Explanipedia

Epithelial Heparan Sulfate Promotes <i>Staphylococcus aureus</i> Corneal Infection by Inhibiting Cathelicidins Open

Kazutaka Hayashida, Jeffrey D. Esko, Richard L. Gallo, Jian Liu, Winston W.‐Y. Kao , et al. · 2025

Cathelicidins are short cationic peptides with potent microbicidal activities and comprise an important arm of host innate immunity. Many cell types can produce cathelicidins, but they are mainly expressed by recruited immune cells and are…

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Jimmy Chen, Jeffrey D. Esko, Philip L.S.M. Gordts, Evan Walker, Sally L. Baxter , et al. · 2025

Antithrombin-binding heparan sulfate is ubiquitously expressed in epithelial cells and suppresses pancreatic tumorigenesis Open

Thomas Mandel Clausen, Ryan J. Weiss, Jacob R. Tremblay, Benjamin P. Kellman, Joanna Coker , et al. · 2025

3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding …

Tumor Acidosis Remodels the Glycocalyx to Control Lipid Scavenging and Ferroptosis Open

Mattias Belting, Anna Bång-Rudenstam, Myriam Cerezo-Magaña, Márton Horváth, Hugo Talbot , et al. · 2025

Aggressive tumours are defined by their ability to adapt to microenvironmental stress and reprogram cellular metabolism to promote therapy resistance. Within this niche, lipid droplet accumulation has emerged as a key strategy to buffer to…

Bruch’s membrane heparan sulfate retains lipoproteins in the early stages of age-related macular degeneration Open

Christopher B. Toomey, Savanna Pflugmacher, K. Park, Jessica Pihl, Sammy Weiser Novak , et al. · 2025

Lipoprotein retention in Bruch’s membrane is a key event in the pathobiology of early and intermediate age-related macular degeneration (AMD). However, the mechanism of lipoprotein retention in BrM is unknown. Given the established role of…

Global siRNA screen identifies human host factors critical for SARS-CoV-2 replication and late stages of infection Open

Xin Yin, Yuan Pu, Shuofeng Yuan, Lars Pache, Christopher Churas , et al. · 2025

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously re…

Release of Extracellular Matrix Components after Human Traumatic Brain Injury Open

Michael Bambrick, Donald A. Godfrey, Mark D. Johnson, Jeffrey D. Esko, Biswa Choudhury , et al. · 2025

Animal studies and human tissue experiments have demonstrated that traumatic brain injury (TBI) causes damage to the extracellular matrix (ECM). To test the hypothesis that TBI causes disruption of sulfated glycosaminoglycan (sGAG) in the …

Multi-omic analysis reveals the unique glycan landscape of the blood-brain barrier glycocalyx Open

Reid O. Larsen, Krzysztof Kucharz, Sidar Aydin, Mariel Kristine B Micael, Biswa Choudhury , et al. · 2025

The blood-brain barrier (BBB) glycocalyx is the dense layer of glycans and glycoconjugates that coats the luminal surface of the central nervous system (CNS) vasculature. Despite being the first point of contact between the blood and brain…

Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction Open

Alejandro Gómez Toledo, Gregory J. Golden, Richard D. Cummings, Johan Malmström, Jeffrey D. Esko · 2025

The endothelial glycocalyx, a glycan-rich layer on the luminal surface of endothelial cells lining blood and lymphatic vessels, plays a crucial role in vascular homeostasis by regulating vascular permeability, immune cell trafficking, and …

SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx Open

Cameron Martino, Benjamin P. Kellman, Daniel R. Sandoval, Thomas Mandel Clausen, Robert Cooper , et al. · 2025

The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans,…

High-Density Lipoproteins Associated with Age-Related Macular Degeneration in the All of Us Research Program Open

Jimmy Chen, Jeffrey D. Esko, Evan Walker, Philip L.S.M. Gordts, Sally L. Baxter , et al. · 2025

Proprietary or commercial disclosure may be found after the references.

Alteration of Neuropilin-1 and Heparan Sulfate Interaction Impairs Murine B16 Tumor Growth Open

Chelsea D. Painter, Nehru Viji Sankaranarayanan, B. Nagarajan, Thomas Mandel Clausen, Alan M.V. West , et al. · 2024

Neuropilin-1 acts as a coreceptor with vascular endothelial growth factor receptors to facilitate binding of its ligand, vascular endothelial growth factor. Neuropilin-1 also binds to heparan sulfate, but the functional significance of thi…

Cell surface ribonucleoproteins cluster with heparan sulfate to regulate growth factor signaling Open

Peiyuan Chai, Jonathan Perr, Lauren Kageler, Charlotta G. Lebedenko, João M.L. Dias , et al. · 2024

Receptor-ligand interactions govern a wide array of biological pathways, facilitating a cell’s ability to interrogate and integrate information from the extracellular space. Here, using an unbiased genome-wide knockout screen, we identify …

Global siRNA Screen Reveals Critical Human Host Factors of SARS-CoV-2 Multicycle Replication Open

Xin Yin, Pu Yuan, Shuofeng Yuan, Lars Pache, Christopher Churas , et al. · 2024

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously re…

Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial Open

Bruno Martins Tomazini, Lucas Tramujas, Fernando Azevedo Medrado, Samara Pinheiro do Carmo Gomes, Karina Leal Negrelli , et al. · 2024

Background Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. Methods We condu…

Transplantation of Wild-Type Hematopoietic Stem and Progenitor Cells Improves Disease Phenotypes in Novel Mucopolysaccharidosis Iiic Mouse Model Open

Rafael A. Badell‐Grau, Kasra Pakravesh, Kevin Thai, Frankie Son, Rola Chen , et al. · 2024

Transplantation of Wild-Type Hematopoietic Stem and Progenitor Cells Improves Disease Phenotypes in Novel Mucopolysaccharidosis Iiic Mouse Model Open

Rafael A. Badell‐Grau, Kasra Pakravesh, Kevin Thai, Frankie Son, Rola Chen , et al. · 2024

B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling Open

Amulya Sreekumar, Michelle Lu, Biswa Choudhury, Tien-Chi Pan, Dhruv K. Pant , et al. · 2023

Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections Open

Alejandro Gómez Toledo, Eleni Bratanis, Erika Velásquez, Sounak Chowdhury, Berit Olofsson , et al. · 2023

Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection Open

Patricia Aguilar‐Calvo, Adela Malik, Daniel R. Sandoval, Christopher V. Barback, Christina D. Orrú , et al. · 2023

Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a abundant extracellular matrix component. HS facilitates fibril formation in vitro , yet how HS impac…

Signalling by senescent melanocytes hyperactivates hair growth Open

Xiaojie Wang, Raúl Ramos, Anne Q. Phan, Kosuke Yamaga, Jessica L. Flesher , et al. · 2023

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration 1 . Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excess…

Neuronal<i>Ndst1</i>depletion accelerates prion protein clearance and slows neurodegeneration in prion infection Open

Patricia Aguilar-Calvo, Adela Malik, Daniel R. Sandoval, Christopher V. Barback, Christina D. Orrú , et al. · 2023

Select prion diseases are characterized by widespread cerebral plaque-like deposits of amyloid fibrils enriched in heparan sulfate (HS), a major extracellular matrix component. HS facilitates fibril formation in vitro , yet how HS impacts …

Release of extracellular matrix components after human traumatic brain injury Open

Michael Bambrick, Mark D. Johnson, Jeffrey D. Esko, Biswa Choudhury, Alejandro Gómez Toledo , et al. · 2023

Most research on the evolution of damage after traumatic brain injury (TBI) focuses on cellular effects, but the analysis of human tissue slices and animal research have shown that TBI causes concomitant damage in the extracellular matrix,…

Identification of global inhibitors of cellular glycosylation Open

Daniel Madriz Sørensen, Christian Büll, Thomas D. Madsen, Erandi Lira‐Navarrete, Thomas Mandel Clausen , et al. · 2023

Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with diffi…

B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling Open

Amulya Sreekumar, Michelle Lu, Biswa Choudhury, Tien-Chi Pan, Dhruv K. Pant , et al. · 2023

Summary Breast cancer mortality results primarily from incurable recurrent tumors seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling dormant RTC survival is therefore essential for impr…

SARS-CoV-2 Spike triggers barrier dysfunction and vascular leak via integrins and TGF-β signaling Open

Scott B. Biering, Francielle Tramontini Gomes de Sousa, Laurentia V. Tjang, Felix Pahmeier, Chi Zhu , et al. · 2022

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is associated with barrier dysfunction, the tr…

Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer Open

Nader Al-Nakouzi, Chris Kedong Wang, Htoo Zarni Oo, Irina Nelepcu, Nada Lallous , et al. · 2022

Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), a major glyc…

Vascular Proteome Responses Precede Organ Dysfunction in a Murine Model of Staphylococcus aureus Bacteremia Open

James T. Sorrentino, Gregory J. Golden, Claire Morris, Chelsea D. Painter, Victor Nizet , et al. · 2022

Sepsis is a life-threatening response to infection that results in immune dysregulation, vascular dysfunction, and organ failure. New methods are needed for the identification of diagnostic and therapeutic targets.

Spike-heparan sulfate interactions in SARS-CoV-2 infection Open

Fiona L. Kearns, Daniel R. Sandoval, Lorenzo Casalino, Thomas Mandel Clausen, Mia A. Rosenfeld , et al. · 2022

Recent biochemical, biophysical, and genetic studies have shown that heparan sulfate, a major component of the cellular glycocalyx, participates in infection of SARS-CoV-2 by facilitating the so-called open conformation of the spike protei…

Impaired mitophagy in Sanfilippo a mice causes hypertriglyceridemia and brown adipose tissue activation Open

Miguel Tillo, William C. Lamanna, Chrissa A. Dwyer, Daniel R. Sandoval, Ariane Pessentheiner , et al. · 2022

Lysosomal storage diseases result in various developmental and physiological complications, including cachexia. To study the causes for the negative energy balance associated with cachexia, we assessed the impact of sulfamidase deficiency …

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