6 Cyanide research, Record Research Expenditures, Adhikari awarded Miller Research Award
Page 8 Hanson Receives NSF Grant
Page 9 Snow Lab Research Team
Page 10 Faculty Awards
Page 11 Drone Day
Page 13 Khalaf Awarded Presidential Award

Development Of Flexible Lactate-Specific Molecularly Imprinted Polymers Based On Laser-Induced Graphene Electrochemical Biosensors For Disease Diagnosis, Christopher Animashaun

Biomedical Engineering Theses & Dissertations

Lactate is a critical biomarker linked to conditions such as sepsis, ischemia, cancer, and heart failure. Current lactate detection methods remain invasive, costly, and unsuitable for real-time, continuous monitoring. This study presents the development of a flexible, non-enzymatic electrochemical biosensor based on laser-induced graphene (LIG) electrodes modified with gold nanoparticles (AuNPs) and molecularly imprinted polymers (MIPs) for highly selective and sensitive lactate measurement. The integration of AuNPs enhanced surface conductivity and provided nanoscale heterogeneity, facilitating superior signal amplification. The optimized LIG/AuNP/MIP sensor achieved an extensive dynamic detection range from 0.1 μM to 1000 μM, with an outstanding detection limit of …

Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …

Expanding The Lexa Bacterial Two-Hybrid System For Human Protein-Protein Interaction Screening: Application To Tumor Suppressor Par-4, Rebecca M. Richardson

Chemistry & Biochemistry Theses & Dissertations

Protein-protein interactions (PPI) are fundamental to cellular function, influencing processes such as signaling, structural organization, and disease progression. Disruptions in PPIs are implicated in cancer and neurodegenerative diseases, highlighting their importance as therapeutic targets. However, traditional methods for studying human PPIs, such as yeast two-hybrid and co-immunoprecipitation mass spectrometry, are costly and technically demanding. This dissertation explores the LexA-based bacterial two-hybrid (LexA-B2H) system as a cost effective and accessible alternative for investigating human PPIs.

This study focuses on the interaction between glucose-regulated protein 78 (GRP78) and cleaved prostate apoptosis response-4 (cl-Par-4), a tumor suppressor protein involved in apoptosis and neurodegenerative …

Next-Generation Biomedical Implants And Stimuli Responsive Soft Optical Arrays Via Surface Functionalized Elastomeric Materials, John M. Kapitan

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The demands of emerging technologies, such as soft robotics, stretchable electronics, and next generation biomedical implants, has led to the development of diverse polymeric and hybrid organic/inorganic materials specifically tuned to meet these challenges. These materials typically have low Young’s moduli and are inert with high chemical stability. However, this has led to materials that are static in nature, lacking any meaningful way of responding to changes in their environment and adapting to these changes. This has driven a shift towards the design, manufacturing, and characterization of various stimuli responsive surfaces, relying on precise control of surface chemical coatings and …

Low Dissolved Oxygen Operation Enhances Biological Phosphorus Removal In Wastewater Treatment, Haley Morgan

Civil & Environmental Engineering Theses & Dissertations

Biological phosphorus (bio-P) removal occurs when bacteria are exposed to anaerobic/aerobic conditions that stimulate polyphosphate-accumulating organisms (PAOs) to uptake phosphorus. In most treatment plants, dissolved oxygen (DO) concentrations in the aeration tanks are commonly at or above 2.0 mg O₂/L, which is often referred to as the most optimal aeration condition for bio-P. If bio-P can happen efficiently at lower DO (< 0.3 mg O₂/L), then the energy demand of aeration can be decreased appreciably. This research was conducted in a biological nutrient removal (BNR) pilot plant to assess the performance of bio-P at progressively lower DO operation. This …

Crispr-Induced Mutagenesis Of Arabidopsis Thaliana Gene Apetala3, Hazel Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

This project aims to create CRISPR-CAS9 mutations in the APETELA3 (AP3) gene of the model plant Arabidopsis thaliana. AP3 is a class B gene critical to the petal and stamen development of Arabidopsis flowers. AP3 is defined in a MADS domain, which binds directly to DNA and may be responsible for the expression of the CaRG-box genes. AP3 works in conjunction with PISTILLATA (PI), AGAMOUS (AG), APETALA1 (AP1), and SEPALLATA (SEP) genes to specify the development in the second and third whorls of the flower. While several alleles of AP3 already exist, these alleles are strong alleles that knockout gene …

Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

No abstract provided.

Dnajb6: A Potent Dnajb Chaperone In Regulating Tau Proteostasis, Abigail R. Esquivel

USF Tampa Graduate Theses and Dissertations

Neurodegenerative diseases often feature the pathological buildup of misfolded proteins, and tau is a principal culprit in multiple tauopathies. One chaperone of emerging interest is DnaJB6b, a member of the Hsp40/DnaJ family, which exhibits potent anti-aggregation activity against several disease-related proteins. Recent investigations highlight its unique capacity to recognize and neutralize aggregation-prone forms of tau. DnaJB6b appears potent against multiple variants of tau and may be acting against tau, in part, by directing misfolded tau toward proteasomal clearance. The first lines of evidence come from systematic chaperone screens, where DnaJB6b repeatedly emerged as a strong suppressor of tau seeding. Further …

Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey

Chemistry & Biochemistry Faculty Works

External stressors modulate the oligomerization state of photosystem I (PSI) in cyanobacteria. The number of red chlorophylls (Chls), pigments lower in energy than the P₇₀₀ reaction center, depends on the oligomerization state of PSI. Here, we use ultrafast transient absorption spectroscopy to interrogate the effective connectivity of the red Chls in excitonic energy pathways in trimeric PSI in native thylakoid membranes of the model cyanobacterium Synechocystis sp. PCC 6803, including emergent dynamics, as red Chls increase in number and proximity. Fluence-dependent dynamics indicate singlet–singlet annihilation within energetically connected red Chl sites in the PSI antenna but not within bulk Chl …

Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy

Honors Program: Senior Projects (Public)

West Nile Virus (WNV), a member of the Flaviviridae family and introduced to the Western hemisphere in 1999, presents a unique and emerging threat to human health. Infection in humans is often mild but can occasionally result in severe neurological impairment and even death. West Nile Virus non-structural protein 3 (NS3) plays an important role in the process of viral genome amplification. More specifically, the C-terminal domain of the protein folds into a helicase enzyme, which is responsible for the “unwinding” of double-stranded RNA intermediates and RNA secondary structure on the WNV genome. This is a vitally important step in …

College Of Natural Sciences 2024 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 2 Dean's Message
Page 3 Department Highlights
Page 4 One Day for State
Page 5 New Students in Wecota
Page 6-8 Faculty Excellence
Page 9 SDSU Physics Students Recognized
Page 9 Prairie Doc Watch Party
Page 10-11 Student Excellence
Page 11 Connections Abroad
Page 12-13 CNS’s Research Centers
Page 14 Connections Abroad
Page 14 Dean Wolf-Hall Retired
Page 15 Outreach Program
Page 15 Events and Traditions
Page 16 Student Spotlight
Page 17 Alumni Spotlight
Page 18-19 SDSU Alum at Paris Paralympics
Page 20 Work Anniversaries & Programs

Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman

Honors Program: Senior Projects (Public)

The reduction potential of flavin bound to Sinorhizobium meliloti proline utilization A (SmPutA) is beneficial in providing vital information on enzyme activity and the active site environment. Flavin is crucial in biological metabolism such as aerobic respiration and other important processes like oxygen activation that are catalyzed by flavin-dependent enzymes. (4). In this study, we seek to determine whether the redox potential of SmPutA-bound flavin can be used to characterize potential long-distance communication and analyze the possibilities of inactivation reversibility. SmPutA is a large bifunctional enzyme that catalyzes the overall oxidation of proline to glutamate via two catalytic domains (1). …

Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena

Electronic Theses and Dissertations

Capillary zone electrophoresis (CZE) is a powerful analytical technique widely used for biomolecular separation due to its high resolution, efficiency, and sensitivity. This report presents the development and validation of a novel CZE system designed to improve modularity, reproducibility, and operational efficiency. The system integrates a laser-induced fluorescence (LIF) detection method with a 488 nm laser, enhanced fluid control through a negative pressure system, and a user-friendly GUI for automated operation and data acquisition. Performance verification included pressure stability tests, fluorescence accuracy assessments, and electrophoretic reproducibility studies. Comparative analysis with a previous CZE iteration confirmed improved baseline stability, peak resolution, …

Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman

Electronic Theses and Dissertations

Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.

A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …

The Expression Profile Of The Rank/Rankl/Opg Pathway In Breast Cancer Stem Cells Isolated From Breast Cancer Cell Lines, Mohamed M. Kamal, Hassnaa H. Elgohary, Sherine Maher Rizk, Nadine H. Maurice

Pharmacy

The RANK/RANKL/OPG signaling pathway plays a crucial role in breast cancer progression and metastasis. However, its expression patterns and potential implications in breast cancer stem cells remain poorly understood. This study aimed to characterize the expression profile of this pathway in breast cancer stem cells isolated from two distinct breast cancer cell lines: MDA‐MB‐231 and MCF‐7. Mammospheres (MS), representing breast cancer stem cells, were generated using agar‐coated 6 well tissue culture plates in suitable mammospheres culture conditions. Flow cytometric analysis showed enrichment of the CD44+/ CD24− subpopulations in the mammospheres cultures, with MDA‐MB‐231 exhibiting a higher percentage compared to MCF‐7. …

Synthesis Of A Series Of Rare-Earth-Based Multi-Anion Chalcogenide Iodides Re3Si2SeXS8-XI (Re = La, Ce, Pr, And Nd) Using The Flux-Assisted Boron-Chalcogen Mixture Method, Gopabandhu Panigrahi, Habiba Binte Kashem, Gregory Morrison, Hans Conrad Zur Loye

Faculty Publications

Single crystals and polycrystalline powders of rare earth mixed chalcogenide iodides La3Si2Se1.21S6.79I, Ce3Si2Se1.39S6.61I, Pr3Si2Se1.22S6.78I, and Nd3Si2Se1.18S6.82I were prepared using the reactive flux-assisted boron-chalcogen mixture (BCM) method at 850 °C. All compounds crystallized in the monoclinic crystal system, space group C2/c (space group number 15). The series adopts the La3Si2O8Cl structure type, containing isolated SiQ4 tetrahedra connected by REQ8 (RE = La, Ce, Pr and Nd) polyhedra; this arrangement creates tunnels that are filled by I atoms. The partial substitution of S by Se was carried out to modulate the optical properties. Phase pure samples and uniform solid solutions were obtained …

Inter-Simple Sequence Repeats Application On The Identification Of Genetic Variation Of A New Indonesian Melon Cultivar “Melona”, Tantri Ajeng Salma Salsabila, Adib Fakhruddin Yusuf, Wiko Arif Wibowo, Prima Sekti Kusnanda, Budi Setiadi Daryono

Makara Journal of Science

The field of identification of molecular markers has seen significant advancements, with the Inter-Simple Sequence Repeat (ISSR) emerging as a prominent tool for characterizing genetic variation within species. This study focuses on the new Indonesian melon cultivar “Melona,” developed through selective breeding of commercial melons. This study aimed to assess the utility of ISSR markers in evaluating the genetic variation and stability of the “Melona” cultivar. Comparisons were made with established cultivars—‘Inthanon,” “Rich Sweetness,” “Chamoe,” and “Hikapel”—using five ISSR primers: UBC 807, UBC 808, UBC 810, UBC 812, and UBC 826. A total of 70 DNA fragments with a high …

Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, …

Molecular Interaction Of Purple Rice Ferulic Acid And Skin Aging-Related Enzymes, Ernanin Dyah Wijayanti, Fatchiyah Fatchiyah, Anna Safitri, Dian Siswanto

Makara Journal of Science

Purple rice is rich in ferulic acid, a phenolic acid abundant in rice. Ferulic acid (FA) has long been recognized for its anti-oxidant properties, which are linked to its skin anti-aging activity owing to its ability to scavenge free radicals and pro-tect cells from damage. Skin anti-aging activity could be assessed by inhibiting skin aging enzymes. However, there was limited information on the mechanism of FA inhibition of these enzymes. This study focused on the molecular interac-tion between purple rice FA and collagenase or tyrosinase, both with and without their substrates. The interaction be-tween FA (CID 445858), collagenase (2Y6I), tyrosinase …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

Biochemical, Structural, And Conformational Characterization Of A Fungal Ethylene-Forming Enzyme, Shramana Chatterjee, Joel A. Rankin, Mark A. Farrugia, Simahudeen Bathir J S Rifayee, Christo Z. Christov, Jian Hu, Et. Al.

Michigan Tech Publications

The ethylene-forming enzyme (EFE) from the fungus Penicillium digitatum strain Pd1 was heterologously produced in Escherichia coli and its properties were compared to the extensively characterized bacterial enzyme from Pseudomonas savastanoi strain PK2. Both enzymes catalyze four reactions: the conversion of 2-oxoglutarate (2OG) to ethylene and CO₂, oxidative decarboxylation of 2OG coupled to _L-arginine (_L-Arg) hydroxylation, uncoupled oxidative decarboxylation of 2OG, and the production of 3-hydroxypropionate (3-HP) from 2OG. The strain Pd1 enzyme exhibited a greater ratio of ethylene production over _L-Arg hydroxylation than the PK2 strain EFE. The uncoupled decarboxylation of 2OG and …