Biochemistry, Biophysics, and Structural Biology Commons^™

Ubiquitination Of Xct: Impacts On The Protein's Stability, Turnover Rate, And Localization, Sofia Rosenberger

23rd Annual A. Paul and Carol C. Schaap Celebration of Undergraduate Research and Creative Activity (2024)

System x_c^- imports cystine and exports glutamate. Its presence on the plasma membrane has been shown to increase directly with oxidative insults. Ubiquitin, a small protein, is directly involved in the trafficking and degradation of numerous proteins within cells and has been shown to bind to System x_c^-. Moreover, upon oxidative insult, protein ubiquitination increases. However, it is not understood how ubiquitination of the transporter impacts its activity. Therefore, the objective of this project is to directly assess how ubiquitination affects the protein’s stability, turnover rate, and localization in the context of oxidative stress. We …

Lc-Ms/Ms For Proteomic Analysis Of Post-Translational Modifications On Xct, Connor Bricco

23rd Annual A. Paul and Carol C. Schaap Celebration of Undergraduate Research and Creative Activity (2024)

Membrane protein xCT and its heavy chain component 4F2HC make up the xc- transport system. 4F2HC may be necessary for membrane localization of the heterodimer and xCT is responsible for transport activity. Under basal conditions, xCT resides in endosomes, but upon oxidative insult, xCT moves to the membrane and functions to reduce oxidative stress. We hypothesize the movement of xCT to the membrane is directed by changes in posttranslational modifications (PTMs) such as phosphorylation, ubiquitination and glycosylation. The overall goal of this project is to use mass spectrometry to detect the PTMs of xCT isolated from cells grown under basal …

Multivalency Of The Mdmx Acidic Domain Slims Use Different Binding Modes To Inhibit Mdmx And P53, Malissa Fenton

USF Tampa Graduate Theses and Dissertations

Regulation of protein binding through autoinhibition commonly occurs via interactions involving intrinsically disordered regions (IDRs). These intramolecular interactions can directly or allosterically inhibit intermolecular protein or DNA binding, regulate enzymatic activity, and control the assembly of large macromolecular complexes. Autoinhibitory interactions mediated by protein disorder are inherently transient, making their identification and characterization challenging. In this work, we explore the structural and functional diversity of disorder-mediated autoinhibition for a variety of biological mechanisms, with a focus on the role of multivalency and effective concentration. We also discuss the evolution of disordered motifs that participate in autoinhibition using examples where sequence …

Akap12 Upregulation Associates With Pde8a To Accelerate Cardiac Dysfunction, Hanan Qasim, Mehrdad Rajaei, Ying Xu, Arfaxad Reyes-Alcaraz, Hala Y Abdelnasser, M David Stewart, Satadru K Lahiri, Xander H T Wehrens, Bradley K Mcconnell

Faculty, Staff and Students Publications

BACKGROUND: In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3',5'-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins) regulate cardiac function and are proposed as targets for precise pharmacology. AKAP12 is expressed in the heart and has been reported to directly bind β2-adrenergic receptor, PKA, and PDE4D. However, its roles in cardiac function are unclear.

METHODS: cAMP accumulation in real time downstream of the β2-adrenergic receptor was detected for …

Influence Of Rna Circularity On Target Rna-Directed Microrna Degradation, Federico Fuchs Wightman, Jerónimo Lukin, Sebastián A Giusti, Michael Soutschek, Laureano Bragado, Berta Pozzi, María L Pierelli, Paula González, Juan P Fededa, Gerhard Schratt, Rina Fujiwara, Jeremy E Wilusz, Damián Refojo, Manuel De La Mata

Faculty, Staff and Students Publications

A subset of circular RNAs (circRNAs) and linear RNAs have been proposed to 'sponge' or block microRNA activity. Additionally, certain RNAs induce microRNA destruction through the process of Target RNA-Directed MicroRNA Degradation (TDMD), but whether both linear and circular transcripts are equivalent in driving TDMD is unknown. Here, we studied whether circular/linear topology of endogenous and artificial RNA targets affects TDMD. Consistent with previous knowledge that Cdr1as (ciRS-7) circular RNA protects miR-7 from Cyrano-mediated TDMD, we demonstrate that depletion of Cdr1as reduces miR-7 abundance. In contrast, overexpression of an artificial linear version of Cdr1as drives miR-7 degradation. Using plasmids that …

Structural Basis Of Dna Crossover Capture By Escherichia Coli Dna Gyrase, Marlène Vayssières, Nils Marechal, Long Yun, Brian Lopez Duran, Naveen Kumar Murugasamy, Jonathan M Fogg, Lynn Zechiedrich, Marc Nadal, Valérie Lamour

Faculty, Staff and Students Publications

DNA supercoiling must be precisely regulated by topoisomerases to prevent DNA entanglement. The interaction of type IIA DNA topoisomerases with two DNA molecules, enabling the transport of one duplex through the transient double-stranded break of the other, remains elusive owing to structures derived solely from single linear duplex DNAs lacking topological constraints. Using cryo–electron microscopy, we solved the structure of Escherichia coli DNA gyrase bound to a negatively supercoiled minicircle DNA. We show how DNA gyrase captures a DNA crossover, revealing both conserved molecular grooves that accommodate the DNA helices. Together with molecular tweezer experiments, the structure shows that the …

Understanding The Mechanism Behind Hfip's Effect On Diastereomeric Separation Of Oligonucleotides, Ian Neidigh

Honors Theses

The goal of this research was to determine the mechanism behind 1,1,1,3,3,3-hexafluoroisopropanol's (HFIP0 ability to suppress the separation of oligonucleotide diastereomers. This was accomplished by selecting different molecules that were like HFIP but differed in specific ways such as polarity, number and type of halogen(s), alcohol group location, carbon chain length, hydrophobicity, and chao/kosmotropicity. These molecules replaced HFIP in an IPRP chromatography method to determine if splitting of the diastereomers was observed and then they would becompared to HFIP's effect. Viscosity tests were to run to acquire quantitative data to determine chao/kosmotropicity. No decisive trend among a single factor was …

Lead Compound Development Of Src-3 Inhibitors With Improved Pharmacokinetic Properties And Anticancer Efficacy, Dong Lu, Jianwei Chen, Li Qin, Imani Bijou, Ping Yi, Feng Li, Xianzhou Song, Kevin R Mackenzie, Xin Yu, Bin Yang, Sandipan Roy Chowdhury, James D Korp, Bert W O'Malley, David M Lonard, Jin Wang

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is a critical mediator of many intracellular signaling pathways that are crucial for cancer proliferation and metastasis. In this study, we performed structure-activity relationship (SAR) exploration and drug-like optimization of the hit compound SI-2, guided by in vitro/in vivo metabolism studies and cytotoxicity assays. Our efforts led to the discovery of two lead compounds, SI-10 and SI-12. Both compounds exhibit potent cytotoxicity against a panel of human cancer cell lines and demonstrate acceptable pharmacokinetic properties. A biotinylated estrogen response element (ERE) pull-down assay demonstrated that SI-12 could disrupt the recruitment of SRC-3 and p300 in …

Using Artificial (Ai) To Predict A Structure Of Protein Complex, Yiqing Zang

SACAD: Scholarly Activities

Proteins play pivotal roles in essential life processes and elucidating their three-dimensional (3D) structures is crucial for understanding their functions. AlphaFold2, an advanced artificial intelligence-based method developed by Google DeepMind, has emerged as a promising tool for predicting protein structures. In this study, we evaluated the predictive capabilities of AlphaFold2. Our findings highlight AlphaFold2's efficacy in providing valuable insights into protein structure prediction, albeit with certain limitations. While AlphaFold2 represents a significant advancement in the field, its utility is best realized when integrated with complementary experimental approaches. Consequently, combining the strengths of AlphaFold2 with experimental validation remains essential for achieving …

Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors In Patients With Type 2 Diabetes: A Cardiology Primer, Allan Zhang, Ramsey Kalil, Alexander Marzec, Stephanie A Coulter, Salim Virani, Kershaw V Patel, Matthew W Segar

Faculty, Staff and Students Publications

Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved …

Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC₅₀ that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …

Social Media Does Not Elicit A Physiological Stress Response As Measured By Heart Rate And Salivary Cortisol Over 20-Minute Sessions Of Cell Phone Use, Suzanne Oppenheimer, Laura Bond, Charity Smith

Biomedical Research Institute Publications and Presentations

The pervasive use of social media has raised concerns about its potential detrimental effects on physical and mental health. Others have demonstrated a relationship between social media use and anxiety, depression, and psychosocial stress. In light of these studies, we examined physiological indicators of stress (heart rate to measure autonomic nervous system activation and cortisol to assess activity of the hypothalamic-pituitary-adrenal axis) associated with social media use and investigated possible moderating influences of sex, age, and psychological parameters. We collected physiological data from 59 subjects ranging in age from 13 to 55 across two cell phone treatments: social media use …

Broad-Spectrum Lignin-Based Adhesives Using Thiol–Silyl Ether Crosslinkers, Yishayah Bension, Siteng Zhang, Tristan Menninger, Ting Ge, Chuanbing Tang

Faculty Publications

Lignin is a renewable feedstock that is abundant and inexpensive but still presents challenges for its valorization. In this work, we converted functionalized lignin into broad-spectrum adhesives using thiol–silyl ether crosslinkers. The curing behavior of adhesives was investigated via rheology of their resin forms. These materials exhibit good adhesion on diverse substrates, including wood, glass, steel, aluminium, carbon fiber, and different plastics, with the most adhesion strength in the range of 1–3 MPa. These adhesives were also explored for applications, ranging from wet conditions to different mechanically responsive materials. The mechanism of adhesion was further examined to understand the bonding …

The Impact Of Mutations In The Arabidopsis Apetela (Ap3) Gene, Hazel R. Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

The purpose of this research is to understand the molecular functioning of the Arabidopsis thaliana Apetela (Ap3) gene. We created mutations in two sites of the gene, AP3-3 and AP3-5. These are predicted to change AP3 protein structure, which may result in a mutated flower. Analyzing the effects of new mutations allows an understanding of protein formation both in plants and humans.

Artificial Intelligence Predictive Analytics In Heart Failure: Results Of The Pilot Phase Of A Pragmatic Randomized Clinical Trial, Konstantinos Sideris, Charlene R Weir, Carsten Schmalfuss, Heather Hanson, Matt Pipke, Po-He Tseng, Neil Lewis, Karim Sallam, Biykem Bozkurt, Thomas Hanff, Richard Schofield, Karen Larimer, Christos P Kyriakopoulos, Iosif Taleb, Lina Brinker, Tempa Curry, Cheri Knecht, Jorie M Butler, Josef Stehlik

Faculty, Staff and Students Publications

OBJECTIVES: We conducted an implementation planning process during the pilot phase of a pragmatic trial, which tests an intervention guided by artificial intelligence (AI) analytics sourced from noninvasive monitoring data in heart failure patients (LINK-HF2).

MATERIALS AND METHODS: A mixed-method analysis was conducted at 2 pilot sites. Interviews were conducted with 12 of 27 enrolled patients and with 13 participating clinicians. iPARIHS constructs were used for interview construction to identify workflow, communication patterns, and clinician's beliefs. Interviews were transcribed and analyzed using inductive coding protocols to identify key themes. Behavioral response data from the AI-generated notifications were collected.

RESULTS: Clinicians …

Parp2 Promotes Break Induced Replication-Mediated Telomere Fragility In Response To Replication Stress, Daniela Muoio, Natalie Laspata, Rachel L Dannenberg, Caroline Curry, Simone Darkoa-Larbi, Mark Hedglin, Shikhar Uttam, Elise Fouquerel

Department of Biochemistry and Molecular Biology Faculty Papers

PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent …

Maldi-Msi Identification Of Tissue-Level N-Glycomic And Proteomic Molecular Biomarkers Of Aggressive Prostate Cancer, Jordan Paige Hartig

MUSC Theses and Dissertations

Prostate Cancer (PCa) poses a significant clinical challenge, characterized by debates on screening efficacy and continuous issues with distinguishing aggressive from non-aggressive tumors. Despite treatment advancements, poor patient outcome at late stages and clinical overtreatment of indolent disease emphasizes the urgent need for markers of PCa aggression. Aberrant glycosylation and extracellular matrix (ECM) remodeling are two complex molecular processes necessary for PCa progression, highlighting a novel area for biomarker discovery. Leveraging formalin-fixed paraffin-embedded tissues, tissue microarrays (TMAs), and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), distinct N-glycan and ECM profiles are identified. Elevated bisecting, multi-antennary, and fucosylated N-glycans indicate early …

Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity …

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Hedgehog Signaling And Congenital Disorders; The Case Of Anencephaly And Polydactyly, Joshua Towery

First-Year Research Immersion (FRI) Scholarship

The Hedgehog pathway is a fundamental signaling pathway in the human body; involved in carcinogenesis, stem cell maintenance, as well as limb patterning in embryonic development. Originally discovered in drosophila, their initial discovery, and subsequent analysis revealed many novel pieces of information about the mechanisms inside the human body, as many core components of the signaling pathway are carried over from fruit flies to humans. Because of the key roles hedgehog signaling plays in human development, dysfunction and mutations in the pathway can be detrimental. This review will focus on two congenital birth defects thought to be caused by hedgehog …

Neurotensin Modulates Ovarian Vascular Permeability Via Adherens Junctions, Andrew Pearson, Ketan Shrestha, Thomas E. Curry, Diane M. Duffy

UK CARES Faculty Publications

Neurotensin (NTS) is a 13-amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates …

Exploring Cation Exchange: Unveiling Its Significance In Biochar And Bioenergetics Applications, Gyanendra Kharel

Chemistry & Biochemistry Theses & Dissertations

Cation exchange, a cornerstone of soil chemistry and nutrient cycling, is a fundamental chemical process that occurs in soils, sediments, membranes, and other solid materials. It involves the interchange of positively charged ions, or cations, between a solid matrix and a surrounding solution. This process is crucial in various natural and engineered systems, leading to a range of applications across different fields.

This dissertation presents an extensive investigation into the applications of cation exchange in the fields of biochar and bioenergetics, encompassing three distinct aims. The first aim concentrates on the surface oxygenation of biochar through ozonization, aiming to achieve …

A Review On Irisin, The Beta 3-Adrenergic Receptor, And Zinc Alpha 2-Glycoprotein’S Impact On Metabolic Health, Dawson Troutman

Honors College Theses

This thesis aims to provide insight into how Irisin, the beta 3-adrenergic receptor, and zinc alpha 2-glycoprotein can impact human metabolism. Analyzing studies on the impact these species have on thermogenesis and lipolysis help provide a clearer picture on their use in potential management of metabolic issues.

Expression And Purification Of Domain 1 Of The Cards Toxin, Dylan Andrews, Allison Woods, Ahmad Galaleldeen

Posters - 2024

Mycoplasma pneumoniae (Mp) is an atypical bacterium that is linked to various respiratory diseases such as walking pneumonia and asthma. Upon infection, Mp produces a 591-aa virulence factor known as Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX). The crystal structure of this 591-aa cytotoxin reveals a triangular molecule comprised of an N-terminal ADP-ribosylating domain and a Cterminal tandem β-trefoil domain that is responsible for vacuolation of the host’s cells. Based on structural and sequence homology to other ADP ribosylating toxins, the NAD+ binding site has been predicted, yet none of the published structures of the CARDS toxin contain NAD+. …

Decreasing The Antibiotic Survival Of Multi-Drug Resistant Gram-Positive Organisms, Areej Malik

Biomedical Sciences Theses & Dissertations

Biofilm production plays a crucial role in bacterial antibiotic tolerance and novel approaches are needed to combat it. The stringent response (SR), activated by nucleotide alarmones (pp)pGpp, is crucial for bacterial transcriptional reprogramming. In Clostridioides difficile, the SR is implicated in antibiotic survival, contributing to infection recurrence. Despite its known roles in sporulation and biofilm production in other bacterial species, the broader influence of the SR on C. difficile physiology remains undiscovered. This study deletes the C. difficile SR gene relQ, revealing the pivotal role of RelQ in regulating SR-dependent phenotypes in this organism. The absence of RelQ …

Tools For Biomolecular Modeling And Simulation, Xin Yang

Mathematics Theses and Dissertations

Electrostatic interactions play a pivotal role in understanding biomolecular systems, influencing their structural stability and functional dynamics. The Poisson-Boltzmann (PB) equation, a prevalent implicit solvent model that treats the solvent as a continuum while describes the mobile ions using the Boltzmann distribution, has become a standard tool for detailed investigations into biomolecular electrostatics. There are two primary methodologies: grid-based finite difference or finite element methods and body-fitted boundary element methods. This dissertation focuses on developing fast and accurate PB solvers, leveraging both methodologies, to meet diverse scientific needs and overcome various obstacles in the field.

Cyclophilin A Supports Translation Of Intrinsically Disordered Proteins And Affects Haematopoietic Stem Cell Ageing, Laure Maneix, Polina Iakova, Charles G Lee, Shannon E Moree, Xuan Lu, Gandhar K Datar, Cedric T Hill, Eric Spooner, Jordon C K King, David B Sykes, Borja Saez, Bruno Di Stefano, Xi Chen, Daniela S Krause, Ergun Sahin, Francis T F Tsai, Margaret A Goodell, Bradford C Berk, David T Scadden, André Catic

Faculty, Staff and Students Publications

Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. …

Cifa And Cifb Expression In Response To Piwi And Aub Knockdown In Jw18 D. Melanogaster Cells, Julieta Alarcon

Posters - 2024

Wolbachia is an intracellular bacterium that is known for inducing cytoplasmic incompatibility (CI) in its Drosophila melanogaster hosts. CI is characterized by embryonic death when males that express cifA and cifB genes mate with unaffected females (Shropshire, Rosenberg, and Bordenstein 2020). PIWI proteins play important roles such as germline determination, spermiogenesis, and transposon silencing (Thomson and Lin 2009). Previous studies have shown that Piwi expression decreases in a developmental window called the “Piwiless pocket” or Pilp. When Aub is depleted in the Pilp, then Piwi expression increases (Théron et al. 2018). We will determine if Piwi and Aub FANA ASO …

Characterization Of Rna Binding Proteins Regulating Axonal Localization Of Prenyl-Cdc42 Mrna, Ashley I. Loomis

Senior Theses

Following traumatic injury, axons in the peripheral nervous system (PNS) can spontaneously regenerate, albeit rather slowly. This regeneration requires messenger RNA (mRNA)-localization into and translation within the axons. One such mRNA originates from the CDC42 gene, which produces two mRNA splice variants: Prenyl-CDC42 and Palm-CDC42 encoding mRNAs. CDC42 promotes axon growth and regeneration by regulating actin filament polymerization in growth cones of axons. This plays an important role to support nerve regeneration in humans. The prenyl-Cdc42 mRNA is found in both central nervous system (CNS) and PNS axons, where it can be locally translated into CDC42 protein, which is subsequently …

A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder

Undergraduate Research Symposium

Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …