Review
Biochemistry & Molecular Biology
Yali Lai, Yue Tian, Xintong You, Jiangnan Du, Jianmei Huang
Summary: Many cardiovascular disorders are characterized by endothelial cell dysfunction, which is closely related to sphingolipid metabolism. Understanding the effects of sphingolipid metabolites and key enzymes on endothelial cells can provide insights into the pathogenesis of cardiovascular diseases and potential therapeutic targets.
LIPIDS IN HEALTH AND DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Mateusz Matwiejuk, Hanna Mysliwiec, Bartlomiej Lukaszuk, Marta Lewoc, Hend Malla, Piotr Mysliwiec, Jacek Dadan, Adrian Chabowski, Iwona Flisiak
Summary: Psoriasis is a complex chronic immunologically mediated disease that affects the skin, nails, and joints. Abnormal levels of sphingolipids significantly differ between psoriatic skin and healthy skin, suggesting their potential role in the pathogenesis of psoriasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mari Kono, Lila E. Hoachlander-Hobby, Saurav Majumder, Ronit Schwartz, Colleen Byrnes, Hongling Zhu, Richard L. Proia
Summary: This study identified genes involved in the uptake and recycling of S1P, an extracellular signaling molecule, and revealed the pathway through which S1P is taken up and recycled in cells. The findings are important for understanding the metabolism of S1P and its role in cellular activities.
JOURNAL OF LIPID RESEARCH
(2022)
Review
Cell Biology
Kana Masuda-Kuroki, Shahrzad Alimohammadi, Anna Di Nardo
Summary: Psoriasis is a chronic skin condition that lacks a complete cure. Recent studies have identified sphingolipid metabolites as significant contributors to psoriasis, particularly ceramide and sphingosine-1-phosphate (S1P). The modulation of S1P and its receptor has shown potential in improving psoriasis inflammation.
Article
Biochemistry & Molecular Biology
Albena Momchilova, Roumen Pankov, Galya Staneva, Stefan Pankov, Plamen Krastev, Evgenia Vassileva, Rusina Hazarosova, Nikolai Krastev, Bozhil Robev, Biliana Nikolova, Adriana Pinkas
Summary: Resveratrol regulates sphingolipid metabolism in lung cancer cells, leading to changes in CER and S1P levels, and showing anti-cancer effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Haaris A. Shiwani, Mohammed Y. Elfaki, Danyal Memon, Suhayb Ali, Abdul Aziz, Emmanuel E. Egom
Summary: Sphingolipids such as Ceramide, Ceramide-1-phosphate, Sphingosine, and Sphingosine-1-phosphate are key signaling molecules that regulate various retinal processes, with potential dual biological effects in retinal diseases. Inhibitors targeting these sphingolipids have shown promise in preserving neuronal viability and retinal function, making them attractive therapeutic targets for retinal degenerations.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Peter Horvath, Lilla Budi, Daniel Hammer, Rita Varga, Gyoergy Losonczy, Adam Domonkos Tarnoki, David Laszlo Tarnoki, Martina Meszaros, Andras Bikov
Summary: Chronic inflammation induced by hypoxia during sleep is an important mechanism of microvascular damage in OSA patients. This study examined the role of the sphingosine rheostat, which has various inflammatory effects. The results showed elevated levels of ceramide antibody and sphingosine-1-phosphate in patients with OSA, suggesting their involvement in the pathomechanism and comorbidities of OSA.
SCIENTIFIC REPORTS
(2023)
Review
Oncology
Antonia Piazzesi, Sumaiya Yasmeen Afsar, Gerhild Van Echten-Deckert
Summary: Cancer development is a complex process involving overcoming obstacles such as unrestricted proliferation, invasion, nutrient supply, and metastasis, while evading the immune system. Inflammation plays a role in cancer development, with sphingolipid metabolism impacting cells' progression from healthy to cancerous phenotypes.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Albena Momchilova, Georgi Nikolaev, Stefan Pankov, Evgenia Vassileva, Nikolai Krastev, Bozhil Robev, Dimo Krastev, Adriana Pinkas, Roumen Pankov
Summary: This study analyzed the effects of quercetin and fingolimod on sphingolipid metabolism in HepG2 cells. The results showed that quercetin and fingolimod, alone or in combination, can reduce sphingolipid levels and activate certain enzymes. The up-regulation and down-regulation of specific enzymes and proteins by quercetin have important implications for cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Analytical
Luke A. Gallion, Yuli Wang, Angelo Massaro, Ming Yao, Brae Petersen, Quanzheng Zhang, Weigang Huang, Adam J. Carr, Qisheng Zhang, Nancy L. Allbritton
Summary: Capillary electrophoresis with fluorescence detection (CE-F) is a powerful method for measuring enzyme activation in single cells. However, the reporter substrates used in cellular enzymatic assays for CE-F may affect enzyme kinetics. To address this issue, a fix and click method was developed to attach a fluorophore to an enzyme activation reporter prior to analysis by CE-F, allowing for the investigation of sphingolipid signaling in single cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Cell Biology
Chiara D'Aprile, Simona Prioni, Laura Mauri, Alessandro Prinetti, Sara Grassi
Summary: Lipid rafts are specialized membrane domains enriched in gangliosides, sphingomyelin, cholesterol, and proteins involved in signal transduction, modulating cell homeostasis. Sphingosine 1-phosphate participates in various signal transduction processes, with enzymes and receptors often localized in lipid rafts.
CELLULAR SIGNALLING
(2021)
Review
Biochemistry & Molecular Biology
Mateusz Matwiejuk, Hanna Mysliwiec, Adrian Chabowski, Iwona Flisiak
Summary: Psoriasis is a complex, chronic, immunologically mediated disease that is associated with numerous other diseases. It can cause impairment of quality of life and may be associated with depressive disorders. The pathophysiology of psoriasis and its comorbidities is not fully understood yet, and disrupted metabolism of sphingolipids may be the link between them.
Review
Virology
Lu Zhang, Juan Liu, Erya Xiao, Qingzhen Han, Lin Wang
Summary: Viruses can create a unique cellular environment that facilitates replication and transmission. The SphK/S1P axis plays a crucial role in regulating cellular activities during viral infections. Depending on the type of virus, the SphK/S1P axis can have pro- or anti-viral activities through the host immune system or intracellular signaling pathways and cell proliferation.
REVIEWS IN MEDICAL VIROLOGY
(2023)
Review
Cell Biology
Yuqing Wu, Yongjie Liu, Erich Gulbins, Heike Grassme
Summary: Sphingolipids play crucial roles in regulating pathobiological processes such as cancer, inflammation, and infectious diseases. Unlike ceramide which promotes microbial infections, sphingosine has bactericidal effects and is an important natural defense component against bacterial pathogens in the respiratory tract. Recent studies suggest that the bactericidal effect of sphingosine may be due to bacterial membrane permeabilization and subsequent bacterial death.
Review
Cell Biology
Federica Cirillo, Marco Piccoli, Andrea Ghiroldi, Michelle M. Monasky, Paola Rota, Paolo La Rocca, Adriana Tarantino, Sara D'Imperio, Paola Signorelli, Carlo Pappone, Luigi Anastasia
Summary: Cardiovascular diseases are a major cause of death globally, with an increasing number of patients posing challenges to healthcare systems. Sphingolipids have emerged as important bioactive compounds that play crucial roles in biological processes and have potential therapeutic implications for managing cardiovascular diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Oncology
Lisa M. Ebert, Kate Vandyke, M. Zahied Johan, Mark DeNichilo, Lih Y. Tan, Kay K. Myo Min, Benjamin M. Weimann, Brenton W. Ebert, Stuart M. Pitson, Andrew C. W. Zannettino, Craig T. Wallington-Beddoe, Claudine S. Bonder
Summary: Desmoglein-2 (DSG2) is found to be overexpressed in approximately 20% of bone marrow biopsies from newly diagnosed multiple myeloma patients, and it is strongly predictive of poor clinical outcome, independent of genetic subtype or routinely measured biomarkers of MM activity. This cell surface protein may serve as a potential biomarker that can be quickly detected by flow cytometry to predict disease trajectory at the time of diagnosis.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Denis Tvorogov, Chloe A. L. Thompson-Peach, Johannes Fosselteder, Mara Dottore, Frank Stomski, Suraiya A. Onnesha, Kelly Lim, Paul A. B. Moretti, Stuart M. Pitson, David M. Ross, Andreas Reinisch, Daniel Thomas, Angel F. Lopez
Summary: Researchers have developed a specific antibody, 4D7, that can selectively target common CALR mutations, inhibiting the proliferation and megakaryocyte differentiation of mutant CALR myelofibrosis progenitors and providing a novel therapeutic approach.
Editorial Material
Genetics & Heredity
Samaneh Farashi, Zhichao Wu, Carla J. Abbott, Alice Pebay, Erica L. Fletcher, Robyn H. Guymer, Melanie Bahlo, Brendan R. E. Ansell
Summary: Reticular pseudodrusen (RPD) is a distinct phenotype associated with late-stage age-related macular degeneration (AMD), characterized by subretinal deposits. The genetic risk associations of RPD overlap with six established AMD-risk regions. Identifying the specific underlying genetic causes of RPD through adequate imaging methods can enhance our understanding of RPD pathophysiology.
TRENDS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Melissa R. Pitman, Alexander C. Lewis, Lorena T. Davies, Paul A. B. Moretti, Dovile Anderson, Darren J. Creek, Jason A. Powell, Stuart M. Pitson
Summary: The study found that JTE-013 has broad off-target effects on sphingolipid metabolism, increasing cellular levels of ceramides, dihydroceramides, sphingosine, and dihydrosphingosine. Additionally, the study revealed that JTE-013 inhibits the activity of several sphingolipid metabolic enzymes.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Melissa K. Bennett, Manjun Li, Melinda N. Tea, Melissa R. Pitman, John Toubia, Paul P-S Wang, Dovile Anderson, Darren J. Creek, Robert Z. Orlowski, Briony L. Gliddon, Jason A. Powell, Craig T. Wallington-Beddoe, Stuart M. Pitson
Summary: The introduction of the proteasome inhibitor bortezomib has improved patient survival in myeloma, but acquired resistance remains a challenge. Researchers have found that inhibiting sphingolipid metabolism can resensitize bortezomib-resistant myeloma, and this approach also works with other proteasome inhibitors like carfilzomib.
Article
Oncology
Anne Gomez-Brouchet, Claire Illac, Adeline Ledoux, Pierre-Yves Fortin, Sandra de Barros, Clementine Vabre, Fabien Despas, Sophie Peries, Christelle Casaroli, Corinne Bouvier, Sebastien Aubert, Gonzague de Pinieux, Frederique Larousserie, Louise Galmiche, Franck Talmont, Stuart Pitson, Marie-Lise Maddelein, Olivier Cuvillier
Summary: The SphK1/S1P signaling pathway is involved in the regulation of HIF-1 alpha expression in osteosarcoma under hypoxia. Inhibiting SphK1 and S1P(1) receptor may be a potential treatment target for osteosarcoma patients. Overexpression of SphK1 and S1P(1) is related to hypoxia marker GLUT-1 in osteosarcoma.
Article
Hematology
Alexander C. Lewis, Victoria S. Pope, Melinda N. Tea, Manjun Li, Gus O. Nwosu, Thao M. Nguyen, Craig T. Wallington-Beddoe, Paul A. B. Moretti, Dovile Anderson, Darren J. Creek, Maurizio Costabile, Saira R. Ali, Chloe A. L. Thompson-Peach, B. Kate Dredge, Andrew G. Bert, Gregory J. Goodall, Paul G. Ekert, Anna L. Brown, Richard D'Andrea, Nirmal Robinson, Melissa R. Pitman, Daniel Thomas, David M. Ross, Briony L. Gliddon, Jason A. Powell, Stuart M. Pitson
Summary: In this study, the accumulation of ceramide in AML cells induced an apoptotic integrated stress response through the activation of transcription factor ATF4. This response led to the degradation of the prosurvival protein Mcl-1, resulting in cell death. Combination treatment with the Bcl-2 inhibitor venetoclax synergistically killed AML cells and reduced leukemic stem cells.
Article
Multidisciplinary Sciences
Mahmoud A. Bassal, Saumya E. Samaraweera, Kelly Lim, Brooks A. Bernard, Sheree Bailey, Satinder Kaur, Paul Leo, John Toubia, Chloe Thompson-Peach, Tran Nguyen, Kyaw Ze Ya Maung, Debora A. Casolari, Diana G. Iarossi, Ilaria S. Pagani, Jason Powell, Stuart Pitson, Siria Natera, Ute Roessner, Ian D. Lewis, Anna L. Brown, Daniel G. Tenen, Nirmal Robinson, David M. Ross, Ravindra Majeti, Thomas J. Gonda, Daniel Thomas, Richard J. D'Andrea
Summary: This study reveals the mutual exclusivity between germline mutations in mitochondrial complex I and somatic mutations in the metabolic enzyme IDH1 in patients with acute myeloid leukemia (AML), and finds that IDH1 mutant cells have increased sensitivity to complex I inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Paris M. M. Kollis, Lisa M. M. Ebert, John Toubia, Cameron R. R. Bastow, Rebecca J. J. Ormsby, Santosh I. I. Poonnoose, Sakthi Lenin, Melinda N. N. Tea, Stuart M. M. Pitson, Guillermo A. A. Gomez, Michael P. P. Brown, Tessa Gargett
Summary: This study characterized the chemokine receptor and integrin expression profiles of endogenous glioblastoma-infiltrating T cells and identified potential homing receptor-ligand pairs that could enhance the tumour-homing properties of future T-cell immunotherapies for glioblastoma.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Ophthalmology
Jenna C. Hall, Daniel Paull, Alice Pebay, Grace E. Lidgerwood
Summary: Human pluripotent stem cells are powerful tools for studying and modeling retinal diseases, including both monogenic and complex conditions.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Harsha Mahabaleshwar, P. Asharani, Tricia Yi Loo, Shze Yung Koh, Melissa R. Pitman, Samuel Kwok, Jiajia Ma, Bo Hu, Fang Lin, Xue Li Lok, Stuart M. Pitson, Timothy E. Saunders, Tom J. Carney
Summary: Mesenchymal cell immigration into growing fins and limb buds drives distal outgrowth, with tensile forces between these cells essential for fin and limb morphogenesis. Morphogens derived from the apical fin domain regulate cell polarity, migration, division, and adhesion of limb mesenchyme cells. The mutant stomp in zebrafish displays defects in fin morphogenesis, including blister formation and loss of orientation and adhesion of immigrating fin mesenchyme cells. The gene encoding Slit3, an axon guidance ligand, is found to be mutated in stomp. Slit ligands derived from immigrating mesenchyme act via Robo receptors at the apical ectodermal ridge (AER) to promote the release of sphingosine-1-phosphate (S1P), which then diffuses back to the mesenchyme to regulate their polarization, orientation, positioning, and adhesion to the interstitial matrix of the fin fold.
Article
Multidisciplinary Sciences
Anne Senabouth, Maciej Daniszewski, Grace E. Lidgerwood, Helena H. Liang, Damian Hernandez, Mehdi Mirzaei, Stacey N. Keenan, Ran Zhang, Xikun Han, Drew Neavin, Louise Rooney, Maria Isabel G. Lopez Sanchez, Lerna Gulluyan, Joao A. Paulo, Linda Clarke, Lisa S. Kearns, Vikkitharan Gnanasambandapillai, Chia-Ling Chan, Uyen Nguyen, Angela M. Steinmann, Rachael A. McCloy, Nona Farbehi, Vivek K. Gupta, David A. Mackey, Guy Bylsma, Nitin Verma, Stuart MacGregor, Matthew J. Watt, Robyn H. Guymer, Joseph E. Powell, Alex W. Hewitt, Alice Pebay
Summary: Age-related macular degeneration (AMD) is a leading cause of vision loss, and there is currently no approved treatment for AMD with geographic atrophy. This study used patient induced pluripotent stem cell-derived retinal pigment epithelium to investigate disease mechanisms and identified differences in retinal pigment epithelium homeostasis associated with geographic atrophy.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Tessa Gargett, Lisa M. Ebert, Nga T. H. Truong, Paris M. Kollis, Kristyna Sedivakova, Wenbo Yu, Erica C. F. Yeo, Nicole L. Wittwer, Briony L. Gliddon, Melinda N. Tea, Rebecca Ormsby, Santosh Poonnoose, Jake Nowicki, Orazio Vittorio, David S. Ziegler, Stuart M. Pitson, Michael P. Brown
Summary: Targeting the tumor-associated antigen GD2 using CAR-T-cell therapy has shown promising results in controlling tumor growth in primary glioblastoma. Highly functional GD2-specific CAR-T cells can be produced using an approved clinical manufacturing process. The use of markers identified in the study has further improved tumor control rates.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Cell Biology
Sueanne Chear, Sharn Perry, Richard Wilson, Aidan Bindoff, Jana Talbot, Tyson L. Ware, Alexandra Grubman, James C. Vickers, Alice Pebay, Jonathan B. Ruddle, Anna E. King, Alex W. Hewitt, Anthony L. Cook
Summary: CLN3 disease is a fatal neurodegenerative disorder caused by mutations in the CLN3 gene. We corrected the mutation in human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 technology and observed disease-related changes in protein synthesis, trafficking and degradation, and neuronal activity.
DISEASE MODELS & MECHANISMS
(2022)
Meeting Abstract
Oncology
R. Hamon, X. Jiang, J. Toubia, C. Coolen, A. Lopez, P. N. Reynolds, S. M. Pitson, J. Woodcock
JOURNAL OF THORACIC ONCOLOGY
(2022)
