Biochemistry, Biophysics, and Structural Biology Commons^™

Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala

All Dissertations

Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …

Heat Stress Response And Excystation In Entamoeba Histolytica, Irem Bastuzel

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal protozoan parasite that causes amoebiasis and liver abscess and is responsible for symptomatic disease in approximately 100 million people each year leading to ~ 100,000 deaths. The most common disease transmission follows the oral-fecal route, but it can also be transmitted by mechanical vectors such as animals carrying the amoeba from contaminated sources to water systems. In rare cases, disease transmission has been recorded in some patients in which men-to-men sexual practices were preferred.

The life cycle of E. histolytica starts through ingestion of infectious cysts, which are non-dividing, quadri-nucleated structures surrounded …

Habitability, And Evolution Of Microorganisms Under Extreme Conditions, Azarin Yazdani

Graduate Theses and Dissertations

The choice of a solvent determines the possible biochemistry of life. Life on Earth is based on carbon biochemistry and has evolved in an environment with water as a solvent. As a polar solvent abundant on Earth, water has unique physical properties, including a large range of liquidity and low viscosity, making it a very good solvent for terrestrial life. Liquids other than water are abundant in the universe, and the chemical nature of these liquids might lead to different chemistries of life. In the first chapter, we review the main characteristics of a good solvent, and then we use …

Identification Of Genomic, Proteomic, And Metabolomic Signatures Associated With Pulmonary Hypertension Syndrome In Broilers, Duaa Almansaf

Graduate Theses and Dissertations

The present dissertation contains a collection of studies that examine the genomic, proteomic, and metabolomic association to pulmonary hypertension or ascites phenotype in fast-growing broilers. Pulmonary hypertension is a multifactorial metabolic disease influenced by physiological, environmental, and nutritional factors. It is characterized by a number of structural changes including, thrombosis and adverse pulmonary vascular remodeling. Thus, the atrial pressure is increased, and the right ventricle becomes hypertrophied, resulting in heart failure and the death of the bird. Pulmonary hypertension or ascites is a global problem that has negatively impacted the economy. The increased mortality rate of broilers (25%) is estimated …

The Role Of Temperature Variation On Macrophage Physiology And Function In Vitro In Mice, Chicken, And Fish, Intisar Abdullah Hassan

Graduate Theses and Dissertations

Fever is an essential component of the immune response. Baseline body temperatures vary in different species, and fever represents increased temperature over baseline. Fever initiates and enhances immune responses as well as creates an environment in which the body has advantages over pathogens. Macrophages are often the first line of cells that come in contact with pathogens, asthey reside in and traffic through tissues. They are important for their engulfment of pathogens that results in the digestion of the pathogen, and they also produce nitric oxide and cytokines that contribute to immune responses in a variety of ways, including initiating …

Chondronecrosis With Osteomyelitis In Broilers: Bacterial Species Involvement And Influence Of Probiotics And Synbiotics, Amer Abdullah Hasan

Graduate Theses and Dissertations

Since 1945, the market for broiler production has evolved from a collection of smallholder poultry farms into an industry worth billions of dollars. Poultry production has not gone without challenges. Lameness in young broilers is presently a serious issue in the poultry industry for reasons of animal health and welfare, as well as significant lost production and revenue. Bacterial chondronecrosis with osteomyelitis (BCO) is a major form of lameness in broilers. This dissertation contains information about (i) the influence of Staphylococcus agnetis, Staphylococcus saprophyticus, Staphylococcus epidermidis and Enterococcus faecalis on inducing BCO lameness, (ii) evaluation of of probiotics for reducing …

Bacterial Chondronecrosis With Osteomyelitis In Broilers: Genomics, Phylogenomics, And Methods To Detect Specific Pathogens During Outbreaks., Abdulkarim Abdulaziz A. Shwani

Graduate Theses and Dissertations

Lameness is a major issue in animal welfare and the broiler industry. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main causes of lameness. Many staphylococcal species, including Staphylococcus agnetis isolate 908, have been isolated from the bones and blood of lame broilers at the University of Arkansas. Staphylococcus agnetis is a coagulase-variable, Gram-positive bacterial species that has been previously associated with subclinical or mild clinical cases of mastitis in dairy cattle. The annotated complete genome of hypervirulent strain 908 was published at NCBI. In this study, it has been compared to nine genomes we assembled for hypervirulent isolates …

Hsp- 70 Mediated Nervous System Enhancement By Etas, Taylor Carter

Theses (2016-Present)

Neurodegenerative disease in the CNS is usually a product of increased oxidative stress in the brain. In this study we tested the ability of an asparagus supplement ETAS to help reduce oxidative stress in the normal brains of Balb C mice. Oxidative stress pathways (Heat shock proteins) are usually cumulative in the damage they cause when disrupted. We treated normal Balb C mice with ETAS and had control groups with no ETAS supplementation in their regular diet. We then sacrificed the mice and conducted microarray studies to compare oxidative stress pathway genes. We also characterized the effects of regular oxidative …

Investigating The Biorisk Of Genetically Engineered Thermosynechococcus Elongatus Bp1, Cherrelle Leah Barnes

Chemistry & Biochemistry Theses & Dissertations

Cyanobacteria, also known as blue-green algae, are an ancient group of microorganisms that use simple materials, such as sunlight, carbon dioxide and water, to produce energy while providing oxygen to the atmosphere by performing photosynthesis. Synthetic biology approaches have been employed with cyanobacteria as a platform to produce a range of products, such as biofuels, by inserting a series of genes into the cyanobacterial genome that will allow the conversion of metabolic intermediates to such desired products. Although these methods are promising, it is important to understand any potential bio-risk they pose. This research evaluates the potential bio-risk of genetically …

Clostridioides Difficile Biofilm And Spore Production In Response To Antibiotics And Immune Stress, Adenrele M. Oludiran

Chemistry & Biochemistry Theses & Dissertations

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. C. difficile, an anaerobic spore-forming Gram-positive pathogenic bacterium, is a major cause of hospital-acquired infections. C. difficile persists in the environment and spreads the infection to new hosts in the form of dormant spores and can persist within hosts as surface-attached biofilms. These studies investigate bacterial vegetative cell survival, biofilm formation, and sporulation in response to stress. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating …

Maladaptive Positive Feedback Production Of Chrebpβ Underlies Glucotoxic Β-Cell Failure, Liora S Katz, Gabriel Brill, Pili Zhang, Anil Kumar, Sharon Baumel-Alterzon, Lee B Honig, Nicolás Gómez-Banoy, Esra Karakose, Marius Tanase, Ludivine Doridot, Alexandra Alvarsson, Bennett Davenport, Peng Wang, Luca Lambertini, Sarah A Stanley, Dirk Homann, Andrew F Stewart, James C Lo, Mark A Herman, Adolfo Garcia-Ocaña, Donald K Scott

Faculty, Staff and Students Publications

Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell "glucolipotoxicity" can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is …

Heart Failure In General And Cardiac Transplant Patients With Covid-19, Munish Sharma, Gowthami Sai Kogilathota Jagirdhar, Kalpalatha K Guntupalli, Rahul Kashyap, Salim Surani

Faculty, Staff and Students Publications

Coronavirus disease 2019 (COVID-19) is primarily an infection of the respiratory tract, but it can have multisystem manifestations. Cardiac complications of COVID-19 can range from acute myocardial injury, cardiac arrhythmias, or heart failure, amongst others. Heart failure (HF) in COVID-19 can be a de novo process or due to worsening of pre-existing cardiovascular ailment. HF in a patient with COVID-19 not only poses challenges in clinical presentation and management of COVID-19 but also affect prognosis of the patient. This article aims to succinctly revisit the implications of this pandemic regarding pre-existing HF or new-onset HF based on prevailing data. It …

Persistent Ethnicity-Associated Disparity In Anti-Tumor Effectiveness Of Immune Checkpoint Inhibitors Despite Equal Access, Marcus A Florez, Jan O Kemnade, Nan Chen, Wendy Du, Anita L Sabichi, Daniel Y Wang, Quillan Huang, Courtney N Miller-Chism, Aparna Jotwani, Albert C Chen, David Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of …

Effect Of High- Vs Low-Dose Tranexamic Acid Infusion On Need For Red Blood Cell Transfusion And Adverse Events In Patients Undergoing Cardiac Surgery: The Optimal Randomized Clinical Trial, Jia Shi, Chenghui Zhou, Wei Pan, Hansong Sun, Sheng Liu, Wei Feng, Weijian Wang, Zhaoyun Cheng, Yang Wang, Zhe Zheng, Optimal Study Group

Faculty, Staff and Students Publications

IMPORTANCE: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.

OBJECTIVE: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to …

Immune Cell-Protein Interactions In Alzheimer’S Disease, Kapur Dhami

Dissertations

Misfolded protein aggregates are one of the significant contributing factors in many neurogenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others. My PhD research project was to study various aspects of amyloid-β peptide, a 40-42-residue peptide and the primary component of the senile plaques found in Alzheimer’s disease (AD) brains. One objective of my research was to purify and characterize the intermediate Aβ42 species using an array of biophysical techniques like size exclusion chromatography, fluorescence assays, circular dichroism, cellular assays, and protein assays. The other major research thrust of my project was to study the role of microglial …

Mtorc1 And Mtorc2 Complexes Regulate The Untargeted Metabolomics And Amino Acid Metabolites Profile Through Mitochondrial Bioenergetic Functions In Pancreatic Beta Cells, Ghada A. Soliman, Rinat Abzalimov, Ye He

Advanced Science Research Center

Background: Pancreatic beta cells regulate bioenergetics efficiency and secret insulin in response to glucose and nutrient availability. The mechanistic Target of Rapamycin (mTOR) network orchestrates pancreatic progenitor cell growth and metabolism by nucleating two complexes, mTORC1 and mTORC2. Objective: To determine the impact of mTORC1/mTORC2 inhibition on amino acid metabolism in mouse pancreatic beta cells (Beta-TC-6 cells, ATCC-CRL-11506) using high-resolution metabolomics (HRM) and live-mitochondrial functions. Methods: Pancreatic beta TC-6 cells were incubated for 24 h with either: RapaLink-1 (RL); Torin-2 (T); rapamycin (R); metformin (M); a combination of RapaLink-1 and metformin (RLM); Torin-2 and metformin (TM); compared to the control. …

Author Correction: In Situ Recording Of Mars Soundscape (Nature, (2022), 605, 7911, (653-658), 10.1038/S41586-022-04679-0), S. Maurice, B. Chide, N. Murdoch, R. D. Lorenz, D. Mimoun, R. C. Wiens, A. Stott, X. Jacob, T. Bertrand, F. Montmessin, N. L. Lanza, C. Alvarez-Llamas, S. M. Angel Ph.D., M. Aung, J. Balaram, O. Beyssac, A. Cousin, G. Delory, O. Forni, T. Fouchet, O. Gasnault, H. Grip, M. Hecht, J. Hoffman, J. Laserna, J. Lasue, J. Maki, J. Mcclean, P. Y. Meslin, S. Le Mouélic, S. Le Mouélic, A. Munguira

Faculty Publications

In the version of this article initially published, the Acknowledgements statement was missing the text “Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004),” which has now been inserted in the HTML and PDF versions of the article.

Growth Outcomes Of Pseudomonas Aeruginosa Inhibitor Of Vertebrate Lysozyme Knockouts In Conditions Mimicking The Cystic Fibrosis Lung Environment, Amani Gaddy

Master of Science in Chemical Sciences Theses

Pseudomonas aeruginosa (PA) is a Gram-negative bacterium, often found in cystic fibrosis (CF) patients and can lead to the decline of lung functioning and premature death in 80% of infected patients when microcolonies form within the mucin of the lung. Due to its major capacity for antibiotic resistance, an alternative strategy towards defending against the bacterial invasion of PA is by the antibacterial activity of our own innate immune system with use of elements such as lysozyme. Pseudomonas aeruginosa inhibitor of vertebrate lysozyme class 1 (Ivyp1) is a periplasmic protein produced by gram-negative bacteria that inhibits the enzymatic activity of …

Structure-Property Investigations In Urea Tethered Iodinated Triphenylamines, Muhammad Saddam Hossain, Fiaz Ahmed, Stavros G. Karakalos, Mark D. Smith, Namrata Pant, Sophya V. Garashchuk, Andrew B, Greytak, Pablo Docampo, Linda S. Shimizu

Faculty Publications

Herein, we report structural, computational, and conductivity studies on urea-directed self-assembled iodinated triphenylamine (TPA) derivatives. Despite numerous reports of conductive TPAs, the challenges of correlating their solid-state assembly with charge transport properties hinder the efficient design of new materials. In this work, we compare the assembled structures of a methylene urea bridged dimer of di-iodo TPA (1) and the corresponding methylene urea di-iodo TPA monomer (2) with a di-iodo mono aldehyde (3) control. These modifications lead to needle shaped crystals for 1 and 2 that are organized by urea hydrogen bonding, π⋯π stacking, I⋯I, and I⋯π interactions as determined by …

A Narrative Review On Yoga: A Potential Intervention For Augmenting Immunomodulation And Mental Health In Covid-19, Indranill Basu-Ray, Kashinath Metri, Dibbendhu Khanra, Rishab Revankar, Kavitha M Chinnaiyan, Nagaratna Raghuram, Mahesh Chandra Mishra, Bhushan Patwardhan, Manjunath Sharma, Ishwar V Basavaraddi, Akshay Anand, Shrinath Reddy, K K Deepak, Marian Levy, Sue Theus, Glenn N Levine, Holger Cramer, Gregory L Fricchione, Nagendra R Hongasandra

Faculty, Staff and Students Publications

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as …

Cellular Mechanisms Underlying State-Dependent Neural Inhibition With Magnetic Stimulation, Hui Ye, Vincent Chiun-Fan Chen, Jenna Hendee

Engineering Science Faculty Publications

Novel stimulation protocols for neuromodulation with magnetic fields are explored in clinical and laboratory settings. Recent evidence suggests that the activation state of the nervous system plays a significant role in the outcome of magnetic stimulation, but the underlying cellular and molecular mechanisms of state-dependency have not been completely investigated. We recently reported that high frequency magnetic stimulation could inhibit neural activity when the neuron was in a low active state. In this paper, we investigate state-dependent neural modulation by applying a magnetic field to single neurons, using the novel micro-coil technology. High frequency magnetic stimulation suppressed single neuron activity …

Using Dietary Additives To Improve Palatability Of Diets Containing Single‐Cell Protein From Methanotrophic Bacteria In Yellowtail Kingfish (Seriola Lalandi) Diets, Luke Pilmer, Lindsey Woolley, Alan J. Lymbery, Michael Salini, Gavin Partridge

Fisheries Research Articles

Single-cell protein (SCP) derived from methanotrophic bacteria has significant potential as a fishmeal alternative in aquafeeds. However, SCP has known palatability issues, to overcome these issues tuna hydrolysate and garlic powder were tested as palatability enhancers against basal diets without these additives. This study tested the inclusion of SCP at four dietary levels of 0%, 10%, 20% and 30%, representing 0%, 25%, 50% and 75% fishmeal replacement in juvenile yellowtail kingfish (Seriola lalandi) (YTK) diets. YTK were fed these diets in triplicate over 35 days. Compared with the control diet, fish fed the SCP10% diet ate less feed, …

Extracellular Domain Of Pept1 Interacts With Tm1 To Facilitate Substrate Transport, Jiemin Shen, Miaohui Hu, Xiao Fan, Zhenning Ren, Corinne Portioli, Xiuwen Yan, Mingqiang Rong, Ming Zhou

Faculty, Staff and Students Publications

Mammalian peptide transporters, PepT1 and PepT2, mediate uptake of small peptides and are essential for their absorption. PepT also mediates absorption of many drugs and prodrugs to enhance their bioavailability. PepT has twelve transmembrane (TM) helices that fold into an N-terminal domain (NTD, TM1–6) and a C-terminal domain (CTD, TM7–12), and has a large extracellular domain (ECD) between TM9–10. It is well-recognized that peptide transport requires movements of the NTD and CTD, but the role of the ECD in PepT1 remains unclear. Here we report the structure of horse PepT1 encircled in lipid nanodiscs and captured in the inward-open apo …

Quantifying Protein Quality To Understand Protein Homeostasis (Supplemental Data), Hsien-Jung Lavender Lin

ScholarsArchive Data

This data set includes the supplementary data for chpaters 3 and 4 in the dissertation Quantifying Protein Quality to Understand Protein Homeostasis. It includes various excel worksheets that were used to generate the data reported in the dissertation. We make this data available to the public so anyone who wants to reproduce the results has the resources and access to other perspectives that weren't discussed in depth in the dissertation. Chapter 3 used mass-spectrometry to quantify the surface accessibility differences in human serum albumin (HSA)between patients with and without rheumatoid arthritis (RA). We found certain residues are less reactive …

Leafing Through Literature: Late Embryogenesis Abundant Proteins Coming Of Age – Achievements And Perspectives, Itzell E. Hernandez-Sanchez, Israel Maruri Lopez, Coral Martinez-Martinez, Brett Janis, Juan Francisco Jimenez Bremont, Alejandra A. Covarrubias, Michael A. Menze, Steffen P. Graether, Anja Thalhammer

Faculty and Staff Scholarship

To deal with increasingly severe periods of dehydration related to global climate change, it becomes increasingly important to understand the complex strategies many organisms have developed to cope with dehydration and desiccation. While it is undisputed that late embryogenesis abundant (LEA) proteins play a key role in the tolerance of plants and many anhydrobiotic organisms to water limitation, the molecular mechanisms are not well understood. In this review we recap the current knowledge of the physiological roles of LEA proteins and discuss their potential molecular functions. As these are ultimately linked to conformational changes in the presence of binding partners, …

Structure-Activity Relationship And Antitumor Activity Of 1,4-Pyrazine-Containing Inhibitors Of Histone Acetyltransferases P300/Cbp, Shenyou Nie, Fangrui Wu, Jingyu Wu, Xin Li, Chao Zhou, Yuan Yao, Yongcheng Song

Faculty, Staff and Students Publications

Acetylation of histone lysine residues by histone acetyltransferase (HAT) p300 and its paralog CBP play important roles in gene regulation in health and diseases. The HAT domain of p300/CBP has been found to be a potential drug target for cancer. Compound screening followed by structure-activity relationship studies yielded a novel series of 1,4-pyrazine-containing inhibitors of p300/CBP HAT with their IC50s as low as 1.4 μM. Enzyme kinetics and other studies support the most potent compound 29 is a competitive inhibitor of p300 HAT against the substrate histone. It exhibited a high selectivity for p300 and CBP, with negligible activity on …

The Importance Of Co2 Recapture In The Co2 Concentrating Mechanism Of Chlamydomonas Reinhardtii, Ashwani Rai

LSU Doctoral Dissertations

The aim of this thesis is to investigate the CO₂ concentrating mechanism (CCM) of Chlamydomonas reinhardtii and to develop a quick method for estimating the activity of carbonic anhydrases (CAs). The first project demonstrates that there are two almost identical mitochondrial CAs in C. reinhardtii, CAH4 and CAH5, that help to maintain photosynthesis and minimize the leak of CO₂ generated by respiration and photorespiration. We used an RNAi approach to reduce the expression of CAH4 and CAH5 so that their physiological functions could be studied. RNAi mutants with low expression of CAH4 and CAH5 have impaired rates …

The Role Of Protein Palmitoylation In Two Disorders; X-Linked Intellectual Disability And Covid-19, Ahmed A. Ramadan

USF Tampa Graduate Theses and Dissertations

The spike proteins of enveloped viruses are transmembrane glycoproteins that typically undergo post-translational attachment of palmitate on cysteine residues on the cytoplasmic facing tail of the protein. The role of spike protein palmitoylation in virus biogenesis and infectivity is being actively studied as a potential target of novel antivirals. Here, we report that palmitoylation of the first five cysteine residues of the C-terminal cysteine-rich domain of the SARS-CoV-2 S protein are indispensable for infection, and palmitoylation-deficient spike mutants are defective in membrane fusion. The DHHC9 palmitoyltransferase interacts with and palmitoylates the spike protein in the ER and Golgi, and knockdown …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

In Vivo Evaluation Of (-)-Zampanolide Demonstrates Potent And Persistent Antitumor Efficacy When Targeted To The Tumor Site., Leila Takahashi-Ruiz, Joseph D Morris, Phillip Crews, Tyler A Johnson, April L Risinger

Natural Sciences and Mathematics | Faculty Scholarship

Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but …