Seattle, United States
Seattle, United States

Benaroya Research Institute is a Seattle, Washington non-profit organization which conducts autoimmune disease medical research. It is housed at Virginia Mason Medical Center. Wikipedia.


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Ziegler S.F.,Benaroya Research Institute
Current Opinion in Immunology | Year: 2010

The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease. © 2010 Elsevier Ltd.


Lord J.D.,Benaroya Research Institute
World Journal of Gastroenterology | Year: 2015

Since their discovery two decades ago, CD4+CD25+Foxp3+ regulatory T cells (Tregs) have become the subject of intense investigation by immunologists. Unlike other T cells, which promote an immune response, Tregs actively inhibit inflammation when activated by their cognate antigen, thus raising hope that these cells could be engineered into a highly targeted, antigenspecific, immunosuppressant therapy. Although Tregs represent less than 10% of circulating CD4+T cells, they have been shown to play an essential role in preventing or limiting inflammation in a variety of animal models and human diseases. In particular, spontaneous intestinal inflammation has been shown to occur in the absence of Tregs, suggesting that there may be a Treg defect central to the pathogenesis of human inflammatory bowel disease (IBD). However, over the past decade, multiple groups have reported no qualitative or quantitative deficits in Tregs from the intestines and blood of IBD patients to explain why these cells fail to regulate inflammation in Crohn's disease and ulcerative colitis. In this review, we will discuss the history of Tregs, what is known about them in IBD, and what progress and obstacles have been seen with efforts to employ them for therapeutic benefit. © 2015 Baishideng Publishing Group Inc. All rights reserved.


Ziegler S.F.,Benaroya Research Institute
Journal of Allergy and Clinical Immunology | Year: 2012

The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways, and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies in both human subjects and murine models have implicated TSLP in the development and progression of allergic diseases. This review will highlight recent advances in the understanding of the role of TSLP in these inflammatory diseases. Importantly, these insights into TSLP's multifaceted role could potentially allow for novel therapeutic manipulations of these disorders. © 2012 American Academy of Allergy, Asthma & Immunology.


Ziegler A.-G.,TU Munich | Nepom G.T.,Benaroya Research Institute
Immunity | Year: 2010

A combination of genetic and immunological features is useful for prediction of autoimmune diabetes. Patterns of immune response correspond to the progression from a preclinical phase of disease to end-stage islet damage, with biomarkers indicating transition from susceptibility to active autoimmunity, and to a final loss of immune regulation. Here, we review the markers that provide evidence for immunological checkpoint failure and that also provide tools for assessment of individualized disease risk. When viewed in the context of genetic variation that influences immune response thresholds, progression from susceptibility to overt disease displays predictable modalities of clinical presentation resulting from a sequential series of failed homeostatic checkpoints for selection and activation of immunity. © 2010 Elsevier Inc.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 686.02K | Year: 2011

DESCRIPTION (provided by applicant): The goal of this proposal is for Matrexa to develop a protein product that will prevent intimal hyperplasia in human saphenous vein grafts (SVG) with the objective of reducing the exceedingly high failure rate of thesesurgical procedures. The strategy involves acute pre-treatment of saphenous veins at the time of surgery with proprietary agents, developed by Matrexa. The target for intervention is the large vascular matrix proteoglycan, versican, which is central to smooth muscle growth and hyperplasia, accumulation of atherogenic lipids, and macrophage ingress into developing lesions. We have successfully targeted versican and prevented these events in animal models of atherosclerosis through over expression of the small variant versican V3 (V3) and through over expression of versican antisense sequences. We have also discovered an additional and unexpected benefit of these approaches in that V3 promotes the synthesis and formation of elastic fibers and markedly improves the mechanical properties and stability of treated vessels. Once formed, the elastic fibers will maintain the structural integrity, anti-hyperplastic and anti-inflammatory nature of the vascular wall. We have further discovered, through deletion studies,that exon 3 of V3 contains this elastogenic activity. We recognize, however, that gene delivery and overexpression of V3 is therapeutically problematic for safety and other reasons and we therefore propose to develop and use rV3 protein and small peptidesas therapeutic agents. In preliminary studies we have been successful in producing rV3 which possesses elastogenic activity. The Aims of the project are 1) to prepare rV3 protein in enough quantity and purity to test its bioactivity in biochemical and invitro cell-based assays and 2) to demonstrate the efficacy of rV3 to prevent intimal hyperplasia and promote elastogenesis in ex vivo cultures of human saphenous vein. PUBLIC HEALTH RELEVANCE:This project is designed to develop therapeutic compounds to treat cardiovascular disease, the number 1 killer of human beings in the western world. We have discovered a specific protein that blocks the development of atherosclerosis (fatty deposits in the artery walls that cause hardening of the arteries) in animal models of this disease and now want to use strategies to produce this protein and test its effectiveness as a therapeutic agent to treat artery bypass failure which is among the most common surgeries in the US, with over 500,000 performed per year. Success with this undertaking will have an enormous impact on health care in this country and worldwide.


Patent
Benaroya Research Institute | Date: 2012-06-14

A composition for treating an airway inflammatory disease having high molecular weight, crosslinked hyaluronan and at least one aeroallergen is provided. A method of inducing immune tolerance to one or more aeroallergens in a mammalian subject suffering from or at risk of developing an airway inflammatory disease, and a method of treating a human subject suffering from or at risk of developing an airway inflammatory disease or condition of the lungs are also provided.


Patent
Benaroya Research Institute | Date: 2014-01-30

A method for identifying an autoimmune or demyelinating disease in a subject is described. The method includes (a) FIRST COHORT obtaining a sample comprising CD4^() T cells from a subject; (b) determining a level of IL-6 responsiveness of CD4^(+) T cells from the sample; (c) comparing the level of IL-6 responsiveness determined in step (b) with a level of IL-6 responsiveness of CD4^(+) T cells in a sample from a healthy subject; and (d) identifying the subject as having an autoimmune or demyelinating disease based upon an elevated level of IL-6 responsiveness in the subject. Biomarkers include, for example, IL-6R and/or pSTAT3. Methods for identifying and characterizing multiple sclerosis and relapsing-remitting multiple sclerosis are also described.


Patent
Benaroya Research Institute | Date: 2013-08-23

Provided herein are methods of detecting and/or monitoring the presence or severity of an immune disorder in a subject, including detecting a frequency of a Th2a subset of CD4+ T cells in a biological sample of the subject. In some embodiments, the detecting includes: (a) detecting a frequency of CD4+ T cells in a biological sample of said subject; (b) detecting a frequency of a Th2a subset of the CD4+ T cells in the biological sample; and (c) comparing the frequency of the Th2a subset with the frequency of the CD4+ T cells.


Patent
Benaroya Research Institute and Stanford University | Date: 2014-08-12

Compositions for treating autoimmune, allergic, or atopic disease comprising a compound that inhibits hyaluronan synthesis and a pharmaceutically acceptable carrier are described. In some embodiments, the compound that inhibits hyaluronan synthesis is 4-methylumbelliferone or a metabolite of 4-methylumbelliferone. Methods for treating autoimmune diabetes, multiple sclerosis and/or autoimmune demyelination, including administering to the subject a composition having a compound in an amount effective to inhibit hyaluronan synthesis in a mammalian subject, are also described.


Patent
Benaroya Research Institute | Date: 2016-01-07

Provided herein are methods of detecting and/or monitoring the presence or severity of an immune disorder in a subject, including detecting a frequency of a Th2a subset of CD4+ T cells in a biological sample of the subject. In some embodiments, the detecting includes: (a) detecting a frequency of CD4+ T cells in a biological sample of said subject; (b) detecting a frequency of a Th2a subset of the CD4+ T cells in the biological sample; and (c) comparing the frequency of the Th2a subset with the frequency of the CD4+ T cells.

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