BENAROYA RESEARCH INSTITUTE (BRI)
REWRITING THE STORY OF AUTOIMMUNITY
Jane Hoyt Buckner, MD PresidentBenaroya Research Institute
Virginia Mason Franciscan Health
February 24, 2023
IMMUNE SYSTEM AND HEALTH
OUR VISION
A healthy immune system for every individual
OUR MISSION
Predict, prevent, reverse and cure diseases of the immune system
OUR SCIENTIFIC APPROACH
Discover / Translate / Intervene / Integrate
OUR APPROACH
WE ARE EXPERTS IN IMMUNOLOGY
We have the tools to study immune diseases
WE ARE AGILE
Infrastructure / Expertise / Clinical Connection
WE ARE COLLABORATIVE
Partnerships: Virginia Mason / Seattle / NIH / Industry
WE ARE COMMITTED TO OUR MISSION
> 35 years of focus on diseases of the immune system
WE HAVE A UNIQUE APPROACH
Immunology an innovation to improve patients lives
Fundamental Discoveries
Understanding Human Immune Diseases
Clinical Intervention
Improving Immune Health for All
RESOURCES
STAFF MEMBERS AND VOLUNTEERS 325+ Research Building Virginia Mason Campus in Seattle $84 Million Annual Research Volume NIH Funding Accounts for 72%
BRI CORES SUPPORT OUR WORK
Shared Resources available to BRI researchers and the Seattle Biotech community
GENOMICS CORE
LABORATORY
CELL AND TISSUE ANALYSIS CORE
TETRAMER CORE
LABORATORY
Illumina RNA and DNA sequencing linked to software pipelines for processing sequencing data, and bioinformatic core support for analysis
The Cell and Tissue Analysis Core Laboratory offers state-of-the-art instruments to analyze and select cells based on a variety of parameters.
Develop and distribute HLA Class II tetramers for the identification of antigen specific T cells.
BRI CORES SUPPORT OUR WORK
Registries & Biorepositories Clinical Research Center
• 14,000 Participants
• 330,000+ Cryopreserved Specimens
• Over 15,000 Specimens Distributed Annually
• Phase 1, 2, and 3 clinical trials
• Investigator-initiated & multicenter trials
• NIH, Foundation and Industry funded studies
CLINICAL RESEARCH AT VIRGINIA MASON
400+ open studies / 200 investigators / ~3000 participants
Interventional Studies by Department
Leader in High Profile Consortia
• Leading recruitment in NIDDK funded DREAM study looking at T1D diagnoses after acute pancreatitis (other sites include Cedars Sinai, USC, Stanford, Johns Hopkins)
• Recognition as a high performing site in Pancreatic Cancer Action Network’s Precision Promise study; asked to present our methods of success to 25+ leading cancer orgs including Dana Farber, Fred Hutch, MSK
11%
Industry 28% Grant/ Foundati on 21% IIT - interventional 2% IIT - noninterventi onal 49%
Average Breakdown by Study Type 53% 11%
4% Canc er 48% Digestive Disease 24% Other 18% Radiology/ urology 10%
TRANSLATION OF FUNDAMENTAL DISCOVERIES IN ACTION
Our investigators believe that what we learn in one disease can inform us about many
DISCOVERING A NEW CELL TYPE ELUCIDATES THE CAUSE FOR INFLAMMATION INDUCED CYTOPENIA
An inflammatory signal a novel cell type anemia & thrombocytopenia
Helps us understand
• Malaria
• Lupus
• Macrophage Activation Syndrome
• Anemia of chronic disease
DISCOVERING A NEW CYTOKINE LEADS TO NEW TREATMENTS FOR ASTHMA & CANCER?
Promotes allergy and asthma
Novel treatment for asthma
(Tezepelumab )
Promotes metastasis and tumor growth
Could this be a target for Cancer therapy too?
TSLP
LEARNING FROM PEOPLE WITH DOWN SYNDROME
Down syndrome: 1:800 live births
Why?
New lessons in DS:
1. Advanced immune aging
2. Autoimmunity-poised state
Up to 100x autoimmunity
Next steps: Mechanism & Therapy
1. Immune aging in health (e.g. vaccine response)
2. Autoimmunity
In people with AND without DS!
Lucas Warren
Rebecca Partridge MD
Bernard Khor MD
T CELLS + GENE EDITING =TREATMENT FOR T1D
20 YEARS IN THE
MAKING
Gene editing FOXP3+ TCR Autoimmune disease Teff T reg Restored tolerance Teff T reg
WE LEAD INTERNATIONAL NETWORKS
• Clinical trials in autoimmunity, allergy/asthma and transplant
• BRI awarded 7 year, $189M coordinating center award in 2021
• In addition to $27M/yr, BRI receives $3-20M in supplemental awards
• Network of researchers and providers at the forefront of T1D research including screening and trials
• BRI has been awarded Chair grant (through 2021) and currently has Hub award
• Collaboration focused on characterizing the status of the immune system in diverse populations
• BRI previously awarded ICAC and IMPACC grants
• In 2022, awarded $11.4M to explore link between viruses and immune system diseases
CHANGING THE STORIES OF OUR PATIENTS
BRI makes discoveries that translate into healthier patients
Changed pediatric medical guidelines on the introduction of peanuts to infants
FDA approval in November for first immunotherapy that can delay onset of T1D.
FUTURE DIRECTIONS WITH COMMONSPIRIT
CommonSpirit leading in the care of people with immune system diseases
Building an infrastructure to identify patients at high risk
• Screening for family history of autoimmunity
• Secondary screening when feasible (antibody or genetic data) • Building a resource HUB for patients, families and providers
• Central resource for information, education
• Risk assessment and treatment recommendations
Source for Clinical trials to treat or prevent autoimmune diseases
Moving beyond autoimmunity to include allergy and immunotherapies
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QUESTIONS?
