Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice

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

doi:10.1126/scitranslmed.aay8798

Research ArticleFibrosis

Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice

View ORCID ProfileSarah Alsamman¹,
View ORCID ProfileStephanie A. Christenson²,
Amy Yu¹,
View ORCID ProfileNadia M. E. Ayad³,⁴,
View ORCID ProfileMeghan S. Mooring⁵,
Joe M. Segal¹,
View ORCID ProfileJimmy Kuang-Hsien Hu⁶,
Johanna R. Schaub⁷,
Steve S. Ho⁷,
View ORCID ProfileVikram Rao⁷,
Megan M. Marlow⁷,
Scott M. Turner⁷,
View ORCID ProfileMai Sedki⁸,
View ORCID ProfileLorena Pantano⁹,
Sarani Ghoshal¹⁰,
View ORCID ProfileDiego Dos Santos Ferreira¹¹,
Hsiao-Yen Ma¹²,
View ORCID ProfileCaroline C. Duwaerts¹,¹³,
Regina Espanol-Suner¹⁴,
View ORCID ProfileLan Wei¹⁰,
View ORCID ProfileBenjamin Newcomb¹⁵,
Izolda Mileva¹⁵,
View ORCID ProfileDaniel Canals¹⁵,
View ORCID ProfileYusuf A. Hannun¹⁵,
View ORCID ProfileRaymond T. Chung¹⁶,
View ORCID ProfileAras N. Mattis¹³,¹⁷,
View ORCID ProfileBryan C. Fuchs¹⁰,
Andrew M. Tager¹⁸,*,
View ORCID ProfileDean Yimlamai⁵,
View ORCID ProfileValerie M. Weaver³,⁴,¹⁴,¹⁹,²⁰,²¹,
View ORCID ProfileAlan C. Mullen¹⁶,
View ORCID ProfileDean Sheppard²,¹²,† and
View ORCID ProfileJennifer Y. Chen ¹,¹³,†

¹Department of Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.
²Division of Pulmonary, Critical Care, Allergy and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
³Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴UC Berkeley–UCSF Graduate Program in Bioengineering, San Francisco, CA 94143, USA.
⁵Division of Pediatric Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, CT 06520, USA.
⁶Division of Oral Biology & Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷Pliant Therapeutics, South San Francisco, CA 94080, USA.
⁸Internal Medicine, Kaiser Permanente, San Francisco, CA 94115, USA.
⁹Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
¹⁰Division of Surgical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
¹¹Athinoula A. Martinos Center for Biomedical Imaging, Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
¹²Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³Liver Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁴Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁵Departments of Medicine and Biochemistry and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA.
¹⁶Liver Center, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁷Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
¹⁸Division of Pulmonary and Critical Care Medicine, Fibrosis Research Center, and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁹Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
²⁰Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
²¹Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.

↵†Corresponding author. Email: dean.sheppard{at}ucsf.edu (D.S.); jennifer.chen4{at}ucsf.edu (J.Y.C.)

↵* Deceased.

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Science Translational Medicine 19 Aug 2020:
Vol. 12, Issue 557, eaay8798
DOI: 10.1126/scitranslmed.aay8798

Sarah Alsamman

1Department of Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.

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Stephanie A. Christenson

2Division of Pulmonary, Critical Care, Allergy and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.

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Amy Yu

1Department of Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.

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Nadia M. E. Ayad

3Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.

4UC Berkeley–UCSF Graduate Program in Bioengineering, San Francisco, CA 94143, USA.

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Meghan S. Mooring

5Division of Pediatric Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, CT 06520, USA.

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Joe M. Segal

1Department of Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.

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Jimmy Kuang-Hsien Hu

6Division of Oral Biology & Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Johanna R. Schaub