Biochemistry, Biophysics, and Structural Biology Commons^™

Structure, Dynamics, And Redox Reactivity Of An All-Purpose Flavodoxin, Sharique Khan, Ahmadullah Ansari, Monica Brachi, Debarati Das, Wassim El Housseini, Shelley Minteer, Anne-Francis Miller

Markey Cancer Center Faculty Publications

The flavodoxin of Rhodopseudomonas palustris CGA009 (Rp9Fld) supplies highly reducing equivalents to crucial en- zymes such as hydrogenase, especially when the organism is iron-restricted. By acquiring those electrons from photodriven electron flow via the bifurcating electron transfer flavoprotein, Rp9Fld provides solar power to vital metabolic processes. To understand Rp9Fld’s ability to work with diverse partners, we solved its crystal structure. We observed the canonical fla- vodoxin (Fld) fold and features common to other long-chain Flds but not all the surface loops thought to recognize part- ner proteins. Moreover, some of the loops display alternative structures and dynamics. To advance studies …

Sedimentation Of Large, Soluble Proteins Up To 140 Kda For 1h-Detected Mas Nmr And 13c Dnp Nmr – Practical Aspects, Dallas Bell, Florian Lindemann, Lisa Gerland, Hanna Aucharova, Alexander Klein, Daniel Friedrich, Matthias Hiller, Kristof Grohe, Tobias Meier, Barth Van Rossum, Anne Diehl, Jon Hughes, Leonard J. Mueller, Rasmus Linser, Anne-Frances Miller, Hartmut Oschkinat

Markey Cancer Center Faculty Publications

Solution NMR is typically applied to biological systems with molecular weights < 40 kDa whereas magic-angle-spinning (MAS) solid-state NMR traditionally targets very large, oligomeric proteins and complexes exceeding 500 kDa in mass, including fibrils and crystalline protein preparations. Here, we propose that the gap between these size regimes can be filled by the approach presented that enables investigation of large, soluble and fully protonated proteins in the range of 40–140 kDa. As a key step, ultracentrifugation produces a highly concentrated, gel-like state, resembling a dense phase in spontaneous liquid-liquid phase separation (LLPS). By means of three examples, a Sulfolobus acidocaldarius bifurcat- ing electron transfer flavoprotein (SaETF), tryptophan synthases from Salmonella typhimurium (StTS) and their dimeric β-subunits from Pyrococcus furiosus (PfTrpB), we show that such samples yield well-resolved proton-detected 2D and 3D NMR spectra at 100 kHz MAS without heterogeneous broadening, similar to diluted liquids. Herein, we provide practical guidance on centrifugation conditions and tools, sample behavior, and line widths expected. We demonstrate that the observed chemical shifts correspond to those obtained from μM/low mM solutions or crystalline samples, indicating structural integrity. Nitrogen line widths as low as 20–30 Hz are observed. The presented approach is advantageous for proteins or nucleic acids that cannot be deuterated due to the expression system used, or where relevant protons cannot be re-incorporated after expression in deuterated medium, and it circumvents crystallization. Importantly, it allows the use of low-glycerol buffers in dynamic nuclear polarization (DNP) NMR of proteins as demonstrated with the cyanobacterial phytochrome Cph1.

Non-Transcriptional Irf7 Interacts With Nf-Κb To Inhibit Viral Inflammation, Shumin Fan, Sonam Popli, Sukanya Chakravarty, Ritu Chakravarty, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Interferon (IFN) regulatory factors (IRF) are key transcrip- tion factors in cellular antiviral responses. IRF7, a virus- inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphory- lation in the cytoplasm, leading to its translocation to the nu- cleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory tran- scription factor NF-κB-p65 and inhibited the induction of in- flammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB–dependent inflammatory …

Foxs1 Is Increased In Liver Fibrosis And Regulates Tgfβ Responsiveness And Proliferation Pathways In Human Hepatic Stellate Cells, Evelyn A. Bates, Zachary A. Kipp, Wang-Hsin Lee, Genesee J. Martinez, Lauren Weaver, Kathryn N. Becker, Sally Pauss, Justin F. Creeden, Garrett B. Anspach, Robert N. Helsley, Mei Xu, Maria E. C. Bruno, Marlene E. Starr, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFβ to activate fibrotic pathways, and FOXS1 …

Β2-Glycoprotein I Promotes The Clearance Of Circulating Mitochondria, Swapan Kumar Dasgupta, Jahnavi Gollamudi, Stefanie Rivera, Ross A Poche, Rolando E Rumbaut, Perumal Thiagarajan

Faculty, Staff and Students Publications

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood. We show that β2-Gp1 binds to cell-free mitochondria (CFM) in the circulation and promotes its phagocytosis by macrophages at physiological plasma concentrations. Exogenous CFM had a short circulation time of less than 10 minutes in mice. Following infusion of CFM, β2-Gp1-deficient mice had significantly higher levels of transfused mitochondria at 5 minutes (9.9 ± 6.4 pg/ml versus 4.0 …

Ibrutinib-Associated Cutaneous Mucormycosis Due To An Apophysomyces Species: Report Of A Case And Review Of The Literature, Trung Minh Nguyen, Eva Amenta, Lynne Chapman, Sarvari Yellapragada, Bhuvaneswari Krishnan, Jonathan Lim, Richard J Hamill

Faculty, Staff and Students Publications

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of …

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal, Prasanti A Kotta, Ajit K Koduri, Jeffrey Berman, Veronica V Rosen, Waleed T Kayani

Faculty, Staff and Students Publications

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Pre-Left Ventricular Assist Device Endoscopic Evaluation Does Not Reduce The Risk Of Later Gastrointestinal Bleeding: A Multicenter Study, Jiahao Peng, Samanthika Devalaraju, Mohamed Azab, William T Cates, Molly Stone, Jonathan Reichstein, Sneha Shaha, Subhasis Chatterjee, Andrew B Civitello, Mourad H Senussi, B Joseph Elmunzer, Michael Volk, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND: Gastrointestinal bleeding (GIB) is a common complication after placement of a left ventricular assist device (LVAD). Some institutions attempt to mitigate post-LVAD GIB using preoperative endoscopy. Our study evaluated whether preoperative endoscopy was associated with a lower risk of post-LVAD GIB.

METHODS: This was a multicenter cohort study of patients who underwent LVAD insertion from 2010-2019 at 3 academic sites. A total of 398 study participants were categorized based on whether they underwent preoperative endoscopy or not. The follow-up period was 1 year and the primary outcome was GIB. Secondary outcomes were severe bleeding and intraprocedural complications.

RESULTS: A …

Risk Factors, Incidence, And Outcomes Associated With Clinically Significant Airway Ischemia, Gloria Li, Zejian Liu, Marcelo Salan-Gomez, Emma Keeney, Ethan D'Silva, Babith Mankidy, Andres Leon, Aladdein Mattar, Abdusallam Elsennousi, Jennalee Coster, Anupam Kumar, Bruno Rodrigues, Meng Li, Alexis Shafii, Puneet Garcha, Gabriel Loor

Faculty, Staff and Students Publications

Airway complications following lung transplantation remain an important cause of morbidity and mortality. We aimed to identify the incidence, risk factors and outcomes associated with clinically significant airway ischemia (CSAI) in our center. We reviewed 217 lung transplants (386 airway anastomoses) performed at our institution between February 2016 and December 2020. Airway images were graded using the 2018 ISHLT grading guidelines modified slightly for retrospective analysis. Airways were considered to have CSAI if they developed ischemia severity >B2, stenosis >50%, and/or any degree of dehiscence within 6-months of transplant. Regression analyses were used to evaluate outcomes and risk factors for …

Using Noninvasive Clinical Parameters To Predict Mortality And Morbidity After Cardiac Interventions In Patients With Cirrhosis: A Systematic Review, Christo Mathew, Ankur Patel, George Cholankeril, Avegail Flores, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular disease commonly affects advanced liver disease patients. They undergo cardiac interventions to improve cardiac outcomes. Cirrhosis increases complication risk, including bleeding, renal and respiratory failure, and further decompensation, including death, posing a clinical dilemma to proceduralists. Predicting outcomes is crucial in managing patients with cirrhosis. Our aim was to systematically review clinical parameters to assess the mortality and complication risk in patients with cirrhosis undergoing cardiac interventions.

METHODS: We searched cirrhosis and cardiovascular intervention terminology in PubMed and Excerpta Medica Database (EMBASE) from inception to January 8, 2023. We included studies reporting clinical scores (e.g. Model for End-stage …

Klebsiella Pneumoniae Carbapenemase Variant 44 Acquires Ceftazidime-Avibactam Resistance By Altering The Conformation Of Active-Site Loops, Zhizeng Sun, Hanfeng Lin, Liya Hu, Neetu Neetu, Banumathi Sankaran, Jin Wang, B V Venkataram Prasad, Timothy Palzkill

Faculty, Staff and Students Publications

Klebsiella pneumoniae carbapenemase 2 (KPC-2) is an important source of drug resistance as it can hydrolyze and inactivate virtually all β-lactam antibiotics. KPC-2 is potently inhibited by avibactam via formation of a reversible carbamyl linkage of the inhibitor with the catalytic serine of the enzyme. However, the use of avibactam in combination with ceftazidime (CAZ-AVI) has led to the emergence of CAZ-AVI-resistant variants of KPC-2 in clinical settings. One such variant, KPC-44, bears a 15 amino acid duplication in one of the active-site loops (270-loop). Here, we show that the KPC-44 variant exhibits higher catalytic efficiency in hydrolyzing ceftazidime, lower …

An Interactive, Case-Based Workshop On The Patient Experience For Internal Medicine Residents, Julian Swanson, Doris Lin, Kristen A Staggers, Priti Dangayach

Faculty, Staff and Students Publications

INTRODUCTION: The technological revolution has narrowed the information gap between physician and patient. This has led to an evolution in medicine from paternalistic to patient-centric, with health care systems now prioritizing patient experience to achieve higher satisfaction scores. Therefore, it is imperative to start early in educating trainees on how to best address the holistic needs of the patient while also delivering high-quality care.

METHODS: We implemented a 1-hour workshop that was repeated weekly over 8 weeks to capture all internal medicine residents in our program. During the workshop, we reviewed the historical evolution of patient care from paternalistic to …

Quantum Dots' Toxicity: A Multi-Level Investigation On The Impact Of Quantum Dots On The Actin Cytoskeleton, Nhi Le

Graduate Theses/Dissertations

Quantum dots (QDs) are fluorescence nanomaterials with unique optical and physical properties. As such, they are highly sought after for their potential use in several biomedical and industrial applications. Despite their vast potential, recent studies have suggested that quantum dots are toxic to cells. Yet, the mechanism of quantum dots’ toxicity remains unclear. As such, my thesis aims to comprehensively examine the mechanism of quantum dots’ toxicity, emphasizing how quantum dots disrupt the actin cytoskeleton. In this study, I used RNA sequencing and mass spectrometry to investigate the influence of CdSe/ZnS QDs on the transcriptomic proteomic level of Saccharomyces cerevisiae …

Nanotoxicology Of Cdse/Zns Quantum Dot Alternatives In Thle-2 And Hepg2 Liver Cells, Seth Harris

Graduate Theses/Dissertations

Fluorescent nanoparticles known as quantum dots (QDs) have unique properties that make them useful in biomedicine. Specifically, CdSe/ZnS QDs, while good at fluorescing, show toxicity. Due to this, safer alternatives have been developed. This study uses an XTT viability assay, ROS fluorescent imaging, and apoptosis to investigate the effect of QD alternatives InP/ZnS, CuInS₂/ZnS, and carbon dots (NCD) in liver cells. The liver is a possible destination for accumulation of QDs making it an appropriate model for testing. A cancerous liver cell line known as HepG2, and an immortalized liver cell line known as THLE-2 were used. At …

Nsp3 Protein-Portion Interaction Of Sars-Cov-2 Using Two Yeast-Hybrid System, Ghadeer Jassem Zakareya

Selected Full-Text Master Theses 2021-

The NSP3 protein of SARS-CoV-2 plays a crucial role in the virus-host interaction during infection. This thesis explores the protein-protein interactions between NSP3 and host factors, shedding light on their significance in viral replication and pathogenesis. NSP3 is known to interact with various host proteins involved in key cellular processes, including innate immune response modulation, RNA processing and protein degradation pathways. Understanding these interactions is essential for developing targeted therapeutic strategies against COVID-19. Application of The Matchmaker GAL4Two-Hybrid Systems, to isolate the NSP3 protein and study the interactions, elucidating the NSP3 host protein interactions and attempting to identify potential key …

The Function Of Protein Glutamylation In Vision, Rawaa Aljammal

Graduate Theses, Dissertations, and Problem Reports (ETD)

Posttranslational glutamylation of protein has emerged as a novel candidate for cellular integrity. In a dynamic process, Tubulin Tyrosine Ligase Like proteins (TTLLs) introduce glutamate groups to their substrates, while Cytosolic Carboxypeptidases members (CCP1-CCP6) remove these glutamate groups. The outcome of this interplay is a wide range of substrates; each is glutamylated to a level crucial for its function.

Protein glutamylation is particularly abundant in neurons and in the axoneme of cilia and flagella. This distribution, along with the correlation between imbalanced glutamylation levels and compromised cellular functions, underscores the significance of protein glutamylation in maintaining cellular viability. However, the …

Transparent And Conductive Gallium Oxide Electrode For Simultaneous Recording And Optogenetic Stimulation, Christopher Patrick Carey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural electrode technology has been around for centuries since the times of Galvani. In early electrophysiology experiments metal wires were used to induce contractions in dissected animals. The metal wire electrode has since been a standard tool to both stimulate and record neural activity. In the past two decades, a new strategy for neural stimulation has been formulated based on the emergent field of optogenetics. Optogenetics refers to the use of light-sensitive proteins genetically imbedded in the membrane of a neuron to elicit neural activity. This technique offers more selectivity in the stimulation of neurons. Typical optogenetic neural electrodes, or …

Inhibition Of Src-3 As A Potential Therapeutic Strategy For Aggressive Mantle Cell Lymphoma, Imani Bijou, Yang Liu, Dong Lu, Jianwei Chen, Shelby Sloan, Lapo Alinari, David M Lonard, Bert W O'Malley, Michael Wang, Jin Wang

Faculty, Staff and Students Publications

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel …

Myokine Probdnf-P75ntr Signaling In Skeletal Muscle Injury And Sterile Inflammation, Katherine Aby

Dissertations and Theses

Originally discovered in the brain, brain-derived neurotrophic factor (BDNF) has been shown to be expressed and released from skeletal muscle as a myokine. However, the function of myokine BDNF is not fully understood. Of interest to this study is the function of the BDNF precursor proBDNF in skeletal muscle. We first show that skeletal muscle expresses unique BDNF splice variants compared to the brain, and at the protein level, skeletal muscle expresses significantly more proBDNF than mature BDNF under basal conditions. Consistent with this, expression of major protein convertases in skeletal muscle were significantly lower. The role of myokine proBDNF …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

Undergraduate Research Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

Synthetic Strategies Toward The Development Of Stable Gold-Based Anticancer Agents And Their Mechanistic Insight, Adedamola Arojojoye

Theses and Dissertations--Chemistry

Despite notable advancements in the design and synthesis of novel chemotherapeutic drugs, cancer continues to be a leading cause of death in the United States. Metallodrugs, especially Au complexes, have played a prominent role in the search for the next generation of chemotherapeutic agents. Herein, I report on the synthetic strategies towards the rational design of stable Au (Au)-based agents, study their reactivity in biological environment, and offer insights into the cytotoxic mechanism of action in cancer. Chemotherapeutic Au compounds exist mainly in +I or +III oxidation states. Repurposing of the Au(I) FDA approved auranofin for the treatment of diseases …

Investigating Dynamics Of Electron Transfer Flavoprotein And Its Partner Flavodoxin Via Small Angle Neutron Scattering And Fluorine Nmr, Sharique Ahmad Khan

Theses and Dissertations--Chemistry

Anaerobic bacteria and archaea thrive in seemingly inhospitable environments because they are extremely energy efficient. Their capacity to fully utilize electrochemical energy is based in large part on their ability to conduct electron transfer bifurcation ('bifurcation') at strongly reducing potentials, thereby producing extremely potent reducing agents able to fix nitrogen and make molecular hydrogen. This chemistry is made possible by the use of a flavin as the site of bifurcation, supported by a specialized protein environment and mechanisms that control the flow of individual electrons.

Bifurcating electron transfer flavoproteins (Bf-ETFs) are versatile protein modules that provide the bifurcating capability associated …

A Wasteside Story: Establishment And Evolution Of A Wastewater Surveillance Lab, Through The Pandemic And Beyond, Syed Shahrukh Hyder

Graduate Research Theses & Dissertations

Wastewater based epidemiology is a fast growing and practical solution to monitor the spread of disease within a population. As the COVID-19 pandemic grounded the world to a standstill, methods to monitor its spread and prepare appropriate responses became vital to begin the return to normalcy. Such was the case in universities around the world where the campus and surrounding community were vital in fulfilling the educational mission in the face of a generational health crisis. The population in a midsize higher educational institute such as Northern Illinois University (NIU) is a broad mix of on-campus and off campus students, …

Pathology And Diagnosis In Inflammatory-Related Diseases: Covid-19 And Age-Related Macular Degeneration, Zane Russell Lacasse

Graduate Research Theses & Dissertations

Chronic inflammation and dysfunctional inflammatory responses are believed to be contributing factors to the severity of many diseases. Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it has been recognized that levels of inflammatory markers and the severity of coronavirus disease-2019 (COVID-19) cases are closely related. The work within this dissertation begins with establishing an alternative platform for the diagnosis of COVID-19 and explores ways to enhance the diagnostic utility of this platform. An alternative route for COVID-19 diagnosis was explored using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS). The platform utilizes a non-invasive sampling technique …

Ascertaining A Biochemical Approach To Chlorophyll D Biosynthesis In Acaryochloris Spp., Rashmi Shivni

Graduate Research Theses & Dissertations

Photosynthesis is one of the most abundant metabolic systems on Earth, and specifically, oxygenic photosynthesis primed the planet for complex, multicellular life. The hallmark of modern oxygenic photosynthesis is the photopigment chlorophyll a found in nearly all oxygenic phototrophs as their primary photopigment in their photosynthesis pathways. There are also many organisms that tap into a variety of chlorophylls to extend the energetic limits of photosynthesis, which are largely found as accessory pigments. One genus of cyanobacteria, Acaryochloris, has garnered attention for the ability to undergo photosynthesis by harnessing the far-red part of the visible light spectrum using chlorophyll d …

Dna I-Motifs: Biophysical Characterization And Structure-Property Correlation As Foundation For Functional Material Design, Alexander Minasyan

Graduate Research Theses & Dissertations

Over the past decades, nucleic acids have emerged as crucial frameworks with significance in biological systems and functional material engineering. Cytosine-rich deoxyribonucleotide sequences can form quadruplex structures a.k.a. i-motifs. Recently, i-motifs have attracted scientific interest in biological and material design areas.

In this work, we systematically investigate an effect of structured and unstructured modifications such as hairpins, stems, loops and overhangs on the kinetic and thermodynamic properties of DNA i-motifs. We demonstrate that the modifications can influence i-motif’s stability and folding/unfolding rates: thus, double stranded stems and hairpins are the best at stabilizing i-motifs and increasing kinetic rates of folding. …

Shedding Light On Ester Drug Metabolism: Investigating Carboxylesterases In Live Cells With Fluorogenic Chemical Tools, Carolyn J. Karns

Masters Theses

No abstract provided.

Elucidating The Role Of Sialic Acid In Tumorigenic Pathways, Kakali Das

Electronic Theses and Dissertations

Hypersialylation is a prognostic biomarker in cancer cells. The upregulated sialic acid expression on cancer cells facilitates tumorigenesis by playing a critical role in cancer cell proliferation and growth, immune evasion, cell signaling, and metastasis by interacting with various carbohydrate-binding molecules. Sialic acids on cancer cell surface undergo various modifications like O-acetylation at positions 4,7,9 de-acetylation and addition of glycolyl group at position 5. In our first chapter we analyzed the effect of de-acetylated sialic acid on migration via selectin binding in colon cancer cell line HCT116 and in lung cancer cell line A549. Selectins are calcium-dependent cell adhesion molecules …

Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch

Graduate Student Theses, Dissertations, & Professional Papers

The COP9 signalosome is a highly conserved eukaryotic complex regulating protein degradation via deneddylation of Cullin-RING E3 ligases. CSN5, the COP9’s fifth component, contains the catalytically active domain for CSN deneddylation. The complex is inactive without CSN5; however, CSN5 engages in COP9-independent binding with several other proteins, typically promoting either destruction or stabilization of its partners. Many of its confirmed interaction partners are also implicated in tumorigenesis (prominent examples being p27 and p53) and a complex cancer interactome has been established for CSN5. Additionally, CSN5 overexpression has been documented in a staggering array of cancers of diverse origins. This discovery …