2013-10-11T11:04:10-05:00 2012-11-30 861065772 DELOITTE TAX LLP 200 RENAISSANCE CENTER STE 3900 DETROIT MI 48243 990 2011-12-01 522000823 VAN ANDEL RESEARCH INSTITUTE VANA 6162345000 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 49503 TIMOTHY J MYERS 6162345368 2013-10-11 1 LORI BOYCE P00121981 3133963000 2011 2016-02-25 16:41:14Z TIMOTHY J MYERS 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 49503 72051806 0 X WWW.VAI.ORG X 1996 MI MEDICAL RESEARCH ORGANIZATION 5 3 367 0 897673 80719 57012820 57997024 1522584 1242591 819423 333140 4334013 10471022 63688840 70043777 340825 341390 0 0 26065382 27658068 0 0 412173 39147197 40558351 65553404 68557809 -1864564 1485968 270167888 267685668 358085475 361102589 -87917587 -93416921 MEDICAL RESEARCH ORGANIZATION 0 0 2140903 0 THE PROGRAM FOR BIOSPECIMEN SCIENCE HAS FOCUSED ON THE CHANGE IN BIOLOGICAL PARAMETERS AND QUALITY OF BIOSPECIMENS CAUSED BY COLLECTION, PROCESSING, AND STORAGE PROCEDURES. THIS RESEARCH IDENTIFIES EFFECTS ON THE CELL BIOLOGY THAT MAY BE UNRELATED TO THE DISEASE AND MORE SO CAUSED BY THE MANAGEMENT OF THE BIOSPECIMEN. THE RESULTS CAN BE USED TO DEVELOP BEST PRACTICES IN THE MANAGEMENT OF BIOSPECIMENS AND ULTIMATELY IMPROVE THE QUALITY OF RESEARCH FINDINGS. SCHEDULE O PROVIDES FURTHER INFORMATION REGARDING THIS PROGRAM'S ACCOMPLISHMENTS. 1731921 500 THE LABORATORY OF MOLECULAR ONCOLOGY HAS FOCUSED ON UNDERSTANDING THE NUMEROUS AND DIVERSE ROLES THAT MET PLAYS IN MALIGNANT PROGRESSION AND METASTASIS. SCHEDULE O PROVIDES FURTHER INFORMATION REGARDING THIS PROGRAM'S ACCOMPLISHMENTS. 1661508 THE LABORATORY OF STRUCTURAL SCIENCES IS FOCUSED ON STUDYING THE STRUCTURES AND FUNCTIONS OF PROTEIN/ LIGAND COMPLEXES THAT PLAY KEY ROLES IN MAJOR HORMONE SIGNALING PATHWAYS. SEE SCHEDULE O FOR FURTHER INFORMATION ABOUT THIS PROGRAM. 39181071 341390 2455766 39181071 341390 2455766 44715403 1 1 0 1 0 0 0 0 0 0 1 0 0 1 1 1 0 1 0 1 1 0 0 0 0 0 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 0 0 1 113 0 367 1 1 1 0 0 0 0 0 0 0 0 0 X 5 3 1 1 0 0 0 1 0 1 1 0 0 1 1 1 1 1 1 1 1 0 MI X TIMOTHY J MYERS CFO 6162345368 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 495032518 X DAVID VAN ANDEL 28.00 X X 411467 0 122461 DR GEORGE VANDE WOUDE 50.00 X 299763 0 25940 DR JAMES FAHNER 1.00 X 10000 0 0 DR FRITZ ROTTMAN PHD 1.00 X 10000 2000 0 DR JEFFREY TRENTTHROUGH 312 50.00 X X 1180739 0 243940 WILLIAM POST THROUGH 312 1.00 X 2000 0 0 DR GARY TARPLEY 1.00 X 0 0 0 R JACK FRICK THROUGH 1211 50.00 X 275769 0 95458 TIMOTHY MYERS 50.00 X 237174 0 78801 DAVID WHITESCARVER 50.00 X 197281 0 49962 DR JANA HALL 50.00 X 0 0 0 DR H ERIC XU 45.00 X 294385 0 49433 JOHN BENDER 45.00 X 235889 0 49192 BRYON CAMPBELL 45.00 X 191590 0 35484 DR GISELLE SAULNIER SHOLLER 45.00 X 222748 0 34912 DR SCOTT JEWELL 45.00 X 296776 0 65194 3865581 2000 850777 43 0 1 0 BANK OF AMERICAMERRILL LYNCH 100 N TRYON ST CHARLOTTE NC 28202 CREDIT ENHANCEMENT FEES 3384333 AON RISK SERVICES CENTER INC 75 REMITTANCE DR STE 1943 CHICAGO IL 606751943 INSURANCE 551182 WARNER NORCROSS & JUDD 111 LYON ST 900 OLD KENT GRAND RAPIDS MI 495032487 LEGAL/ CONSULTING 547737 PRIORITY HEALTH 1686 RELIABLE PARKWAY CHICAGO IL 60686 HEALTH INSURANCE ADMIN 464179 DK SECURITY 5160 FALCONVIEW AVE SE KENTWOOD KENTWOOD MI 49512 SECURITY SERVICES 370952 19 47258660 6031998 4706366 12000 57997024 RESEARCH BILLED REV 541700 1242591 345420 897171 1242591 214931 214931 253826 253826 2602254 1308 1506788 806 1095466 502 1095968 1095466 502 618644 500435 118209 118209 118209 REL. PARTY ADMIN SUPPO 561000 5425172 5425172 REIMBURSED EXPENSES 900099 3654325 3654325 41731 41731 9121228 70043777 1559095 897673 9589985 341390 341390 2248987 1128006 1120981 19866298 10781536 8793980 290782 1515029 841171 651804 22054 2549100 1413005 1098522 37573 1478654 818280 638320 22054 926115 55923 870192 132611 15194 117417 68133 68133 2245213 1495233 749980 709562 10046 699516 136899 77504 59395 366110 155278 210832 2448990 1904532 544458 695945 445065 250880 164918 91507 73411 11375530 8869107 2506423 9970658 8061216 1909442 440991 289362 151629 LAB SUPPLIES & SERVICES 3248873 3248873 EQUIPMENT & SOFTWARE 2033196 1077077 956119 OTHER SCIENTIFIC 1143154 1143154 SCIENTIFIC PURCH. SVC. 663483 663483 3787970 1789461 1958799 39710 68557809 44715403 23430233 412173 954773 1687416 1194099 2507373 2551038 1262403 1664455 1647915 1271897 1153469 266334661 62385484 210880670 203949177 1367061 1431848 97917 0 50185978 54046067 270167888 267685668 55926177 61769366 1756331 388625 220385000 221189000 80017967 77755598 358085475 361102589 X -80494164 -95108778 -7425523 1689257 2100 2600 -87917587 -93416921 270167888 267685668 X 1485968 -6985302 X X 0 1 1 X 1 1 X SPECTRUM HEALTH GRAND RAPIDS MI RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED 0 68133 68133 68489676 68557809 1000000 250000 0 0 1000000 1000000 1500000 68133 68133 250000 250000 375000 PART IV, SUPPLEMENTAL INFORMATION: VARI EMPLOYEES MANAGE RELATIONSHIPS WITH OUTSIDE CONSULTANTS AND DID NOT PARTICIPATE IN DIRECT LOBBYING. THEREFORE, NO COMPENSATION EXPENSE HAS BEEN ALLOCATED TO LOBBYING EXPENSE. X 1 1 5288315 5288315 218645316 32192644 186452672 40708927 30154521 10554406 1692103 38319 1653784 203949177 BOND ISSUANCE COSTS NET OF ACCUMULATED AMORTIZATION 1516067 PLEDGED SECURITIES 52530000 54046067 ACCRUED POSTRETIREMENT BENEFIT OBLIGATION 1524181 UNREALIZED LOSS ON BOND SWAP 69959449 MSU COLLEGE OF HUMAN MEDICINE- CONTRIBUTION PAYABLE 6205908 CAPITAL LEASE 66060 77755598 70043777 68557809 1485968 64787 -7050089 -6985302 -5499334 64297349 64787 100790 165577 64131772 5912006 5912006 70043778 69796683 7150879 7150879 62645804 5912006 5912006 68557810 DESCRIPTION OF INTENDED USE OF ENDOWMENT FUNDS: PART V, LINE 4: TO SUPPORT THE CORE RESEARCH OF VARI BY SUPPLYING A STEADY SOURCE OF INCOME FOR ITS OPERATING EXPENDITURES. PART XI, LINE 8 - OTHER ADJUSTMENTS: LOSS ON INTEREST RATE SWAP -7,050,089. PART X, LINE 1(1) AND LINE 2: MANAGEMENT BELIEVES THE LIKELIHOOD VARI, OR ANY RELATED ORGANIZATION, WILL BE REQUIRED TO MAKE ANY ADDITIONAL PAYMENTS IS REMOTE. PART XI, LINE 8: NET LOSS RELATED TO THE INTEREST RATE SWAP. PART XII, LINE 2D: RECLASS OF TRANSMED SYSTEMS (A RELATED PARTY) COST OF GOODS SOLD TO PRESENT ON STATEMENT OF REVENUE RATHER THAN STATEMENT OF FUNCTIONAL EXPENSES. PART XIII, LINE 2D: INCLUDES BOTH THE NET LOSS RELATED TO THE INTEREST RATE SWAP AND RECLASS OF TRANSMED SYSTEMS COST OF GOODS SOLD TO PRESENT ON STATEMENT OF REVENUE RATHER THAN STATEMENT OF FUNCTIONAL EXPENSES. PART XII AND XIII, LINE 4B: EXPENSE ALLOCATIONS PRESENTED WITHIN REVENUE. PART V - ALL ENDOWMENT FUNDS ARE HELD AT THE VAN ANDEL INSTITUTE (A RELATED ORGANIZATION). 1 EAST ASIA & THE PACIFIC 0 2 PROGRAM SERVICES RESEARCH COLLABORATION - RESEARCH SERVICES 455219 0 2 0 0 0 2 455219 0 455219 0 0 0 0 0 0 1 GRADUATE STUDENT STIPENDS FOR VAN ANDEL GRADUATE SCHOOL AND MICHIGAN STATE UNIVERSITY STUDENTS 8 198410 12000 TUITION PAID FOREIGN NATIONAL STUDENT STIPENDS 13 105980 SCHEDULE I, PART I, LINE 2: STIPENDS ARE PROVIDED TO THE RESEARCH STUDENTS FOR LIVING AND INSURANCE ASSISTANCE. X X 0 1 X X X X X 0 0 0 0 0 0 0 1 0 DAVID VAN ANDEL 300014 0 86404 0 25049 0 121954 0 507 0 533928 0 86404 0 DR GEORGE VANDE WOUDE 258791 0 22000 0 18972 0 24500 0 1440 0 325703 0 0 0 DR JEFFREY TRENTTHROUGH 312 837136 0 248256 0 95347 0 242500 0 1440 0 1424679 0 248256 0 R JACK FRICK THROUGH 1211 219566 0 54223 0 1980 0 86320 0 9138 0 371227 0 54223 0 TIMOTHY MYERS 180247 0 56627 0 300 0 69663 0 9138 0 315975 0 56627 0 DAVID WHITESCARVER 101372 0 0 0 95909 0 46154 0 3808 0 247243 0 0 0 DR H ERIC XU 258778 0 35157 0 450 0 40295 0 9138 0 343818 0 22251 0 JOHN BENDER 207680 0 7590 0 20619 0 40055 0 9137 0 285081 0 7590 0 BRYON CAMPBELL 176668 0 14232 0 690 0 26347 0 9137 0 227074 0 14232 0 DR GISELLE SAULNIER SHOLLER 145942 0 20000 0 56806 0 28821 0 6091 0 257660 0 20000 0 DR SCOTT JEWELL 254861 0 40625 0 1290 0 56057 0 9137 0 361970 0 40625 0 PART I, LINE 1A VARI ALLOWS FOR FIRST-CLASS OR CHARTER TRAVEL FOR OFFICERS AND TRUSTEES. PART I, LINE 1B: HOUSING ALLOWANCE AND RESIDENCE FOR PERSONAL USE ARE MANAGED BY HUMAN RESOURCES ON A CASE BY CASE BASIS, BOTH OF WHICH EXCLUSIVELY OCCUR IN CONNECTION WITH RELOCATION TO GRAND RAPIDS. PART I, LINE 1B A WRITTEN POLICY IS IN PLACE FOR FIRST CLASS/ CHARTER TRAVEL. PART I, LINE 7 ALL OFFICERS AND OTHER HIGHLY COMPENSATED EMPLOYEES ARE INCLUDED IN A VARIABLE PAY PLAN BASED ON ACHIEVEMENTS OF THE ORGANIZATION AS WELL AS RESPECTIVE INDIVIDUAL PREDETERMINED GOALS AND OBJECTIVES. MICHIGAN STRATEGIC FUND LIMITED OBLIGATION REVENUE 521417332 594698EG3 2008-04-10 220000000 BUILD, EQUIP & FURNISH PHASE II RESEARCH FACILITY, & REFUND $50M PRIOR LTD 0 0 0 223154512 113036720 110117792 2009 1 0 1 1 0 1 1 1 1 1 0.01090 0.01090 1 1 1 0 0 0 0 X FORM 990, PART VI, SECTION A, LINE 2 VARI AND VAEI SHARE COMMON MANAGEMENT. AS OFFICERS OF VARI, DAVID VAN ANDEL, R. JACK FRICK, DR. JANA HALL, TIMOTHY MYERS AND DAVID WHITESCARVER INTERACT AND WORK TOGETHER WITH STEVE TRIEZENBERG, AN OFFICER OF VAEI. FORM 990, PART VI, SECTION A, LINE 2 VARI AND THE TRANSLATIONAL GENOMICS INSTITUTE (TGEN) SHARED COMMON GOVERNANCE. DR. WILLIAM J. POST, DR. JOSE CARDENAS, AND DR. JEFF TRENT ALL SERVED AS DIRECTORS FOR BOTH VARI AND TGEN (A RELATED ORGANIZATION). AS OF MARCH 12, 2012, VARI AND TGEN TERMINATED THEIR ALLIANCE AND AFFILIATION AGREEMENT. FORM 990, PART VI, SECTION A, LINE 3 DURING THE FISCAL YEAR, JERRY CALLAHAN, AN INDEPENDENT CONTRACTOR, SERVED AS THE VICE PRESIDENT OF BUSINESS DEVELOPMENT AND EXTRAMURAL ADMINISTRATION. AS OF JANUARY 2013, MR. CALLAHAN BECAME A FULL TIME EMPLOYEE. FORM 990, PART VI, SECTION A, LINE 7A THE TRUSTEES OF VAN ANDEL INSTITUTE HAVE THE AUTHORITY TO ELECT ONE OR MORE MEMBERS OF VARI'S GOVERNING BODY. FORM 990, PART VI, SECTION B, LINE 11 FOLLOWING COMPLETION OF THE FINANCIAL STATEMENT AUDIT, THE FORM 990 IS PREPARED AND REVIEWED BY MANAGEMENT. IT IS THEN CIRCULATED TO THE FULL BOARD FOR REVIEW AND FINAL APPROVAL PRIOR TO FILING WITH THE IRS. FORM 990, PART VI, SECTION B, LINE 12C VARI HAS A WRITTEN CONFLICT OF INTEREST POLICY FOR WHICH THE ORGANIZATION ENFORCES A PROCESS TO IDENTIFY, EVALUATE, AND CORRECT OR REMOVE POTENTIAL CONFLICTS OF INTEREST. THIS POLICY HAS BEEN BOARD APPROVED. THE VAN ANDEL INSTITUTE ADMINISTERS THE CONFLICT OF INTEREST (COI) POLICY, ON BEHALF OF VARI, THROUGH TWO COMMITTEES: THE CONFLICTS COMMITTEE ("CC") AND THE INSTITUTIONAL COI COMMITTEE ("ICOIC"). THE COI POLICY SERVES AS GUIDE FOR ALL STAFF MEMBERS OF THE ORGANIZATION. THE POLICY IS INTENDED TO 1) PROVIDE STAFF WITH A USEFUL RESOURCE WHEN DEVELOPING ACTIVITIES WITH OUTSIDE INDUSTRY AND 2) PROVIDE ASSURANCE TO STAFF THAT THERE IS A COMMITTEE TO REVIEW AND RESOLVE POTENTIAL CONFLICTS OF INTEREST IF / WHEN THEY ARISE. THE CC, CHAIRED BY THE DIRECTOR OF COMPLIANCE, GENERATES AN ANNUAL DISCLOSURE QUESTIONNAIRE DISTRIBUTED TO ALL STAFF TO ENFORCE THE POLICY. THE CC IS RESPONSIBLE FOR MAKING RECOMMENDATIONS TO THE DIRECTOR. RESOLUTIONS ARE IMPLEMENTED WITH APPROVAL OF THE COMMITTEE AND IN DISCUSSION WITH THE CHAIRMAN. THE COI POLICY ALSO SERVES AS A GUIDE FOR ALL MEMBERS OF THE BOARD OF TRUSTEES AND SENIOR EXECUTIVES. THE ICOIC REQUIRES TRUSTEES TO COMPLETE AN ANNUAL DISCLOSURE STATEMENT. THIS STATEMENT AFFIRMS THEIR UNDERSTANDING OF THE POLICY, REQUIRES THEIR ACKNOWLEDGEMENT OF THE ORGANIZATION'S NONPROFIT STATUS, AND REQUESTS DISCLOSURE IF / WHEN POTENTIAL CONFLICTS ARISE. IN THE EVENT A POTENTIAL CONFLICT ARISES AT THE BOARD OR SENIOR OFFICER LEVEL, THE CHIEF LEGAL OFFICE REVIEWS AND MEETS WITH THE BOARD OF TRUSTEES TO RESOLVE POTENTIAL CONFLICTS. FORM 990, PART VI, SECTION B, LINE 15 COMPARABILITY DATA FROM EXPERT, THIRD PARTY IS OBTAINED AND REVIEWED BY VAN ANDEL INSTITUTE'S INDEPENDENT COMPENSATION COMMITTEE TO DETERMINE APPROPRIATE COMPENSATION FOR THE CEO, EXECUTIVE MANAGEMENT OFFICIALS, EXECUTIVE DIRECTOR, OFFICERS, AND KEY EMPLOYEES, ON BEHALF OF VAN ANDEL RESEARCH INSTITUTE. FORM 990, PART VI, SECTION C, LINE 19 THE CONFLICT OF INTEREST POLICY AND FINANCIAL STATEMENTS ARE AVAILABLE TO THE PUBLIC UPON REQUEST. FORM 990, PART VII, PAGE 7 DAVID VAN ANDEL, R. JACK FRICK, DR. JANA HALL, TIMOTHY MYERS, AND DAVID WHITESCARVER ALSO PERFORMED WORK FOR VAN ANDEL INSTITUTE, VAN ANDEL EDUCATION INSTITUTE, AND VAN ANDEL INSTITUTE GRADUATE SCHOOL (RELATED ENTITIES). CHANGES IN NET ASSETS OR FUND BALANCES: FORM 990, PART XI, LINE 5: NET UNREALIZED GAINS ON INVESTMENTS: 64,787. LOSS ON INTEREST RATE SWAP -7,050,089. TOTAL TO FORM 990, PART XI, LINE 5: -6,985,302. FORM 990, PART XII, LINE 2C THE PROCESS FOR SELECTING THE AUDITOR FOR VAN ANDEL RESEARCH INSTITUTE'S FINANCIAL STATEMENTS DID NOT CHANGE DURING 2012. PART III, LINE 3 EFFECTIVE MARCH 12, 2012, VARI AND TGEN TERMINATED THEIR ALLIANCE AND AFFILIATION AGREEMENT AND TGEN CONVERTED FROM A MEMBER-BASED ARIZONA NOT-FOR-PROFIT CORPORATION TO A DIRECTOR-BASED ARIZONA NOT-FOR-PROFIT CORPORATION, WHEREBY VARI IS NO LONGER THE SOLE MEMBER OF TGEN. THE RESULTS OF OPERATIONS OF TGEN THROUGH THE EFFECTIVE TERMINATION DATE, ARE REFLECTED AS DISCONTINUED OPERATIONS WITHIN THE VAN ANDEL INSTITUTE AND AFFILIATES CONSOLIDATED AND CONSOLIDATING STATEMENTS OF ACTIVITIES AND CHANGES IN NET ASSETS (WHICH VARI IS PART OF). TGEN ASSETS, LIABILITIES AND NET ASSETS TRANSFERRED TOTALED $57,577,000, $21,348,000 AND $36,229,000, RESPECTIVELY. TGEN REVENUE AND SUPPORT EARNED BEFORE THE AGREEMENT TERMINATION, DURING FISCAL YEAR 2012 TOTALED $9,012,000. TGEN EXPENSES INCURRED BEFORE THE AGREEMENT TENNINATION, DURING FISCAL YEAR 2012 TOTALED $13,193,000. TGEN REVENUE AND SUPPORT EARNED FOR FISCAL YEAR ENDED NOVEMBER 30, 2011 TOTALED $54,670,000. TGEN EXPENSES INCURRED FOR FISCAL YEAR ENDED NOVEMBER 30, 2011 TOTALED $68,855,000. FORM 990, PART III, LINES 4A-4C LINE 4A - PROGRAM SERVICE ACTIVITY #1 THE PROGRAM FOR BIOSPECIMEN SCIENCE HAS FOCUSED ON THE CHANGE IN BIOLOGICAL PARAMETERS AND QUALITY OF BIOSPECIMENS CAUSED BY COLLECTION, PROCESSING, AND STORAGE PROCEDURES. THE BIOREPOSITORY WITHIN THE PROGRAM FOR BIOSPECIMEN SCIENCE INCLUDES SCIENTIFIC EVALUATION ON THE PATTERNS OF DEGRADATION IN BIOSPECIMENS, DATABASE TRACKING AND MANAGEMENT OF BIOSPECIMEN INVENTORY; BIOSPECIMEN KIT DEVELOPMENT AND MANUFACTURING; SHIPPING AND TRACKING SERVICES; PROCUREMENT OF SURGICAL TISSUE AND BIOSPECIMENS FROM PATIENT POPULATIONS; QUALITY CONTROL ASSESSMENT OF OPERATIONS FOR THE COLLECTION AND BANKING OF BIOSPECIMENS; AND BIOSPECIMEN PROJECT MANAGEMENT. THE VARI BIOREPOSITORY CONTAINS APPROXIMATELY 10,000 FROZEN HUMAN TISSUES AND THEIR DERIVATIVES AND A PARAFFIN BLOCK ARCHIVE OF HUMAN DIAGNOSTIC TISSUES CURRENTLY EXCEEDING 900,000 BLOCKS. TISSUE ACQUISITION IS IN COLLABORATION WITH WEST MICHIGAN HOSPITALS, PROVIDING FRESH-FROZEN AND PARAFFIN-EMBEDDED SURGICAL TISSUES AND BLOOD FROM CONSENTING PATIENTS. THE BIOREPOSITORY IS DESIGNED TO PROVIDE HUMAN TUMORS TO INVESTIGATORS WITH IRB-APPROVED BASIC AND TRANSLATIONAL RESEARCH PROJECTS. ACCOMPLISHMENTS INCLUDE; MANAGING BIOREPOSITORY SERVICES FOR THE MULTIPLE MYELOMA RESEARCH FOUNDATION, THE NATIONAL CANCER INSTITUTE'S CANCER HUMAN BIOBANK (CAHUB), MULTIPLE BIOSPECIMEN ACQUISITION AND BIOREPOSITORY MANAGEMENT PROJECTS FOR VARI INVESTIGATORS, BIOREPOSITORY ACCREDITATION FROM THE COLLEGE OF AMERICAN PATHOLOGIST (CAP), AND A FOUNDING MEMBER OF THE GREAT LAKES BIOREPOSITORY RESEARCH NETWORK (GLBRN). LINE 4B - PROGRAM SERVICE ACTIVITY #2 SINCE DISCOVERING THE C-MET RECEPTOR AND ITS LIGAND HEPATOCYTE GROWTH FACTOR (HGF/SF) IN THE MID-1980S, THE LABORATORY OF MOLECULAR ONCOLOGY HAS FOCUSED ON INVESTIGATING THE PARAMOUNT ROLE THESE PROTEINS PLAY IN MALIGNANT PROGRESSION AND METASTASIS. MET IS OVEREXPRESSED IN MANY TYPES OF HUMAN CANCER, AND ITS EXPRESSION CORRELATES WITH AN AGGRESSIVE DISEASE AND POOR PROGNOSIS (HTTP://WWW.VAI.ORG/MET/). THE ABERRANT EXPRESSION OF MET IN MANY HUMAN TUMORS ALSO NECESSITATED THE DEVELOPMENT OF COMPANION DIAGNOSTICS TO IDENTIFY THOSE PATIENTS WHO COULD BENEFIT FROM MET TARGETED THERAPIES. AS PART OF THE ONGOING EFFORT TO FURTHER ENHANCE OUR UNDERSTANDING OF THE HGF/SF-MET SIGNALING PATHWAY, OUR LAB CURRENTLY FOCUSES ON THE PROJECTS DESCRIBED BELOW: - CONTINUING TO DEVELOP AND CHARACTERIZE NOVEL RESEARCH MODELS FOR A VARIETY OF HUMAN CANCERS (LIVER, BRAIN, BREAST, LUNG AND OTHERS) AND USING THEM FOR PRE-CLINICAL EVALUATION OF NEW C-MET INHIBITORS AS WELL AS OTHER THERAPEUTIC STRATEGIES - EVALUATING HGF AUTOCRINE AS A THERAPEUTIC MARKER PREDICTING SENSITIVITY TO C-MET INHIBITION USING VARIOUS GLIOBLASTOMA AND HEPATOCELLULAR CARCINOMA MODELS - STUDYING THE MECHANISMS RESPONSIBLE FOR PHENOTYPIC SWITCHING (E-MT/M-ET) AND EVALUATING THE ROLE OF CHROMOSOME INSTABILITY IN TUMOR PROGRESSION - INVESTIGATING THE ROLES OF MIG-6 AND THE MECHANISMS OF ITS ACTION IN CANCER DEVELOPMENT AND IN THE MAINTENANCE OF JOINT HOMEOSTASIS - PLANNING FURTHER IN VIVO DRUG COMBINATION STUDIES FOR DEVELOPING BETTER THERAPEUTIC STRATEGIES THAT WILL BE MORE EFFECTIVE THAN C-MET INHIBITOR AS A SINGLE AGENT IN TREATING MET-EXPRESSING TUMORS - INVESTIGATING HOW MET SIGNALING INTERACTS WITH THE ERBB FAMILY OF RECEPTORS IN THE PROGRESSION AND THERAPEUTIC RESISTANCE OF ERBB2-POSITIVE AND TRIPLE-NEGATIVE BREAST CANCERS - USING OUR UNIQUE HUMAN-HGF TRANSGENIC SCID MOUSE MODEL TO EXPLORE THE EFFECTIVENESS OF MET TARGETED THERAPY IN TREATING HUMAN CANCERS SUCH AS NON-SMALL CELL LUNG CANCER AND THE POTENTIAL MET DRUG RESISTANCE MECHANISM LINE 4C - PROGRAM SERVICE ACTIVITY #3 THE LABORATORY OF STRUCTURAL SCIENCES IS FOCUSED ON STUDYING THE STRUCTURES AND FUNCTIONS OF PROTEIN/ LIGAND COMPLEXES THAT PLAY KEY ROLES IN MAJOR HORMONE SIGNALING PATHWAYS. THE LABORATORY ALSO WORKS ON EXPLORING THE STRUCTURAL INFORMATION TO DEVELOP THERAPEUTIC AGENTS FOR TREATING HUMAN DISEASE, INCLUDING CANCER AND DIABETES. LAB STUDIES USE MULTIDISCIPLINARY APPROACHES, INCLUDING MOLECULAR AND CELLULAR BIOLOGY, BIOCHEMISTRY, ANIMAL PHYSIOLOGY, AND X-RAY CRYSTALLOGRAPHY. RESEARCH IN THIS GROUP CURRENTLY FOCUSES ON THREE AREAS: NUCLEAR HORMONE RECEPTORS, THE MET TYROSINE KINASE RECEPTOR, AND G PROTEIN-COUPLED RECEPTORS. THESE PROTEINS, BEYOND THEIR FUNDAMENTAL ROLES IN BIOLOGY, ARE IMPORTANT DRUG TARGETS. RECENT DISCOVERIES INCLUDE: THE CRYSTAL STRUCTURES OF EACH PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) LIGAND-BINDING DOMAIN (LBD) BOUND TO MANY DIVERSE LIGANDS IN ORDER TO UNDERSTAND THE MOLECULAR BASIS OF LIGAND-MEDIATED SIGNALING BY PPAR'S; THE CRYSTAL STRUCTURES OF THE RECEPTORS BOUND TO COACTIVATORS OR CO-REPRESSORS, WHICH PROVIDES A FRAMEWORK FOR UNDERSTANDING THE MECHANISMS OF PPAR AGONISTS AND ANTAGONIST AND THE RECRUITMENT OF COACTIVATORS AND CO-REPRESSORS; ANDROGEN RECEPTOR (AR) MUTATION IN PROSTATE CANCERS OFTEN RESULTS IN ENHANCED BINDING TO A PARTICULAR COACTIVATOR, SRC-3 (WHICH IS ALSO CALLED "AMPLIFIED IN BREAST CANCER1", OR AIB1); AND RETINOIC ACID IS A LOW-AFFINITY LIGAND FOR COUP-TF, WHICH IS ONE OF THE MOST CONSERVED NUCLEAR RECEPTORS AND HAS ESSENTIAL ROLES IN ANGIOGENESIS, HEART DEVELOPMENT, CNS ACTIVITY, AND METABOLIC HOMEOSTASIS. FOR THE MET TYROSINE KINASE RECEPTOR, THE LAB HAS DETERMINED THE CRYSTAL STRUCTURE OF THE C-MET LIGAND, HEPATOCYTE GROWTH FACTOR, NK1 AND NK2 VARIANTS, AND FOR G PROTEIN-COUPLED RECEPTORS (GPCRS) WE HAVE DETERMINED CRYSTAL STRUCTURES OF THE LIGAND BINDING DOMAIN OF THE PTH RECEPTOR AND THE CRF RECEPTOR, AND WE ARE DEVELOPING HORMONE ANALOGS FOR TREATING OSTEOPOROSIS, DEPRESSION, AND DIABETES. IN ADDITION, WE ARE DEVELOPING A MAMMALIAN OVEREXPRESSION SYSTEM AND PLAN TO USE IT TO EXPRESS FULL-LENGTH GPCRS FOR CRYSTALLIZATION AND STRUCTURAL STUDIES. THE LAB ALSO STUDIES THE PLANT HORMONE ABSCISIC ACID (ABA) SIGNALING PATHWAYS, WITH THEIR STRUCTURES OF ABA RECEPTORS BEING HIGHLIGHTED AS ONE OF TOP 10 SCIENTIFIC BREAKTHROUGHS BY SCIENCE IN 2009. FORM 990, PART III, LINE 4D IN 2012, VARI RESEARCHERS FOUND WAYS TO POTENTIALLY DIAGNOSE AND FIGHT SEVERAL DIFFERENT TYPES OF CANCER AND NEURODEGENERATIVE DISEASES. BELOW ARE EXAMPLES OF SIGNIFICANT RESEARCH FINDINGS: - VARI RESEARCHERS PROVIDED A MORE COMPLETE UNDERSTANDING OF THE BIOLOGY OF TYPE 2 PAPILLARY RENAL CELL CARCINOMA (PRCC2), AN AGGRESSIVE TYPE OF KIDNEY CANCER WITH NO EFFECTIVE TREATMENT, WHICH WILL HELP DEVELOP EFFECTIVE TREATMENT STRATEGIES. - VARI RESEARCHERS INTEGRATED GENE EXPRESSION PROFILING AND RNAI SCREENING DATA TO IDENTIFY GENES INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF CLEAR CELL RENAL CELL CARCINOMA (CCRCC), A SUB TYPE THAT ACCOUNTS FOR 75 PERCENT OF ALL KIDNEY CANCERS AND THAT, UNLIKE PRCC2, RESPONDS FAVORABLY TO DRUGS TARGETING VASCULAR ENDOTHELIAL GROWTH FACTOR. THE STUDY INDICATED THAT CELL-CYCLE-RELATED GENES, IN PARTICULAR PLK1, WERE ASSOCIATED WITH DISEASE AGGRESSIVENESS AND HIGHLIGHT PLK1 AS A PROMISING POTENTIAL THERAPEUTIC TARGET. - VARI RESEARCHERS DETERMINED THAT COMBINATION DRUG THERAPY MAY BE NEEDED TO COMBAT NON-SMALL CELL LUNG CANCER (NSCLC). THEY FOUND THAT PROTEIN SIGNALING PLAYS A CRITICAL ROLE IN TUMOR CELL DEVELOPMENT, ACTIVATING THE STAT3 GENE, AN OVERACTIVE GENE IN SEVERAL TYPES OF CANCER, IN SOME NSCLC CELL LINES. THIS TYPE OF PROTEIN-GENE SIGNALING PLAYS A CRUCIAL ROLE IN TUMOR CELL BEHAVIOR THAT MAY NOT BE IMPACTED BY DRUGS THAT SELECTIVELY TARGET THESE MUTATIONS. - AN INTERNATIONAL TEAM LED BY THE NCCS-VARI TRANSLATIONAL RESEARCH LABORATORY REPORTED THE FIRST COMPREHENSIVE GENOMIC STUDY OF BILE DUCT CANCER, DISCOVERING CRITICAL GENES RESPONSIBLE FOR THE ONSET OF THE DISEASE. IDENTIFYING NEW GENES FREQUENTLY MUTATED IN BILE DUCT CANCERS WILL LEAD TO A BETTER UNDERSTANDING OF HOW BILE DUCT CANCERS DEVELOP. - VARI BECAME PART OF A NATIONAL RESEARCH EFFORT TO HELP PATIENTS WITH MULTIPLE MYELOMA BY EXTRACTING AND STORING DNA AND RNA FROM TISSUE SAMPLES FOR NEXT-GENERATION SEQUENCING ANALYSIS. RESEARCHERS HOPE TO SHED NEW LIGHT ON THE RELATIONSHIP BETWEEN MOLECULAR VARIATION AND PATIENTS' RESPONSE OR RESISTANCE TO THERAPY. - VARI RESEARCHERS AND COLLEAGUES IN CHINA DEMONSTRATED THAT AN ELEVATED PERCENTAGE OF TH17 CELLS IN THE TUMOR MICROENVIRONMENT PLAY A CRUCIAL ROLE IN THE PRODUCTION AND ACCUMULATION OF A CELL CORRELATED TO SURVIVAL OF PATIENTS WITH NASOPHARYNGEAL CARCINOMA (NPC), A CANCER OF THE HEAD AND NECK. - RESEARCHERS FROM LUND UNIVERSITY IN SWEDEN, UNDER THE DIRECTION OF DR. PATRIK BRUNDIN, DIRECTOR OF THE VARI CENTER FOR NEURODEGENERATIVE SCIENCE ANNOUNCED A BREAKTHROUGH IN RESTORING NEURON FUNCTION TO PARTS OF THE BRAIN DAMAGED BY HUNTINGTON'S DISEASE BY SUCCESSFULLY TRANSPLANTING INDUCED PLURIPOTENT STEM (IPS) CELLS INTO ANIMAL MODELS. THEY ALSO PUBLISHED A STUDY DETAILING HOW PARKINSON'S DISEASE SPREADS THROUGH THE BRAIN. - VARI RESEARCHERS IDENTIFIED PLASMA-BASED MOLECULAR BIOMARKERS. MOLECULAR BIOMARKERS WOULD BE HIGHLY USEFUL CLINICAL TOOLS TO DETECT PARKINSON'S PRIOR TO THE DEVELOPMENT OF THE DISEASE'S MOTOR SYMPTOMS. - VARI SCIENTISTS MAPPING THE STRUCTURE OF THE RECEPTOR FOR ABSCISIC ACID (ABA), A PLANT HORMONE THAT CONTROLS GROWTH, DEVELOPMENT AND RESPONSES TO ENVIRONMENTAL STRESS, DISCOVERED THAT ABA REGULATES THE STRESS-RESPONSE PATHWAY BY AFFECTING AN ENZYME BELONGING TO THE PHOSPHATASE FAMILY. FORM 990, PART X, LINE 33 VARI NET ASSETS SHOULD BE CONSIDERED ON A CONSOLIDATED BASIS WITH VAN ANDEL INSTITUTE (VAI), VAN ANDEL EDUCATION INSTITUTE (VAEI), AND THE TRANSLATIONAL GENOMICS RESEARCH INSTITUTE (TGEN), RELATED PARTIES. ON A CONSOLIDATED BASIS, NET ASSETS ARE $1,024,607,000 PER AUDITED FINANCIAL STATEMENTS. THE NEGATIVE NET ASSET BALANCE AT VARI IS DUE TO VAI FUNDING EXPENSES ON A CASH BASIS AND THE UNREALIZED LOSS RECORDED IN ASSOCIATION WITH THE INTEREST RATE SWAP. FORM 990, PART IX, COLUMN D FUNDRAISING EXPENSES AT VARI WERE INCURRED TO SUPPORT THE MISSION OF THE RESEARCH INSTITUTE THROUGH GRANT SOLICITATION AND EXTRAMURAL PROPOSAL PREPARATION. 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