2012-10-12T13:21:17-05:00 2011-11-30 DELOITTE TAX LLP 200 RENAISSANCE CENTER STE 3900 DETROIT MI 48243 990 2010-12-01 522000823 VAN ANDEL RESEARCH INSTITUTE VANA 6162345000 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 49503 TIMOTHY J MYERS 6162345368 2012-10-12 1 LORI BOYCE 3133963000 2010 2016-02-24 21:20:13Z TIMOTHY J MYERS 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 49503 64949975 0 X WWW.VAI.ORG X 1996 MI MEDICAL RESEARCH ORGANIZATION 7 4 345 0 1293324 319272 69868505 57012820 1332729 1522584 -272304 819423 5766282 4334013 76695212 63688840 221029 340825 0 0 22508665 26065382 0 0 465513 69776826 39147197 92506520 65553404 -15811308 -1864564 253776425 270167888 312690617 358085475 -58914192 -87917587 MEDICAL RESEARCH ORGANIZATION 0 0 2294558 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. 1913728 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. 1374533 1137649 THE LABORATORY FOR TRANSLATIONAL MEDICINE IS FOCUSED ON THE DEVELOPMENT AND UTILIZATION OF MOLECULAR AND COMPUTATIONAL TECHNOLOGIES TO STUDY HOW A TUMOR SPREADS TO DISTANT PARTS OF THE BODY FROM ITS ORIGINAL LOCATION (METASTASIS), AND IDENTIFYING APPROACHES TO TREAT SUCH AGGRESSIVE CANCERS USING A "PERSONALIZED MEDICINE" APPROACH. SEE SCHEDULE O FOR FURTHER INFORMATION ABOUT THIS PROGRAM. 38027999 490825 2080528 38027999 490825 2080528 43610818 1 1 0 1 0 0 1 0 0 1 0 0 1 1 0 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 91 0 345 1 1 1 0 0 0 0 0 0 0 0 0 X 7 4 1 1 0 0 0 1 0 1 1 0 0 1 0 0 0 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 412250 0 129965 GEORGE VANDE WOUDE 50.00 X 325763 0 44345 DR JAMES FAHNER 1.00 X 10000 0 0 DR FRITZ ROTTMAN PHD 1.00 X 10000 2000 0 DR JEFFREY TRENT 50.00 X X 1043405 0 303030 JOSE CARDENAS 1.00 X 10000 0 0 WILLIAM POST 1.00 X 0 0 0 R JACK FRICK 50.00 X 265597 0 101087 TIMOTHY MYERS 50.00 X 156599 0 90958 JEFFREY BATTERSHALL 1.00 X 0 0 0 DAVID WHITESCARVER 50.00 X 0 0 0 KATHLEEN VOGELSANG 45.00 X 180737 0 35576 DR H ERIC XU 45.00 X 267231 0 48773 DR JAMES RESAU 45.00 X 192433 0 39977 JOHN BENDER 45.00 X 233240 0 31603 BRYON CAMPBELL 45.00 X 179498 0 35557 STEVE HEACOCK FORMER 8.00 X 615119 0 23095 3901872 2000 883966 36 1 1 0 HUNT - OWEN AMES & KIMBALL (SEE SCHEDULE 6720 SCOTTSDALE DR STE 300 SCOTTSDALE AZ 85253 CONSTRUCTION SERVICES 12393896 BANK OF AMERICAMERRILL LYNCH 100 N TRYON ST CHARLOTTE NC 28202 CREDIT ENHANCEMENT FEES 3600486 AON RISK SERVICES CENTER INC 75 REMITTANCE DR STE 1943 CHICAGO IL 606751943 INSURANCE 543679 WARNER NORCROSS & JUDD 111 LYON ST 900 OLD KENT GRAND RAPIDS MI 495032487 LEGAL/ CONSULTING 444669 DK SECURITY INC 5160 FALCONVIEW AVE SE KENTWOOD MI 49512 SECURITY SERVICES 420458 24 47313999 6982060 2716761 57012820 RESEARCH BILLED REV 541700 1522584 235284 1287300 1522584 159959 159959 242481 242481 2183955 11679 1147826 5655 1036129 6024 1042153 1036129 6024 767118 107654 659464 659464 659464 REL. PARTY ADMIN SUPPO 561000 4274282 4274282 REIMBURSED EXPENSES 900099 263846 263846 LOSS ON INVESTMENTS 523000 -1491927 -1491927 3178 3178 3049379 63688840 1930877 1293324 3451819 340825 340825 2799911 1527558 1272353 18030691 9952428 7662767 415496 1517854 904745 587999 25110 2388416 1423583 925003 39830 1328510 791961 514902 21647 1133197 69871 1063326 176968 176968 50000 50000 2384795 1805653 579142 452400 36261 416139 141280 82483 58797 317986 134979 183007 2570936 1985561 585375 768754 551253 217501 126927 94418 32509 11205203 8647481 2557722 10123630 8209616 1914014 370573 239644 130929 LAB SUPPLIES & SERVICES 3464855 3464855 EQUIPMENT & SOFTWARE 1944232 1106860 837372 OTHER SCIENTIFIC 764424 764424 SCIENTIFIC PURCHASED SE 705358 705358 RECRUITING AND RELOCATI 586227 227871 358356 1859452 543130 1352892 -36570 65553404 43610818 21477073 465513 6671503 954773 2623400 1194099 1236706 2551038 2351000 1664455 823236 1271897 263656878 52776208 219778822 210880670 1887951 1367061 97917 97917 18305890 50185978 253776425 270167888 25465798 55926177 1453448 1756331 220000000 220385000 65771371 80017967 312690617 358085475 X -39862048 -80494164 -19053644 -7425523 1500 2100 -58914192 -87917587 253776425 270167888 X -1864564 -27138831 X X 0 1 1 X 1 1 X SPECTRUM HEALTH GRAND RAPIDS MI RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED 0 1 0 0 0 0 1 50000 0 0 50000 0 PART IV, SUPPLEMENTAL INFORMATION: PAID MANAGEMENT WAS ONLY UTILIZED TO MANAGE RELATIONSHIPS WITH OUTSIDE CONSULTANTS AND DID NOT PARTICIPATE IN DIRECT LOBBYING. THEREFORE, NO COMPENSATION EXPENSE HAS BEEN ALLOCATED TO LOBBYING EXPENSE. 435037 X 0 1 1 5288315 5288315 218665823 26474773 192191050 38310415 26272369 12038046 1392325 29066 1363259 210880670 BOND ISSUANCE COSTS NET OF ACCUMULATED AMORTIZATION 1565978 PLEDGED SECURITIES 48620000 50185978 ACCRUED POSTRETIREMENT BENEFIT OBLIGATION 1364665 UNREALIZED LOSS ON BOND SWAP 62909361 MSU MED SCHOOL - CONTRIBUTION PAYABLE 7696315 CAPITAL LEASE 47626 TGEN - CONTRIBUTION PAYABLE 8000000 80017967 63688840 65553404 -1864564 -251644 -26887187 -27138831 -29003395 59181889 -251644 18975 -232669 59414558 4274282 4274282 63688840 88185284 26906162 26906162 61279122 4274282 4274282 65553404 PART III, LINE 4: THE GLASS CHIHULY SCULPTURE IS A UNIQUE, ONE-OF-A-KIND CHANDELIER REMINISCENT OF THE DNA DOUBLE HELIX. THE CHANDELIER, WHICH IS PLACED IN THE RECEPTION AREA, PROVIDES MOTIVATION AND INSPIRATION AS SCIENTISTS ARE DRIVEN TO UNDERSTAND THE GENETIC BASIS OF DISEASES IN THEIR PURSUIT OF CURES AND OTHER THERAPIES. 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 BUDGETS. PART X: IN JUNE 2006, FASB ISSUED ASC 740, INCOME TAXES (FORMERLY FASB INTERPRETATION (FIN) NO. 48, ACCOUNTING FOR UNCERTAINTY IN INCOME TAXES - AN INTERPRETATION OF FASB STATEMENT NO. 109). ASC 740 PRESCRIBES A RECOGNITION THRESHOLD AND MEASUREMENT ATTRIBUTE FOR THE FINANCIAL STATEMENT RECOGNITION AND MEASUREMENT OF A TAX POSITION TAKEN OR EXPECTED TO BE TAKEN IN A TAX RETURN. ASC 740 ALSO PROVIDES GUIDANCE ON DERECOGNITION, CLASSIFICATION, INTEREST AND PENALTIES, ACCOUNTING FOR INTERIM PERIODS, DISCLOSURE, AND TRANSITION. ASC 740 IS EFFECTIVE FOR FISCAL YEARS BEGINNING AFTER DECEMBER 15, 2008. THIS STANDARD WAS ADOPTED FOR FISCAL YEAR ENDED NOVEMBER 30, 2010. THERE WAS NO MATERIAL IMPACT ON THE CONSOLIDATED FINANCIAL STATEMENTS FOR THE YEAR ENDED NOVEMBER 30, 2011. PART XI, LINE 8: NET LOSS RELATED TO THE INTEREST RATE SWAP. PART XII, LINE 2D: RECLASS OF TMS 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 TMS COST OF GOODS SOLD TO PRESENT ON STATEMENT OF REVENUE RATHER THAN STATEMENT OF FUNCTIONAL EXPENSES. PART XII AND XIII, LINE 4B: EXPENSE ALLOCATIONS 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 429197 2 0 2 429197 0 429197 0 0 0 0 0 0 1 GRADUATE STUDENT STIPENDS FOR VAN ANDEL GRADUATE SCHOOL AND MICHIGAN STATE UNIVERSITY STUDENTS 8 235354 10500 TUITION PAID FOREIGN NATIONAL STUDENT STIPENDS 14 94971 OTHER INFORMATION: PART IV: SCHEDULE I, PART I, LINE 2: FUNDS PROVIDED TO THE RESEARCH STUDENTS ARE CONTINUALLY MONITORED TO ENSURE THAT ALL FUNDS ARE USED FOR MISSION-DRIVEN PURPOSES. STIPENDS ARE PROVIDED DIRECTLY TO THE STUDENTS FOR LIVING ASSISTANCE. X X X 0 1 X X X X X 1 1 0 0 0 0 0 0 0 DAVID VAN ANDEL 300014 0 89284 0 22952 0 129426 0 539 0 542215 0 0 0 GEORGE VANDE WOUDE 281791 0 15000 0 28972 0 43022 0 1323 0 370108 0 0 0 DR JEFFREY TRENT 853335 0 130000 0 60070 0 291278 0 11752 0 1346435 0 0 0 R JACK FRICK 217709 0 45908 0 1980 0 92939 0 8148 0 366684 0 0 0 TIMOTHY MYERS 146863 0 9449 0 287 0 82810 0 8148 0 247557 0 0 0 KATHLEEN VOGELSANG 164031 0 16016 0 690 0 27429 0 8147 0 216313 0 0 0 DR H ERIC XU 245796 0 20985 0 450 0 40626 0 8147 0 316004 0 0 0 DR JAMES RESAU 186741 0 3712 0 1980 0 31830 0 8147 0 232410 0 0 0 JOHN BENDER 209861 0 10000 0 13379 0 23455 0 8148 0 264843 0 0 0 BRYON CAMPBELL 172363 0 6445 0 690 0 27410 0 8147 0 215055 0 0 0 STEVE HEACOCK FORMER 90579 0 60371 0 464169 0 18751 0 4344 0 638214 0 0 0 PART I, LINE 1A VARI ALLOWS FOR FIRST-CLASS OR CHARTER TRAVEL TO OFFICERS AND TRUSTEES. FITNESS CENTER MEMBERSHIP DUES WERE PAID BY VARI FOR STEVE HEACOCK TOTALING $500 FOR CALENDAR YEAR 2010. PART I, LINE 1B: THERE IS NOT A POLICY FOR HOUSING ALLOWANCE OR RESIDENCE FOR PERSONAL USE. THIS IS OFFERED ONLY ON RARE OCCASIONS AND FOR SPECIAL CIRCUMSTANCES. HUMAN RESOURCES MANAGES THIS ON A CASE BY CASE BASIS. PART I, LINE 1B A WRITTEN POLICY IS IN PLACE FOR FIRST CLASS/ CHARTER TRAVEL AND HEALTH/ SOCIAL CLUB DUES/ FEES. SUPPLEMENTAL INFORMATION PART III PART I, LINE 4A: SEVERANCE PAID TO STEVE HEACOCK TOTALED $0 IN FISCAL YEAR 2011, $448,871 IN CALENDAR YEAR 2010 PART I, LINE 4B: STEVE HEACOCK $0 FOR FISCAL YEAR 2011 AND $3,808 CALENDAR YEAR 2010 GEORGE VANDE WOUDE $16,500 FISCAL YEAR 2011 AND CALENDAR YEAR 2010 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 0.00860 0.00860 1 1 1 0 0 0 0 FORM 990, PART VI, SECTION A, LINE 2 VARI AND VAEI SHARE COMMON MANAGEMENT. AS OFFICERS OF VARI, DAVID VAN ANDEL, R. JACK FRICK, TIMOTHY MYERS AND DAVID WHITESCARVER INTERACT AND WORK TOGETHER WITH STEVE TRIEZENBERG, A KEY EMPLOYEE OF VAEI. FORM 990, PART VI, SECTION A, LINE 3 JERRY CALLAHAN, AN INDEPENDENT CONTRACTOR, SERVES AS THE VICE PRESIDENT OF BUSINESS DEVELOPMENT, TECHNOLOGY TRANSFER, AND OFFICE OF GRANTS AND CONTRACTS. 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 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 12 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. THE VAN ANDEL INSTITUTE ADMINISTERS THE CONFLICT OF INTEREST (COI) POLICY THROUGH TWO COMMITTEES: THE INDIVIDUAL COI COMMITTEE AND THE INSTITUTIONAL COI COMMITTEE. 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 INDIVIDUAL COI COMMITTEE, CHAIRED BY THE DIRECTOR OF COMPLIANCE, GENERATES AN ANNUAL DISCLOSURE QUESTIONNAIRE DISTRIBUTED TO ALL STAFF TO ENFORCE THE POLICY. THE CONFLICTS COMMITTEE IS RESPONSIBLE FOR MAKING RECOMMENDATIONS TO THE DIRECTOR. RESOLUTIONS ARE IMPLEMENTED WITH APPROVAL OF THE COMMITTEE AND IN DISCUSSION WITH THE VAI CHAIRMAN. THE COI POLICY ALSO SERVES AS A GUIDE FOR ALL MEMBERS OF THE BOARD OF TRUSTEES AND SENIOR EXECUTIVES. THE INSTITUTIONAL COI COMMITTEE 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 OFFICE OF THE GENERAL COUNSEL REVIEWS AND MEETS WITH THE BOARD OF TRUSTEES TO RESOLVE POTENTIAL CONFLICTS. FORM 990, PART VI, SECTION B, LINE 15 COMPENSATION FOR THE CEO, EXECUTIVE MANAGEMENT OFFICIALS, EXECUTIVE DIRECTOR, OFFICERS, AND KEY EMPLOYEES IS REVIEWED AND APPROVED ANNUALLY BY THE VAN ANDEL INSTITUTE'S INDEPENDENT COMPENSATION COMMITTEE. RECORDS AND DOCUMENTATION, INCLUDING COMPARABILITY DATA, ARE KEPT AND SUPPORT DECISIONS MADE ON BEHALF OF THESE ARRANGEMENTS AND ARE CONTEMPORANEOUSLY DOCUMENTED. FORM 990, PART VI, SECTION C, LINE 19 THESE DOCUMENTS ARE AVAILABLE TO THE PUBLIC UPON REQUEST. FORM 990, PART VII, SECTION B COMPENSATION FOR HUNT - OWEN AMES & KIMBALL EXCLUDES ESTIMATED MATERIALS AND INCLUDES ESTIMATED LABOR ON HUNT MANAGED SUB-CONTRACTORS. FORM 990, PART VII, SECTION B JEFFREY BATTERSHALL IS LISTED AS SECRETARY ON PAGE 7. HE SERVED ON AN INTERIM BASIS AND WAS CONTRACTED FOR THIS PURPOSE THROUGH THE LAW FIRM WARNER, NORCROSS, & JUDD THROUGH OCTOBER 2011. ALL PAYMENTS FOR HIS SERVICES WERE PAID DIRECTLY TO WARNER, NORCROSS, & JUDD. FORM 990, PART VII, PAGE 7 DAVID VAN ANDEL, R. JACK FRICK, TIMOTHY MYERS, JEFFREY BATTERSHALL, 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 LOSSES ON INVESTMENTS: -251,644. LOSS ON BOND INTEREST SWAP -26,887,187. TOTAL TO FORM 990, PART XI, LINE 5: -27,138,831. FORM 990, PART XII, LINE 2C THE PROCESS FOR SELECTING THE AUDITOR FOR VAN ANDEL RESEARCH INSTITUTE'S FINANCIAL STATEMENTS DID NOT CHANGE DURING 2011. VARI'S THREE LARGEST PROGRAM SERVICES BY EXPENSES FORM 990, PART III, LINES 4A-4C LINE 4A - PROGRAM SERVICE ACTIVITY #1 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, X-RAY CRYSTALLOGRAPHY, AND PLANT HORMONE ABSCISIC ACID (ABA) RECEPTORS. 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. 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 MAJOR ADVANCES MADE IN THE PAST DECADE IN UNDERSTANDING HGF/SF-MET CELLULAR SIGNALING HAVE PROVIDED POWERFUL RATIONALE FOR THE DEVELOPMENT OF INHIBITORS TARGETING IT. SEVERAL OF THESE INNOVATIVE INHIBITORS ARE CURRENTLY BEING EVALUATED IN CLINICAL TRIALS (HTTP://WWW.VAI.ORG/METCLINICALTRIALS/). 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. IN COLLABORATION WITH DR. BRIAN CAO, WE HAVE DEVELOPED A MONOCLONAL ANTIBODY (DESIGNATED MET4), WHICH WE BELIEVE WILL PROVE VALUABLE AS A DIAGNOSTIC REAGENT AS WELL AS AN ESSENTIAL RESEARCH TOOL. AS PART OF THE ONGOING EFFORT TO FURTHER ENHANCE OUR UNDERSTATING OF THE HGF/SF-MET SIGNALING SYSTEM, 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 IN 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 -INVESTIGATING THE UNIQUE ROLES THAT C-MET AND ERBB2 PLAY IN THE PROGRESSION AND METASTASIS OF AGGRESSIVE BREAST CANCERS -STUDYING THE MECHANISMS RESPONSIBLE FOR PHENOTYPIC SWITCHING (E-MT/M-ET) AND EVALUATING THE ROLE OF CHROMOSOME INSTABILITY IN TUMOR PROGRESSION -DETERMINING THE TUMOR SUPPRESSOR ROLE OF MIG-6 AS WELL AS INVESTIGATING THE MOLECULAR MECHANISM UNDERLYING ITS FUNCTION IN BOTH CANCER AND OSTEOARTHRITIS LINE 4C - PROGRAM SERVICE ACTIVITY #3 THE LABORATORY OF TRANSLATIONAL MEDICINE (LTM) IS FOCUSED ON TWO CRITICAL AREAS OF CANCER RESEARCH. AT THE BASIC SCIENCE LEVEL, THE LAB IS UTILIZING A RANGE OF MOLECULAR AND COMPUTATIONAL TECHNOLOGIES TO STUDY HOW TUMORS SPREAD TO DISTANT PARTS OF THE BODY FROM ITS ORIGINAL LOCATION - THIS PROCESS, KNOWN AS METASTASIS, IS ACCOUNTABLE FOR >90% OF CANCER RELATED DEATHS, AND THE IDENTIFICATION OF NEW DIAGNOSTIC AND TREATMENT STRATEGIES TARGETING THIS LETHAL PHENOTYPE OF CANCER ARE OF UTTERMOST IMPORTANCE. IN THE AREA OF APPLIED RESEARCH, THE LTM IS FOCUSED ON DEVELOPING AND IMPLEMENTING STRATEGIES TO "PERSONALIZE" THE TREATMENT OF A RANGE OF AGGRESSIVE CANCERS WITH MOLECULARLY-GUIDED THERAPIES. THE LTM CONTINUES TO BE AT THE FOREFRONT OF DESIGNING AND IMPLEMENTING APPROACHES IN WHICH THE TREATMENT OF AN INDIVIDUAL PATIENT'S CANCER IS BASED UPON THE MOLECULAR ANALYSIS OF THAT PATIENT AND THEIR SPECIFIC DISEASE. TO FACILITATE THIS, THE LAB DESIGNED AND DEVELOPED AN INTEGRATED, BIOMEDICAL INFORMATICS SYSTEM FOR DATA MANAGEMENT, ANALYSIS, AND REPORTING (KNOWN AS XENOBASE BIOINTEGRATION SUITE (XB-BIS)). IN ADDITION, THE LAB HAS BEEN HEAVILY INVOLVED IN COMMUNITY FOUNDING PARTNERSHIPS THAT HAVE INCLUDED THE FORMATION OF A BIOMARKER-DRIVEN CLINICAL TRIALS CONSORTIUM (CLINXUS), A HIGH COMPLEXITY CLIA CERTIFIED LABORATORY (THE CENTER FOR MOLECULAR MEDICINE), AND A PERSONALIZED MEDICINE INFORMATION SERVICE COMPANY (INTERVENTION INSIGHTS) WHICH COLLECTIVELY, PERMIT THE APPLICATION OF PERSONALIZED THERAPY FOR LATE STAGE CANCER PATIENTS. RECENT ACCOMPLISHMENTS INCLUDE THE DEVELOPMENT AND COMMERCIALIZATION OF AN INTEGRATED INFORMATICS SOLUTION (XB-BIS), WHICH ENABLES EFFICIENT EXCHANGE OF INFORMATION BETWEEN THE BASIC RESEARCH LABORATORY AND THE CLINIC FOR EFFECTIVE TRANSLATIONAL RESEARCH. XB-BIS HAS BEEN LICENSED TO TRANSMED SYSTEMS WHICH IS NOW SUPPORTING ITS ADOPTION ACROSS MULTIPLE GROUPS ENGAGED IN TRANSLATIONAL RESEARCH BOTH WITHIN THE UNITED STATES AND BEYOND. IN PART THROUGH THE USE OF XB-BIS, THE LAB RECENTLY COMPLETED A FEASIBILITY STUDY OF 50 LATE-STAGE PEDIATRIC AND ADULT CANCER PATIENTS IN WHICH TUMOR-DERIVED GENE EXPRESSION PROFILES WERE ANALYZED TO IDENTIFY POTENTIAL DRUGS TO TARGET PERTURBED MOLECULAR COMPONENTS OF EACH PATIENT'S SPECIFIC TUMOR. ANECDOTAL SIGNS OF SUCCESS IN A HANDFUL OF PATIENTS PROVIDED THE IMPETUS TO LAUNCH A SERIES OF FOLLOW-UP STUDIES WITHIN FOCUSED PATIENT POPULATIONS, AND ALSO LED TO THE FORMATION OF INTERVENTION INSIGHTS, A PERSONALIZED MEDICINE INFORMATION SERVICE THAT SUPPORTS COMMUNITY AND ACADEMIC ONCOLOGISTS ACROSS THE UNITED STATES. AT VARI, THE LTM CONTINUES TO ADVANCE THE MOLECULAR AND COMPUTATIONAL TECHNOLOGIES AND IS CURRENTLY INVESTIGATING THE POTENTIAL USE OF NEXT GENERATION SEQUENCING TECHNOLOGIES IN TARGETED TRIALS OF NEUROBLASTOMA (SPONSORED BY THE NEUROBLASTOMA AND MEDULLOBLASTOMA TRANSLATIONAL RESEARCH CONSORTIUM (NMTRC) AND IN PARTNERSHIP WITH DELL AND INTERVENTION INSIGHTS), METASTATIC MELANOMA (SPONSORED BY A RECENT STAND UP 2 CANCER GRANT), TRIPLE NEGATIVE BREAST CANCER (SPONSORED BY A KOMEN PROMISE GRANT), AND GLIOBLASTOMA (SPONSORED BY HENRY FORD HOSPITAL AND A RECENT NIH GRANT). FORM 990, PART III, LINE 4D ALL OTHER PROGRAM SERVICE ACTIVITIES IN 2011, VARI RESEARCHERS FOUND WAYS TO POTENTIALLY DIAGNOSE AND FIGHT SEVERAL DIFFERENT TYPES OF CANCER. IN 2011, VARI ALSO ANNOUNCED A PATENT WITH GENTEL BIOSCIENCES, A LEADER IN PROTEOMICS TOOLS, FOR A NEW APPROACH TO IDENTIFY BIOLOGICAL MARKERS TO HELP DIAGNOSE DISEASES SUCH AS CANCER. BELOW ARE OTHER EXAMPLES OF SIGNIFICANT RESEARCH FINDINGS: -VARI ANNOUNCED THE CREATION OF THE VARI PEDIATRIC CANCER TRANSLATIONAL RESEARCH PROGRAM, A PROJECT THAT UNITES BASIC RESEARCH AND CLINICAL CARE THROUGH A NATIONWIDE CONSORTIUM OF PARTNERS. -RESEARCHERS DETERMINED HOW THE ANTI-CANCER ANTIBIOTIC GELDANAMYCIN AND ITS DERIVATIVE 17AAG WORK IN MORE DETAIL AND HAVE UNCOVERED A POSSIBLE EXPLANATION FOR SIDE EFFECTS, WHICH COULD INFORM FUTURE DRUG DESIGN. -RESEARCHERS IDENTIFIED MK-STYX AS AN ENZYME THAT HELPS TO REGULATE CELL DEATH, AND FOUND OUT MORE ABOUT SPECIFICALLY HOW MK-STYX WORKS. -RESEARCHERS IDENTIFIED THE GENE POLO-LIKE KINASE 1 (PLK1) AS A NEW POTENTIAL DRUG TARGET TO TREAT CLEAR CELL RENAL CELL CARCINOMA (CCRCC), THE MOST COMMON FORM OF KIDNEY CANCER. THEY ALSO FOUND THAT THE PLK1 INHIBITOR BI 2536, CURRENTLY IN CLINICAL TRIALS FOR THE TREATMENT OF SEVERAL CANCERS, LED TO DRAMATIC REGRESSION OF CCRCC TUMORS. -RESEARCHERS IDENTIFIED AN ENZYME, LRRK2, THAT SEEMS TO COOPERATE WITH MET, AN IMPORTANT GENE IN SEVERAL CANCERS, TO PROMOTE TUMOR CELL GROWTH AND SURVIVAL, SPECIFICALLY IN PAPILLARY RENAL AND THYROID CARCINOMAS. -RESEARCHERS IDENTIFIED SPECIFIC PROTEINS THAT CARRY THE CA 19-9, THE BEST INDICATOR OF PANCREATIC CANCER, ANTIGEN AND MEASURED CA 19-9 LEVELS ON EACH PROTEIN IN AN EFFORT TO ENHANCE BLOOD TESTING. BETTER KNOWLEDGE OF THESE CARRIERS IN VARIOUS DISEASE STATES COULD LEAD TO IMPROVED DIAGNOSTIC TESTS. -RESEARCHERS INVESTIGATED THE ROLE OF THE PROTEIN HEPATOMA-DERIVED GROWTH FACTOR (HDGF) IN BREAST AND PROSTATE CANCERS AND FOUND THAT IT MAY PROMOTE CELL GROWTH IN THESE CANCERS AND COULD BE A THERAPEUTIC TARGET. -RESEARCHERS FOUND THAT IN SK-MEL-28 MELANOMA CELLS, MEK2, AND NOT MEK1, IS SUFFICIENT FOR CELL PROLIFERATION, BUT THAT MEK1 CAN COMPENSATE FOR THE LOSS OF MEK2 ACTIVITY. THESE INSIGHTS MAY AID IN THE DESIGN OF MORE EFFECTIVE THERAPIES FOR TREATING MELANOMA AND OTHER MEK-DEPENDENT CANCERS. -IN COLLABORATION WITH RESEARCHERS FROM ANOTHER ORGANIZATION, RESEARCHERS IDENTIFIED A NOVEL MARKER THAT COULD HELP DIAGNOSE TYPE II EATL, WHICH IS THE TYPE MORE COMMON IN ASIA AND NOT ASSOCIATED WITH COELIAC DISEASE. -IN ADDITION TO THOSE LISTED ABOVE, THERE WERE ALSO FINDINGS WITHIN MELANOMA, BRAIN CANCER, HEAD AND NECK CANCER, ALZHEIMER'S DIABETES, AUTOIMMUNE DISEASE, RETINOPATHY, AND HOOKWORM. 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 $896,445,000 PER AUDITED FINANCIAL STATEMENTS. THE NEGATIVE NET ASSETS AT VARI ARE DUE TO VAI FUNDING EXPENSES ON A CASH BASIS AND GUARANTEEING VARI'S LONG-TERM DEBT AND UNREALIZED BOND SWAP LOSS. 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. FORM 990, PART VI, LINES 12-14 THE INSTITUTE DOES HAVE A WRITTEN CONFLICT OF INTEREST POLICY, A WRITTEN WHISTLEBLOWER POLICY, AND A WRITTEN DOCUMENT RETENTION POLICY; HOWEVER, IS REQUIRED TO CHECK NO BASED ON THE IRS INSTRUCTIONS AS THESE POLICIES HAVE NOT BEEN OFFICIALLY APPROVED BY OUR BOARD. 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