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Challenges in IBD Research: Preclinical Human IBD Mechanisms

Pizarro, Theresa T. and Stappenbeck, Thaddeus S. and Rieder, Florian and Rosen, Michael J. and Colombel, Jean-Frédéric and Donowitz, Mark and Towne, Jennifer and Mazmanian, Sarkis K. and Faith, Jeremiah J. and Hodin, Richard A. and Garrett, Wendy S. and Fichera, Alessandro and Poritz, Lisa S. and Cortes, Constanza J. and Shtraizent, Nataly and Honig, Gerard and Snapper, Scott B. and Hurtado-Lorenzo, Andrés and Salzman, Nita H. and Chang, Eugene B. (2019) Challenges in IBD Research: Preclinical Human IBD Mechanisms. Inflammatory Bowel Diseases, 25 (S2). S5-S12. ISSN 1078-0998. doi:10.1093/ibd/izz075.

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Preclinical human IBD mechanisms is part of five focus areas of the Challenges in IBD research document, which also include environmental triggers, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the preclinical human IBD mechanisms manuscript is focused on highlighting the main research gaps in the pathophysiological understanding of human IBD. These research gap areas include: 1) triggers of immune responses; 2) intestinal epithelial homeostasis and wound repair; 3) age-specific pathophysiology; 4) disease complications; 5) heterogeneous response to treatments; and 6) determination of disease location. As an approach to address these research gaps, the prioritization of reverse translation studies is proposed in which clinical observations are the foundation for experimental IBD research in the lab, and for the identification of new therapeutic targets and biomarkers. The use of human samples in validating basic research findings and development of precision medicine solutions is also proposed. This prioritization aims to put emphasis on relevant biochemical pathways and humanized in vitro and in vivo models that extrapolate meaningfully to human IBD, to eventually yield first-in-class and effective therapies.

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Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( Received: 29 March 2019; Published: 16 May 2019. The authors thank Rosemary Bianculli for design of figures; Orna Ehrlich for coordination with the publisher; Rebecca Kaplan for facilitating public comments; and the following individuals for review and recommendations on the manuscript: Robert Hinton; Douglas Levine; Jeremy Adler; Neil Hyman; Sridhar Mani; Antonina Mikocka-Walus; Chao Li; Carolina Ciacci; Damian Garcia-Olmo; J. Todd Kuenstner; Maria Lia Scribano; Alan Baird; Emina Huang; Giovanni C. Actis; Harris Ahmad; Herbert Van Kruiningen; J.M. Mullin; Pietro Tonelli; Richard M Soll; Simone Saibeni and Ulla Knaus. Supported by: Crohn’s & Colitis Foundation.
Funding AgencyGrant Number
Crohn’s and Colitis FoundationUNSPECIFIED
Subject Keywords:Crohn’s disease, ulcerative colitis, preclinical, immune response, epithelium, wound repair, fistula, stricture, fibrosis, organoid
Issue or Number:S2
Record Number:CaltechAUTHORS:20190520-100852631
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Official Citation:Theresa T Pizarro, Thaddeus S Stappenbeck, Florian Rieder, Michael J Rosen, Jean-Frédéric Colombel, Mark Donowitz, Jennifer Towne, Sarkis K Mazmanian, Jeremiah J Faith, Richard A Hodin, Wendy S Garrett, Alessandro Fichera, Lisa S Poritz, Constanza J Cortes, Nataly Shtraizent, Gerard Honig, Scott B Snapper, Andrés Hurtado-Lorenzo, Nita H Salzman, Eugene B Chang, Challenges in IBD Research: Preclinical Human IBD Mechanisms, Inflammatory Bowel Diseases, Volume 25, Issue Supplement_2, June 2019, Pages S5–S12,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95596
Deposited By: Tony Diaz
Deposited On:20 May 2019 17:21
Last Modified:16 Nov 2021 17:13

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