Microbiology Commons^™

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 …

A Comprehensive Overview Of Chronic Wound Infections And Current Treatment Methods, Sarah Fakher, David J. Westenberg

Biological Sciences Faculty Research & Creative Works

Chronic wound infections pose significant healthcare challenges due to persistent biofilms, antibiotic resistance, and impaired healing pathways. These wounds are characterized by prolonged inflammation, microbial colonization, and disrupted tissue regeneration, leading to substantial morbidity and healthcare costs. This article reviews current knowledge on chronic wound types, their pathophysiology, and the mechanisms underlying biofilm formation to examine the latest advancements in antimicrobial-based strategies aimed at addressing these challenges. It highlights how diverse materials and technologies have been engineered to improve infection management, enhance tissue regeneration, and overcome the limitations of traditional treatments as well as advances that leverage innovations such as …

Pathogenic Xpo1 Variants Cause A Dominant Neurodevelopmental Disorder, Amber S E Van Oirsouw, Pavla Nedbalova, Miroslava Hancarova, Jan Prchal, Darina Prchalova, Marketa Vlckova, Sarka Bendova, Kristin G Monaghan, Lisa M Dyer, Yanmin Chen, Deanna Alexis Carere, Emma A M Te Bogt, Heather Fisher, Angela E Scheuerle, Stephanie Riley, Mahim Jain, Weiyi Mu, Joann N Bodurtha, Albertien M Van Eerde, Marijn F Stokman, Nicola Longo, Meena Balasubramanian, Michael Spiller, Gregory Costain, Charlotte Von Der Lippe, Kristian Tveten, Marianne Jortveit, Øystein L Holla, Bertrand Isidor, Benjamin Cogné, Kevin E Glinton, Blake Vuocolo, Roberta Ann Sierra, Brad Angle, Kelly Bontempo, Klaas Koop, Rachel Rabin, John Pappas, David A Staffenberg, Pascal Joset, Peter Miny, Isabel Filges, Abdulrazak Alali, Kara Vitalone, Jill A Rosenfeld, Weimin Bi, Samuel Bradbrook, Renee Perrier, Subhadra Ramanathan, June-Anne Gold, María Palomares Bralo, María Ángeles Gómez-Cano, Ann Haskins Olney, Shelly Nielsen, Alban Ziegler, Dominique Bonneau, Clément Prouteau, Ange-Line Bruel, Charlotte Caille-Benigni, Laëtitia Lambert, Andrea C Yu, Nathaniel H Robin, Dana Goodloe, Jan Fischer, Joseph Porrmann, Yvonne D Hennig, Rami Abou Jamra, Isabella Herman, Ivy R Johnson, Lucas Hérissant, Guillaume Jouret, Koen L I Van Gassen, Ellen Van Binsbergen, Bert Van Der Zwaag, Alwin Kamermans, Renske Oegema, Zdenek Sedlacek, Michaela Fenckova, Richard H Van Jaarsveld

Faculty, Staff and Students Publications

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date.

Methods: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning.

Results: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We …

Molecular Mechanisms In Masld/Mash-Related Hcc, Xiaobo Wang, Liang Zhang, Bingning Dong

Faculty, Staff and Students Publications

Liver cancer is the third leading cause of cancer-related deaths and ranks as the sixth most prevalent cancer type globally. NAFLD or metabolic dysfunction-associated steatotic liver disease, and its more severe manifestation, NASH or metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health concern, affecting approximately 20%-25% of the population. The increased prevalence of metabolic dysfunction-associated steatotic liver disease and MASH is parallel to the increasing rates of obesity-associated metabolic diseases, including type 2 diabetes, insulin resistance, and fatty liver diseases. MASH can progress to MASH-related HCC (MASH-HCC) in about 2% of cases each year, influenced by various factors such …

Chemical Modulation Of Gut Bacterial Metabolism Induces Colanic Acid And Extends The Lifespan Of Nematode And Mammalian Hosts, Guo Hu, Marzia Savini, Matthew Brandon Cooke, Xin Wei, Dinghuan Deng, Shihong M Gao, Ruyue Alps Xia, Youchen Guan, Alice X Wen, Xin Yu, Jin Wang, Chao Jiang, Christophe Herman, Jiefu Li, Meng C Wang

Faculty, Staff and Students Publications

Microbiota-derived metabolites have emerged as key regulators of longevity. The metabolic activity of the gut microbiota, influenced by dietary components and ingested chemical compounds, profoundly impacts host fitness. While the benefits of dietary prebiotics are well-known, chemically targeting the gut microbiota to enhance host fitness remains largely unexplored. Here, we report a novel chemical approach to induce a pro-longevity bacterial metabolite in the host gut. We discovered that wild-type Escherichia coli strains overproduce colanic acids (CAs) when exposed to a low dose of cephaloridine, leading to an increased life span in the host organism Caenorhabditis elegans. In the mouse gut, …

Dysregulated Mitochondrial Energy Metabolism Drives The Progression Of Mucosal Field Effects To Invasive Bladder Cancer, Sangkyou Lee, Sung Yun Jung, Pawel Kuś, Jolanta Bondaruk, June Goo Lee, Roman Jaksik, Nagireddy Putluri, Khanh N Dinh, David Cogdell, Huiqin Chen, Yishan Wang, Jiansong Chen, Neema Navai, Colin Dinney, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Charles C Guo, Peng Wei, Marek Kimmel, Bogdan Czerniak

Faculty, Staff and Students Publications

Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …

Cohesin Haploinsufficiency Is Tolerated In Cbfb::Myh11-Driven Murine Acute Myeloid Leukemia, Shannon E Conneely, Alexis Quezada, Kristen J Kurtz, Nenggang Zhang, Josephine De La Fuente, Nesa Mercer, Jason H Rogers, Rogelio Aguilar, Geraldo Medrano, Margaret A Goodell, Paul P Liu, Debananda Pati, Rachel E Rau

Faculty, Staff and Students Publications

Cohesin gene mutations occur in many malignancies, including acute myeloid leukemia (AML). Loss-of-function mutations in the four major cohesin complex genes (RAD21, SMC3, SMC1a, and STAG2) occur across most major genetic subtypes of AML but are notably absent in AML harboring CBFB::MYH11, suggesting that cohesin mutations yield distinct biological outcomes dependent on the genetic AML driver. We hypothesized that CBFB::MYH11-expressing leukemias would be dependent on intact cohesin genes given their near-mutual exclusivity. To investigate this, we combined either germline or inducible heterozygous deletions in cohesin genes Smc3 or Rad21, respectively, with an inducible murine model of Cbfb::MYH11 AML. This approach …