2024-05-10T10:43:53-05:00 2023-06-30 470617373 COMMONSPIRIT HEALTH 198 INVERNESS DRIVE WEST ENGLEWOOD CO 80112 990 2022-07-01 910653422 BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON BENA 2063426500 1201 NINTH AVENUE SEATTLE WA 98101 MICHAEL LABOSIER TREASURER 2063426500 2024-05-10 1 MICHAEL LABOSIER 999009999 1 HEATHER ADKINS P01725376 3032989100 2 AAL1 IAL1 2022 2023-04-26 12:10:37Z JANE BUCKNER MD 1201 NINTH AVENUE SEATTLE WA 981012795 82477055 0 X HTTP://WWW.BENAROYARESEARCH.ORG X 1956 WA TO ADVANCE THE SCIENCE THAT WILL PREDICT, PREVENT, REVERSE, AND CURE DISEASES OF THE IMMUNE SYSTEM. 13 13 353 0 0 0 78966995 75771314 5286187 5702614 9899625 282812 708469 708503 94861276 82465243 33518144 31762808 0 0 33277902 34326207 0 0 0 16989508 17237972 83785554 83326987 11075722 -861744 100143058 94354363 45307373 42735678 54835685 51618685 X TO ADVANCE THE SCIENCE THAT WILL PREDICT, PREVENT, REVERSE, AND CURE DISEASES OF THE IMMUNE SYSTEM SUCH AS AUTOIMMUNE DISEASE, ALLERGY, AND ASTHMA. 0 0 39677626 24639484 0 INTERVENTIONAL IMMUNOLOGYINTERVENTIONAL 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 DISEASE (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.DURING THIS PERIOD, MAJOR ACTIVITIES REMAINED DIVERSE BUT CONTINUED TO CENTER AROUND MAINTAINING THE ITN'S COHESIVE, PROJECT-FOCUSED ENVIRONMENT, WHICH HAS BEEN HIGHLY SUCCESSFUL IN MANAGING THIS LARGE COOPERATIVE AGREEMENT GRANT.KEY OUTCOMES DURING THIS PERIOD INCLUDE:1. LEADERSHIP CHANGES: WITH THE CHANGES TO THE OVERALL ITN LEADERSHIP STRUCTURE OUTLINED IN THE 2021 GRANT APPLICATION FULLY IMPLEMENTED. DR. JERRY NEPOM STEPPED DOWN AS THE NETWORK DIRECTOR AND PRINCIPAL INVESTIGATOR, AND ALTHOUGH NOW RETIRED, REMAINS INVOLVED WITH THE ITN IN A SENIOR ADVISOR ROLE. THE PRIMARY INVESTIGATOR FOR THE UM1 GRANT IS NOW DR. JANE BUCKNER, PRESIDENT OF BRI. SHE ALSO SERVES ON THE ITN STEERING COMMITTEE AND THE ITN NETWORK EXECUTIVE COMMITTEE, PLAYING AN ACTIVE ROLE IN TRACKING PROGRESS TOWARDS NETWORK GOALS AND DEVELOPING STRATEGIES TO MEET NETWORK OBJECTIVES. THE FUNCTION OF THE NETWORK DIRECTOR'S OFFICE AT BRI CONTINUES WITH NO CHANGES, EXCEPT FOR A NAME CHANGE TO THE ITN COORDINATING CENTER. THE NETWORK DIRECTOR POSITION MOVED TO DR. MARK ANDERSON AT UCSF, FUNDED THROUGH A SUBAWARD FROM THE BRI ITN COORDINATING CENTER. 2. THE ITN CROSS-NETWORK INTEGRATION: SINCE 2014, DR. NEPOM HAS LED THE ITN WITH A STRONG FOCUS ON METICULOUS PLANNING AND COLLABORATION ACROSS THE ITN'S MAJOR CENTERS, LOCATED IN SEATTLE (BRI), SAN FRANCISCO (UCSF), DURHAM, NC (DUKE), BOSTON (BWH), ATLANTA (EMORY), AND ANN ARBOR (U OF MICHIGAN). EFFECTIVE COLLABORATION WAS PARTICULARLY EVIDENT WHEN, DESPITE THE GLOBAL PANDEMIC, THE ITN CONDUCTED ITS NETWORK STEERING COMMITTEE (NSC) REMOTELY, APPROVING FIVE NEW CLINICAL TRIALS DURING THE REPORTING PERIOD. IN 2022/2023, THE ITN RETURNED TO CONDUCTING IN-PERSON NSC MEETINGS, WHICH CONTINUED WITHOUT INTERRUPTION. WITH STRONG APPROVAL FROM NIAID FOR THE ITN'S OVERALL INFRASTRUCTURE AND THE DESIRE TO KEEP THE COORDINATING CENTER OPERATIONS AT BRI WITH DR. BUCKNER, THERE ARE NO PLANNED CHANGES THROUGHOUT THE CURRENT GRANT CYCLE, WHICH EXTENDS UNTIL 2027.3. OPERATIONS AND CLINICAL TRIAL SUPPORT: THE ITN COORDINATING CENTER AT BRI ISSUED OVER 250 SUBAWARDS DURING THIS REPORTING PERIOD TO SUPPORT 24 ACTIVE ITN CLINICAL TRIALS AND NUMEROUS SUPPORTING ITN MECHANISTIC TRIALS. AN ADDITIONAL 22 SUBAWARDS WERE NEGOTIATED IN SUPPORT OF THE TWO REMAINING NIAID COVID TRIALS.4. SUPPLEMENTAL FUNDING / PARTNERSHIPS: THE ITN COORDINATING CENTER CONTINUED TO FOCUS ON IDENTIFYING ADDITIONAL OPPORTUNITIES FOR SUPPLEMENTAL FUNDING AND FUNDING PARTNERSHIPS. NEGOTIATIONS FOR A PARTNERSHIP TO PROVIDE PARTIAL FINANCIAL SUPPORT FOR AT LEAST ONE CLINICAL TRIAL IN DEVELOPMENT ARE ACTIVELY UNDERWAY.DURING THIS REPORTING PERIOD, THE ITN ALSO SUPPORTED THE CONTRACTING COMPONENT FOR TWO NIAID-SPONSORED COVID-19 CLINICAL TRIALS FUNDED THROUGH ADMINISTRATIVE SUPPLEMENTS. BOTH TRIALS ARE ON TRACK TO CONCLUDE BY Q4 2024:(A) SUPPLEMENTAL FUNDING OPPORTUNITIES: THE ITN COORDINATING CENTER AT BRI SUBMITTED TWO SUPPLEMENTAL FUNDING REQUESTS IN 2022, WHICH WERE CARRIED OVER INTO 2023. THESE SUPPLEMENTS ACCOUNT FOR AN ADDITIONAL $7 MILLION ALLOCATED TO THE ITN PROGRAM AT BRI DURING THIS TIME PERIOD.(B) PARTNERSHIPS: THE ITN CONTINUED ITS PARTNERSHIP WITH PHARMACEUTICAL COMPANY FOR PARTIAL FUNDING FOR AN ITN STUDY. NIAID IS THE CLINICAL SPONSOR OF THIS TRIAL, WHICH IS PROGRESSING AS PLANNED FOR COMPLETION IN Q2 2024.5. PUBLICATION ACTIVITY: IN TOTAL, 44 ITN PUBLICATIONS WERE PUBLISHED DURING THIS REPORTING PERIOD IN PRESTIGIOUS RESEARCH JOURNALS AND WERE PRESENTED AT DOMESTIC AND INTERNATIONAL RESEARCH CONFERENCES. THESE PUBLICATIONS REPRESENTED ITN RESEARCH IN ALL THERAPEUTIC FOCUS AREAS: AUTOIMMUNITY, TRANSPLANTATION, AND ALLERGY. 21063694 6517681 0 TYPE ONE DIABETES RESEARCHBRI IS DEDICATED TO SEEKING WAYS TO ELIMINATE TYPE 1 DIABETES (T1D) BY FINDING WAYS TO PREDICT THE DISEASE BEFORE CLINICAL SYMPTOMS OCCUR AND TO IDENTIFY THERAPIES THAT PREVENT, REVERSE AND INTERVENE IN THE DISEASE AT ANY STAGE. BRI IS AN INTERNATIONAL LEADER IN TYPE 1 DIABETES RESEARCH AND HAS INVESTIGATED IT FOR MORE THAN 36 YEARS, STARTING WITH IDENTIFICATION OF A GENETIC MARKER FOR THE DISEASE. BRI SUPPORTS TYPE 1 DIABETES TRIALNET, A NATIONAL INSTITUTES OF HEALTH FUNDED CLINICAL TRIAL NETWORK FOR TYPE 1 DIABETES PREVENTION AND EARLY TREATMENT, SERVING AS THE TRIALNET HUB OF 18 CLINICAL CENTERS WORLDWIDE WORKING WITH MORE THAN 150 SCREENING AND CLINICAL RESEARCH SITES. BRI IS ALSO A CLINICAL CENTER FOR THE TRIALNET PATHWAY TO PREVENTION STUDY, SCREENING RELATIVES OF PEOPLE WITH TYPE 1 DIABETES TO FIND OUT IF THESE FAMILY MEMBERS ARE AT RISK FOR DEVELOPING DIABETES. RELATIVES OF PEOPLE WITH TYPE 1 DIABETES ARE AT 15 TIMES GREATER RISK OF DEVELOPING TYPE 1 DIABETES. THOSE WHO QUALIFY HAVE THE OPPORTUNITY TO ENROLL IN A PREVENTION TRIAL. THOSE WITH TWO OR MORE AUTOANTIBODIES ARE CLOSELY MONITORED FOR EARLY DETECTION OF TYPE 1 DIABETES. CLOSE MONITORING OF AT-RISK FAMILY MEMBERS CAN REDUCE THE CHANCES OF BEING DIAGNOSED IN DIABETIC KETOACIDOSIS (DKA), A POTENTIALLY LIFE-THREATENING COMPLICATION. BRI SCIENTISTS LED BY CARLA GREENBAUM, MD, DIRECTOR OF BRI'S CENTER FOR INTERVENTIONAL IMMUNOLOGY, ALONG WITH THE TRIALNET CONSORTIUM SPENT DECADES TRYING TO DETERMINE HOW TO STOP T1D BEFORE IT STARTS. THEIR HARD WORK CAME TO FRUITION IN NOVEMBER 2022, WHEN THE FDA APPROVED A THERAPY THAT MARKED A MILESTONE IN PREVENTING T1D. THE THERAPY, TEPLIZUMAB, CAN DELAY T1D FOR A MEDIAN OF TWO YEARS. IT IMPACTS T CELLS IN THE IMMUNE SYSTEM, DAMPENING THE IMMUNE RESPONSE. IN T1D, THE IMMUNE SYSTEM IS ATTACKING THE INSULIN-PRODUCING BETA CELLS; TEPLIZUMAB HELPS SLOW THE ATTACK ON THESE CELLS.AND, A STUDY LED BY BRI'S CATE SPEAKE, PHD, FOUND THAT INTERVENTIONS INVOLVING IL-6-TARGETED THERAPIES IMPACTED IMMUNE OUTCOMES IN PEOPLE WITH T1D, DEPENDING ON THE TARGET OF THE THERAPEUTIC INTERVENTIONS (IL-6 VERSUS IL-6R) AND DRUG CONCENTRATION. THE FINDINGS INDICATE THAT THESE THERAPIES DRIVE T CELL CHANGES THAT CAN INFLUENCE THERAPEUTIC OUTCOMES.ALSO IN 2022, BRI SCIENTISTS ALONG WITH INVESTIGATORS AT SEATTLE CHILDREN'S RESEARCH INSTITUTE MADE A SIGNIFICANT ADVANCE IN DEVELOPING A T CELL THERAPY TO T1D TREAT TYPE 1 DIABETES (T1D). THE STUDY, PUBLISHED IN OCTOBER 2022 IN SCIENCE TRANSLATIONAL MEDICINE, OUTLINED AN APPROACH TO ENGINEER REGULATORY T CELLS (TREGS) TO STOP THE IMMUNE CELL ATTACK ON THE PANCREAS THAT CAUSES T1D.DR. JANE BUCKNER, PRESIDENT OF BRI, AND DR. DAVID RAWLINGS, DIRECTOR OF THE CENTER FOR IMMUNITY AND IMMUNOTHERAPY AT SEATTLE CHILDREN'S RESEARCH INSTITUTE, AND THEIR TEAMS HAD WORKED TOWARD THIS GOAL FOR MORE THAN TEN YEARS. FIRST, THEY DEVELOPED GENE EDITING METHODS TO MANUFACTURE HUMAN TREGS, AN IMPORTANT STEP FOR OVERCOMING CHALLENGES WITH PURIFYING AND EXPANDING TREGS FROM BLOOD FOR CLINICAL PRODUCTION. THIS WORK DEMONSTRATED THAT ENGINEERED TREGS (ENGTREGS) WERE FUNCTIONAL, SUPPRESSING THE IMMUNE RESPONSE IN PRE-CLINICAL MODELS OF INFLAMMATORY DISEASES.THE NEXT STEP WAS TO MAKE THESE ENGTREGS SPECIFIC TO THE PANCREAS, SO THAT THEY WOULD GO TO THE PANCREAS AND SUPPRESS THE AUTOIMMUNE RESPONSE THAT CAUSES T1D. TO DO THIS, THE SCIENTISTS USED THEIR KNOWLEDGE OF T CELL RECEPTORS (TCRS), PROTEINS ON THE T CELL SURFACE THAT DETERMINE THE TARGET OF T CELLS. THEY COMBINED GENE EDITING WITH GENE TRANSFER OF TCRS TO GENERATE ENGTREGS THAT SPECIFICALLY TARGET THE ISLET IN THE PANCREAS.DR. SOO JUNG YANG IN DR. BUCKNER'S LAB DEMONSTRATED THAT THESE ISLET-SPECIFIC ENGTREGS HAVE THE CAPACITY TO SUPPRESS T CELLS ATTACKING THE PANCREAS USING CELL CULTURE MODELS OF CELLS ISOLATED FROM INDIVIDUALS WITH T1D. DR. RAWLINGS AND HIS TEAM THEN DEMONSTRATED THAT THESE ISLET-SPECIFIC ENGTREGS TARGET THE PANCREAS AND PREVENT DIABETES IN A MOUSE MODEL OF DIABETES. TOGETHER THESE FINDINGS DEMONSTRATE THE THERAPEUTIC POTENTIAL FOR ISLET-SPECIFIC ENGTREGS IN HUMAN T1D. THIS RESEARCH WAS SPONSORED BY A GRANT FROM THE LEONA M. AND HARRY B. HELMSLEY CHARITABLE TRUST.VIRAL AND POLLUTANT EXPOSURES AND POTENTIAL TREATMENTS FOR PEOPLE AT RISK FOR ASTHMA MATT ALTMAN, MD, MPHIL, WHO CONDUCTS ASTHMA RESEARCH AT BRI AND TREATS ASTHMA PATIENTS AT UW MEDICINE, WAS SENIOR AUTHOR OF A STUDY THAT IDENTIFIED A POTENTIALLY PROMISING NEW ASTHMA TREATMENT FOR URBAN KIDS AT RISK FOR THE DISEASE. THE STUDY FROM THE INNER-CITY ASTHMA CONSORTIUM (ICAC) FOUND THAT A THERAPY CALLED MEPOLIZUMAB CAN REDUCE ASTHMA ATTACKS AMONG CHILDREN IN LOW-INCOME HISPANIC AND BLACK COMMUNITIES. MEPOLIZUMAB WORKS BY BLOCKING A PROTEIN NECESSARY FOR THE DEVELOPMENT OF EOSINOPHIL, A TYPE OF WHITE BLOOD CELL. IN ANOTHER STUDY, PUBLISHED IN THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, BRI RESEARCHERS IN COLLABORATION WITH SEATTLE CHILDREN'S, THE UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE AND THE UNIVERSITY OF WISCONSIN DISCOVERED WHY INDIVIDUALS WITH ALLERGIC ASTHMA MAY HAVE REDUCED SUSCEPTIBILITY TO COVID-19 AND AN IMPORTANT MECHANISM BY WHICH ALLERGIC INFLAMMATION DIMINISHES SARS-COV-2 INFECTION, DESPITE WELL-KNOWN SUSCEPTIBILITIES TO OTHER RESPIRATORY VIRAL INFECTIONS. ALLERGIC DISEASES SUCH AS ASTHMA ARE CHARACTERIZED BY TYPE-2 INFLAMMATION IN THE AIRWAYS. BRI'S NARESH DONI JAYAVELU, PHD, AND THE RESEARCH TEAM LOOKED AT MECHANISMS WHEREBY TYPE-2 INFLAMMATION IN THE AIRWAY SURPRISINGLY PROTECTS AGAINST SARS-COV-2 IN CHILDREN. THE FINDINGS ALSO ILLUSTRATE A NOTABLE MECHANISM OF INTRINSIC PROTECTION AGAINST SARS-COV-2. SINCE THE STUDY FINDINGS WERE BASED ON IN VITRO CELL CULTURE EXPERIMENTS, DRS. JAYAVELU AND ALTMAN SUBSEQUENTLY BEGAN TO INVESTIGATE TO WHAT DEGREE TYPE-2 INFLAMMATION DECREASES VIRAL REPLICATION AND SEVERE DISEASE IN A LARGE OBSERVATIONAL COHORT THAT WAS ENROLLED AT THE BEGINNING OF THE PANDEMIC TO MORE FULLY UNDERSTAND THE CLINICAL IMPACT OF THEIR RESULTS. THIS RESEARCH WAS FUNDED BY THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, PART OF THE NATIONAL INSTITUTES OF HEALTH, AND OTHER SOURCES, BUILDING ON A PREVIOUS STUDY THAT SET THE GROUNDWORK FOR A HYPOTHETICAL MECHANISM OF PROTECTION. A SEPARATE STUDY FUNDED BY THE NIH LINKED SPECIFIC OUTDOOR AIR POLLUTANTS TO ASTHMA ATTACKS IN URBAN CHILDREN. IN THE STUDY, MODERATE LEVELS OF TWO OUTDOOR AIR POLLUTANTS, OZONE AND FINE PARTICULATE MATTER, WERE ASSOCIATED WITH NON-VIRAL ASTHMA ATTACKS IN CHILDREN AND ADOLESCENTS WHO LIVE IN LOW-INCOME URBAN AREAS. THE STUDY ALSO IDENTIFIED ASSOCIATIONS BETWEEN EXPOSURE TO THE TWO POLLUTANTS AND MOLECULAR CHANGES IN THE CHILDREN'S AIRWAYS DURING NON-VIRAL ASTHMA ATTACKS, SUGGESTING POTENTIAL MECHANISMS FOR THOSE ATTACKS. THIS STUDY WAS CONDUCTED BY THE NIAID-FUNDED INNER CITY ASTHMA CONSORTIUM UNDER THE LEADERSHIP OF DR. ALTMAN ALONG WITH DANIEL J. JACKSON, M.D. OF THE UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE.THE OBSERVATIONAL STUDY IS ONE OF THE FIRST TO LINK ELEVATED LEVELS OF SPECIFIC OUTDOOR AIR POLLUTANTS IN PARTICULAR URBAN LOCATIONS TO DISTINCT CHANGES IN THE AIRWAYS DURING ASTHMA ATTACKS NOT TRIGGERED BY RESPIRATORY VIRUSES, ACCORDING TO THE INVESTIGATORS. THE FINDINGS WERE PUBLISHED IN THE JOURNAL THE LANCET PLANETARY HEALTH.THE SCIENTISTS FOUND THAT ASTHMA ATTACKS HAD A NON-VIRAL CAUSE IN NEARLY 30% OF CHILDREN, TWO TO THREE TIMES THE PROPORTION SEEN IN NON-URBAN CHILDREN, ACCORDING TO PREVIOUSLY PUBLISHED REPORTS. THESE ATTACKS WERE ASSOCIATED WITH LOCALLY ELEVATED LEVELS OF FINE PARTICULATE MATTER AND OZONE IN OUTDOOR AIR. THE INVESTIGATORS LINKED CHANGES IN THE EXPRESSION OF SPECIFIC SETS OF GENES THAT PLAY A ROLE IN AIRWAY INFLAMMATION TO ELEVATED LEVELS OF THESE TWO POLLUTANTS BY ANALYZING NASAL CELL SAMPLES OBTAINED FROM THE CHILDREN DURING RESPIRATORY ILLNESSES. 6363186 448628 0 AUTOIMMUNE DISEASE RESEARCH IN THE DOWN SYNDROME POPULATIONIN OCTOBER 2022, THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) ANNOUNCED A NEW $3.4 MILLION-DOLLAR FIVE-YEAR RESEARCH PROJECT GRANT (R01) TO BRI TO STUDY WHY IMMUNE RESPONSES ARE ALTERED IN THOSE WITH DOWN SYNDROME (DS).BERNARD KHOR, MD, PHD, IN PARTNERSHIP WITH VIRGINIA MASON PEDIATRICIAN AND BRI RESEARCHER REBECCA PARTRIDGE, MD, LEADS THE R01 GRANT THAT BUILDS ON HIS PRIOR FINDINGS THAT ANY GIVEN PERSON WITH DS HAS AN IMMUNE SYSTEM THAT RESEMBLES THAT OF A SIGNIFICANTLY OLDER INDIVIDUAL WITHOUT DS. WITH THIS GRANT, HE WILL EXAMINE THE MECHANISMS BEHIND ADVANCED IMMUNE AGING AND EXPLORE HOW THIS IMPACTS CLINICALLY RELEVANT RESPONSES, SUCH AS THE ABILITY TO MOUNT AN EFFECTIVE RESPONSE TO VACCINATION. HIS WORK IS MADE POSSIBLE BY THE BRI BIOREPOSITORIES OF BLOOD AND TISSUE SAMPLES FROM PEOPLE WITH DS.IN HIS PREVIOUS STUDIES, DR. KHOR AND HIS TEAM USED MASS CYTOMETRY TO EXAMINE THE IMMUNE SYSTEMS OF 28 PEOPLE WITH DS AND, THROUGH THE CREATION OF A NEW ANALYTICAL SOFTWARE, SHOWED HOW THESE IMMUNE SYSTEMS SHARE CHARACTERISTICS WITH THOSE OF MUCH OLDER SUBJECTS WHO DO NOT HAVE DS, AS WELL AS WITH INDIVIDUALS WITH CERTAIN AUTOIMMUNE DISEASES. FOR THE FIRST TIME, A PROTEIN CALLED IL-6 WAS ASSOCIATED WITH CHANGES THAT DRIVE AGING OF THE IMMUNE SYSTEM.THE TEAM BELIEVES THEIR FINDINGS MAY ALSO HELP EXPLAIN WHY PEOPLE WITH DS ARE MORE LIKELY TO DEVELOP AUTOIMMUNE DISEASES SUCH AS TYPE 1 DIABETES, CELIAC DISEASE AND RHEUMATOID ARTHRITIS. 1948500 157015 5702614 EXAMINING THE IMMUNE SYSTEM IN HEALTH AND DISEASE BRI ALONG WITH COLLABORATORS AT THE UW PUBLISHED FINDINGS IN THE JOURNAL OF EXPERIMENTAL MEDICINE THAT ILLUSTRATE A NOVEL MECHANISM FOR THE ROLE OF REGULATORY T CELLS (TREGS) IN MAINTAINING BALANCE IN A HEALTHY IMMUNE SYSTEM. TREGS PREVENT THE IMMUNE SYSTEM FROM OVERREACTING TO HARMLESS SUBSTANCES AND FROM REACTING TO THE BODY'S OWN CELLS, WHICH LEADS TO AUTOIMMUNITY. WHILE SEVERAL MECHANISMS FOR HOW TREGS SUPPRESS IMMUNE SYSTEM ACTIVATION HAVE BEEN PROPOSED, THE MOLECULAR CHANGES THAT TREGS INDUCE TO SUPPRESS THE IMMUNE RESPONSE HAVE PREVIOUSLY REMAINED UNCLEAR. THE NEW RESULTS SHOWED THAT WHEN TREGS INTERACT WITH CD4 EFFECTOR T CELLS (TEFFS), THE CELLS THAT PROMOTE AN INFLAMMATORY RESPONSE, THEY SUPPRESS PROTEIN SYNTHESIS, PREVENTING CELL DIVISION AND THE PRODUCTION OF MORE TEFFS.STEVEN ZIEGLER, PHD, BRI PRINCIPAL INVESTIGATOR AND CO-AUTHOR ON THE STUDY, NOTED THE RESEARCH FURTHERS UNDERSTANDING OF HOW TREGS WORK IN THE BODY TO MAINTAIN IMMUNE BALANCE.DR. BUCKNER, ALSO A CO-AUTHOR ON THE STUDY, SAID THE RESULTS FURTHER OUR UNDERSTANDING OF HOW TREGS WORK TO CONTROL INFLAMMATION AND HOW WE CAN ENHANCE THEM TO SUPPRESS THE DEVELOPMENT OF AUTOIMMUNE DISEASES.IN RESEARCH PUBLISHED IN SCIENCE IMMUNOLOGY, SCIENTISTS FROM BRI WITH COLLABORATORS AT PENNSYLVANIA STATE UNIVERSITY COLLEGE OF MEDICINE SHOWED THAT THYMIC STROMAL LYMPHOPOIETIN (TSLP) SIGNALING REGULATES GERMINAL CENTER (GC) FUNCTION. DURING AN INFECTION, GCS FORM IN THE SECONDARY LYMPHOID TISSUES, SUCH AS THE LYMPH NODES, TONSILS AND SPLEEN, AMONG OTHER TISSUES. THESE GCS ARE DYNAMIC MICROENVIRONMENTS THAT OPTIMIZE ANTIGEN SPECIFICITY OF B CELLS AND WHOSE ACTIVITY RESULTS IN LONG-LIVED AND HIGH-AFFINITY ANTIBODIES, WHICH ULTIMATELY PROVIDES LONG-TERM IMMUNITY AGAINST INFECTION. YET, THE SIGNALING MOLECULES THAT REGULATE GC FUNCTION ARE STILL BEING IDENTIFIED.STEVEN ZIEGLER, PHD, BRI PRINCIPAL INVESTIGATOR AND CO-AUTHOR ON THE STUDY, SAID THAT IN ADDITION TO IDENTIFYING TSLP AS A NOVEL REGULATOR OF THE GC, THE TEAM WAS ABLE TO DEMONSTRATE HOW THE TSLP SIGNALING PATHWAY IMPACTS B AND T CELL RESPONSES SEPARATELY TO REGULATE THE GC AND THE MAGNITUDE AND QUALITY OF ANTIBODY RESPONSES.PHILLIP DOMEIER, PHD, BRI POST-DOCTORAL SCIENTIST AND CO-AUTHOR ON THE STUDY, NOTED THAT THE STUDY COULD SERVE AS A FOUNDATION FOR FUTURE RESEARCH ON VACCINES, ALLERGIES AND AUTOIMMUNE DISEASES. 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 2,264 STUDY PARTICIPANTS INTO VIRGINIA MASON TRIALS.ESTABLISHED IN 2023, THE INNOVATION FUND AWARD IS TO BE GIVEN TWICE A YEAR TO INTERNAL RECIPIENTS AT BRI. THE OBJECTIVE IS TO FACILITATE DEVELOPMENT AND IMPLEMENTATION OF NEW TECHNOLOGIES THAT WILL ADVANCE WORK ACROSS OUR INSTITUTION, THROUGH THE FUNDING OF COLLABORATIVE PROJECTS.. EACH AWARD IS TO BE FUNDED FROM PHILANTHROPIC GIFTS.BRI'S REGULAR TRACK AND RESEARCH TRACK FACULTY ARE AWARD ELIGIBLE. PROJECTS ARE REQUIRED TO INCLUDE TWO OR MORE BRI FACULTY AND ADDRESS INNOVATIONS USEFUL TO MULTIPLE RESEARCH GROUPS WITHIN THE INSTITUTE. FURTHER, IT IS REQUIRED THAT THE PROTOCOLS AND RESULTS GENERATED IN THE PROJECT WILL BE MADE AVAILABLE TO ALL BRI INVESTIGATORS. THE FIRST AWARDEES, JOHN RAY, PHD, AND JESSICA HAMERMAN, PHD, DEVELOPED METHODS TO CARRY OUT LARGE GENETIC SCREENS IN SINGLE CELLS FROM THEIR RESPECTIVE LABS AND THROUGH COLLABORATION BETWEEN THE SYSTEMS AND FUNDAMENTAL IMMUNOLOGY CENTERS. THEIR PROJECT BROUGHT TOGETHER TWO MAJOR ADVANCES IN GENOMICS: SINGLE CELL SEQUENCING TO PROFILE MANY DIFFERENT CELLS AT ONCE, AND CRISPR UTILIZED TO MODIFY GENES IN IMMUNE CELLS AND SEE THEIR EFFECTS. THEIR APPROACH ALLOWS US TO UNDERSTAND HOW GENES AND GENE VARIANTS ASSOCIATED WITH COMPLEX DISEASES IMPACT THE IMMUNE SYSTEM AS WELL AS DISEASE PROCESSES IN HUMAN CELLS AND ANIMAL MODELS. 1948500 157015 5702614 69053006 1 1 0 1 0 0 0 0 0 0 1 1 0 0 1 1 0 1 0 0 1 1 0 0 0 0 0 1 0 1 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 46 0 1 353 1 0 0 0 0 0 0 0 0 0 0 0 0 X 13 13 0 0 0 0 1 1 1 1 1 0 0 0 1 1 1 1 1 1 1 0 WA X MICHAEL LABOSIER CFO 2063426505 1201 NINTH AVENUE SEATTLE WA 98101 KETUL PATEL CHIEF EXECUTIVE OFFICER VMFH 10.00 2.00 X 3067968 0 29536 JANE BUCKNER MD PRESIDENT 40.00 0.00 X 542818 0 28212 MARGARET MCCORMICK PHD EXECUTIVE DIRECTOR & COO 40.00 0.00 X 291304 0 31548 WILLIAM KWOK PHD RESEARCH MEMBER 40.00 0.00 X 275293 0 30612 STEVEN ZIEGLER PHD DIRECTOR, ACADEMIC AFFAIRS 40.00 0.00 X 265710 0 25235 MICHAEL LABOSIER CFO 40.00 0.00 X 222274 0 33674 DANIEL CAMPBELL PHD DIRECTOR, CENTER FOR FUNDAMENTAL IMMUNOLOGY 40.00 0.00 X 221949 0 20034 CARMEN MIKACENIC MD ASSOCIATE RESEARCH MEMBER 40.00 0.00 X 216914 0 27748 JAMES LORD RESEARCH ASSISTANT MEMBER 40.00 0.00 X 213844 0 24228 BOB CARLILE DIRECTOR 2.00 2.00 X 0 0 0 ULI CHI PHD DIRECTOR/CHAIR 2.00 2.00 X X 0 0 0 SISTER JUDE CONNELLY OSF DIRECTOR 2.00 2.00 X 0 0 0 CAROLYN CORVI DIRECTOR 2.00 2.00 X 0 0 0 SISTER RUTH GOODWIN OSF DIRECTOR 2.00 2.00 X 0 0 0 TOD HAMACHEK DIRECTOR 2.00 2.00 X 0 0 0 MICHAEL HOFFMAN DIRECTOR (THRU 12/31/22) 2.00 2.00 X 0 0 0 DENNIS HUNTHAUSEN DIRECTOR 2.00 2.00 X 0 0 0 KAREN LEE DIRECTOR 2.00 2.00 X 0 0 0 ROBERT LEMON DIRECTOR/VICE CHAIR 2.00 2.00 X X 0 0 0 GREGG MEYER MD MSC DIRECTOR 2.00 2.00 X 0 0 0 JOHN OPPENHEIMER DIRECTOR 2.00 2.00 X 0 0 0 MARVIN O'QUINN DIRECTOR 2.00 2.00 X 0 0 0 DIANN PULS DIRECTOR 2.00 2.00 X 0 0 0 MIRIAM CHAMBLISS CORPORATE SECRETARY / VP DIV GENERAL COUNSEL 2.00 2.00 X 0 0 0 DAVID NOSACKA TREASURER / SVP & CFO VMFH 0.00 2.00 X 0 0 0 5318074 0 250827 80 0 1 1 INFINITY BIOLOGIX LLC PO BOX 23532 NEW YORK NY 100873532 LABORATORY SERVICES 565530 NORTH FORK HOLDNGS LLC 1933 N MEACHAM RD STE 220 SCHAUMBURG IL 60173 IT CONSULTING SERVICES 123571 DAVIS WRIGHT TREMAINE 920 FIFTH AVE SUITE 3300 SEATTLE WA 981041610 LEGAL SERVICES 113661 3 57335563 18435751 75771314 COMMERCIAL STUDIES 621500 4631252 4631252 0 0 EXTERNAL CORE INCOME 621500 1071362 1071362 0 0 5702614 221304 221304 708503 0 708503 708503 708503 73320 0 11812 73320 -11812 61508 61508 82465243 5702614 0 991315 29385333 29385333 2377475 2377475 1350348 721434 628914 24832360 17432538 7399822 2176220 1492422 683798 4085116 2801517 1283599 1882163 1290762 591401 17780 17780 2785558 2271324 514234 5012 12 5000 81078 19722 61356 2116340 828792 1287548 3356020 2840776 515244 326310 281250 45060 102669 84402 18267 911481 792989 118492 1159407 982409 176998 203971 63314 140657 MEDICAL SUPPLIES 3928476 3837397 91079 0 PATIENT COSTS 1167239 1167239 0 0 MISCELLANEOUS EXPENSES 501383 66903 434480 0 OTHER PURCHASED SERVICE 364934 105948 258986 0 210314 209048 1266 83326987 69053006 14273981 0 5284443 8265497 265617 1478988 12547565 8245451 2609477 984414 0 0 0 0 933865 937229 30996619 2369584 28368284 28627035 4828401 11284790 43567602 33041866 0 0 1737804 1489093 100143058 94354363 5302398 6437799 0 8974466 6319599 28998108 28272047 0 0 0 0 2032401 1706233 45307373 42735678 X 17597685 16899685 37238000 34719000 54835685 51618685 100143058 94354363 -861744 -2355256 0 X 0 1 X 1 1 1 X VIRGINIA MASON MEDICAL CENTER SEATTLE WA 62867601 60664155 34152956 78966994 75771314 312423020 62867601 60664155 34152956 78966994 75771314 312423020 21441891 290981129 945520 1174418 525133 8844594 929807 12419472 9656398 6105766 3157242 5286187 5702614 29908207 354750699 0.82020 0.80750 X SCHEDULE A, PART II, LINE 10, EXPLANATION OF OTHER INCOME: CLINICAL RESEARCH PROGRAM REVENUE - 2018 AMOUNT: $ 4,280,875. 2019 AMOUNT: $ 5,569,393. 2020 AMOUNT: $ 2,665,138. 2021 AMOUNT: $ 4,732,659. 2022 AMOUNT: $ 4,631,252. COLLABORATIVE RESEARCH AGREEMENT PROJECTS - 2018 AMOUNT: $ 4,453,944. EXTERNAL CORE INCOME - 2018 AMOUNT: $ 886,743. 2019 AMOUNT: $ 430,308. 2020 AMOUNT: $ 394,817. 2021 AMOUNT: $ 553,528. 2022 AMOUNT: $ 1,071,362. MISCELLANEOUS INCOME - 2018 AMOUNT: $ 34,836. 2019 AMOUNT: $ 106,065. 2020 AMOUNT: $ 97,287. RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED X 142625 11240 153865 1235710652 1235864517 1000000 250000 0 0 1000000 1000000 1000000 1000000 4000000 6000000 209447 205420 219020 153865 787752 250000 1000000 250000 250000 1750000 2625000 129023 126542 203020 142625 601210 0 1 14110000 14110000 12362749 864139 11498610 4205998 1505445 2700553 317872 317872 28627035 INTEREST IN NET ASSETS OF VIRGINIA MASON MEDICAL CENTER 33041866 F 33041866 LEASE LIABILITY (RELATES TO RIGHT-OF-USE ASSET) 1597822 DUE TO RELATED PARTIES 108411 1706233 X PART X, LINE 2: BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON'S FINANCIAL INFORMATION IS INCLUDED IN COMMONSPIRIT HEALTH'S CONSOLIDATED AUDITED FINANCIAL STATEMENTS, WHICH INCLUDES THE FOLLOWING DISCLOSURE: COMMONSPIRIT REVIEWS ITS TAX POSITIONS QUARTERLY AND HAS DETERMINED THAT THERE ARE NO MATERIAL UNCERTAIN TAX POSITIONS THAT REQUIRE RECOGNITION IN THE ACCOMPANYING CONSOLIDATED FINANCIAL STATEMENTS. PART X, LINE 1 IN ACCORDANCE WITH ASC TOPIC 842 LEASES, THE RESEARCH INSTITUTE ADOPTED THE LEASE STANDARD AND RECORDED LEASE LIABILITIES OVER THE LEASE TERMS BETWEEN 3 AND 10 YEARS. THE LEASES ARE PRIMARILY FOR REAL ESTATE, INCLUDING OFF-CAMPUS OUTPATIENT FACILITIES, MEDICAL OFFICE BUILDINGS, AND CORPORATE AND ADMINISTRATIVE OFFICES. PART V ENDOWMENT FUNDS BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON'S (BRI) SOLE CORPORATE MEMBER IS VIRGINIA MASON FRANCISCAN HEALTH (VMFH). VMFH IS A SUPPORTING ORGANIZATION OF BRI AND VIRGINIA MASON MEDICAL CENTER (VMMC). VMMC HOLDS ENDOWMENT FUNDS THAT SUPPORT BRI RESEARCH AIMED AT DIABETES, RHEUMATOLOGY, IMMUNOLOGY, AND OTHER RESEARCH. THE BALANCE OF THESE ENDOWMENTS WAS $36.0 MILLION AND $33.0 MILLION ON JUNE 30, 2022 AND JUNE 30, 2023, RESPECTIVELY. 1 EUROPE (INCLUDING ICELAND AND GREENLAND) 0 0 GRANT MEDICAL RESEARCH 2243875 EAST ASIA AND THE PACIFIC 0 0 GRANT MEDICAL RESEARCH 133600 0 0 0 0 0 0 2377475 0 2377475 EUROPE (INCLUDING ICELAND AND GREENLAND) GENERAL SUPPORT 325612 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND AND GREENLAND) GENERAL SUPPORT 1483977 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND AND GREENLAND) GENERAL SUPPORT 46052 WIRE TRANSFER 0 EUROPE (INCLUDING ICELAND AND GREENLAND) GENERAL SUPPORT 388235 WIRE TRANSFER 0 EAST ASIA AND THE PACIFIC GENERAL SUPPORT 133600 WIRE TRANSFER 0 5 0 0 0 0 0 0 PART III ACCOUNTING METHOD: PART I, LINE 2: SUB-RECIPIENT MONITORING POLICY -MEDICAL RESEARCH SUB AWARD BRI HAS FORMAL POLICIES AND PRODECURES TO ASSURE FULL COMPLIANCE WITH APPLICABLE POLICIES AND LAWS GOVERNING FEDERAL GRANTS. THE SUB-RECIPIENT MONITORING POLICY PROVIDES ASSURANCE THAT SUB-RECIPIENTS COMPLY WITH FEDERAL GRANT REGULATIONS. THIS POLICY SETS THE CRITERIA TO ESTABLISH ELIGIBILITY OF SUB-RECIPIENTS TO PROVIDE ANNUAL AUDITED FINANCIAL REPORTS AND THE ANNUAL OMB SINGLE AUDIT REPORT THAT IDENTIFY COMPLIANCE WITH FEDERAL LAWS AND REGULATIONS. THE REPORTS ARE ANALYZED WITH EMPHASIS ON AUDITOR'S ASSESSMENT OF SUB-RECIPIENT INTERNAL CONTROLS AND A STANDARDIZED RISK ASSESSMENT IS PRESENTED TO MANAGEMENT ON EACH SUB-RECIPIENT. A MANAGEMENT LETTER IS ISSUED TO EACH SUB-RECIPIENT SHOWING ANY FINDINGS ON THEIR OMB SINGLE AUDIT REPORT, AND MEASUREMENTS ARE SET FOR INCREASED MONITORING WHEN AN ELEVATED LEVEL OF RISK IS ESTABLISHED. MANAGEMENT HAS COMMUICATED WITH AN EDUCATED ADMINISTRATIVE STAFF REGARDING IMPLEMENTATION OF THIS POLICY. THE DIRECTOR OF GRANTS AND CONTRACTS IS RESPONSIBILE FOR MONITORING SUB-RECIPIENT ADHERENCE TO FINANCIAL REGULATIONS. THE PRINCIPAL INVESTIGATOR IS RESPONSIBLE FOR OVERSEEING THE SATISFACTORY PERFORMANCE OF THE SUB-AWARD TO ENSURE THAT GOALS ARE ACHIEVED. IF THERE ARE UNUSUAL OR UNFORESEEN ITEMS, THESE WILL BE INVESTIGATED. PART 1, LINE 3F THE EXPENDITURES WERE ACTUAL EXPENSES INCURRED IN THE REGION BASED ON INDIVIDUAL EXPENSE REPORTS AND TRACKING OF EXPENDITURES BY GRANT OR DEPARTMENT ON THE ACCRUAL BASIS OF ACCOUNTING. PART II, LINE 1 THE EXPENDITURES WERE EXPENSES INCURRED IN THE REGION BASED ON AWARD GOALS ON THE ACCRUAL BASIS OF ACCOUNTING. 1 ADVARRA INC PO BOX 74008070 CHICAGO IL 606748070 311358981 170484 0 MEDICAL FND SUPPORT ARKANSAS CHILDREN'S RESEARCH INSTITUTE ONE CHILDRENS WAY FINANCIAL SVCS SLOT 663 LITTLE ROCK AR 722023591 710694931 509C3 41065 0 MEDICAL FND SUPPORT AZENTA LIFE SCIENCES PO BOX 3865 CAROL STEAM IL 601323865 200628587 501C3 1334126 0 MEDICAL FND SUPPORT BAYLOR COLLEGE OF MEDICINE ONE BAYLOR PLAZA SUITE 600-D HOUSTON TX 770303411 741613878 501C3 81590 0 MEDICAL FND SUPPORT BOSTON CHILDREN'S HOSPITAL 300 LONGWOOD AVENUE BOSTON MA 02115 042774441 501C3 316816 0 MEDICAL FND SUPPORT BRIGHAM AND WOMEN'S HOSPITAL BANK OF AMERICA NA PO BOX 3887 BOSTON MA 022413887 042312909 501C3 1437026 0 MEDICAL FND SUPPORT CHILDREN'S HOSPITAL OF PHILADELPHIA PO BOX 8550 LOCKBOX 1457 PHLILADELPHIA PA 191781457 231352166 501C3 14635 0 MEDICAL FND SUPPORT DANA-FARBER CANCER INSTITUTE INC ATTN RESEARCH ACCOUNTING BOSTON MA 02215 042263040 501C3 160790 0 MEDICAL FND SUPPORT DUKE UNIVERSITY PO BOX 602651 CHARLOTTE NC 282602651 560532129 501C3 1767347 0 MEDICAL FND SUPPORT EMORY UNIVERSITY PO BOX 935084 ATLANTA GA 311935084 580566256 501C3 468542 0 MEDICAL FND SUPPORT FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH 350 COMMUNITY DRIVE MANHASSET NY 11030 112673595 501C3 344781 0 MEDICAL FND SUPPORT FRED HUTCHINSON CANCER CENTER 1100 FAIRVIEW AVE NMAILSTOP J6-330 SEATTLE WA 98109 911935159 501C3 523050 0 MEDICAL FND SUPPORT HOSPITAL FOR SPECIAL SURGERY 535 EAST 70TH STREET NEW YORK NY 10021 131624135 501C3 72094 0 MEDICAL FND SUPPORT ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI ONE GUSTAVE L LEVY PLACE BOX 3500 NEW YORK NY 100296574 136171197 501C3 2441029 0 MEDICAL FND SUPPORT IHC HEALTH SERVICES INC 36 SOUTH STATE STREET SUITE 2200 SALT LAKE CITY UT 84111 942854057 110292 0 MEDICAL FND SUPPORT INDIANA UNIVERSITY 620 UNION DRIVE ROOM 618 INDIANAPOLIS IN 462025167 356001673 501C3 45095 0 MEDICAL FND SUPPORT JOHNS HOPKINS UNIVERSITY 12529 COLLECTIONS CENTER DRIVE CHICAGO IL 60693 520595110 501C3 4594301 0 MEDICAL FND SUPPORT JOSLIN DIABETES CENTER ONE JOSLIN PLACE BOSTON MA 022155306 042203836 501C3 18800 0 MEDICAL FND SUPPORT LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT H 1124 W CARSON STREET TORRANCE CA 905022006 952138184 501C3 49727 0 MEDICAL FND SUPPORT MASSACHUSETTS GENERAL HOSPITAL 55 FRUIT STREET BOSTON MA 02114 042697983 501C3 645781 0 MEDICAL FND SUPPORT MAYO CLINIC 200 FIRST STREET SOUTHWEST ROCHESTER MN 55905 416011702 501C3 137750 0 MEDICAL FND SUPPORT MAYO CLINIC JACKSONVILLE 4500 SAN PABLO ROAD JACKSONVILLE FL 32224 593337028 501C3 82893 0 MEDICAL FND SUPPORT METROPLEX CLINICAL RESEARCH CENTER 8144 WALNUT HILL LANE SUITE 810 DALLAS TX 75231 208454424 26190 0 MEDICAL FND SUPPORT MY OWN MED INC 4825 ESSEX AVENUE CHEVY CHASE MD 20815 462108432 501C3 47875 0 MEDICAL FND SUPPORT NATIONAL JEWISH HEALTH 1400 JACKSON STREET M216 DENVER CO 80206 742044647 501C3 264894 0 MEDICAL FND SUPPORT NEW YORK UNIVERSITY-SCHOOL OF MEDICINE PO BOX 415026 BOSTON MA 022415026 135562308 501C3 748533 0 MEDICAL FND SUPPORT NORTHWESTERN UNIVERSITY 633 CLARK ROOM G547 EVANSTON IL 60208 362167817 501C3 27977 0 MEDICAL FND SUPPORT OHIO STATE UNIVERSITY 1960 KENNY ROAD COLUMBUS OH 43210 316025986 501C3 56912 0 MEDICAL FND SUPPORT OHSU-PATIENT BUSINESS SVC PO BOX 3595 PORTLAND OR 97207 931176109 501C3 17133 0 MEDICAL FND SUPPORT REGENTS OF THE UNIVERSITY OF CALIFORNIA AT IRVINE 228 ALDRICH HALL IRVINE CA 926971050 952226406 501C3 35488 0 MEDICAL FND SUPPORT REGENTS OF THE UNIVERSITY OF COLORADO PO BOX 910238 AURORA CO 80045 846000555 501C3 358841 0 MEDICAL FND SUPPORT RESEARCH FOUNDATION OF SUNY 35 STATE STREET ALBANY NY 122072826 141368361 501C3 26056 0 MEDICAL FND SUPPORT RHO FEDERAL SYSTEMS DIVISION INC 2635 E NC HWY 54 DURHAM NC 27713 561927659 49975 0 MEDICAL FND SUPPORT SANFORD RESEARCH 2301 E 60TH ST SIOUX FALLS SD 57104 460450378 501C3 15570 0 MEDICAL FND SUPPORT SEATTLE CHILDREN'S HOSPITAL RESEARCH INSTITUTE 818 STEWART 3RD FLOOR SEATTLE WA 981240728 910564748 501C3 366782 0 MEDICAL FND SUPPORT STANFORD UNIVERSITY PO BOX 884253 LOS ANGELES CA 900884253 941156365 501C3 289711 0 MEDICAL FND SUPPORT SWEDISH HEALTH SERVICES - 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THE SUB-RECIPIENT MONITORING POLICY PROVIDES ASSURANCE THAT SUB-RECIPIENTS COMPLY WITH FEDERAL GRANT REGULATIONS. THIS POLICY SETS THE CRITERIA TO ESTABLISH ELIGIBILITY OF SUB-RECIPIENTS TO PROVIDE ANNUAL AUDITED FINANCIAL REPORTS AND THE ANNUAL OMB SINGLE AUDIT REPORT THAT IDENTIFY COMPLIANCE WITH FEDERAL LAWS AND REGULATIONS. THE REPORTS ARE ANALYZED WITH EMPHASIS ON AUDITOR'S ASSESSMENT OF SUB-RECIPIENT INTERNAL CONTROLS AND A STANDARDIZED RISK ASSESSMENT IS PRESENTED TO MANAGEMENT ON EACH SUB-RECIPIENT. A MANAGEMENT LETTER IS ISSUED TO EACH SUB-RECIPIENT SHOWING ANY FINDINGS ON THEIR OMB SINGLE AUDIT REPORT, AND MEASUREMENTS ARE SET FOR INCREASED MONITORING WHEN AN ELEVATED LEVEL OF RISK IS ESTABLISHED. MANAGEMENT HAS COMMUICATED WITH AN EDUCATED ADMINISTRATIVE STAFF REGARDING IMPLEMENTATION OF THIS POLICY. THE DIRECTOR OF GRANTS AND CONTRACTS IS RESPONSIBILE FOR MONITORING SUB-RECIPIENT ADHERENCE TO FINANCIAL REGULATIONS. THE PRINCIPAL INVESTIGATOR IS RESPONSIBLE FOR OVERSEEING THE SATISFACTORY PERFORMANCE OF THE SUB-AWARD TO ENSURE THAT GOALS ARE ACHIEVED. IF THERE ARE UNUSUAL OR UNFORESEEN ITEMS, THESE WILL BE INVESTIGATED. X X X X 0 1 0 0 0 0 0 0 0 KETUL PATEL CHIEF EXECUTIVE OFFICER VMFH 1348212 0 1189554 0 530202 0 17750 0 11786 0 3097504 0 192482 0 JANE BUCKNER MD PRESIDENT 480808 0 62010 0 0 0 27000 0 1212 0 571030 0 0 0 MARGARET MCCORMICK PHD EXECUTIVE DIRECTOR & COO 271356 0 19948 0 0 0 27000 0 4548 0 322852 0 0 0 WILLIAM KWOK PHD RESEARCH MEMBER 274893 0 400 0 0 0 27000 0 3612 0 305905 0 0 0 STEVEN ZIEGLER PHD DIRECTOR, ACADEMIC AFFAIRS 265310 0 400 0 0 0 20111 0 5124 0 290945 0 0 0 MICHAEL LABOSIER CFO 221874 0 400 0 0 0 27000 0 6674 0 255948 0 0 0 DANIEL CAMPBELL PHD DIRECTOR, CENTER FOR FUNDAMENTAL IMM 220149 0 1800 0 0 0 14634 0 5400 0 241983 0 0 0 CARMEN MIKACENIC MD ASSOCIATE RESEARCH MEMBER 216514 0 400 0 0 0 20500 0 7248 0 244662 0 0 0 JAMES LORD RESEARCH ASSISTANT MEMBER 213444 0 400 0 0 0 19500 0 4728 0 238072 0 0 0 PART I, LINE 3 DURING THE CALENDAR YEAR 2022, COMPENSATION FOR THE TOP MANAGEMENT OFFICIAL WAS ESTABLISHED BY COMMONSPIRIT HEALTH. COMMONSPIRIT HEALTH USED THE FOLLOWING TO ESTABLISH THE TOP MANAGEMENT OFFICIAL'S COMPENSATION: (1) COMPENSATION COMMITTEE; (2) INDEPENDENT COMPENSATION CONSULTANT; (3) COMPENSATION SURVEY OR STUDY; (4) APPROVAL BY THE BOARD OR COMPENSATION COMMITTEE. PART I, LINE 4B CERTAIN REPORTABLE INDIVIDUALS ARE COVERED BY AN EXECUTIVE SEVERANCE POLICY THAT PROVIDES MARKET-STANDARD COMPENSATION, RANGING FROM PAYMENTS OF 9 MONTHS TO 2 YEARS OF BASE COMPENSATION, DEPENDING ON THE EXECUTIVE'S POSITION, IN THE EVENT OF A POSITION ELIMINATION OR OTHER INVOLUNTARY TERMINATION, IN ACCORDANCE WITH THE GUIDELINES OF THE POLICY. DURING THE 2022 CALENDAR YEAR, COMMONSPIRIT HEALTH ("COMMONSPIRIT") MAINTAINED A SUPPLEMENTAL NON-QUALIFIED DEFERRED COMPENSATION PLAN FOR DIVISION CEOS/PRESIDENTS AND OTHER DESIGNATED COMMONSPIRIT EXECUTIVES AT THE LEVEL OF SENIOR VICE PRESIDENT AND ABOVE. DURING 2022 THE FOLLOWING DISTRIBUTIONS WERE MADE BY COMMONSPIRIT FROM THE DEFERRED COMPENSATION PLAN: KETUL J PATEL, $303,924. DUE TO THE "SUPER" VESTING RULES UNDER COMMONSPIRIT'S DEFERRED COMPENSATION PLAN, PARTICIPANTS WHO HAVE MET CERTAIN REQUIREMENTS SUCH AS INVOLUNTARY TERMINATION WITHOUT CAUSE, AGE, AGE AND YEARS OF SERVICE, OR MORE THAN 5 YEARS OF PLAN PARTICIPATION ARE ELIGIBLE TO RECEIVE THEIR 2022 CONTRIBUTIONS IN CASH. THESE CASH PAYOUTS ARE INCLUDED IN THE PARTICIPANT'S REPORTABLE COMPENSATION IN COLUMN (III) OTHER REPORTABLE COMPENSATION ON SCHEDULE J PART II. DURING 2022, THE FOLLOWING PAYMENTS WERE MADE PURSUANT TO THE SUPER VESTING RULES: KETUL J PATEL, $212,946. SCHEDULE J, PART II: BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON FOLLOWS COMMONSPIRIT'S EXECUTIVE COMPENSATION PHILOSOPHY. COMMONSPIRIT'S EXECUTIVE COMPENSATION PHILOSOPHY IS DESIGNED TO ASSIST COMMONSPIRIT IN ATTRACTING AND RETAINING THE CALIBER OF EXECUTIVES REQUIRED TO ENABLE COMMONSPIRIT TO FULFILL ITS MISSION OF PROVIDING HIGH QUALITY HEALTHCARE FOR ALL PERSONS REGARDLESS OF THEIR ABILITY TO PAY FOR SERVICES, IMPROVING THE QUALITY OF LIFE IN THE COMMUNITIES COMMONSPIRIT SERVES, PROMOTING PATIENT AND EMPLOYEE SATISFACTION, AND ENSURING FINANCIAL STABILITY. A SUBSTANTIAL PORTION OF EXECUTIVE COMPENSATION IS PERFORMANCE BASED AND IS LINKED TO ORGANIZATIONAL GOALS APPROVED IN ADVANCE BY THE HUMAN RESOURCES AND COMPENSATION COMMITTEE. THESE GOALS INCLUDE ATTAINMENT OF ANNUAL AND LONG-TERM FINANCIAL PERFORMANCE, CERTAIN HEALTHCARE QUALITY STANDARDS AND COMMONSPIRIT'S COMMITMENT TO SERVING THE POOR AND DISENFRANCHISED IN THE COMMUNITIES IT SERVES. TOTAL COMPENSATION, WHICH INCLUDES BASE SALARY, ANNUAL, AND LONG-TERM INCENTIVE COMPENSATION, IS ESTABLISHED TO APPROXIMATE THE PREVAILING MARKET CONDITIONS FOR EXECUTIVES OF COMPANIES OF SIMILAR SIZE, REVENUES AND COMPLEXITY. PAYMENTS PURSUANT TO A LONG-TERM FINANCIAL PERFORMANCE GOAL WERE PAID IN CALENDAR YEAR 2022. KETUL PATEL WAS COMPENSATED BY COMMONSPIRIT HEALTH FOR HIS SERVICES TO BENAROYA RESEARCH INSTITUTE. FOR 990 PURPOSES, COMMONSPIRIT HEALTH IS AN UNRELATED ORGANIZATION, SO COMPENSATION HAS BEEN PRESENTED AS PAID BY BENAROYA RESEARCH INSTITUTE. A WA ECON DEVEL FIN AUTH-2019 SERIES A 911493002 000000000 2019-02-26 25716490 SEE PART VI 0 1 0 B WA ECON DEVEL FIN AUTH-2019 SERIES B 911493002 000000000 2019-02-26 6000000 SEE PART VI 0 1 0 A 2881683 25716490 25716490 1 0 1 1 B 297627 6000000 6000000 2023 1 0 1 1 A 0 0 0 1 1 0.03840 0.03840 0 0 1 B 0 0 0 1 1 0.03840 0.03840 0 0 1 A 0 1 0 0 1 0 0 0 1 B 0 1 0 0 1 0 0 0 1 A 1 B 1 PART 1, LINE A, COLUMN F PURPOSES: TO REFUND WEDFA SERIES 2012 B BONDS ISSUED 06/01/2012, AND WEDFA SERIES 2016 BONDS ISSUED ON 06/01/2016. PART 1, LINE B, COLUMN F PURPOSES: TO FUND RESEARCH FACILITY IMPROVEMENTS AND EQUIPMENT PURCHASES ON A DRAW-DOWN BASIS OVER A THREE-YEAR PERIOD ENDING IN 2022. FORM 990, PART III, LINE 4: AT BRI, WE INTEGRATE THREE TYPES OF MEDICAL RESEARCH - LABORATORY RESEARCH, TRANSLATIONAL RESEARCH, AND CLINICAL RESEARCH - TO IMPROVE LIVES. ALL OUR SCIENTISTS COLLABORATE TO EXPLORE BASIC SCIENCE AS WELL AS CLINICAL APPLICATIONS, WHICH WE BELIEVE IS THE BEST WAY TO DESIGN STUDIES WITH THE HIGHEST POTENTIAL FOR SUCCESS. AT BRI, DISCOVERY STARTS IN THE LABORATORY BUT IS SPARKED BY THE NEEDS AND EXPERIENCES OF PATIENTS. FORM 990, PART III, LINE 1: BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON (BRI) IS ONE OF THE FEW RESEARCH INSTITUTES IN THE WORLD DEVOTED TO FINDING CAUSES AND CURES FOR AUTOIMMUNE AND IMMUNE SYSTEM DISEASES, INCLUDING TYPE 1 DIABETES, MULTIPLE SCLEROSIS, RHEUMATOID ARTHRITIS, LUPUS, INFLAMMATORY BOWEL DISEASE, CANCERS, ALLERGIES AND INFECTIOUS DISEASES. BRI IS AFFILIATED WITH VIRGINIA MASON FRANCISCAN HEALTH, WHICH PROVIDES GOVERNANCE AND OVERSIGHT, AND THE VIRGINIA MASON FOUNDATION, WHICH PROVIDES DEVELOPMENT SUPPORT. BRI'S BOLD MISSION IS TO ADVANCE THE SCIENCE TO PREDICT, PREVENT, REVERSE AND CURE DISEASES OF THE IMMUNE SYSTEM TO ACHIEVE OUR VISION OF A HEALTHY IMMUNE SYSTEM FOR EVERYONE. BRI IS LED BY PRESIDENT JANE H. BUCKNER, MD, AND EXECUTIVE DIRECTOR/COO MARGARET MCCORMICK, PHD. DISCOVERIES AT BRI ARE ACCELERATED BY OUR TALENTED RESEARCHERS, COLLABORATIVE CULTURE AND APPLICATION OF NEW TECHNOLOGIES AND DATA ANALYTICS IN A QUEST TO UNDERSTAND WHAT CAN CAUSE THE IMMUNE SYSTEM TO FALL OUT OF BALANCE AND HOW TO RESTORE IT TO HEALTH. TO THAT END, OUR SCIENTIFIC ACTIVITIES ARE ORGANIZED INTO FOUR CENTERS OF DISCOVERY TO FACILITATE KNOWLEDGE SHARING AND FOR CENTERS AND CORE LABS TO BUILD ON DISCOVERIES FROM INDIVIDUAL LABS: - INTERVENTIONAL IMMUNOLOGY, DIRECTED BY CARLA GREENBAUM, MD - TRANSLATIONAL IMMUNOLOGY, DIRECTED BY KAREN CEROSALETTI, PHD - FUNDAMENTAL IMMUNOLOGY, DIRECTED BY DANIEL CAMPBELL, PHD - SYSTEMS IMMUNOLOGY, DIRECTED BY ADAM LACY-HULBERT, PHD THE CENTER FOR INTERVENTIONAL IMMUNOLOGY (CII) USES SMALL AND LARGE-SCALE CLINICAL STUDIES TO TRANSLATE LAB DISCOVERIES TO PATIENT THERAPIES. CII STUDIES ENCOMPASS ALL PHASES OF CLINICAL RESEARCH, FROM BRI'S BIOREPOSITORIES, WHICH ENROLL INDIVIDUALS WITH AND WITHOUT IMMUNE SYSTEM DISEASES, TO MULTI-CENTER CLINICAL TRIALS OF DISEASE-MODIFYING THERAPIES. INVESTIGATOR-INITIATED STUDIES OF SHORT-COURSE IMMUNOTHERAPY OR VACCINES SHOW HOW PERTURBING THE IMMUNE SYSTEM CAN REVEAL THE DIFFERENTIAL FUNCTIONS OF THE IMMUNE SYSTEM IMPACTED BY DISEASE. THE IMMUNE TOLERANCE NETWORK, A GLOBAL CONSORTIUM FOCUSED ON CONDUCTING CLINICAL TRIALS TO PROMOTE TOLERANCE IN AUTOIMMUNITY, ORGAN TRANSPLANT AND ALLERGY/ASTHMA IS PART OF THIS CENTER. THE CENTER FOR TRANSLATIONAL IMMUNOLOGY (CTI) INVOLVES STUDYING BLOOD AND TISSUE SAMPLES FROM PEOPLE WITH IMMUNE SYSTEM DISEASES INCLUDING AUTOIMMUNE DISEASES, ALLERGIES, INFECTIOUS DISEASES AND CANCER. CTI USES ADVANCED SYSTEMS IMMUNOLOGY TOOLS TO EXAMINE GENES, CELLS AND MOLECULES INVOLVED IN THESE DISEASES. ITS STUDIES AIM TO DISCOVER HOW DISEASES START AND PROGRESS; IDENTIFY BIOLOGICAL CHARACTERISTICS TIED TO CERTAIN DISEASES OR RESPONSE TO THERAPY; AND TO FIND NEW DRUG TARGETS. THE BRI BIOREPOSITORY IS A COLLECTION OF BLOOD, SERUM AND TISSUE SAMPLES AND MEDICAL HISTORIES FROM VOLUNTEERS WITH AND WITHOUT DISEASE. 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 PURPOSES OF COMPARISON. THE CENTER FOR FUNDAMENTAL IMMUNOLOGY (CFI) INVESTIGATES THE IMMUNE SYSTEM TO UNDERSTAND HOW IT WORKS IN HEALTH AND DISEASE. INVESTIGATORS IN THE CFI LOOK AT THE CELLULAR AND MOLECULAR PATHWAYS THAT CONTROL THE IMMUNE SYSTEM, FOCUSING ON GENES, CELLS AND MOLECULES TO BUILD COMPLEX MODELS OF AUTOIMMUNE AND INFLAMMATORY DISEASES TO STUDY THEM IN PRECISE DETAIL. THE CENTER FOR SYSTEMS IMMUNOLOGY (CSI) USES THE LATEST TOOLS TO COLLECT, PROCESS AND EXAMINE DATA FROM STUDIES ACROSS BRI AND AROUND THE WORLD. CSI SELECTS AND IMPLEMENTS NEW TECHNOLOGIES AND DEVELOPS APPROACHES TO ORGANIZE AND ANALYZE LARGE DATA SETS. ITS GOAL IS TO MAKE NEW INSIGHTS ABOUT THE IMMUNE SYSTEM AND THE DISEASES THAT AFFECT IT. EXTERNAL AND ACADEMIC AFFAIRS AT BRI WE BUILD THE NEXT GENERATION OF LEADERS IN IMMUNOLOGY BY WORKING ACROSS OUR CENTERS WITH INTERNS, GRADUATE STUDENTS AND POSTDOCS. WE ALSO TEAM UP WITH OTHER RESEARCH INSTITUTES AND INDUSTRY PARTNERS TO TACKLE NEW RESEARCH QUESTIONS AND ACCELERATE DISCOVERIES. JESSICA HAMERMAN, PHD, IS OUR DIRECTOR FOR ACADEMIC AFFAIRS AND STEVEN ZIEGLER, PHD IS OUR DIRECTOR OF EXTERNAL COLLABORATION. IN DECEMBER 2022, WASHINGTON RESEARCH FOUNDATION ANNOUNCED ITS SIXTH ANNUAL COHORT OF POSTDOCTORAL FELLOWS, TO BE SUPPORTED BY WRF FOR THREE YEARS. AMONG THEM IS BRI'S SHEENAM VERMA, PHD, WHO EARNED A DOCTORATE IN STRUCTURAL BIOLOGY FROM THE REGIONAL CENTRE FOR BIOTECHNOLOGY IN INDIA. IN HER FELLOWSHIP SHE WILL STUDY HOW AUTOANTIBODIES THAT TARGET MICROBIOTA ANTIGENS MIGHT CONTRIBUTE TO AUTOIMMUNITY, WITH THE GOAL OF IDENTIFYING NOVEL BIOMARKER CANDIDATES FOR DIAGNOSIS OF AUTOIMMUNE DISORDERS. BRI HOSTED VIRTUAL SEMINARS FOR WASHINGTON STATE OPPORTUNITY SCHOLARSHIP (WSOS) STEM, CAREER AND TECHNICAL SCHOLARS TO INTRODUCE THEM TO OUR INSTITUTE, WHAT WE DO AND HOW STAFF AND RESEARCHERS WORK TOGETHER TO ADVANCE SCIENCE THAT WILL PREDICT, PREVENT, REVERSE AND CURE DISEASES OF THE IMMUNE SYSTEM. BRI STAFF ALSO TOOK PART IN OPPORTUNITIES SUCH AS A BLACK MENTORS IN MEDICINE PANEL FOR HIGH SCHOOL STUDENTS IN A SEATTLE PUBLIC SCHOOL PROGRAM, WHOLE, AND A BLACK HISTORY MONTH EVENT AT WHY NOT YOU ACADEMY (WNYA), A PUBLIC HIGH SCHOOL CO-FOUNDED BY RUSSELL AND CIARA WILSON IN WHICH STUDENTS LEARNED IN AN IDENTITY-AFFIRMING SCHOOL CULTURE WITH RELEVANT AND CULTURALLY RESPONSIVE PROJECTS. FORM 990, PART III, LINE 4A (CONTINUED) CONTINUED BLOCKING ASTHMA AND ALLERGIES IN PEOPLE AT RISK MATT ALTMAN, MD, MPHIL, WHO CONDUCTS ASTHMA RESEARCH AT BRI AND TREATS ASTHMA PATIENTS AT UW MEDICINE, WAS SENIOR AUTHOR OF A STUDY THAT IDENTIFIED A POTENTIALLY PROMISING NEW ASTHMA TREATMENT FOR URBAN KIDS AT RISK FOR THE DISEASE. THE STUDY FROM THE INNER-CITY ASTHMA CONSORTIUM (ICAC) FOUND THAT A THERAPY CALLED MEPOLIZUMAB CAN REDUCE ASTHMA ATTACKS AMONG CHILDREN IN LOW-INCOME HISPANIC AND BLACK COMMUNITIES. MEPOLIZUMAB WORKS BY BLOCKING A PROTEIN NECESSARY FOR THE DEVELOPMENT OF EOSINOPHIL, A TYPE OF WHITE BLOOD CELL. THE LAB OF ERIK WAMBRE, PHD, IDENTIFIES AND CHARACTERIZES RARE ANTIGEN-SPECIFIC T CELL RESPONSES TO GAIN INSIGHTS INTO HOW TO TREAT ALLERGIES AND OTHER DISEASES OF THE IMMUNE SYSTEM. IN A STUDY TO DEVELOP MORE EFFECTIVE THERAPIES FOR PEOPLE WITH PEANUT ALLERGIES, THE TEAM DEFINED KEY CORRELATIONS WITH THE REDUCTION OF CLINICAL REACTIVITY TO PEANUTS OBSERVED IN PEANUT-ALLERGIC INDIVIDUALS TREATED WITH PNOIT, THE ONLY KNOWN DISEASE-MODIFYING TREATMENT FOR PEANUT ALLERGY. THEY SHOWED THAT SKEWING ALLERGEN-SPECIFIC T CELLS AWAY FROM THE PATHOGENIC TH2A RESPONSES REPRESENTED A KEY EVENT IN THE DESENSITIZATION TO PEANUTS. TARGETING SOLID TUMORS AND PEDIATRIC BLOOD CANCERS STEVE ZIEGLER, PHD, KAZUSHIGE NINOMIYA, PHD AND TEAM FOUND THAT A SPECIFIC CYTOKINE COULD SERVE AS A BIOMARKER HERALDING THE DEVELOPMENT OF COLON CANCER, AND HOLDS PROMISE AS A THERAPEUTIC TARGET TO FIGHT COLORECTAL CANCERS. IN THE STUDY, THE TEAM FOUND THEY COULD INHIBIT COLORECTAL TUMORS BY BLOCKING TSLP, WHICH SUGGESTS THAT THE CYTOKINE MAY CONTROL THE PROGRESSION OF THE CANCER THROUGH THE REGULATION OF T CELL FUNCTION. HAMID BOLOURI, PHD LED A STUDY WHERE BRI RESEARCHERS AND CHILDREN'S ONCOLOGY GROUP COLLABORATORS USED RNA SEQUENCE DATA TO UNDERSTAND THE ASSOCIATION BETWEEN INFLAMMATORY CYTOKINES AND POOR OUTCOMES OF PEDIATRIC ACUTE MYELOID LEUKEMIA (PAML). TREATMENT WITH JAK/STAT PATHWAY INHIBITORS OR ANTIBODIES THAT NEUTRALIZE IL-6 HAS ALREADY SHOWN PROMISE IN ADULT CASES. UNDERSTANDING THE ROLE OF IL-6 SIGNALING IN PEDIATRIC CASES - AND THE ASSOCIATION OF IL-6 WITH THE PEDIATRIC PAML SUBTYPES WITH POOR CLINICAL OUTCOMES - AIDS THE DEVELOPMENT OF THERAPIES FOR CHILDREN WITH AML. FORM 990, PART VI, SECTION A, LINE 1A THE GOVERNING BODY DELEGATES TO AN EXECUTIVE COMMITTEE COMPRISED OF FOUR OFFICERS OF THE BOARD AND THE CHAIRS OF EACH STANDING BOARD COMMITTEE, THE AUTHORITY OF THE BOARD OF DIRECTORS IN THE MANAGEMENT OF THE CORPORATION AS MAY BE DEEMED BY THE EXECUTIVE COMMITTEE TO BE APPROPRIATE, TO BE EXERCISED IN TIME PERIODS BETWEEN REGULARLY SCHEDULED MEETINGS OF THE BOARD OF DIRECTORS; PROVIDED THAT THE EXECUTIVE COMMITTEE HAS THE AUTHORITY TO ACT ONLY IN TIME SENSITIVE OR EMERGENCY SITUATIONS. THE DIRECTOR AND THE EXECUTIVE DIRECTOR OF THE CORPORATION SERVE AS EX OFFICIO MEMBERS OF THE EXECUTIVE COMMITTEE WITHOUT VOTING RIGHTS. THE EXECUTIVE COMMITTEE DOES NOT HAVE THE AUTHORITY TO AMEND, ALTER OR REPEAL THE BYLAWS; ELECT, APPOINT OR REMOVE ANY MEMBER OF SUCH EXECUTIVE COMMITTEE OR ANY DIRECTOR OR OFFICER OF THE CORPORATION; AMEND THE ARTICLES OF INCORPORATION; ADOPT A PLAN OF MERGER OR ADOPT A PLAN OF CONSOLIDATION WITH ANOTHER CORPORATION; AUTHORIZE THE SALE, LEASE OR EXCHANGE OF ALL OR SUBSTANTIALLY ALL THE PROPERTY AND ASSETS OF THE CORPORATION NOT IN THE ORDINARY COURSE OF BUSINESS; AUTHORIZE THE VOLUNTARY DISSOLUTION OF THE CORPORATION OR REVOKE PROCEEDINGS THEREFORE; ADOPT A PLAN FOR THE DISTRIBUTION OF THE ASSETS OF THE CORPORATION; OR AMEND, ALTER OR REPEAL ANY RESOLUTION OF THE BOARD WHICH BY ITS TERMS PROVIDES THAT IT SHALL NOT BE AMENDED, ALTERED OR REPEALED BY SUCH EXECUTIVE COMMITTEE. THE EXECUTIVE COMMITTEE ALSO SERVES AS THE PLANNING COMMITTEE FOR THE BOARD OF DIRECTORS AND OVERSEES ANY COMPLIANCE ISSUES RAISED BY THE BOARD OF DIRECTORS. FORM 990, PART VI, SECTION A, LINE 6 ACCORDING TO THE BYLAWS OF BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON THE ENTITY'S SOLE MEMBER IS VIRGINIA MASON FRANCISCAN HEALTH, A WASHINGTON NONPROFIT CORPORATION. FORM 990, PART VI, SECTION A, LINE 7A VIRGINIA MASON FRANCISCAN HEALTH ("VMFH") IS THE SOLE CORPORATE MEMBER OF BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON ("BRI"). ACCORDING TO THE ORGANIZATION'S BYLAWS, DIRECTORS SHALL BE APPOINTED OR REFUSED BY THE CORPORATE MEMBER. THE CORPORATE MEMBER MAY APPOINT ONE OR MORE INDIVIDUALS TO THE BOARD OF DIRECTORS, AND MAY AT ANY TIME REMOVE, WITH OR WITHOUT CAUSE, ANY MEMBER OF THE BOARD OF DIRECTORS. FORM 990, PART VI, SECTION A, LINE 7B VIRGINIA MASON FRANCISCAN HEALTH ("VMFH") IS THE SOLE CORPORATE MEMBER OF BENAROYA RESEARCH INSTITUTE AT VIRGINIA MASON ("BRI"). EXCEPT AS OTHERWISE PROVIDED IN THE CORPORATION'S ARTICLES OF INCORPORATION, ELSEWHERE IN THESE BYLAWS, OR IN THE LAWS OF THE STATE OF WASHINGTON, THE CORPORATE MEMBER SHALL HAVE THE SPECIFIC RIGHTS SET FORTH IN THE GOVERNANCE MATRIX. THE RIGHTS OF THE CORPORATE MEMBER SHALL BE FURTHER SUBJECT TO THE POWERS RESERVED TO CSH UNDER THE GOVERNANCE MATRIX (SUBJECT TO THE BYLAWS OF THE CORPORATE MEMBER) AND AS OTHERWISE SET FORTH IN THE BYLAWS OF THE CORPORATE MEMBER. IN ADDITION, SUBJECT TO THE BYLAWS OF THE CORPORATE MEMBER, THE RESERVED POWERS OF CSH SET FORTH IN THE GOVERNANCE MATRIX MAY BE UNILATERALLY EXERCISED BY CSH ON BEHALF OF THE CORPORATION, AT CSH'S SOLE DISCRETION, IF THE CORPORATION'S BOARD OF DIRECTORS FAILS TO ACT UPON SUCH MATTERS DESCRIBED IN THESE BYLAWS, OR IF THE CORPORATION'S BOARD OF DIRECTORS ATTEMPTS TO ACT IN A MANNER THAT CONFLICTS WITH OR OVERRIDES THE ACTIONS OR DESIRES OF CSH WITH RESPECT TO SUCH MATTERS. THE GOVERNANCE MATRIX MAY BE AMENDED FROM TIME TO TIME BY CSH, AND SUCH AMENDMENTS SHALL BE DEEMED TO BE A PART OF THESE BYLAWS WITHOUT FURTHER ACTION. THE CORPORATION SHALL BE DEEMED A "SUBSIDIARY" OF CSH FOR PURPOSES OF THE GOVERNANCE MATRIX. IN ADDITION TO THE RIGHTS RESERVED TO CSH UNDER THE GOVERNANCE MATRIX, CSH SHALL HAVE THE POWER TO TRANSFER ASSETS OF THE CORPORATION OR TO REQUIRE THE CORPORATION TO TRANSFER ASSETS TO CSH, TO THE EXTENT NECESSARY TO ACCOMPLISH CSH'S GOALS AND OBJECTIVES, AND TO PROVIDE FOR THE PAYMENT OF ALL INDEBTEDNESS OF CSH OR AN ENTITY CONTROLLED BY, CONTROLLING, OR UNDER COMMON CONTROL WITH CSH (FOR PURPOSES OF THIS SECTION, A "CSH AFFILIATE"), ISSUED OR INCURRED BY OR ON BEHALF OF CSH OR A CSH AFFILIATE IN FURTHERANCE OF CSH'S GOALS AND OBJECTIVES. THE CORPORATION SHALL NOT BE REQUIRED TO VIOLATE ITS CHARITABLE PURPOSES, THESE BYLAWS OR ITS ARTICLES OF INCORPORATION, THE TERMS OF ANY RESTRICTED GIFTS, OR THE COVENANTS OF ITS DEBT INSTRUMENTS OR OTHER CONTRACTS AS A RESULT OF ANY ASSET TRANSFERS MADE OR DIRECTED BY CSH. EXCEPT FOR TRANSFERS PREVIOUSLY APPROVED BY CSH, EITHER INDIVIDUALLY OR AS PART OF THE CSH HEALTHCARE SYSTEM BUDGET PROCESS, AND EXCEPT FOR TRANSFERS TO AN AFFILIATE OR SUBSIDIARY OF THE CORPORATION, THE CORPORATION SHALL NOT TRANSFER ASSETS TO ENTITIES OTHER THAN CSH OR CSH AFFILIATES WITHOUT THE APPROVAL OF CSH. FORM 990, PART VI, SECTION B, LINE 11B NO REVIEW WAS OR WILL BE CONDUCTED. FORM 990, PART VI, SECTION B, LINE 12C THE ORGANIZATION HAS A CONFLICTS OF INTEREST ("COI") POLICY (THE "POLICY") IN PLACE TO PROTECT THE INTERESTS OF COMMONSPIRIT HEALTH ("COMMONSPIRIT") IN CIRCUMSTANCES THAT MAY RESULT IN A CONFLICT BETWEEN PERSONAL INTERESTS OF A PERSON AND THE INTERESTS OF THE ORGANIZATION AND THOSE IT SERVES. COMMONSPIRIT'S COI POLICY APPLIES TO COMMONSPIRIT, ITS DIRECT AFFILIATES AND SUBSIDIARIES AND ANY RELATED ENTITY THE GOVERNING DOCUMENTS OF WHICH REQUIRE THE ENTITY TO COMPLY WITH COMMONSPIRIT POLICY (COLLECTIVELY THE "SYSTEM ENTITIES"). THE FOLLOWING PERSONS ARE REQUIRED TO DISCLOSE ACTUAL OR POTENTIAL CONFLICTS OF INTEREST AT LEAST ANNUALLY (VIA A FORMAL SYSTEM-ADMINISTERED SURVEY) IF THE PERSON'S AFFILIATION WITH COMMONSPIRIT CONTINUES: - MEMBERS OF CORPORATE AND COMMUNITY BOARDS OF SYSTEM ENTITIES - MEMBERS OF COMMITTEES OF CORPORATE AND COMMUNITY BOARDS OF SYSTEM ENTITIES - MEMBERS OF THE EXECUTIVE LEADERSHIP TEAM ("ELT") OF COMMONSPIRIT - CORPORATE OFFICERS OF SYSTEM ENTITIES - KEY EMPLOYEES AND HIGHEST COMPENSATED EMPLOYEES AS SPECIFIED BY THE INTERNAL REVENUE SERVICE FOR FORM 990 PURPOSES WHO ARE NOT OTHERWISE INCLUDED IN THE CATEGORIES ABOVE - EMPLOYEES OF SYSTEM ENTITIES AT THE VICE PRESIDENT LEVEL AND ABOVE - ALL INDIVIDUALS ENGAGED IN RESEARCH AT INSTITUTIONS OWNED OR OPERATED BY A SYSTEM ENTITY - SELECT EMPLOYEES AS DETERMINED FROM TIME TO TIME BY LEADERSHIP DISCLOSURE, REVIEW, AND MANAGEMENT OF PERCEIVED, POTENTIAL, OR ACTUAL CONFLICTS OF INTEREST ARE ACCOMPLISHED THROUGH A DEFINED COI DISCLOSURE REVIEW PROCESS. EACH PERSON IS REQUIRED TO PROMPTLY AND FULLY DISCLOSE ANY SITUATION OR CIRCUMSTANCE THAT MAY CREATE A CONFLICT OF INTEREST AS SOON AS SHE/HE BECOMES AWARE OF IT. IN ADDITION, AT THE INCEPTION OF AN INDIVIDUAL'S RELATIONSHIP WITH COMMONSPIRIT (E.G. HIRING, BOARD APPOINTMENT), AND FOR CERTAIN POSITIONS, ANNUALLY THEREAFTER, WRITTEN CONFLICT OF INTEREST DISCLOSURE FORMS MUST BE COMPLETED. A FAILURE TO DISCLOSE MAY RESULT IN DISCIPLINARY OR CORRECTIVE ACTIONS. REPORTED POTENTIAL OR ACTUAL CONFLICTS OF INTEREST ARE INITIALLY REVIEWED BY LEGAL, CORPORATE RESPONSIBILITY OR RESEARCH INTEGRITY STAFF. IF NECESSARY, A CONFLICT OF INTEREST MANAGEMENT PLAN IS DEVELOPED, WHICH PLAN SHALL BE SUBJECT TO ACCEPTANCE BY THE APPROPRIATE DIRECT MANAGER, SUPERVISOR, MEDICAL STAFF OFFICE, BOARD OR BOARD COMMITTEE (FOR BOARD, BOARD COMMITTEE, ELT OR CORPORATE OFFICER CONFLICTS), OR OTHER APPROPRIATE INDIVIDUAL OR BODY. ONCE ACCEPTED, THE CONFLICT OF INTEREST MANAGEMENT PLAN IS COMMUNICATED TO THE PERSON WITH THE ACTUAL OR POTENTIAL CONFLICT AND THE INDIVIDUAL MUST CONDUCT THEMSELVES IN CONFORMITY WITH THE PLAN. IN THE EVENT THAT A TRANSACTIONAL CONFLICT INTEREST ARISES IN CONNECTION WITH A SYSTEM ENTITY BOARD MEETING, THE CONFLICTED INDIVIDUAL MUST DISCLOSE THAT CONFLICT PRIOR TO OR AT THE BEGINNING OF THE MEETING IN WHICH THE MATTER IS TO BE CONSIDERED. THE CONFLICTED INDIVIDUAL IS EXCLUDED FROM VOTING ON THE TRANSACTION AND IS PROHIBITED FROM USING PERSONAL INFLUENCE WITH RESPECT TO THE MATTER, BUT IS NOT PROHIBITED FROM PROVIDING INPUT IF REQUESTED TO DO SO. FORM 990, PART VI, SECTION B, LINE 15 THE VMMC COMPENSATION AND BENEFITS BOARD COMMITTEE, A COMMITTEE COMPOSED SOLELY OF INDEPENDENT DIRECTORS NONE OF WHOM HAVE A CONFLICT OF INTEREST, IS ACCOUNTABLE FOR SETTING REASONABLE TOTAL COMPENSATION PACKAGES THE PRESIDENT AND CHIEF EXECUTIVE CONSISTENT WITH BRI'S COMPENSATION PHILOSOPHY AND PRINCIPLES. THE COMMITTEE APPROVES ANNUAL GOALS AND PERFORMANCE CRITERIA WHICH ARE USED IN DETERMINING MERIT INCREASES AND VARIABLE COMPENSATION OPPORTUNITIES. THE COMMITTEE ASSESSES PERFORMANCE AGAINST THESE GOALS. THE COMMITTEE SELECTS AND ENGAGES A QUALIFIED INDEPENDENT COMPENSATION CONSULTANT TO REVIEW AND ANALYZE THE TOTAL COMPENSATION AND BENEFITS PACKAGES OF THE EXECUTIVES. THE COMMITTEE AS PART OF ITS ANALYSIS OBTAINS FROM THE COMPENSATION CONSULTANT APPROPRIATE COMPARABILITY DATA INCLUDING TOTAL COMPENSATION PAID BY SIMILARLY SITUATED ORGANIZATIONS FOR POSITIONS THAT ARE FUNCTIONALLY COMPARABLE TO EACH OF THE EXECUTIVES. THE COMMITTEE WILL CONSIDER THE SIGNIFICANT TERMS OF THE AGREEMENT WITH EACH EXECUTIVE INCLUDING THE TOTAL COMPENSATION TO BE PAID AND THE EMPLOYEE'S DUTIES AND RESPONSIBILITIES. CONSISTENT WITH THE COMPENSATION PHILOSOPHY AND PRINCIPLES, THE COMMITTEE APPROVES TOTAL COMPENSATION PACKAGES FOR EACH OF THE EXECUTIVES BASED ON INFORMATION PRESENTED TO THE COMMITTEE, REASONABLENESS, AND THE BEST INTEREST OF BRI. THE COMMITTEE'S DECISIONS REGARDING COMPENSATION FOR EACH EXECUTIVE ARE DOCUMENTED IN WRITTEN RESOLUTIONS AND MINUTES OF THE COMMITTEE. THE COMMITTEE PROMPTLY REPORTS ITS ACTIONS TO THE VMMC BOARD WHICH REPORTS ARE REFLECTED IN THE BOARD'S MINUTES. FORM 990, PART VI, SECTION C, LINE 19 THE ORGANIZATION'S ARTICLES, BYLAWS, CONFLICT OF INTEREST POLICY AND FINANCIAL STATEMENTS ARE MADE AVAILABLE UPON REQUEST. 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