Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation

Alan T. Tang; Katie R. Sullivan; Courtney C. Hong; Lauren M. Goddard; Aparna Mahadevan; Aileen Ren; Heidy Pardo; Amy Peiper; Erin Griffin; Ceylan Tanes; Lisa M. Mattei; Jisheng Yang; Li Li; Patricia Mericko-Ishizuka; Le Shen; Nicholas Hobson; Romuald Girard; Rhonda Lightle; Thomas Moore; Robert Shenkar; Sean P. Polster; Claudia J. Roedel; Ning Li; Qin Zhu; Kevin J. Whitehead; Xiangjian Zheng; Amy Akers; Leslie Morrison; Helen Kim; Kyle Bittinger; Christopher J. Lengner; Markus Schwaninger; Anna Velcich; Leonard Augenlicht; Salim Abdelilah-Seyfried; Wang Min; Douglas A. Marchuk; Issam A. Awad; Mark L. Kahn

doi:10.1126/scitranslmed.aaw3521

Research ArticleCEREBRAL CAVERNOUS MALFORMATION

Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation

Alan T. Tang ¹,
Katie R. Sullivan¹,
Courtney C. Hong¹,
Lauren M. Goddard¹,
Aparna Mahadevan¹,
Aileen Ren¹,
Heidy Pardo²,
Amy Peiper²,
Erin Griffin²,
Ceylan Tanes³,
Lisa M. Mattei³,
Jisheng Yang¹,
Li Li¹,
Patricia Mericko-Ishizuka¹,
Le Shen⁴,
Nicholas Hobson⁴,
Romuald Girard⁴,
Rhonda Lightle⁴,
Thomas Moore⁴,
Robert Shenkar⁴,
Sean P. Polster⁴,
Claudia J. Roedel⁵,
Ning Li⁶,
Qin Zhu⁷,
Kevin J. Whitehead⁸,
Xiangjian Zheng⁹,¹⁰,
Amy Akers¹¹,
Leslie Morrison¹²,
Helen Kim¹³,
Kyle Bittinger³,
Christopher J. Lengner⁶,¹⁴,¹⁵,
Markus Schwaninger¹⁶,
Anna Velcich¹⁷,
Leonard Augenlicht¹⁷,
Salim Abdelilah-Seyfried⁵,¹⁸,
Wang Min¹⁹,
Douglas A. Marchuk²,
Issam A. Awad⁴ and
Mark L. Kahn ¹,*

¹Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.
²Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
³Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁴Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.
⁵Institute for Biochemistry and Biology, Department of Animal Physiology, Potsdam University, Karl-Liebknecht-Str. 24-25, Haus 26, 14476 Potsdam, Germany.
⁶Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁸Division of Cardiovascular Medicine and the Program in Molecular Medicine, University of Utah, Salt Lake City, UT 84112, USA.
⁹Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
¹⁰Centenary Institute, Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia.
¹¹Angioma Alliance, Norfolk, VA 23517, USA.
¹²Department of Neurology and Pediatrics, University of New Mexico, Albuquerque, NM 87106, USA.
¹³Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.
¹⁴Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁵Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁶Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23562 Lübeck, Germany.
¹⁷Department of Cell Biology, Albert Einstein College of Medicine/Albert Einstein Cancer Center, NY 10461, USA.
¹⁸Institute of Molecular Biology, Hannover Medical School, Carl-Neuberg Str. 1, D-30625 Hannover, Germany.
¹⁹Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06510, USA.

↵*Corresponding author. Email: markkahn{at}pennmedicine.upenn.edu

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Science Translational Medicine 27 Nov 2019:
Vol. 11, Issue 520, eaaw3521
DOI: 10.1126/scitranslmed.aaw3521

Alan T. Tang

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Katie R. Sullivan

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Courtney C. Hong

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Lauren M. Goddard

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Aparna Mahadevan

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Aileen Ren

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Heidy Pardo

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

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Amy Peiper

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

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Erin Griffin

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

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Ceylan Tanes

Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

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Lisa M. Mattei

Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

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Jisheng Yang

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Li Li

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Patricia Mericko-Ishizuka

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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Le Shen

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Nicholas Hobson

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Romuald Girard

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Rhonda Lightle

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Thomas Moore

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Robert Shenkar

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Sean P. Polster

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Claudia J. Roedel

Institute for Biochemistry and Biology, Department of Animal Physiology, Potsdam University, Karl-Liebknecht-Str. 24-25, Haus 26, 14476 Potsdam, Germany.

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Ning Li

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Qin Zhu

Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Kevin J. Whitehead

Division of Cardiovascular Medicine and the Program in Molecular Medicine, University of Utah, Salt Lake City, UT 84112, USA.

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Xiangjian Zheng

Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.Centenary Institute, Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia.

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Amy Akers

Angioma Alliance, Norfolk, VA 23517, USA.

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Leslie Morrison

Department of Neurology and Pediatrics, University of New Mexico, Albuquerque, NM 87106, USA.

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Helen Kim

Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.

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Kyle Bittinger

Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

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Christopher J. Lengner

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Markus Schwaninger

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23562 Lübeck, Germany.

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Anna Velcich

Department of Cell Biology, Albert Einstein College of Medicine/Albert Einstein Cancer Center, NY 10461, USA.

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Leonard Augenlicht

Department of Cell Biology, Albert Einstein College of Medicine/Albert Einstein Cancer Center, NY 10461, USA.

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Salim Abdelilah-Seyfried

Institute for Biochemistry and Biology, Department of Animal Physiology, Potsdam University, Karl-Liebknecht-Str. 24-25, Haus 26, 14476 Potsdam, Germany.Institute of Molecular Biology, Hannover Medical School, Carl-Neuberg Str. 1, D-30625 Hannover, Germany.

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Wang Min

Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06510, USA.

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Douglas A. Marchuk

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

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Issam A. Awad

Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

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Mark L. Kahn

Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

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For correspondence: markkahn@pennmedicine.upenn.edu

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Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation

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