Article
Biochemistry & Molecular Biology
Gabriele Stankeviciute, Peijun Tang, Ben Ashley, Joshua D. Chamberlain, Matthew E. B. Hansen, Aimiyah Coleman, Rachel D'Emilia, Larina Fu, Eric C. Mohan, Hung Nguyen, Ziqiang Guan, Dominic J. Campopiano, Eric A. Klein
Summary: The bacterial domain produces a variety of sphingolipids with different functions, which play important roles in modulating the host inflammatory system in the human microbiome. Through genomic and biochemical approaches, a complete pathway for bacterial ceramide synthesis was identified, with further discovery of a Gram-positive species capable of producing ceramides. Biochemical evidence suggests that the bacterial ceramide synthesis pathway operates differently from that in eukaryotes, and phylogenetic analyses support the independent evolution of bacterial and eukaryotic ceramide pathways.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jan-Hannes Schaefer, Carolin Koerner, Bianca M. Esch, Sergej Limar, Kristian Parey, Stefan Walter, Dovile Januliene, Arne Moeller, Florian Froehlich
Summary: This study presents the high-resolution cryo-EM structures of the yeast SPT complex with Tsc3, Orm1, and Sac1. The interaction between ceramide and Orm1 is found to inhibit the activity of yeast SPT. Furthermore, the binding of ceramide and ergosterol suggests a co-regulation of sphingolipid biogenesis and sterol metabolism within the SPOTS complex.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Belavendra Antonisamy, Harshita Shailesh, Yahya Hani, Lina Hayati M. Ahmed, Safa Noor, Salma Yahya Ahmed, Mohamed Alfaki, Abidan Muhayimana, Shana Sunny Jacob, Saroja Kotegar Balayya, Oleksandr Soloviov, Li Liu, Lisa Sara Mathew, Kun Wang, Sara Tomei, Alia Al Massih, Rebecca Mathew, Mohammed Yousuf Karim, Manjunath Ramanjaneya, Stefan Worgall, Ibrahim A. Janahi
Summary: This paper describes an ongoing study on sphingolipids in childhood asthma and obesity, aiming to examine the pathophysiology and explore biomarkers through multi-omics approaches. The study recruits children from different groups and collects clinical measurements and biological samples for analysis. The goal is to understand the role of dysregulated sphingolipid metabolism in obesity and asthma, and identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways linking the two diseases.
Article
Biochemistry & Molecular Biology
Linda Sasset, Kamrul H. Chowdhury, Onorina L. Manzo, Luisa Rubinelli, Csaba Konrad, J. Alan Maschek, Giovanni Manfredi, William L. Holland, Annarita Di Lorenzo
Summary: Disruption of sphingolipid homeostasis and signaling can cause various diseases. However, the mechanisms of cellular sensing and regulation of sphingolipid homeostasis are still not well understood. This study identifies S1P as a key sphingolipid sensed by cells to maintain homeostasis, and S1P-S1PR signaling stabilizes ORMDLs to restrain SPT activity. Disruption of the S1PR/ORMDL axis leads to ceramide accrual, mitochondrial dysfunction, and endothelial dysfunction, which are early events in cardio- and cerebrovascular diseases.
Article
Clinical Neurology
Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D. Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K. G. Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C. Spillmann, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J. Bellen, Simon Edvardson, Florian Eichler, Teresa M. Dunn
Summary: Sphingolipids, abundant in myelin membranes, are crucial for the structural and signalling functions in the mammalian nervous system. Serine palmitoyltransferase (SPTSSA) is the enzyme responsible for the rate-limiting reaction in sphingolipid synthesis and its activity is tightly regulated by ORMDL proteins. Excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase was found to be responsible for defects in early brain development and function. SRivastava et al. identified SPTSSA variants that disrupt ORMDL-mediated regulation of SPT, leading to hereditary spastic paraplegia.
Article
Oncology
Ping Lu, Shai White-Gilbertson, Gyda Beeson, Craig Beeson, Besim Ogretmen, James Norris, Christina Voelkel-Johnson
Summary: The study reveals differences in sphingolipid metabolism between non-polyploid and polyploid cancer cells, showing that CerS6 in polyploid cells enhances the ability of the tumor suppressor p53 to inhibit progeny formation. Modulation of C-16-ceramide can prevent polyploid giant cancer cells from generating offspring, and targeting sphingolipid metabolism pathway holds potential for clinical intervention.
Article
Biochemistry & Molecular Biology
Olga Gruzdeva, Yulia Dyleva, Ekaterina Belik, Evgenia Uchasova, Anastasia Ponasenko, Sergey Ivanov, Maxim Zinets, Alexander Stasev, Anton Kutikhin, Victoria Markova, Alena Poddubnyak, Evgenia Gorbatovskaya, Elena Fanaskova, Olga Barbarash
Summary: We investigated the expression of ceramide metabolism enzymes in different adipose tissues of patients with coronary artery disease (CAD) and valvular heart disease (VHD). The results showed higher expression of genes involved in ceramide synthesis and utilization in the epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) of CAD patients. In VHD patients, there was high expression of specific genes in EAT and PVAT. The findings suggest that ceramide synthesis and accumulation occur mainly in EAT in cardiovascular disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Guiming Li, Qiaoling Wang, Qian Meng, Guanhua Wang, Fan Xu, Qian Chen, Fang Liu, Yulin Hu, Ming Luo
Summary: Cotton is an important natural fiber crop worldwide, and the ceramide synthase gene GhCS1 plays a crucial role in cotton fiber cell development. GhCS1 affects fiber cell initiation and elongation by modulating substrate utilization.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Andrei Ogonkov, Cora L. L. Dieterich, Roy A. A. Meoded, Joern Piel, Amy E. E. Fraley, Severin Sasso
Summary: We report the discovery of a rare type I fatty acid synthase (FasT) from the cyanobacterium Chlorogloea sp. CCALA695, which possesses an unusual off-loading domain that acts as an alpha-oxoamine synthase in vitro. This off-loading domain catalyzes the decarboxylative Claisen condensation between l-serine and a fatty acyl thioester, similar to serine palmitoyltransferases from sphingolipid biosynthesis. Our findings suggest a novel route to alpha-amino ketones by the direct condensation of long-chain fatty acids with l-serine.
Article
Cell Biology
Jiyoon L. Kim, Beatriz Mestre, Sun-Hye Shin, Anthony H. Futerman
Summary: Sphingolipids are a crucial family of lipids in cell function and survival, and recent research in this field has been led by a closely-knit group of researchers, including the late Dr. Lina Obeid. Dr. Obeid's valuable contributions to sphingolipid research centered on the "many-worlds" view of ceramides and the role of ceramide synthases (CerS) in the sphingolipid metabolic pathway.
CELLULAR SIGNALLING
(2021)
Article
Physiology
Alaa Othman, Mingxia Liu, Heiko Bode, Elena Boudyguina, Arnold von Eckardstein, John S. Parks, Thorsten Hornemann
Summary: ATP binding cassette transporter A1 (ABCA1) limits the formation of high density lipoproteins (HDL), and the loss of ABCA1 function leads to severe deficiency of HDL in Tangier disease patients. Hepatocyte-specific knockout of ABCA1 in mice (Abca1 HSKO) significantly reduces plasma HDL-cholesterol levels, indicating that hepatic ABCA1 plays a major role in the HDL phenotype. The impact of Tangier disease on plasma sphingolipid levels and the contribution of hepatic ABCA1 to plasma sphingolipids are still unknown.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
Fei-Yang Tzou, Tsu-Yi Su, Wan-Syuan Lin, Han-Chun Kuo, Yu-Lian Yu, Yu-Han Yeh, Chung-Chih Liu, Ching-Hua Kuo, Shu-Yi Huang, Chih-Chiang Chan
Summary: Disruption of sphingolipid homeostasis can lead to neurological disorders, with specific sphingolipid species modulating pathogenesis through mechanisms that remain unclear. DEGS1/ifc deficiency causes dihydroceramide accumulation, leading to Rac1 mislocalization and NOX-dependent neurodegeneration. The Rac1-NOX complex plays a crucial role in the accumulation of reactive oxygen species in the absence of DEGS1/ifc.
Article
Biochemistry & Molecular Biology
Alec Millner, Logan Running, Nicole Colon-Rosa, Diana S. Aga, Jonna Frasor, G. Ekin Atilla-Gokcumen
Summary: This study identifies a novel lipid regulator involved in therapy-induced senescence and suggests that ceramide kinase could be a potential target enzyme to decrease the levels of therapy-induced senescent cells.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Antia Custodia, Marta Aramburu-Nunez, Clara Correa-Paz, Adrian Posado-Fernandez, Ana Gomez-Larrauri, Jose Castillo, Antonio Gomez-Munoz, Tomas Sobrino, Alberto Ouro
Summary: This article summarizes the role of ceramide in cellular processes and highlights its importance in neurodegenerative diseases, particularly in Parkinson's disease.
Review
Oncology
Farjana Afrin, Sameena Mateen, Jordan Oman, James C. K. Lai, Jared J. Barrott, Srinath Pashikanti
Summary: This review focuses on the role of ceramide and associated enzymes in cell function and their involvement in cancer progression. It provides information on the pathways and enzymes involved in ceramide metabolism and discusses the potential of targeting these enzymes for cancer treatment.
Article
Immunology
Reetika Bhardwaj, Jessie W. Yester, Sandeep K. Singh, Debolina D. Biswas, Michael J. Surace, Michael R. Waters, Kurt F. Hauser, Zhenqiang Yao, Brendan F. Boyce, Tomasz Kordula
JOURNAL OF IMMUNOLOGY
(2015)
Article
Neurosciences
Angela S. Gupta, Michael R. Waters, Debolina D. Biswas, Lashardai N. Brown, Michael J. Surace, Constantinos Floros, Ulrich Siebenlist, Tomasz Kordula
Article
Oncology
Michael R. Waters, Angela S. Gupta, Karli Mockenhaupt, LaShardai N. Brown, Debolina D. Biswas, Tomasz Kordula
Article
Immunology
Angela S. Gupta, Debolina D. Biswas, La Shardai N. Brown, Karli Mockenhaupt, Michael Marone, Andrew Hoskins, Ulrich Siebenlist, Tomasz Kordula
JOURNAL OF NEUROINFLAMMATION
(2019)
Review
Immunology
M. Elizabeth Deerhake, Debolina D. Biswas, William E. Barclay, Mari L. Shinohara
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Cell Biology
Anna F. Fusco, Logan A. Pucci, Pawel M. Switonski, Debolina D. Biswas, Angela L. McCall, Amanda F. Kahn, Justin S. Dhindsa, Laura M. Strickland, Albert R. La Spada, Mai K. ElMallah
Summary: SCA7 is an autosomal-dominant neurodegenerative disorder characterized by ataxia, dysarthria, dysphagia, and retinal degeneration. A knock-in mouse model with 266 CAG repeats displayed breathing deficits, neurodegeneration, and neuroinflammation, indicating the importance of phrenic and hypoglossal motor neuron pathology in respiratory failure.
DISEASE MODELS & MECHANISMS
(2021)
Review
Biotechnology & Applied Microbiology
Angela L. Roger, Ronit Sethi, Meredith L. Huston, Evelyn Scarrow, Joy Bao-Dai, Elias Lai, Debolina D. Biswas, Lea El Haddad, Laura M. Strickland, Priya S. Kishnani, Mai K. ElMallah
Summary: Pompe disease is a genetic disorder that can be treated with enzyme replacement therapy, but gene therapy offers a potential alternative with several advantages. Gene therapy provides prolonged and consistent gene expression, and can correct muscle and neurological pathology.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Debolina D. Biswas, Laura M. Strickland, Justin S. Dhindsa, Yihan Shi, Ronit Sethi, Sean Kehoe, Elias X. Lai, Meredith L. Huston, Evelyn R. Scarrow, Mai K. Elmallah
Article
Immunology
Debolina D. Biswas, Rebecca K. Martin, LaShardai N. Brown, Karli Mockenhaupt, Angela S. Gupta, Michael J. Surace, Anuj Tharakan, Jessie W. Yester, Reetika Bhardwaj, Daniel H. Conrad, Tomasz Kordula
Summary: The study reveals the crucial role of cIAP2 in modulating neuroinflammation, cell death, and survival during experimental autoimmune encephalomyelitis (EAE), providing insights for potential MS therapeutics development focusing on limiting microglia activation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Clinical Neurology
Debolina D. Biswas, Lea El Haddad, Ronit Sethi, Meredith L. Huston, Elias Lai, Mariam M. Abdelbarr, Doreen Z. Mhandire, Mai K. ElMallah
Summary: The spinocerebellar ataxias (SCA) are a group of heterogeneous neurodegenerative disorders with symptoms including poor coordination and balance. The exact mechanism and extent of respiratory-related complications in SCA patients are still unclear.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Weronika Sowinska, Mateusz Wawro, Debolina D. Biswas, Jakub Kochan, Katarzyna Pustelny, Aleksandra Solecka, Angela S. Gupta, Karli Mockenhaupt, Jaroslaw Polak, Borys Kwinta, Tomasz Kordula, Aneta Kasza
Summary: The precise functions of Regnase-2 (Reg-2/ZC3H12B/MCPIP2) and its regulatory mechanisms remain unclear. This study shows that Reg-2 actively controls neuroinflammation in nontransformed cells, particularly primary astrocytes. It downregulates the mRNA levels of proinflammatory cytokines IL-1 beta and IL-6, as well as regulates the expression of Regnase-1 (Reg-1/ZC3H12A/MCPIP1). The expression levels of Reg-2 and Reg-1 are inversely related and their imbalance is associated with glioblastoma progression and patient prognosis.
Meeting Abstract
Biochemistry & Molecular Biology
Debolina Biswas, Justin Dhindsa, Laura Strickland, Logan Pucci, Mai ElMallah
Meeting Abstract
Neurosciences
K. Mockenhaupt, K. M. Tyc, A. McQuiston, A. Hariprashad, D. D. Biswas, A. S. Gupta, A. L. Olex, S. K. Singh, M. R. Waters, J. L. Dupree, M. G. Dozmorov, T. Kordula
Article
Physiology
Angela L. McCall, Justin S. Dhindsa, Logan A. Pucci, Amanda F. Kahn, Anna F. Fusco, Debolina D. Biswas, Laura M. Strickland, Henry C. Tseng, Mai K. ElMallah
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2020)