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

View ORCID ProfileAlan T. Tang ¹,
View ORCID ProfileKatie R. Sullivan¹,
Courtney C. Hong¹,
Lauren M. Goddard¹,
View ORCID ProfileAparna Mahadevan¹,
View ORCID ProfileAileen Ren¹,
Heidy Pardo²,
View ORCID ProfileAmy Peiper²,
View ORCID ProfileErin Griffin²,
Ceylan Tanes³,
Lisa M. Mattei³,
Jisheng Yang¹,
Li Li¹,
Patricia Mericko-Ishizuka¹,
View ORCID ProfileLe Shen⁴,
View ORCID ProfileNicholas Hobson⁴,
View ORCID ProfileRomuald Girard⁴,
Rhonda Lightle⁴,
Thomas Moore⁴,
View ORCID ProfileRobert Shenkar⁴,
Sean P. Polster⁴,
View ORCID ProfileClaudia J. Roedel⁵,
Ning Li⁶,
View ORCID ProfileQin Zhu⁷,
View ORCID ProfileKevin J. Whitehead⁸,
View ORCID ProfileXiangjian Zheng⁹,¹⁰,
Amy Akers¹¹,
View ORCID ProfileLeslie Morrison¹²,
View ORCID ProfileHelen Kim¹³,
Kyle Bittinger³,
View ORCID ProfileChristopher J. Lengner⁶,¹⁴,¹⁵,
View ORCID ProfileMarkus Schwaninger¹⁶,
Anna Velcich¹⁷,
View ORCID ProfileLeonard Augenlicht¹⁷,
View ORCID ProfileSalim Abdelilah-Seyfried⁵,¹⁸,
Wang Min¹⁹,
Douglas A. Marchuk²,
Issam A. Awad⁴ and
View ORCID ProfileMark 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

See allHide authors and affiliations

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

Alan T. Tang

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Alan T. Tang

Katie R. Sullivan

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Katie R. Sullivan

Courtney C. Hong

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Lauren M. Goddard

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Aparna Mahadevan

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Aparna Mahadevan

Aileen Ren

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Aileen Ren

Heidy Pardo

2Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Amy Peiper

2Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Amy Peiper

Erin Griffin

2Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Erin Griffin

Ceylan Tanes

3Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Lisa M. Mattei

3Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jisheng Yang

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Li Li

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Patricia Mericko-Ishizuka

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Le Shen

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Le Shen

Nicholas Hobson

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Nicholas Hobson

Romuald Girard

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Romuald Girard

Rhonda Lightle

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Thomas Moore

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Robert Shenkar

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Robert Shenkar

Sean P. Polster

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Claudia J. Roedel

5Institute for Biochemistry and Biology, Department of Animal Physiology, Potsdam University, Karl-Liebknecht-Str. 24-25, Haus 26, 14476 Potsdam, Germany.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Claudia J. Roedel

Ning Li

6Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Qin Zhu

7Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Qin Zhu

Kevin J. Whitehead

8Division of Cardiovascular Medicine and the Program in Molecular Medicine, University of Utah, Salt Lake City, UT 84112, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Kevin J. Whitehead

Xiangjian Zheng

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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Xiangjian Zheng

Amy Akers

11Angioma Alliance, Norfolk, VA 23517, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Leslie Morrison

12Department of Neurology and Pediatrics, University of New Mexico, Albuquerque, NM 87106, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Leslie Morrison

Helen Kim

13Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Helen Kim

Kyle Bittinger

3Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Christopher J. Lengner

6Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, 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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Christopher J. Lengner

Markus Schwaninger

16Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23562 Lübeck, Germany.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Markus Schwaninger

Anna Velcich

17Department of Cell Biology, Albert Einstein College of Medicine/Albert Einstein Cancer Center, NY 10461, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Leonard Augenlicht

17Department of Cell Biology, Albert Einstein College of Medicine/Albert Einstein Cancer Center, NY 10461, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Leonard Augenlicht

Salim Abdelilah-Seyfried

5Institute for Biochemistry and Biology, Department of Animal Physiology, Potsdam University, Karl-Liebknecht-Str. 24-25, Haus 26, 14476 Potsdam, Germany.

18Institute of Molecular Biology, Hannover Medical School, Carl-Neuberg Str. 1, D-30625 Hannover, Germany.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Salim Abdelilah-Seyfried

Wang Min

19Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06510, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Douglas A. Marchuk

2Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Issam A. Awad

4Neurovascular Surgery Program, Section of Neurosurgery, Department of Surgery, University of Chicago School of Medicine and Biological Sciences, Chicago, IL 60637, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Mark L. Kahn

1Department of Medicine and Cardiovascular Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Mark L. Kahn
For correspondence: markkahn@pennmedicine.upenn.edu

Article
Figures & Data
Info & Metrics
eLetters
PDF

eLetters is an online forum for ongoing peer review. Submission of eLetters are open to all. Please read our Terms of Service before submitting your own eLetter.

Submit a Response to This Article

Compose eLetter

Title

Contents

More information about text formats

Plain text

Plain text
No HTML tags allowed.
Web page addresses and e-mail addresses turn into links automatically.
Lines and paragraphs break automatically.

Author Information

Contributors
First name and middle name First or given name, e.g. 'Peter'. Last Name Your last, or family, name, e.g. 'MacMoody'. Email Your email address, e.g. higgs-boson@gmail.com Role / Occupation Your role and/or occupation, e.g. 'Orthopedic Surgeon'. Affiliation Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.

Statement of Competing Interests

Competing interests?

Yes

Please describe the competing interests

CAPTCHA

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

No eLetters have been published for this article.

View Full Text

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

Plain text

Vertical Tabs

Science Translational Medicine

Article Tools