Benaroya Research Institute At Virginia Mason

TO ADVANCE THE SCIENCE THAT WILL PREDICT, PREVENT, REVERSE, AND CURE DISEASES OF THE IMMUNE SYSTEM.

INTERVENTIONAL IMMUNOLOGY - INCLUDES IMMUNE TOLERANCE NETWORK PROGRAM. SEE SCHEDULE O.

TRANSLATIONAL IMMUNOLOGY. SEE SCHEDULE O.

FUNDAMENTAL IMMUNOLOGY. SEE SCHEDULE O.

INTERVENTIONAL IMMUNOLOGY - INCLUDES TOLERANCE NETWORK PROGRAM. ADVANCEMENTS OF THE IMMUNE TOLERANCE NETWORK ARE HIGHLIGHTED BELOW.FUNDING FOR THE IMMUNE TOLERANCE NETWORK (ITN) WAS AWARDED TO BRI'S DR. JERRY NEPOM IN 2014, AND WAS REAWARDED IN 2021, FROM THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASE (NIAID) OF THE NATIONAL INSTITUTES OF HEALTH (NIH). THIS 7-YEAR AWARD TOTALING $27 MILLION ANNUALLY SUPPORTED THE RESEARCH CONSORTIUM ESTABLISHED IN 1999 WITH A PRIMARY FOCUS ON THE DEVELOPMENT OF NEW TOLEROGENIC APPROACHES FOR THE TREATMENT AND PREVENTION OF DISEASE IN THREE CLINICAL AREAS: ASTHMA AND ALLERGIC DISEASES; AUTOIMMUNE DISEASES; AND IMMUNE-MEDIATED REJECTION OF TRANSPLANTED SOLID ORGANS, TISSUES AND CELLS. AS THE PRIME RECIPIENT OF THIS GRANT, BRI IS RESPONSIBLE FOR THE MANAGEMENT OF THE OVERALL GRANT FROM NIAID; INCLUDING OVERSIGHT OF ALL ASPECTS OF THE NETWORK'S INFRASTRUCTURE. THE MAJOR ACTIVITIES IN 2020-2021 WERE DIVERSE BUT CONTINUED TO CENTER ON PRESERVING THE ITN'S COHESIVE PROJECT FOCUSED ENVIRONMENT AND ITS FRAMEWORK, WHICH HAS PROVEN SO SUCCESSFUL IN THE MANAGEMENT OF A LARGE COOPERATIVE AGREEMENT GRANT. KEY OUTCOMES INCLUDE THE FOLLOWING: 1. GRANT RENEWAL: THE ITN WAS NOTIFIED IN LATE 2020 THAT THE ITN GRANT RENEWAL HAD BEEN AWARDED TO DR. JERRY NEPOM AT THE BENAROYA RESEARCH INSTITUTE. THIS IS A 7-YEAR, ~189M AWARD THAT BEGAN IN 2021. 2. CROSS NETWORK INTEGRATION: THE COVID 19 PANDEMIC PRESENTED A TEMPORARY SHIFT IN ITN PRIORITIES AS PERSONNEL SPREAD ACROSS THE ITN'S THREE MAIN OPERATIONAL SITES MOVED TO A WORK FROM HOME (WFH) MODEL. THIS SHIFT WAS LARGELY SEAMLESS DUE TO PAST FOCUS ON CAREFUL PLANNING AND EMPHASIS ON COLLABORATION ACROSS THE ITN'S MAJOR CENTERS, LOCATED IN SEATTLE, SAN FRANCISCO AND BETHESDA. NO CHANGES TO EXISTING NETWORK INTEGRATION WERE NEEDED AS THE CURRENT MODEL CONTINUED TO SUCCESSFULLY SUPPORT THE OVERALL ITN PROGRAM. ESTABLISHING NEW RELATIONSHIPS AND VITAL CONNECTIONS WITHIN THE RESEARCH COMMUNITY CONTINUED TO BE AN ITN GOAL. 3. OPERATIONS AND CLINICAL TRIAL SUPPORT: THE ITN PROGRAM TEAM AT BRI ISSUED 211 SUB AWARDS IN SUPPORT OF 22 ACTIVE ITN CLINICAL TRIALS AND NUMEROUS SUPPORTING ITN MECHANISTIC TRIALS. 4. SUPPLEMENTAL FUNDING / PARTNERSHIPS: ITN CENTRAL ADMINISTRATION CONTINUED TO FOCUS ON IDENTIFYING ADDITIONAL OPPORTUNITIES FOR SUPPLEMENTAL FUNDING AND/OR FUNDING PARTNERSHIPS. IN 2020, THE ITN RECEIVED SUPPLEMENTAL FUNDING AS THE CONTRACTING COMPONENT FOR SEVERAL NIAID SPONSORED COVID-19 CLINICAL TRIALS. (A) SUPPLEMENTAL FUNDING OPPORTUNITIES: THE ITN PROGRAM TEAM AT BRI SUBMITTED FOUR SUPPLEMENTAL FUNDING REQUEST IN 2020. THIS REQUEST WAS AWARDED, BRINGING IN AN ADDITIONAL $5.9M IN FUNDING TO THE ITN BRI. (B) PARTNERSHIPS: THE ITN CONTINUED ITS RELATIONSHIP WITH TWO PHARMACEUTICAL PARTNERS FOR PARTIAL FUNDING ON TWO ONGOING ITN STUDIES. NIAID IS THE CLINICAL SPONSOR ON BOTH OF THESE TRIALS. 5. PUBLICATION ACTIVITY: IN 2020, 31 ITN PUBLICATIONS WERE PUBLISHED IN PRESTIGIOUS RESEARCH JOURNALS AND WERE PRESENTED AT DOMESTIC AND INTERNATIONAL RESEARCH CONFERENCES. THESE PUBLICATIONS REPRESENTED ITN RESEARCH IN ALL THERAPEUTIC FOCUS AREAS OF THE ITN: TYPE 1 DIABETES, TRANSPLANT, AUTOIMMUNE DISEASE AND ALLERGY AND ASTHMA.

TRANSLATIONAL IMMUNOLOGY: TRANSLATIONAL IMMUNOLOGY RESEARCH OBSERVATIONS ARE MADE IN THE BASIC RESEARCH LAB, THEN QUICKLY TESTED IN THE CLINIC WITH PATIENTS, WITH RESULTS BROUGHT BACK TO THE LAB AGAIN IN AN EXPEDIENT AND SYSTEMATIC WAY. THIS TYPE OF RESEARCH "TRANSLATES" NEW METHODS TO IMPROVE OUR ABILITY TO PREDICT DISEASE RISK, PREVENT ONSET OF DISEASE, SLOW DISEASE PROGRESSION AND IMPROVE SAFETY AND EFFICACY OF TREATMENTS. AT BRI, TRANSLATIONAL RESEARCH ADDRESSES AUTOIMMUNE AND IMMUNE-MEDIATED DISEASES.THE BRI BIOREPOSITORY IS A COLLECTION OF BLOOD, SERUM AND TISSUE SAMPLES, AS WELL AS MEDICAL HISTORIES, FROM VOLUNTEERS WITH AND WITHOUT DISEASES INVOLVING THE IMMUNE SYSTEM. BRI SCIENTISTS AND PHYSICIAN COLLABORATORS WORK TOGETHER TO STUDY TISSUE, BLOOD AND SERUM SAMPLES ALONG WITH THE MEDICAL AND DEMOGRAPHIC DATA. BRI'S BIOREPOSITORY SAMPLES DATE BACK TO 2000 AND INCLUDE MULTIPLE DISEASE CATEGORIES AND A BIOREPOSITORY OF HEALTHY PEOPLE FOR COMPARISON PURPOSES.ADVANCEMENTS INCLUDED THE FOLLOWING:SOUND LIFE PROJECT BRI COMPLETED VOLUNTEER ENROLLMENT FOR THIS STUDY IN WHICH RESEARCHERS ARE TRACKING HEALTHY IMMUNE SYSTEMS OVER TIME. SEATTLE-AREA ADULTS IN TWO AGE COHORTS 25-35 AND 55-65 ARE PARTICIPATING IN THIS GROUNDBREAKING STUDY TO BUILD A BASELINE OF KNOWLEDGE ABOUT THE HUMAN IMMUNE SYSTEM TO UNDERSTAND DISEASE. THE GOAL IS TO LAY THE GROUNDWORK FOR BETTER WAYS TO DIAGNOSE, TREAT AND PREVENT IMMUNE SYSTEM DISEASES SUCH AS RHEUMATOID ARTHRITIS, TYPE 1 DIABETES AND MULTIPLE SCLEROSIS. VOLUNTEERS PROVIDE BLOOD SAMPLES AND HEALTH INFORMATION THROUGH IN-PERSON VISITS AND A PHONE APP DEVELOPED AT BRI, ALLOWING RESEARCHERS TO TRACK THEIR IMMUNE SYSTEMS OVER THE COURSE OF TWO YEARS. THE PROJECT IS THE INITIAL PHASE OF A RESEARCH PARTNERSHIP LED BY THE ALLEN INSTITUTE FOR IMMUNOLOGY. BRI IS PROVIDING DETAILED INFORMATION ABOUT HEALTHY IMMUNE SYSTEMS TO SERVE AS A FOUNDATION FOR EXISTING AND FUTURE DISEASE RESEARCH PROGRAMS.AUTOIMMUNE DISEASE RESEARCH IN THE DOWN SYNDROME POPULATIONBRI'S BERNARD KHOR, MD, PHD, AND VIRGINIA MASON PEDIATRICIAN REBECCA PARTRIDGE, MD, CONTINUED THEIR WORK LEVERAGING A GRANT FROM THE NATIONAL INSTITUTES OF HEALTH TO BUILD A DOWN SYNDROME (DS) BIOREPOSITORY TO RESEARCH THE CONNECTION BETWEEN DS AND AUTOIMMUNE DISEASE. THE COLLECTION INCLUDES BLOOD, SERUM AND TISSUE SAMPLES, AS WELL AS MEDICAL HISTORIES, FROM VOLUNTEERS, PEOPLE WITH DS AND THEIR RELATIVES, WITH AND WITHOUT AUTOIMMUNE DISEASES. THE DS POPULATION HAS LONG BEEN UNDERREPRESENTED IN MEDICAL RESEARCH, AS NEARLY 50 PERCENT OF THIS POPULATION IS LIVING WITH AT LEAST ONE AUTOIMMUNE DISEASE. BRI IS AMONG THE FIRST TO BE AWARDED A GRANT DEDICATED TO AUTOIMMUNE DISEASE IN THE DS POPULATION. TYPE 1 DIABETES "FAST PROGRESSORS AND PREVENTION STRATEGIES - ALICE LONG, PHD, AND COLLEAGUES PURSUED THEIR LANDMARK DISCOVERY THAT IS LEADING TO NEW TREATMENT STRATEGIES FOR TYPE 1 DIABETES (T1D). IN SOME PEOPLE NEWLY DIAGNOSED WITH THE DISEASE, IT PROGRESSES SO QUICKLY THAT THEIR PANCREAS STOPS MAKING INSULIN WITHIN A YEAR. FOR OTHERS, THE PROCESS IS SLOWER AND THIS CAN MAKE THE DISEASE EASIER TO MANAGE. THE RESEARCHERS' DISCOVERY ENABLES EARLY IDENTIFICATION OF "FAST PROGRESSORS" TO POTENTIALLY MATCH THEM WITH TREATMENTS TO HELP THEM STAY HEALTHIER FOR MUCH LONGER. THE RESEARCHERS IDENTIFIED IMPORTANT DIFFERENCES BETWEEN "FAST PROGRESSORS AND PEOPLE WHOSE DISEASE PROGRESSES SLOWLY. DR. LONG'S TEAM SHOWED THAT "SLOW PROGRESSORS" HAVE HIGHER LEVELS OF EXHAUSTED CD8 T CELLS CELLS THAT ARE WORN OUT FROM ATTACKING THE PANCREAS. THE DISCOVERY COULD LEAD TO A TEST THAT IDENTIFIES HOW QUICKLY INDIVIDUAL PATIENTS WILL LOSE THEIR ABILITY TO MAKE INSULIN. THEN, DR. LONG RECEIVED ADDITIONAL FUNDING TO INVESTIGATE WHY CD8 T CELLS BECOME EXHAUSTED. FOR PEOPLE WITH T1D, A THERAPY THAT WOULD SLOW DOWN (OR EVEN STOP) ATTACKER CELLS WOULD PROLONG THEIR ABILITY TO MAKE INSULIN, WHICH MAKES THEIR LIVES MUCH EASIER AND SIGNIFICANTLY REDUCES THEIR LONG-TERM HEALTH RISKS.PETER LINSLEY, PHD, LED BRI'S BIOINFORMATICS TEAM IN HELPING TO ANALYZE A VAST AMOUNT OF DATA FROM THE CELLS. WHILE RESEARCHERS ARE TYPICALLY ONLY ABLE TO LOOK AT TWO OR THREE ASPECTS OF EACH CELL, DR. LINSLEY'S TEAM USED INNOVATIVE TECHNOLOGY TO HELP DR. LONG AND COLLEAGUES COLLECT AND ANALYZE DATA ON UP TO 30 ASPECTS OF EACH CELL.IN 2020, BRI ALSO RECEIVED A $5.4 MILLION CONTRACT AWARD FROM THE NIH TO IMPROVE TREATMENTS FOR PATIENTS DIAGNOSED WITH RHEUMATOID ARTHRITIS.

FUNDAMENTAL IMMUNOLOGY: THE CENTER FOR FUNDAMENTAL IMMUNOLOGY INVESTIGATES THE IMMUNE SYSTEM TO UNDERSTAND HOW IT WORKS IN HEALTH AND DISEASE. AT BRI, WE EMPLOY A VARIETY OF METHODS TO EXAMINE THE IMMUNE SYSTEM FUNCTION AT THE GENETIC, MOLECULAR AND CELLULAR LEVELS. THESE INCLUDE DEVELOPING NOVEL MODEL SYSTEMS OF AUTOIMMUNE AND INFLAMMATORY DISEASE, USED TO DETERMINE HOW ACTIVITIES OF THE IMMUNE SYSTEM ARE REGULATED AND HOW REGULATORY MECHANISMS BREAK DOWN IN AUTOIMMUNITY, ALLERGY, ASTHMA AND COVID-19. WE ALSO LEVERAGE SAMPLES FROM HEALTHY SUBJECTS AND PATIENTS WITH IMMUNE-MEDIATED DISEASES TO STUDY IMMUNE SYSTEM FUNCTION AND IDENTIFY POTENTIAL THERAPEUTIC TARGETS.SYSTEMS IMMUNOLOGY: WITH THE EXPLOSION OF DATA FROM GENOME STUDIES AND MOLECULAR PROFILING TECHNOLOGIES, HUGE AMOUNTS OF BIOLOGICAL INFORMATION ARE NOW AVAILABLE. BRI SCIENTISTS IN THIS CENTER USE COMPLEX SYSTEMS THEORY AND HIGH THROUGHPUT TECHNIQUES AS WELL AS MATHEMATICAL AND COMPUTATIONAL TOOLS TO UNDERSTAND THE FUNCTIONING OF THE IMMUNE SYSTEM IN HEALTH AND DISEASE.

BRI OVERSEES THE CLINICAL RESEARCH PROGRAM AT VIRGINIA MASON MEDICAL CENTER, UNIQUELY COMBINING THE EXPERTISE OF A WORLD-RENOWNED MEDICAL RESEARCH INSTITUTE WITH THE CARE OF A HEALTHCARE QUALITY LEADER. THE CLINICAL RESEARCH PROGRAM SUPPORTS VIRGINIA MASON CLINICAL INVESTIGATORS IN STUDIES ACROSS A WIDE VARIETY OF AUTOIMMUNE AND IMMUNE-MEDIATED DISEASES AND CONDITIONS, AS WELL AS A BROAD RANGE OF OTHER DISEASES SUCH AS CANCER AND CARDIAC DISEASE. THE CLINICAL RESEARCH PROGRAM STAFF ANNUALLY ENROLLS APPROXIMATELY 1500 STUDY PARTICIPANTS INTO VIRGINIA MASON TRIALS, BUT NUMBERS WERE FEWER IN YEAR 2020 DUE TO THE PANDEMIC.TESTING A NEW MS THERAPY A RESEARCH STUDY AT BRI AND VIRGINIA MASON IS SEEKING TO FIND OUT IF AN EXPERIMENTAL ORAL DRUG, SIMILAR TO A CURRENTLY AVAILABLE MS MEDICATION, WOULD BE JUST AS EFFECTIVE AS THE CURRENT ONE, BUT WITH FEWER GASTROINTESTINAL SIDE EFFECTS. IN AN EARLIER STUDY, HALF THE RESEARCH PARTICIPANTS TOOK THIS EXPERIMENTAL DRUG AND HALF TOOK THE CURRENT DRUG. PARTICIPANTS WHO FINISHED THE FIVE-WEEK STUDY THEN ENROLLED IN A TWO-YEAR STUDY OF THE EXPERIMENTAL DRUG.