Emulate, Inc.

Cedars-sinai Medical Center

Cedars-sinai Medical

Stephen R Targan

Daniel Levner

Christopher David Hinojosa

Geraldine A Hamilton

Norman Wen

Clive N Svendsen

S Jordan Kerns

Robert N Barrett

Jacob Fraser

Dhruv Sareen

Magdalena Kasendra

Jefferson Puerta

Carol Lucchesi

Michael Workman

Uthra Rajamani

Jerome I Rotter

Huiying Yang

Eric A Vasiliauskas

Phillip R Fleshner

David Q Shih

William S Mow

Chris Hinojosa

Jordan Kerns

Magdelena Kasendra

Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.

Systems and methods for growth of intestinal cells in microfluidic devices

This invention relates transgenic animals that overexpress TL1A in a tissue specific manner to model inflammatory bowel disease (IBM such as colitis, Crohn's disease and ulcerative colitis, fibrosis, and related inflammatory diseases and conditions. TL1A transgenic animals constitutively express both TL1A and GFP in lymphoid and myeloid cell lineages, allowing convenient identification and sorting of immune cells involved in IBD disease progression, such as T-cells, antigen presenting cells (APC), and dendritic cells (DC). TL1A transgenic animals may be induced to exhibit gross fibrosis, or isolated cells may be implanted into immunodeficient mice to establish colitis.

TL1A model of inflammation fibrosis and autoimmunity

The invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease in a subject having Crohn's disease by determining the presence or absence of IgA anti-I2 antibodies in the subject, where the presence of the IgA anti-I2 antibodies indicates that the subject has a clinical subtype of Crohn's disease. In one embodiment, a method of the invention is practiced by further determining the presence or absence in the subject of a NOD2 variant, anti-antibodies (ASCA), IgA anti-OmpC antibodies, or perinuclear anti-neutrophil cytoplasmic antibodies (pANCA). The methods of the invention can be used to diagnose or predict susceptibility to a clinical subtype of Crohn's disease, for example, a fibrostenotic subtype, a subtype characterized by the need for small bowel surgery, or a subtype characterized by the absence of features of ulcerative colitis.

Methods of assessing Crohn's disease patient phenotype by I2 serologic response

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Santa Monica, CA, United States of America

Stephen R Targan