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6. Neutral ceramidase-active site inhibitor chemotypes and binding modes

Author

Coant, Nicolas, Bickel, John D., Rahaim, Ronald, Otsuka, Yuka, Choi, Yong-Mi, Xu, Ruijuan, Simoes, Michael, Cariello, Chris, Mao, Cungui, Saied, Essa M., Arenz, Christoph, Spicer, Timothy P., Bannister, Thomas D., Tonge, Peter J., Airola, Michael V., Scampavia, Louis, Hannun, Yusuf A., Rizzo, Robert C., and Haley, John D.

Published
2023
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9. Contributors

Author

Abbas Bukhari, Syed Nasir, primary, Abhilash, M., additional, Abinaya, K., additional, Adefegha, Stephen A., additional, Adeleke, Oluwakemi V., additional, Aggarwal, Sumit Kumar, additional, Arni, Raghuvir Krishnaswamy, additional, Azam, Mohammad, additional, Baldissera, Antonielle, additional, Bano, Sarika, additional, Bedir, Ipek, additional, Bhatt, Lokesh Kumar, additional, Bhushan, Bharat, additional, Binu, P., additional, Castelli, María Eugenia, additional, Cerminati, Sebastián, additional, Chakraborti, Sajal, additional, Chakraborti, Tapati, additional, Chaudhary, Dharam Paul, additional, Chaurasiya, Shivendra K., additional, Clarke, Christopher J., additional, Correa, Fernando, additional, Dagla, Manesh Chander, additional, De Laurentiis, Andrea, additional, de Oliveira Leite, Isabel, additional, Devadasan, Velmurugan, additional, Dey, Sanjay Kumar, additional, Dhalla, Naranjan S., additional, Ejike, Uju Dorathy Iliemene, additional, Etcheverry, Tomás, additional, Farina, Mariana, additional, Fujita, Masaaki, additional, Ghandour, Botheina, additional, Ghumman, Shazia Akram, additional, Gismene, Carolina, additional, Gonzalez, Jorge Enrique Hernandez, additional, Gremski, Luiza Helena, additional, Hails, Guillermo, additional, Hannun, Yusuf A., additional, Hasan, Sara, additional, Ijaz, Bushra, additional, Jain, Kripa, additional, Jat, Bahadur Singh, additional, Jiang, Xian-Cheng, additional, Jiménez, Jaime Andrés Pereañez, additional, Kumar, Pardeep, additional, Kumar, Satish, additional, Lacava, Franco Emanuel, additional, Liman, Mubarak Labaran, additional, Lo Vasco, Vincenza Rita, additional, Marchisio, Fiorela, additional, Mariutti, Ricardo Barros, additional, Mathew, Bijina J., additional, Matsubara, Fernando Hitomi, additional, Menzella, Hugo Gabriel, additional, Mohammed, Samia, additional, Molehin, Olorunfemi R., additional, Mondal, Kausik, additional, Murakami, Makoto, additional, Muthezhilan, R., additional, Nair, R. Harikumaran, additional, Naz, Anjum, additional, Nezir, Ayca Ece, additional, Noreen, Sobia, additional, Olonishuwa, Paul T., additional, Onal, Meltem Selen, additional, Ozturk, Kaan, additional, Pal, Ajay, additional, Pandey, Amit Kumar, additional, Paoletti, Luciana, additional, Polli, Nayanne Louise Costacurta, additional, Puviarasan, K., additional, Rai, Rupal, additional, Raman, Pachaiappan, additional, Ren, Jihui, additional, Ruwali, Munindra, additional, Senff-Ribeiro, Andrea, additional, Sengupta, Sayan, additional, Singh, Alla, additional, Singh, Amarjeet, additional, Singh, Vinayak, additional, Sonkar, Kamankshi, additional, Takada, Yoko K., additional, Takada, Yoshikazu, additional, Taketomi, Yoshitaka, additional, Tan, Choo Hock, additional, Tan, Kae Yi, additional, Tappia, Paramjit S., additional, Telci, Dilek, additional, Vadak, Namrata, additional, Val, Diego S., additional, Varghese, Mathews V., additional, and Veiga, Silvio Sanches, additional

Published
2023
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11. Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice

Author

Alsamman, Sarah, Christenson, Stephanie A, Yu, Amy, Ayad, Nadia ME, Mooring, Meghan S, Segal, Joe M, Hu, Jimmy Kuang-Hsien, Schaub, Johanna R, Ho, Steve S, Rao, Vikram, Marlow, Megan M, Turner, Scott M, Sedki, Mai, Pantano, Lorena, Ghoshal, Sarani, Ferreira, Diego Dos Santos, Ma, Hsiao-Yen, Duwaerts, Caroline C, Espanol-Suner, Regina, Wei, Lan, Newcomb, Benjamin, Mileva, Izolda, Canals, Daniel, Hannun, Yusuf A, Chung, Raymond T, Mattis, Aras N, Fuchs, Bryan C, Tager, Andrew M, Yimlamai, Dean, Weaver, Valerie M, Mullen, Alan C, Sheppard, Dean, and Chen, Jennifer Y

Subjects
Cancer, 2.1 Biological and endogenous factors, Aetiology, Acid Ceramidase, Adaptor Proteins, Signal Transducing, Animals, Fibrosis, Hepatic Stellate Cells, Humans, Mice, Signal Transduction, Biological Sciences, Medical and Health Sciences
Abstract

Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein β-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis.

Published
2020

12. Neutral Sphingomyelinase 2 Inhibition Limits Hepatic Steatosis and Inflammation

Author

Al-Rashed, Fatema, primary, Arefanian, Hossein, additional, Madhoun, Ashraf Al, additional, Bahman, Fatemah, additional, Sindhu, Sardar, additional, AlSaeed, Halemah, additional, Jacob, Texy, additional, Thomas, Reeby, additional, Al-Roub, Areej, additional, Alzaid, Fawaz, additional, Malik, MD Zubbair, additional, Nizam, Rasheeba, additional, Thanaraj, Thangavel Alphonse, additional, Al-Mulla, Fahd, additional, Hannun, Yusuf A., additional, and Ahmad, Rasheed, additional

Published
2024
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14. Exploring the Therapeutic Landscape of Sphingomyelinases

Author

Shanbhogue, Prajna, Hannun, Yusuf A., Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, and Gomez-Cambronero, Julian, editor

Published
2020
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15. Expression of Ceramide Synthases in Mice and Their Roles in Regulating Acyl-Chain Sphingolipids: A Framework for Baseline Levels and Future Implications in Aging and Disease

Author

Richardson, Whitney J., primary, Humphrey, Sophia B., additional, Sears, Sophia M., additional, Hoffman, Nicholas A., additional, Orwick, Andrew J., additional, Doll, Mark A., additional, Doll, Chelsea L., additional, Xia, Catherine, additional, Hernandez-Corbacho, Maria, additional, Snider, Justin M., additional, Obeid, Lina M., additional, Hannun, Yusuf A., additional, Snider, Ashley J., additional, and Siskind, Leah J., additional

Published
2023
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19. Metabolism and Roles of Sphingolipids in Yeast Saccharomyces cerevisiae

Author

Ren, Jihui, Hannun, Yusuf A., Timmis, Kenneth N., Editor-in-Chief, Boll, Matthias, Series Editor, Geiger, Otto, Series Editor, Goldfine, Howard, Series Editor, Krell, Tino, Series Editor, Lee, Sang Yup, Series Editor, McGenity, Terry J., Series Editor, Rojo, Fernando, Series Editor, Sousa, Diana Z, Series Editor, Stams, Alfons J. M., Series Editor, Steffan, Robert, Series Editor, and Wilkes, Heinz, Series Editor

Published
2019
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25. Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands

Author

Staquicini, Daniela I., primary, Cardó-Vila, Marina, additional, Rotolo, Jimmy A., additional, Staquicini, Fernanda I., additional, Tang, Fenny H. F., additional, Smith, Tracey L., additional, Ganju, Aditya, additional, Schiavone, Carmine, additional, Dogra, Prashant, additional, Wang, Zhihui, additional, Cristini, Vittorio, additional, Giordano, Ricardo J., additional, Ozawa, Michael G., additional, Driessen, Wouter H. P., additional, Proneth, Bettina, additional, Souza, Glauco R., additional, Brinker, Lina M., additional, Noureddine, Achraf, additional, Snider, Ashley J., additional, Canals, Daniel, additional, Gelovani, Juri G., additional, Petrache, Irina, additional, Tuder, Rubin M., additional, Obeid, Lina M., additional, Hannun, Yusuf A., additional, Kolesnick, Richard N., additional, Brinker, C. Jeffrey, additional, Pasqualini, Renata, additional, and Arap, Wadih, additional

Published
2023
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34. Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality

Author

Snider, Justin M., You, Jeehyun Karen, Wang, Xia, Snider, Ashley J., Hallmark, Brian, Zec, Manja M., Seeds, Michael C., Sergeant, Susan, Johnstone, Laurel, Wang, Qiuming, Sprissler, Ryan, Carr, Tara F., Lutrick, Karen, Parthasarathy, Sairam, Bime, Christian, Zhang, Hao Helen, Luberto, Chiara, Kew, Richard R., Hannun, Yusuf A., Guerra, Stefano, McCall, Charles E., Yao, Guang, Del Poeta, Maurizio, and Chilton, Floyd H.

Subjects
Mitochondria -- Physiological aspects -- Health aspects, Phospholipases -- Physiological aspects -- Health aspects, Health care industry
Abstract

There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 ([sPLA.sub.2]) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active [sPLA.sub.2] group IIA ([sPLA.sub.2]-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated [sPLA.sub.2]-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified [sPLA.sub.2]-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified [sPLA.sub.2]-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma [sPLA.sub.2]-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies [sPLA.sub.2]-IIA as a therapeutic target to reduce COVID-19 mortality., Introduction Host resistance and disease tolerance are essential to mounting a successful defense against infections such as SARS-CoV-2. Up to 80% of individuals infected with SARS-CoV-2 are asymptomatic or develop [...]

Published
2021
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36. Dietary Choline and Betaine Intake and Risk of Colorectal Cancer in an Iranian Population

Author

Seyyedsalehi, Monireh Sadat, primary, Rossi, Marta, additional, Hadji, Maryam, additional, Rashidian, Hamideh, additional, Marzban, Maryam, additional, Parpinel, Maria, additional, Fiori, Federica, additional, Naghibzadeh-Tahami, Ahmad, additional, Hannun, Yusuf A., additional, Luberto, Chiara, additional, Zendehdel, Kazem, additional, and Boffetta, Paolo, additional

Published
2023
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37. Peripheral Sphingolipids as Potential Biomarkers of Parkinson disease Including Sex-Related Differences (P3-11.007)

Author

Ortega, Roberto, primary, Burbulla, Lena, additional, Mileva, Izolda, additional, Taylor, Graeme, additional, Cuperlovic-Culf, Miroslava, additional, Glickman, Amanda, additional, Pullman, Mariel, additional, Scherzer, Clemens, additional, Raymond, Deborah, additional, Miltenyi-Miltenberger, Gabriel, additional, Yoo, Andrea, additional, Nichols, William, additional, Krainc, Dimitri, additional, Bressman, Susan, additional, Obeid, Lina, additional, Hannun, Yusuf, additional, Bennett, Steffany, additional, and Saunders-Pullman, Rachel, additional

Published
2023
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38. Data from Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti–PD-1 Therapy Efficacy

Author

Montfort, Anne, primary, Bertrand, Florie, primary, Rochotte, Julia, primary, Gilhodes, Julia, primary, Filleron, Thomas, primary, Milhès, Jean, primary, Dufau, Carine, primary, Imbert, Caroline, primary, Riond, Joëlle, primary, Tosolini, Marie, primary, Clarke, Christopher J., primary, Dufour, Florent, primary, Constantinescu, Andrei A., primary, Junior, Nilton De França, primary, Garcia, Virginie, primary, Record, Michel, primary, Cordelier, Pierre, primary, Brousset, Pierre, primary, Rochaix, Philippe, primary, Silvente-Poirot, Sandrine, primary, Therville, Nicole, primary, Andrieu-Abadie, Nathalie, primary, Levade, Thierry, primary, Hannun, Yusuf A., primary, Benoist, Hervé, primary, Meyer, Nicolas, primary, Micheau, Olivier, primary, Colacios, Céline, primary, and Ségui, Bruno, primary

Published
2023
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39. Supplementary Data File S1 from Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti–PD-1 Therapy Efficacy

Author

Montfort, Anne, primary, Bertrand, Florie, primary, Rochotte, Julia, primary, Gilhodes, Julia, primary, Filleron, Thomas, primary, Milhès, Jean, primary, Dufau, Carine, primary, Imbert, Caroline, primary, Riond, Joëlle, primary, Tosolini, Marie, primary, Clarke, Christopher J., primary, Dufour, Florent, primary, Constantinescu, Andrei A., primary, Junior, Nilton De França, primary, Garcia, Virginie, primary, Record, Michel, primary, Cordelier, Pierre, primary, Brousset, Pierre, primary, Rochaix, Philippe, primary, Silvente-Poirot, Sandrine, primary, Therville, Nicole, primary, Andrieu-Abadie, Nathalie, primary, Levade, Thierry, primary, Hannun, Yusuf A., primary, Benoist, Hervé, primary, Meyer, Nicolas, primary, Micheau, Olivier, primary, Colacios, Céline, primary, and Ségui, Bruno, primary

Published
2023
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40. Supplementary Data from Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation

Author

Xie, Stephanie Z., primary, Kaufmann, Kerstin B., primary, Wang, Weijia, primary, Chan-Seng-Yue, Michelle, primary, Gan, Olga I., primary, Laurenti, Elisa, primary, Garcia-Prat, Laura, primary, Takayanagi, Shin-ichiro, primary, Ng, Stanley W.K., primary, Xu, ChangJiang, primary, Zeng, Andy G.X., primary, Jin, Liqing, primary, McLeod, Jessica, primary, Wagenblast, Elvin, primary, Mitchell, Amanda, primary, Kennedy, James A., primary, Liu, Qiang, primary, Boutzen, Héléna, primary, Kleinau, Melissa, primary, Jargstorf, Joseph, primary, Holmes, Gareth, primary, Zhang, Yang, primary, Voisin, Veronique, primary, Bader, Gary D., primary, Wang, Jean C.Y., primary, Hannun, Yusuf A., primary, Luberto, Chiara, primary, Schroeder, Timm, primary, Minden, Mark D., primary, and Dick, John E., primary

Published
2023
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41. Supplementary Tables and Figures from Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti–PD-1 Therapy Efficacy

Author

Montfort, Anne, primary, Bertrand, Florie, primary, Rochotte, Julia, primary, Gilhodes, Julia, primary, Filleron, Thomas, primary, Milhès, Jean, primary, Dufau, Carine, primary, Imbert, Caroline, primary, Riond, Joëlle, primary, Tosolini, Marie, primary, Clarke, Christopher J., primary, Dufour, Florent, primary, Constantinescu, Andrei A., primary, Junior, Nilton De França, primary, Garcia, Virginie, primary, Record, Michel, primary, Cordelier, Pierre, primary, Brousset, Pierre, primary, Rochaix, Philippe, primary, Silvente-Poirot, Sandrine, primary, Therville, Nicole, primary, Andrieu-Abadie, Nathalie, primary, Levade, Thierry, primary, Hannun, Yusuf A., primary, Benoist, Hervé, primary, Meyer, Nicolas, primary, Micheau, Olivier, primary, Colacios, Céline, primary, and Ségui, Bruno, primary

Published
2023
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42. Data from Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation

Author

Xie, Stephanie Z., primary, Kaufmann, Kerstin B., primary, Wang, Weijia, primary, Chan-Seng-Yue, Michelle, primary, Gan, Olga I., primary, Laurenti, Elisa, primary, Garcia-Prat, Laura, primary, Takayanagi, Shin-ichiro, primary, Ng, Stanley W.K., primary, Xu, ChangJiang, primary, Zeng, Andy G.X., primary, Jin, Liqing, primary, McLeod, Jessica, primary, Wagenblast, Elvin, primary, Mitchell, Amanda, primary, Kennedy, James A., primary, Liu, Qiang, primary, Boutzen, Héléna, primary, Kleinau, Melissa, primary, Jargstorf, Joseph, primary, Holmes, Gareth, primary, Zhang, Yang, primary, Voisin, Veronique, primary, Bader, Gary D., primary, Wang, Jean C.Y., primary, Hannun, Yusuf A., primary, Luberto, Chiara, primary, Schroeder, Timm, primary, Minden, Mark D., primary, and Dick, John E., primary

Published
2023
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43. Supplementary Tables from Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation

Author

Xie, Stephanie Z., primary, Kaufmann, Kerstin B., primary, Wang, Weijia, primary, Chan-Seng-Yue, Michelle, primary, Gan, Olga I., primary, Laurenti, Elisa, primary, Garcia-Prat, Laura, primary, Takayanagi, Shin-ichiro, primary, Ng, Stanley W.K., primary, Xu, ChangJiang, primary, Zeng, Andy G.X., primary, Jin, Liqing, primary, McLeod, Jessica, primary, Wagenblast, Elvin, primary, Mitchell, Amanda, primary, Kennedy, James A., primary, Liu, Qiang, primary, Boutzen, Héléna, primary, Kleinau, Melissa, primary, Jargstorf, Joseph, primary, Holmes, Gareth, primary, Zhang, Yang, primary, Voisin, Veronique, primary, Bader, Gary D., primary, Wang, Jean C.Y., primary, Hannun, Yusuf A., primary, Luberto, Chiara, primary, Schroeder, Timm, primary, Minden, Mark D., primary, and Dick, John E., primary

Published
2023
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44. Supplementary figures merged from Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation

Author

Xie, Stephanie Z., primary, Kaufmann, Kerstin B., primary, Wang, Weijia, primary, Chan-Seng-Yue, Michelle, primary, Gan, Olga I., primary, Laurenti, Elisa, primary, Garcia-Prat, Laura, primary, Takayanagi, Shin-ichiro, primary, Ng, Stanley W.K., primary, Xu, ChangJiang, primary, Zeng, Andy G.X., primary, Jin, Liqing, primary, McLeod, Jessica, primary, Wagenblast, Elvin, primary, Mitchell, Amanda, primary, Kennedy, James A., primary, Liu, Qiang, primary, Boutzen, Héléna, primary, Kleinau, Melissa, primary, Jargstorf, Joseph, primary, Holmes, Gareth, primary, Zhang, Yang, primary, Voisin, Veronique, primary, Bader, Gary D., primary, Wang, Jean C.Y., primary, Hannun, Yusuf A., primary, Luberto, Chiara, primary, Schroeder, Timm, primary, Minden, Mark D., primary, and Dick, John E., primary

Published
2023
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45. Supplementary Methods from Off-Target Function of the Sonic Hedgehog Inhibitor Cyclopamine in Mediating Apoptosis via Nitric Oxide–Dependent Neutral Sphingomyelinase 2/Ceramide Induction

Author

Meyers-Needham, Marisa, primary, Lewis, Jocelyn A., primary, Gencer, Salih, primary, Sentelle, R. David, primary, Saddoughi, Sahar A., primary, Clarke, Christopher J., primary, Hannun, Yusuf A., primary, Norell, Haakan, primary, da Palma, Telma Martins, primary, Nishimura, Michael, primary, Kraveka, Jacqueline M., primary, Khavandgar, Zohreh, primary, Murshed, Monzur, primary, Cevik, M. Ozgur, primary, and Ogretmen, Besim, primary

Published
2023
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46. Data from Off-Target Function of the Sonic Hedgehog Inhibitor Cyclopamine in Mediating Apoptosis via Nitric Oxide–Dependent Neutral Sphingomyelinase 2/Ceramide Induction

Author

Meyers-Needham, Marisa, primary, Lewis, Jocelyn A., primary, Gencer, Salih, primary, Sentelle, R. David, primary, Saddoughi, Sahar A., primary, Clarke, Christopher J., primary, Hannun, Yusuf A., primary, Norell, Haakan, primary, da Palma, Telma Martins, primary, Nishimura, Michael, primary, Kraveka, Jacqueline M., primary, Khavandgar, Zohreh, primary, Murshed, Monzur, primary, Cevik, M. Ozgur, primary, and Ogretmen, Besim, primary

Published
2023
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47. Supplementary Figures 1 - 7 from Off-Target Function of the Sonic Hedgehog Inhibitor Cyclopamine in Mediating Apoptosis via Nitric Oxide–Dependent Neutral Sphingomyelinase 2/Ceramide Induction

Author

Meyers-Needham, Marisa, primary, Lewis, Jocelyn A., primary, Gencer, Salih, primary, Sentelle, R. David, primary, Saddoughi, Sahar A., primary, Clarke, Christopher J., primary, Hannun, Yusuf A., primary, Norell, Haakan, primary, da Palma, Telma Martins, primary, Nishimura, Michael, primary, Kraveka, Jacqueline M., primary, Khavandgar, Zohreh, primary, Murshed, Monzur, primary, Cevik, M. Ozgur, primary, and Ogretmen, Besim, primary

Published
2023
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