Microbiology Commons^™

Strategic Enhancement Of Biofuel Production Using Bacillus Subtilis As A Model Organism: A Dual Approach Of Gene Essentiality Mapping And Optimization, Angela A. Zebede

Electronic Theses and Dissertations

With rising global demand for renewable energy, enhancing microbial platforms for biofuel production is vital. This study engineered Bacillus subtilis to improve resilience to solvent stress by targeting membrane lipid biosynthesis pathways essential for integrity. Growth curve analysis (OD₆₀₀) showed that phosphatidylserine (PS) and phosphatidylethanolamine (PE) knockout strains grew significantly slower than wild type (168), indicating the importance of these lipids under stress. Laurdan fluorescence spectroscopy was used to assess membrane properties. Generalized polarization (GP) analysis revealed a concentration-dependent reduction in membrane order upon 1%–2% 1-butanol exposure. GP values declined progressively from control to 2% treatment, reflecting increased membrane fluidity …

Twim #222: Biosensors In Bacteria, Madison Hayes, Alexis Austin, Dillon Nguyen, Angela Wilson, Rebecca Seipelt-Thiemann

School of Medical Diagnostics & Translational Sciences Publications

Podcast annotation TWiM #222: Biosensors in Bacteria from the weekly podcast series "This Week in Microbiology" (TWiM), a podcast where experts in microbiology discuss academic papers in their field in an informal way.

Twim #243: Beef And Bacillus, Sakiem Winston, Madison Wolford, Rebecca Seipelt-Thiemann, Angela Wilson

School of Medical Diagnostics & Translational Sciences Publications

Podcast annotation TWiM #243: Beef and Bacillus from the weekly podcast series "This Week in Microbiology" (TWiM), a podcast where experts in microbiology discuss academic papers in their field in an informal way.

Twim #286: Integrons And Invasion, Andrea Ayala-Lopez, Brittney Heist,, Thomas Salazar, Rebecca Seipelt-Thiemann, Mel Melendrez-Vallard, Angela Wilson

School of Medical Diagnostics & Translational Sciences Publications

Podcast annotation TWiM #286: Integrons and Invasion from the weekly podcast series "This Week in Microbiology" (TWiM), a podcast where experts in microbiology discuss academic papers in their field in an informal way.

Tracing The Journey Of Dissolved Organic Matter: From Leaf Litter Photodegradation To Microbial Processing In Tropical Streams, Samantha Nicole Sullivan

Chemistry & Biochemistry Theses & Dissertations

Dissolved organic matter (DOM) is a major reservoir of organic carbon in aquatic ecosystems and plays a central role in global carbon cycling through its transformation and remineralization to carbon dioxide (CO₂). As DOM moves from terrestrial environments into streams and rivers, its chemical composition is altered by a combination of microbial and photochemical oxidation processes that regulate both its reactivity and its persistence during transport. However, the molecular mechanisms governing these oxidative transitions, particularly in tropical ecosystems characterized by strong hydrologic seasonality and substantial inputs of plant-derived material, remain insufficiently resolved. This dissertation integrates ultrahigh-resolution mass spectrometry, optical characterization, …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

Antifungal Effects Of Fatty Acids On The Growth Of Ophidiomyces Ophiodiicola In A Simulated Snake Skin Environment, Krupa S. Patel, Lizbeth Delarosa, Jacey Cardenas, Thalia Rodriguez, John Niedzwiecki

Science University Research Symposium (SURS)

Emerging infectious diseases have increasingly threatened wildlife populations worldwide, with devastating impacts observed in frogs, bats, and more recently, snakes. Snake fungal disease (SFD), caused by the pathogenic fungus Ophidiomyces ophiodiicola (Oo), currently poses a serious threat to snake populations across multiple regions. Infected snakes exhibit disrupted skin shedding, rough or scaly patches, crusty sores, and ulcers that compromise their health and survival. Although the mechanisms underlying transmission and susceptibility to SFD remain unclear, the snake cutaneous microbiome is known to act as a defensive barrier, mediating interactions between the host and invading pathogens. The lipid layer is a key …

Fungal Foes And Fatty Defenses: How Simulated Snake Skin Lipids Influence Ophidiomyces Ophiodiicola Growth, Thalia Rodriguez, Jacey Cardenas, Lizbeth Delarosa, Krupa Patel, John Niedzwiecki

Science University Research Symposium (SURS)

Emerging fungal diseases are a continuous threat to wildlife health as well as biodiversity. Fungal diseases, such as white nose syndrome in bats, can devastate populations by disrupting their ecosystems. Many other species around the world are affected by fungal diseases, such as amphibians, birds, and snakes. In more recent years, snake fungal disease (SFD) emerged due to the fungal pathogen Ophidiomyces ophiodiicola (O.o). Like Pseudogymnoascus destructans, the fungal pathogen responsible for white nose syndrome, O.o targets the skin which contains many fatty acids. Some studies have shown that fatty acids present in bat skin are able to inhibit fungal …

Investigating The Mechanisms Of Microbial Interactions Using A Model Cystic Fibrosis Polymicrobial Community, Bassam El Hafi

Dartmouth College Ph.D Dissertations

Cystic fibrosis (CF) airway microbial communities are complex ecosystems where interspecies interactions influence pathogen survival and disease progression. We leverage a CF-relevant in vitro four-species model composed of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica, alongside a microbiome dataset with over 4,000 respiratory samples from publicly available sequencing data of CF patient samples, to explore the dynamics of microbial interactions in CF. On a broader scale, we performed microbial network analysis to examine how the latest modulator therapy, elexacaftor/tezacaftor/ivacaftor (ETI), might influence CF microbial communities. Our analysis revealed a reduction in node connections and …

First Report Of A Bat Guano Fire From A Cave In Southeast Asia, Sopark Jantarit, Martin Ellis, Pruet Kalasuwan, Neeranuch Phusunti, Pimonsri Mittraparp-Arthorn, Jiranan Pattano, Arnon Chukamnerd, Turdtun Tong-In, Natthawut Khrueaaunruean

International Journal of Speleology

Fires occurring in cave guano are a rare and unusual phenomenon and the occurrence of such events in Southeast Asia is particularly novel. In this study, we document the first recorded instance of a bat guano fire in a tropical cave at Tham Chao Ram in Sukhothai province, northern Thailand. A bacteriological analysis was made of the guano at the fire site and from a control site within the cave. We give a comprehensive review of global reports on bat guano fires in caves, conduct an initial investigation of the physical factors at the fire site and discuss the potential …

Vitamin D Is Glucoprotective In Aging Males But Not Females, Olivia Z B Ginnard, Maria Morales, Ji Youn Youn, Yong Xu, Stephanie R Sisley

Faculty, Staff and Students Publications

Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

In Vitro Antiviral Activity Of Cat’S Claw (Uncaria Tomentosa) Bark Extract Against Human Influenza A Virus, Juliann N. Makau, Keith K. Talaam, Mike Odiwuor, Janet M. Majanja, Sophia Musenjeri, Ratika Rahmasari, Samoel A. Khamadi, Ken Watanabe

Pharmaceutical Sciences and Research

Influenza A viruses mutate very fast and this leads to the development of resistance to antivirals, hence the need to find new therapeutics. Due to their extensive traditional use, natural products are crucial resources for the discovery of drugs. Cat’s claw (Uncaria tomentosa), is a tropical vine known for various health benefits and in this study we evaluated its anti-influenza activity. Pulverized material of the stem bark was extracted using 80% ethanol, hot water, and 1% sodium bicarbonate. The extracts were dried and dissolved in dimethylsulfoxide before testing for cytotoxicity and antiviral activity using crystal violet assay. The …

Preclinical Efficacy Of Tasquinimod-Based Combinations In Advanced Myeloproliferative Neoplasms In Blastic Phase, Warren Fiskus, Lucia Masarova, Christopher P Mill, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Taghi Manshouri, Andrew Dunbar, Surbhi Sharma, Tapan M Kadia, Courtney D Dinardo, Prithviraj Bose, Naveen Pemmaraju, Sanam Loghavi, Xiaoping Su, Raajit K Rampal, Marie Törngren, Kapil N Bhalla

Faculty, Staff and Students Publications

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. A8 and A9 are secreted into the extracellular space and plasma, in which they interact with Toll-like receptor 4, receptor for advanced glycation end products, and CD33. In these studies, we determined the preclinical efficacy of tasquinimod (TQ) against advanced myeloproliferative neoplasm (MPN) cell lines and patient-derived (PD) CD34+ blastic phase (BP; >5% blasts in the peripheral blood) MPN cells. TQ induced loss of viability in cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. In TQ-treated PD …

Mentoring First-Year Stem Students Through Collaborative Research In The Haynes Scholars Program, Alex Capaldi, Laura Tipton

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Mathematically Modeling Stoichiometric Drivers Of Heterotrophic N2 Fixation, Corday R. Selden, Rebecca Everett, Halvor H. Halvorson, Megan E. Berberich, Luca Schenone, Angela Peace, Renn Schipper, Edwin Cruz-Rivera, James Powell, Keisuke Inomura, Robinson W. Fulweiler, Amy M. Marcarelli, J Thad Scott

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Fostering Entrepreneurial Thinking And Practice Through Teaching And Learning Integration, Mohammad G. Sabbir

Learning and Educational Center Virtual Teaching and Learning Conference

This session explores an innovative, evidence-based approach to integrating entrepreneurial thinking into undergraduate neuroscience education through hands-on gene editing experiences. Using the commercially available Bio-Rad CRISPR/Cas9-based “Out of the Blue” kit for bacterial LacZ gene editing, students are guided not only through the scientific principles underlying modern gene editing technologies but also through the entrepreneurial challenge of replicating and manufacturing the kit using existing lab resources. This model empowers students to extend their learning beyond the classroom by engaging in cost-effective, scalable biotechnology practices—particularly valuable for institutions with limited funding. Classroom-based research demonstrates increased student engagement, deeper conceptual understanding, and …

A Multi-Faceted Study Of Antibiotic-Resistant, Opportunistic Pathogens In Wastewater And Environmental Water, Jeanette Calarco

USF Tampa Graduate Theses and Dissertations

More than 2.8 million infections due to antibiotic-resistant bacteria occur annually in the United States, and more than 35,000 people die as a result. Domestic wastewater (sewage), which contains antibiotic-resistant bacteria and antibiotic resistance genes, is collected at treatment plants for removal of contaminants, e.g. pathogenic microorganisms and nutrients. While wastewater treatment is designed to remove antibiotic-resistant bacteria and other microorganisms through treatment and disinfection, some bacteria may escape treatment. Treated wastewater effluent is generally discharged into surface waters; however, some fraction of the effluent may be used as recycled water. Compromised wastewater collection infrastructure and sewage spills can disseminate …

Disparate Leukemia Mutations Converge On Nuclear Phase-Separated Condensates, Gandhar K Datar, Elmira Khabusheva, Archish Anand, Joshua Beale, Marwa Sadek, Chun-Wei Chen, Evdokiia Potolitsyna, Nayara Alcantara-Contessoto, Guangyuan Liu, Josephine De La Fuente, Christina Dollinger, Anna Guzman, Alejandra Martell, Katharina Wohlan, Abhishek Maiti, Nicholas J Short, S Stephen Yi, Vibeke Andresen, Bjørn Tore Gjertsen, Brunangelo Falini, Rachel E Rau, Lorenzo Brunetti, Nidhi Sahni, Margaret A Goodell, Joshua A Riback

Faculty, Staff and Students Publications

During cancer development, mutations promote changes in gene expression that cause transformation. Leukemia associated with aberrant HOXA expression is driven by translocations of nucleoporin genes or KMT2A as well as mutations in NPM1. The mechanistic convergence of these disparate mutations remains elusive. Here, we demonstrate that mutant nucleophosmin 1 (NPM1c) forms nuclear condensates in human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to recruit NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting …

Serum Response Factor Is Essential For Endometrial Function And Prevention Of Inflammatory Fibrosis, Ryan M Marquardt, Sara A Grimm, San-Pin Wu, Peter F Lais, Shu-Yun Li, Xin Xu, Erin Smithberger, David Cunefare, Charan Ganta, David Olson, Eunhee M Jeong, Jae-Wook Jeong, Bruce A Lessey, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Pregnancy requires a supportive uterine environment facilitated by steroid hormone–regulated differentiation of endometrial stromal fibroblasts into decidual cells and tight control of inflammation. Serum response factor (SRF) is a widely expressed transcription factor essential for mesenchymal cell growth and differentiation with noted roles in hormonal regulation of muscle tissues but little characterization in reproductive organs. Here, we reveal that endometrial SRF is dysregulated in human endometriosis and is critical for female reproductive success in mice through regulation of endometrial stromal and epithelial cells. Immunohistochemical analysis identified decreased endometrial SRF expression in infertile endometriosis patient tissues. RNAi-based SRF knockdown in human …

Solvent Extracts Of Pulvigera Papillosa (Orthotrichaceae) Show No Antimicrobial Properties In Disk Diffusion Tests, Ryan A. Solorzano, Justin Paulin, Grayson Prater, Michael Lanier

Humboldt Journal of Microbiology

Abstract As antibiotic-resistant bacteria become more prevalent, the search for novel forms of antibiotics in the natural world has become an increasingly worthwhile endeavor. Many mosses have been found to contain antimicrobial properties, including those in the family Orthotrichaceae. Pulvigera papillosa, an Orthotrichaceous moss native to California, has thus far not been investigated to determine whether it contains antimicrobial properties. Extraction techniques using polar and nonpolar solvents have proven to be effective in extracting the secondary metabolites that allow mosses to defend themselves against a hostile microbial world. This study takes a preliminary look into the antimicrobial properties of P. …

Assessing Antimicrobial Properties Of Plant-Derived Ellagic Acid Supplements, Noah S. Schuhmann, Andrew Mclaughlin, Julian Barrera

Humboldt Journal of Microbiology

Bacteria present in the human gut microbiota are affected by compounds with antimicrobial properties. Phenolic compounds extracted from plants have been shown to exhibit significant antimicrobial capacity at certain concentrations, which makes them an area of interest to researchers. Ellagic acid is one such phenolic compound, present in nuts and berries that many people consume on a regular basis. Supplements containing concentrated ellagic acid provide an additional source for the compound. It is known that, in the body, ellagic acid is metabolized into urolithins, which contribute to health through their anticancer and anti-inflammatory qualities. In this study, we investigated the …

Comparative Analysis Of Probiotic Viability In Alcoholic And Non-Alcoholic Kombucha, Isabella N. Cerrone, Brooke Pirkle, Danielle Williamson, Gianna Vendrell, Chloe Kraft

Humboldt Journal of Microbiology

Kombucha is a fermented tea beverage valued for its probiotic and antimicrobial properties that arise from complex molecular interactions between yeast, acetic acid bacteria (AAB), lactic acid bacteria (LAB), and metabolic byproducts of fermentation. With the rising demand for non-alcoholic versions of traditionally alcoholic kombucha beverages, ethanol reduction methods have become common, though their impact on probiotic viability and antimicrobial properties remains poorly understood. This study investigates the effects of ethanol removal on kombucha’s functional properties, including probiotic survival, antimicrobial activity, and organic acid composition (pH). We compared alcoholic and non-alcoholic versions of JuneShine kombucha across five flavors. Probiotic viability …

Growth Trends In Abundance And Diversity Of Synthetic Microbial Communities Over Varying Thermal Conditions, Mariska M. Kessler, Jocelyn Wolfinger, Destiny S. Alcaraz

Humboldt Journal of Microbiology

Microorganisms create various communities that act as the foundation of ecosystems. Abiotic factors such as temperature variability and environmental fluctuations are known to produce shifts in the abundance and diversity of microbial communities, but our current understanding is limited. In this study, we aimed to address this gap by observing abundance and diversity growth patterns under different temperature conditions within individual species and communities. Samples of 4 isolates and 4 artificial communities were grown at constant and fluctuating temperatures. Results found that the isolate samples had the highest abundance under constant high temperatures, whereas the community samples had the highest …

Elucidating The Relationship Between Water Quality And Antibiotic Resistance Of Rainwater Microbes Across Western Humboldt County, Theo P. Murphy, Eve Wendley, Justice Laskowski, Tyler Paredes

Humboldt Journal of Microbiology

Limited studies have been conducted regarding the fecal contamination and microbial dispersal through rainwater, with no known studies investigating the potential connection between antibiotic resistant microbes and water quality in rainwater. This study seeks to identify the presence of a correlation between water quality and incidence of antibiotic resistance in rainwater microbes. We hypothesize that there will be a correlation between these two variables. We additionally anticipate a high incidence of fecal contamination across rural and urban collection sites alike, with fecal contamination being more prevalent in rural areas than urban locals. To determine water quality, we measured the concentration …

Comparative Analysis Of Taproot And Fibrous Root System Microbiomes Under Flooding Stress, Natalie S. Kozlowski, Leighanna Jake

Humboldt Journal of Microbiology

There has been increased interest in understanding how the microbiomes of vascular plants respond to flooding stress and, many studies have focused on monocotyledonous plants with fibrous root systems. This leaves a gap in knowledge of dicotyledonous plants with taproot systems, as previous studies have been in the context of flooding to cropland affecting major food crops which are often monocotyledonous plants with fibrous root systems. Since the structural and functional differences between these root systems may influence microbial community stability and response to flooding conditions, a study looking at both is long overdue As such, this study aims to …

Increasing Pediatric Hpv Vaccination Rates, Brooke A. Nicholas

Dissertations

Increasing Pediatric HPV Vaccination Rates

Abstract

Problem: The human papillomavirus (HPV) is a sexually transmitted infection that affects more than 80% of the population within the United States (Eisenhauer et al., 2020). HPV can develop into cervical, anogenital, and oropharyngeal cancers (Eisenhauer et al., 2020). About 4,000 individuals die from cervical cancer alone each year (O’Leary, 2022). The HPV vaccine, though recommended by the ACIP and AAP, is below national vaccination rates in comparison to other vaccines (O’Leary, 2022).

Methods: This quality improvement project is a non-randomized controlled trial that observed HPV vaccine dose completion rates for patients aged 9-14 …

Orphan Nuclear Receptor 4a1 (Nr4a1) And Nr4a2 Are Endogenous Regulators Of Cd71 And Their Ligands Induce Ferroptosis In Breast Cancer, Arafat Rahman Oany, Srijana Upadhyay, Wai Ning Tiffany Tsui, Amanuel Hailemariam, Sarah Latka, John D Landua, Sandra D Scherer, Alana L Welm, Hugo Villanueva, Michael T Lewis, Stephen Safe

Faculty, Staff and Students Publications

Ferroptosis is an iron-dependent cell death pathway that involves multiple genes, including the transferrin receptor (TFRC/CD71), glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11). This study is based on the hypothesis that orphan nuclear receptor 4A1 (NR4A1) and NR4A2 maintain low levels of ferroptosis in triple negative breast cancer (TNBC) cells and bis-indole derived (CDIM) compounds act as NR4A1/2 ligands that induce ferroptosis by enhancing CD71 expression. 1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs were investigated for their cytotoxicity and effects on NR4A1 and NR4A2 regulated genes and induction of ferroptosis. Several assays also determined enhanced lipoperoxidation, reactive oxygen species and malondialdehyde formation in …

Integrative Proteogenomics And Forward Genetics Reveal A Novel Mitotic Vulnerability In Triple-Negative Breast Cancer, Nicholas J Neill, Shankha Satpathy, Karsten Krug, Jitendra K Meena, Nivetha Ramesh Babu, Cheyenne Calderon, Desmon Reed, Marcus J Weber, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Meenakshi Anurag, Kimberly R Holloway, Chen Huang, Suhas Vasaikar, Maria F Cardenas, Beom-Jun Kim, Doug W Chan, Shayan C Avanessian, Siddhartha Tyagi, Mayra Orellana, Sufeng Mao, Heyuan Li, Fade Gong, Sarah J Kurley, Kristen L Meerbrey, Calla M Olson, Amritha Nair, Tingting Sun, Hsiang-Ching Chung, Elizabeth A Bowling, Jarey H Wang, Pengju Zhang, Peng Xiao, Duxiao Yang, Fabio Stossi, Mei-Yin C Polley, Alexander B Saltzman, Filip Mundt, D R Mani, Michael A Gillette, Susan G Hilsenbeck, George Miles, Carolina Gutierrez, C Kent Osborne, Charles Y Lin, Nathanael S Gray, Jinpeng Sun, David A Wheeler, Charles M Perou, Anna Malovannaya, Michael T Lewis, Bing Zhang, Matthew J Ellis, Steven A Carr, Thomas F Westbrook

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTAs) are frontline chemotherapies for TNBC; however, the molecular pathways that cause TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consistent …

Gut Bacterial Dysbiosis In Pediatric Severe Malaria Associates With Post-Discharge Mortality, Olivia Bednarski, Sawyer Lehman, David Mzinza, Caroline Kazinga, Ruth Namazzi, Robert Opoka, Jie Ren, Tuan Tran, Terrie Taylor, Karl Seydel

Paediatrics and Child Health, East Africa

Gut microbiota have been implicated in severe malaria in murine models, but their contribution to the pathogenesis of severe malaria in children is unknown. Here we show through analysis of gut bacteria in stool samples from two separate African studies enrolling children with severe malaria, and children from local communities, that children with severe malaria have gut bacteria dysbiosis. Among children with severe malaria, there is increased abundance of Enterobacteriaceae that associates with multiple clinical complications of severe malaria. Moreover, increased abundance of Escherichia coli was a predictor of post-discharge mortality. Metagenome analysis identify elevated metabolic pathways and genes supporting …