Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis

Jesse Lyons; Douglas K. Brubaker; Phaedra C. Ghazi; Katherine R. Baldwin; Amanda Edwards; Myriam Boukhali; Samantha Dale Strasser; Lucia Suarez-Lopez; Yi-Jang Lin; Vijay Yajnik; Joseph L. Kissil; Wilhelm Haas; Douglas A. Lauffenburger; Kevin M. Haigis

doi:10.1126/scisignal.aan3580

Research ArticleInflammation

Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis

View ORCID ProfileJesse Lyons¹,²,*,
View ORCID ProfileDouglas K. Brubaker¹,²,*,
View ORCID ProfilePhaedra C. Ghazi¹,
View ORCID ProfileKatherine R. Baldwin¹,³,
View ORCID ProfileAmanda Edwards⁴,⁵,
Myriam Boukhali⁴,⁵,
Samantha Dale Strasser¹,²,⁶,
View ORCID ProfileLucia Suarez-Lopez¹,⁷,
View ORCID ProfileYi-Jang Lin¹,
View ORCID ProfileVijay Yajnik⁸,
Joseph L. Kissil⁹,
View ORCID ProfileWilhelm Haas⁴,⁵,
View ORCID ProfileDouglas A. Lauffenburger²,⁷, and
View ORCID ProfileKevin M. Haigis¹,⁵,¹⁰,†

¹Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.
²Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³Department of Pediatric Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
⁶Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁸Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁹Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
¹⁰Harvard Digestive Disease Center, Harvard Medical School, Boston, MA 02115, USA.

↵†Corresponding author. Email: khaigis{at}bidmc.harvard.edu

↵* These authors contributed equally to this work.

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Science Signaling 27 Feb 2018:
Vol. 11, Issue 519, eaan3580
DOI: 10.1126/scisignal.aan3580

Jesse Lyons

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Douglas K. Brubaker

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Phaedra C. Ghazi

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

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Katherine R. Baldwin

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

3Department of Pediatric Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.

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Amanda Edwards

4Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.

5Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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Myriam Boukhali

4Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.

5Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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Samantha Dale Strasser

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

6Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Lucia Suarez-Lopez

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

7David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Yi-Jang Lin

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

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Vijay Yajnik

8Department of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.

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Joseph L. Kissil

9Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.

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Wilhelm Haas

4Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.

5Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

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Douglas A. Lauffenburger

2Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

7David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Kevin M. Haigis

1Cancer Research Institute and Department of Medicine, Beth-Israel Deaconess Medical Center, Boston, MA 02215, USA.

5Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

10Harvard Digestive Disease Center, Harvard Medical School, Boston, MA 02115, USA.

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For correspondence: khaigis@bidmc.harvard.edu

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