BENAROYA RESEARCH INSTITUTE AT VIRGINIA

INTERVENTIONAL IMMUNOLOGY AND ADVANCEMENTS OF THE IMMUNE TOLERANCE NETWORK (ITN) ARE HIGHLIGHTED BELOW:FUNDING FOR THE IMMUNE TOLERANCE NETWORK (ITN) WAS INITIALLY AWARDED TO DR. JERRY NEPOM AT BRI IN 2014 BY THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) OF THE NATIONAL INSTITUTES OF HEALTH (NIH). IT WAS LATER RENEWED FOR A SECOND GRANT CYCLE IN 2021, PROVIDING APPROXIMATELY $27 MILLION ANNUALLY TO SUPPORT THE ITN. THIS RESEARCH CONSORTIUM, ESTABLISHED IN 1999, PRIMARILY FOCUSES ON DEVELOPING NEW TOLEROGENIC APPROACHES FOR TREATING AND PREVENTING DISEASES IN THREE CLINICAL AREAS: ASTHMA AND ALLERGIC DISEASES, AUTOIMMUNE DISEASES, AND IMMUNE-MEDIATED REJECTION OF TRANSPLANTED SOLID ORGANS, TISSUES, AND CELLS. BRI, AS THE PRIME RECIPIENT OF THIS GRANT, IS RESPONSIBLE FOR MANAGING THE OVERALL GRANT FROM NIAID, INCLUDING OVERSEEING ALL ASPECTS OF THE NETWORK'S INFRASTRUCTURE. AS OF 2022 FOLLOWING THE RETIREMENT OF DR. JERRY NEPOM, DR. JANE BUCKNER, PRESIDENT OF BRI, ASSUMED THE ROLE OF PRINCIPAL INVESTIGATOR OF THE ITN GRANT. DR. BUCKNER SERVES ON THE ITN STEERING COMMITTEE (NSC) AND THE ITN NETWORK EXECUTIVE COMMITTEE (NEC), AND PLAYED AN ACTIVE ROLE IN BOTH COMMITTEES AT OUR BIANNUAL IN-PERSON MEETINGS, PLAYING A CRITICAL ROLE IN TRACKING PROGRESS TOWARDS NETWORK GOALS AND DEVELOPING STRATEGIES TO MEET NETWORK OBJECTIVES.KEY OUTCOMES DURING THIS PERIOD INCLUDE:THE ITN CROSS-NETWORK INTEGRATION: SINCE 2014, THE ITN HAS EXCELLED WITH A STRONG FOCUS ON METICULOUS PLANNING AND COLLABORATION ACROSS THE ITN'S MAJOR CENTERS, LOCATED IN SEATTLE (BRI), SAN FRANCISCO (UNIVERSITY OF CALIFORNIA SAN FRANCISCO), DURHAM, NC (DUKE), BOSTON (BRIGHAM WOMEN'S HOSPITAL), ATLANTA (EMORY), AND ANN ARBOR (U OF MICHIGAN). THAT SUCCESSFUL COLLABORATION CONTINUED WITH THE FOLLOWING KEY OUTCOMES DURING THIS PERIOD:1. EFFECTIVE COLLABORATION WAS PARTICULARLY EVIDENT THIS PAST YEAR WITH THE PUBLICATION OF THE PRIMARY MANUSCRIPT FROM THE LEAP TRIO STUDY, THE SECOND FOLLOW-UP TO THE ITN'S GROUNDBREAKING LEAP STUDY, WHICH DEMONSTRATED THAT EARLY INTRODUCTION OF PEANUTS EFFECTIVELY HELPS PREVENT THE DEVELOPMENT OF PEANUT ALLERGY. THE FIRST FOLLOW-UP STUDY, LEAP-ON (2016), SHOWED THAT THIS PROTECTION PERSISTED EVEN AFTER A YEAR OF PEANUT AVOIDANCE (BETWEEN AGES 5 AND 6). NOW, DATA FROM THE LEAP TRIO STUDY, WHICH EXAMINED THE DURABILITY OF PEANUT TOLERANCE AT 144 MONTHS (AGE 12) AFTER YEARS OF AD LIBITUM PEANUT CONSUMPTION, DEMONSTRATE THAT TOLERANCE TO PEANUTS LASTS INTO ADOLESCENCE, IRRESPECTIVE OF SUBSEQUENT PEANUT CONSUMPTION. THESE FINDINGS HIGHLIGHT THAT LONG-TERM PREVENTION AND TOLERANCE IN FOOD ALLERGY CAN BE ACHIEVED.2. IN LINE WITH THE NIH DATA SHARING POLICY, THE ITN COORDINATING CENTER REVIEWED AND APPROVED 14 SAMPLE AND DATA SHARING REQUESTS THROUGH ITN TRIALSHARE, THE ITN'S DATA-SHARING PORTAL.3. OPERATIONS AND CLINICAL TRIAL SUPPORT: THE ITN COORDINATING CENTER AT BRI ISSUED OVER 275 SUBAWARDS DURING THIS REPORTING PERIOD TO SUPPORT 23 ACTIVE ITN CLINICAL TRIALS AND NUMEROUS SUPPORTING ITN MECHANISTIC TRIALS. DURING THIS REPORTING PERIOD, THE COORDINATING CENTER ALSO COMPLETED THE CONTRACTING COMPONENT FOR ONE OF THE TWO NIAID-SPONSORED COVID-19 CLINICAL TRIALS THEY HAD SUPPORTED AND FUNDED THROUGH ADMINISTRATIVE SUPPLEMENTS, WITH THE FINAL STUDY SET TO CONCLUDE IN Q3 2025.4. SUPPLEMENTAL FUNDING / PARTNERSHIPS: THE ITN COORDINATING CENTER CONTINUED TO FOCUS ON IDENTIFYING ADDITIONAL OPPORTUNITIES FOR SUPPLEMENTAL FUNDING AND FUNDING PARTNERSHIPS.A) SUPPLEMENTAL FUNDING: THE ITN COORDINATING CENTER AT BRI SUCCESSFULLY SUBMITTED ONE SUPPLEMENTAL FUNDING REQUEST IN 2023, WHICH WILL PROVIDE AN ADDITIONAL $1 MILLION PER YEAR THROUGH 2027. B) PARTNERSHIPS: THE ITN SUCCESSFULLY FULFILLED ITS PARTNERSHIP WITH A PHARMACEUTICAL COMPANY FOR PARTIAL FUNDING FOR AN ITN STUDY THAT ENDED IN LATE 2023. C) PARTNERSHIPS: SUCCESSFULLY NEGOTIATED COMMITMENTS FOR PARTIAL FINANCIAL SUPPORT FOR THREE ITN TRIALS TOTALING $7.3 MILLION. THOSE FUNDING AGREEMENTS WILL BE FINALIZED IN EARLY 2025. 5. PUBLICATION ACTIVITY: IN TOTAL, 35 ITN PUBLICATIONS WERE PUBLISHED DURING THIS REPORTING PERIOD IN PRESTIGIOUS RESEARCH JOURNALS AND PRESENTED AT DOMESTIC AND INTERNATIONAL RESEARCH CONFERENCES. THESE PUBLICATIONS REPRESENTED ITN RESEARCH IN ALL THERAPEUTIC FOCUS AREAS: AUTOIMMUNITY, TRANSPLANTATION, AND ALLERGY.

SCREENING FOR AUTOIMMUNE DISEASESIN 2024, BRI LAUNCHED ONE OF THE FIRST-EVER SCREENING INITIATIVES FOR AUTOIMMUNE DISEASES IN PRIMARY CARE. WHILE SCREENING IS COMMONPLACE FOR CANCER AND HEART DISEASE, SCREENING FOR AUTOIMMUNE DISEASES HAS NOT BEEN WIDELY AVAILABLE. A TEAM FROM BRI'S CENTER FOR INTERVENTIONAL IMMUNOLOGY LED BY CATE SPEAKE, PHD, AND SANDRA LORD, MD, LAUNCHED A STUDY TO IMPLEMENT SCREENING FOR TYPE 1 DIABETES, RHEUMATOID ARTHRITIS AND CELIAC DISEASE IN PRIMARY CARE. THE RESEARCH TEAM HAS NOW LAUNCHED SCREENING EFFORTS IN TWO VIRGINIA MASON FRANCISCAN HEALTH PRIMARY CARE CLINICS, EXAMINING HOW TO MAKE TESTING AS EASY AND EFFICIENT AS POSSIBLE FOR PATIENTS AND PROVIDERS. ONCE THIS STUDY IS COMPLETE, RESEARCHERS HOPE TO IMPLEMENT THIS SCREENING ACROSS VIRGINIA MASON FRANCISCAN HEALTH AND ULTIMATELY MAKE IT A STANDARD PART OF PRIMARY CARE. THIS COULD HELP VAST NUMBERS OF PEOPLE ACROSS THE COUNTRY UNDERSTAND THEIR RISK, START TREATMENT EARLY AND AVOID SEVERE COMPLICATIONS LIKE DIABETIC KETOACIDOSIS IN T1D.THIS STUDY IS FUNDED BY A GENEROUS DONATION FROM THE JOLENE MCCAW FAMILY FOUNDATION. NEW FRONTIERS IN TISSUE-SPECIFIC IMMUNOLOGYTRADITIONALLY, SCIENTISTS HAVE STUDIED IMMUNE SYSTEM DISEASES BY LOOKING AT BLOOD SAMPLES. BUT THEY'VE ALSO KNOWN THAT STUDYING THE ACTUAL TISSUE THAT THOSE DISEASES AFFECT THE JOINTS IN RHEUMATOID ARTHRITIS (RA) OR THE SKIN IN SCLERODERMA COULD PROVIDE EVEN MORE INFORMATION. THE PROBLEM IS, TISSUE IS HARD TO COME BY. IT'S MORE FEASIBLE TO COLLECT AND STUDY BLOOD SAMPLES THAN IT IS TO DO THE SAME WITH TISSUE FROM JOINTS OR THE SKIN. THAT'S WHY TISSUE-SPECIFIC IMMUNOLOGY HAS BECOME A CORE FOCUS FOR BRI, EXPLORING NEW WAYS TO STUDY TISSUES IN THE DISEASES WHERE THEY HAPPEN. THANKS TO OUR PARTNERSHIP WITH VIRGINIA MASON FRANCISCAN HEALTH, BRI'S EDDIE JAMES, PHD, IS STUDYING RHEUMATOID ARTHRITIS (RA) IN TISSUE SAMPLES FROM PEOPLE WHO HAVE HAD JOINT REPLACEMENTS. INSTEAD OF DISCARDING THE JOINT TISSUE REMOVED DURING SURGERY, SOME PATIENTS OPT TO DONATE THAT TISSUE TO RESEARCH. DR. JAMES AND HIS TEAM CAN THEN STUDY THAT TISSUE TO BETTER UNDERSTAND EXACTLY WHY IMMUNE SYSTEM CELLS ARE ATTACKING THE JOINTS IN RA AND HOW WE CAN STOP THAT ATTACK TO TREAT OR PREVENT RA. BRI'S PETER MORAWSKI, PHD, AND HIS TEAM STUDY AUTOIMMUNE DISEASES THAT AFFECT THE SKIN INCLUDING PSORIASIS AND SCLERODERMA. THEY STUDY SKIN TISSUE IN THREE DIFFERENT FORMS: 3D ENGINEERED MODELS, DONATED TISSUE SAMPLES FROM PEOPLE WHO HAVE HAD TUMMY TUCKS, AND DONATED PUNCH BIOPSIES (TISSUE SAMPLES ABOUT THE SIZE OF A PENCIL ERASER) FROM PEOPLE WITH AND WITHOUT SCLERODERMA. A GROUNDBREAKING TOOL CALLED SPATIAL TRANSCRIPTOMICS IS HELPING THE TEAM BETTER UNDERSTAND HOW SCLERODERMA STARTS AND PROGRESSES. THIS TECHNOLOGY LETS THE RESEARCHERS LOOK DEEP INTO THE TISSUE AND SEE THE EXACT LOCATIONS OF INDIVIDUAL CELLS, HOW THEY INTERACT, AND EVEN THEIR INDIVIDUAL GENE EXPRESSION. THEY'LL USE THIS TOOL TO STUDY ONE AREA OF SKIN THAT SHOWS SYMPTOMS (SKIN THAT'S THICK, WAXY AND SOMETIMES A DIFFERENT COLOR THAN UNAFFECTED SKIN) AND ANOTHER AREA NOT SHOWING SIGNS OF DISEASE IN THE SAME PERSON. THEN THEY'LL DIRECTLY COMPARE THEM SIDE-BY-SIDE. THIS WILL HELP THE RESEARCH TEAM BETTER UNDERSTAND HOW THE DISEASE STARTS AND PROGRESSES AND MOVE CLOSER TO BETTER TREATMENTS AND PREVENTION. BRI'S JAMES LORD, MD, PHD, IS A PHYSICIAN-RESEARCHER FOCUSED ON INFLAMMATORY BOWEL DISEASES (IBD). ONE OF THE BIGGEST CHALLENGES OF TREATING IBD IS THAT THERE ARE MANY DIFFERENT TREATMENTS AND NO WAY TO KNOW WHICH ONE WILL WORK BEST FOR WHICH PERSON. HIS TEAM IS WORKING TO CHANGE THAT BY STUDYING SMALL BIOPSY SAMPLES FROM COLONOSCOPIES FROM PEOPLE TAKING A MEDICINE CALLED VENDOLIZUMAB FOR IBD. THOSE SAMPLES WILL HELP HIS TEAM BETTER UNDERSTAND EXACTLY WHICH CELLS THE TREATMENT AFFECTS AND WHY IT WORKS FOR SOME PEOPLE BUT NOT OTHERS.