2015-10-14T12:38:36-05:00 2014-11-30 861065772 DELOITTE TAX LLP 200 RENAISSANCE CENTER STE 3900 DETROIT MI 48243 990 2013-12-01 522000823 VAN ANDEL RESEARCH INSTITUTE VANA 6162345000 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 49503 TIMOTHY J MYERS CFO 6162345368 2015-10-14 1 LORI BOYCE P00121981 3133963000 2013 2016-02-25 16:41:14Z TIMOTHY J MYERS 333 BOSTWICK AVENUE NE GRAND RAPIDS MI 49503 76553584 0 X WWW.VAI.ORG X 1996 MI MEDICAL RESEARCH ORGANIZATION 5 3 402 0 646113 158398 54068694 67009142 693011 1460533 64454 260434 7773170 6325873 62599329 75055982 302224 201907 0 0 28311621 29232885 0 0 1314444 39419946 37139975 68033791 66574767 -5434462 8481215 224789773 251725432 290456167 327697622 -65666394 -75972190 X MEDICAL RESEARCH ORGANIZATION VAN ANDEL RESEARCH INSTITUTE IS AN INDEPENDENT BIOMEDICAL RESEARCH ORGANIZATION COMMITTED TO IMPROVING THE HEALTH AND ENHANCING THE LIVES OF CURRENT AND FUTURE GENERATIONS. 1 0 9445653 162442 998737 CENTER FOR CANCER AND CELL BIOLOGY SCHEDULE O PROVIDES FURTHER INFORMATION REGARDING THIS PROGRAM'S ACCOMPLISHMENTS. 3648152 39465 54077 CENTER FOR EPIGENETICSSCHEDULE O PROVIDES FURTHER INFORMATION REGARDING THIS PROGRAM'S ACCOMPLISHMENTS. 3523348 CENTER FOR NEURODEGENERATIVE SCIENCESEE SCHEDULE O FOR FURTHER INFORMATION ABOUT THIS PROGRAM'S ACCOMPLISHMENTS. 27399460 407719 27399460 407719 44016613 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 1 0 0 0 1 1 0 0 0 1 1 1 1 0 0 1 119 0 402 1 1 1 0 0 0 0 0 0 0 0 0 X 5 3 1 0 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 DAVID VAN ANDEL CHAIRMAN / CEO 36.00 17.00 X X 416751 0 133745 DR GEORGE VANDE WOUDE TRUSTEE/ INVESTIGATOR 50.00 0.00 X 300227 0 26792 DR JAMES FAHNER TRUSTEE 1.00 1.00 X 10000 2000 0 DR GARY TARPLEY TRUSTEE 1.00 0.00 X 10000 0 0 DR RALPH WEICHSELBAUM TRUSTEE 1.00 0.00 X 4500 0 0 TIMOTHY MYERS V.P. & CHIEF FINANCIAL OFFICER 50.00 3.00 X 235524 0 79088 DAVID WHITESCARVER SECRETARY/V.P. & CHIEF LEGAL OFFICER 50.00 3.00 X 356220 0 128674 DR JANA HALL CHIEF OPERATIONS OFFICER 50.00 3.00 X 316987 0 99279 DR H ERIC XU INVESTIGATOR 45.00 0.00 X 296596 0 53125 DR SCOTT JEWELL INVESTIGATOR 45.00 0.00 X 317294 0 66139 LOVE COLLINS III V.P. OF DEVELOPMENT, COMM. & MKTNG. 45.00 0.00 X 292750 0 89544 DR PATRIK BRUNDIN VARI ASSOCIATE DIRECTOR OF RESEARCH 45.00 0.00 X 475233 0 112798 GERALD CALLAHAN V.P. OF BUSINESS DEVELOPMENT 45.00 0.00 X 231554 0 85150 R JACK FRICK DONE 121111 CHIEF ADMINISTRATIVE OFFICER -FORMER 0.00 0.00 X 187705 0 0 3451341 2000 874334 44 1 1 0 DK SECURITY INC 5160 FALCONVIEW AVE SE KENTWOOD MI 49512 SECURITY SERVICES 384716 HONIGMAN MILLER SCHWARTZ LLC 130 SOUTH FIRST ST 4TH FL ANN ARBOR MI 482263506 LEGAL/ CONSULTING 271701 FEDERAL EXPRESS PO BOX 223125 PITTSBURGH PA 152512125 SHIPPING 227088 OLYMPIA ENTERTAINMENT INC 2211 WOODWARD AVE 5TH DETROIT MI 48201 ADVERTISING 225300 FAIRLY PAINLESS ADVERTISING 44 EAST EIGHTH STREET HOLLAND MI 49423 ADVERTISING 218702 19 54244758 8081101 4683283 152911 67009142 RESEARCH BILLED REV 541700 1460533 851139 609394 1460533 255626 255626 491283 491283 1487416 1468592 18824 18824 18824 33818 29010 4808 4808 4808 REL. PARTY ADMIN SUPPO 561000 5401058 5401058 REIMBURSED EXPENSES 900099 271487 271487 STATE TAX REFUNDS 900099 36719 36719 106502 106502 5815766 75055982 874771 646113 6525956 201907 201907 2384297 769206 1615091 21012535 11883978 8420804 707753 1716490 1035265 628557 52668 2903422 1751315 1061301 90806 1216141 733574 444428 38139 407217 63881 343336 105100 105100 262848 262848 2711964 2024936 558301 128727 1226668 4637 1079977 142054 99650 49654 49689 307 361357 142065 203435 15857 2511541 2235158 274077 2306 875355 436370 387963 51022 195902 133428 59489 2985 8633669 7182829 1450840 9128908 7880962 1247946 438396 268277 170119 LAB SUPPLIES & SERVICES 3223883 3214501 9382 EQUIPMENT & SOFTWARE 2607673 1276892 1312073 18708 OTHER SCIENTIFIC 1303572 1295845 7727 BAD DEBT EXPENSE 523400 523400 2522872 1431933 1027827 63112 66574767 44016613 21243710 1314444 487783 12177780 2496299 2575159 1841254 2523497 18355 9657 1596595 1555278 1127550 1522498 269164333 75691793 197287670 193472540 943113 1268817 18991154 36620206 224789773 251725432 26805514 44640472 474750 2206247 220000000 220000000 43175903 60850903 290456167 327697622 X -66813709 -78281142 1143715 2215852 3600 93100 -65666394 -75972190 224789773 251725432 X 8481215 34742 -18821753 X 0 1 X 1 1 1 X SPECTRUM HEALTH GRAND RAPIDS MI TRINITY HEALTH GRAND RAPIDS MI RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED 367563 367563 66207204 66574767 1000000 250000 0 0 1000000 1000000 1000000 3000000 4500000 68133 85680 367563 521376 250000 250000 250000 750000 1125000 5288315 5288315 219768174 43371435 176396739 41304971 32310457 8994514 2802873 9901 2792972 193472540 BOND ISSUANCE COSTS NET OF ACCUMULATED AMORTIZATION 310206 PLEDGED SECURITIES 36310000 36620206 ACCRUED POSTRETIREMENT BENEFIT OBLIGATION 1956084 UNREALIZED LOSS ON INTEREST RATE SWAP 56314598 MSU COLLEGE OF HUMAN MEDICINE- CONTRIBUTION PAYABLE 2500000 CAPITAL LEASE 80221 60850903 X 71409773 321600 1468592 1790192 69619581 5436401 5436401 75055982 81715569 20577203 20577203 61138366 5436401 5436401 66574767 PART X, LINE 2: PART X, LINE 1(1) AND LINE 2: THERE ARE NO UNCERTAIN TAX POSITIONS RELATED TO VARI. PART XI, LINE 2D - OTHER ADJUSTMENTS: RENTAL EXPENSES 1,468,592. PART XI, LINE 4B - OTHER ADJUSTMENTS: NET ALLOCATED 5,401,058. STATE TAX REFUNDS 35,343. PART XII, LINE 2D - OTHER ADJUSTMENTS: LOSS ON INTERST RATE SWAP 19,108,611. RENTAL EXPENSES 1,468,592. PART XII, LINE 4B - OTHER ADJUSTMENTS: NET ALLOCATED 5,401,058. STATE TAX REFUNDS 35,343. PART V THE VAN ANDEL INSTITUTE (A RELATED ORGANIZATION) MAINTAINS ENDOWED FUNDS FOR THE BENEFIT OF BOTH VARI AND THE VAN ANDEL EDUCATION INSTITUTE (A RELATED ORGANIZATION) TO FUND OPERATING EXPENSES. PART XI AND XII, LINE 4B EXPENSE ALLOCATIONS PRESENTED WITHIN REVENUE. EAST ASIA & THE PACIFIC 0 1 PROGRAM SERVICES RESEARCH COLLABORATION - RESEARCH SERVICES 382768 EUROPE 0 0 PROGRAM SERVICES REVIEW OF PAPER 2000 EUROPE 0 0 UNRELATED TRADE OR BUSINESS FEE FOR SERVICES EUROPE 0 0 RESEARCH SERVICES LICENSING FEES 0 1 0 0 0 1 384768 0 384768 0 0 0 0 0 0 1 GRADUATE STUDENT STIPENDS FOR MICHIGAN STATE UNIVERSITY STUDENTS 5 141319 0 FOREIGN NATIONAL STIPENDS 12 60588 PART I, LINE 2: STIPENDS ARE PROVIDED TO THE RESEARCH STUDENTS FOR LIVING AND INSURANCE ASSISTANCE. X 1 1 X X X X X 1 0 0 0 0 0 0 1 0 DAVID VAN ANDEL CHAIRMAN / CEO 310965 0 85054 0 20732 0 133230 0 515 0 550496 0 85054 0 DR GEORGE VANDE WOUDE TRUSTEE/ INVESTIGATOR 280255 0 0 0 19972 0 25500 0 1292 0 327019 0 0 0 TIMOTHY MYERS V.P. & CHIEF FINANCIAL OFFICER 202295 0 32779 0 450 0 70760 0 8328 0 314612 0 32779 0 DAVID WHITESCARVER SECRETARY/V.P. & CHIEF LEGAL OFFICER 261267 0 76243 0 18710 0 120346 0 8328 0 484894 0 51243 0 DR JANA HALL CHIEF OPERATIONS OFFICER 285763 0 15000 0 16224 0 97544 0 1735 0 416266 0 0 0 DR H ERIC XU INVESTIGATOR 275613 0 20533 0 450 0 44797 0 8328 0 349721 0 20533 0 DR SCOTT JEWELL INVESTIGATOR 275109 0 40205 0 1980 0 57812 0 8327 0 383433 0 25795 0 LOVE COLLINS III V.P. OF DEVELOPMENT, COMM. & MKTNG. 251626 0 39834 0 1290 0 81217 0 8327 0 382294 0 39834 0 DR PATRIK BRUNDIN VARI ASSOCIATE DIRECTOR OF RESEARCH 395776 0 65000 0 14457 0 105165 0 7633 0 588031 0 43763 0 GERALD CALLAHAN V.P. OF BUSINESS DEVELOPMENT 221140 0 0 0 10414 0 83859 0 1291 0 316704 0 0 0 R JACK FRICK DONE 121111 CHIEF ADMINISTRATIVE OFFICER -FORMER 0 0 26585 0 161120 0 0 0 0 0 187705 0 26585 0 PART I, LINE 1A VARI ALLOWS FOR FIRST-CLASS OR CHARTER TRAVEL FOR OFFICERS AND TRUSTEES. PART I, LINE 4A R. JACK FRICK RECEIVED SEVERANCE PAYMENTS OF $161,120 DURING CALENDAR YEAR 2013. PART I, LINE 7 THREE NON-FIXED BONUSES WERE PAID AT THE DISCRETION OF THE CEO. A MICHIGAN STRATEGIC FUND 521417332 2013-04-01 220000000 REFUND BOND ISSUE 4/10/08 0 0 0 A 220000000 220000000 1 0 1 1 A 0 1 1 1 1 1 0.00950 0.00950 0 0 1 A 0 0 0 1 1 0 0 0 1 A 1 DATE REBATE COMPUTATION PERFORMED ISSUER NAME: MICHIGAN STRATEGIC FUND DATE THE REBATE COMPUTATION WAS PERFORMED: 11/30/2013 PATRIK BRUNDIN HIGHEST COMPENSATION EMPLOYEE CONTRACT X 25000 9657 0 0 1 9657 JVAE FOUNDATION COMMON TRUSTEE 155123 IT SVCS 0 X CAPITAL EQUIP 1 152458 FMV X EQUIPMENT 1 400 FMV X FOOD 1 53 FMV 0 0 0 0 PART I, COLUMN (B): NUMBER OF CONTRIBUTIONS IS BASED ON NUMBER OF GIFTS. FORM 990, PART III, LINE 2 IN 2014, VARI STARTED THE CENTER FOR EPIGENETICS. THE CENTER IS DEDICATED TO THE STUDY OF EPIGENETICS AND EPIGENOMICS IN HEALTH AND DISEASE, WITH THE ULTIMATE GOAL OF DEVELOPING NOVEL THERAPIES TO TREAT CANCER AND NEURODEGENERATIVE DISEASES. FORM 990, PART VI, SECTION A, LINE 2 VARI AND VAEI SHARE COMMON MANAGEMENT. AS OFFICERS OF VARI, DAVID VAN ANDEL, DR. JANA HALL, TIMOTHY MYERS AND DAVID WHITESCARVER INTERACT AND WORK TOGETHER WITH DR. STEVE TRIEZENBERG, AN OFFICER OF VAEI. 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 WRITTEN CONFLICT OF INTEREST ("COI") POLICIES AND PROCEDURES (ADMINISTERED BY VAN ANDEL INSTITUTE) WHICH ADMINISTER AND ENFORCE A PROCESS TO IDENTIFY, EVALUATE, AND MANAGE POTENTIAL CONFLICTS OF INTEREST. THESE POLICIES HAVE BEEN BOARD APPROVED. VAI ADMINISTERS THE COI POLICIES AND PROCEDURES THROUGH TWO COMMITTEES: THE CONFLICTS COMMITTEE ("CC") AND THE INSTITUTIONAL COI COMMITTEE ("ICOIC"). THE COI POLICIES AND PROCEDURES APPLY TO AND SERVE AS A GUIDE FOR EVERYONE IN THE ORGANIZATION. THEY 1) PROVIDE A USEFUL RESOURCE WHEN DEVELOPING ACTIVITIES OR RELATIONSHIPS WITH OUTSIDE ENTITIES OR PERSONS, AND 2) ESTABLISH COMMITTEES TO REVIEW AND MANAGE POTENTIAL CONFLICTS OF INTEREST AS THEY MAY ARISE. THE CC, CHAIRED BY THE CHIEF LEGAL OFFICER, REQUIRES ANNUAL AND UPDATED DISCLOSURES BY COVERED PERSONS AND REVIEWS AND APPROVES MANAGEMENT PLANS. THE INSTITUTIONAL COI POLICIES AND PROCEDURES SERVE AS A GUIDE FOR MEMBERS OF THE BOARDS OF TRUSTEES AND SENIOR EXECUTIVES. IN THE EVENT A POTENTIAL COI ARISES AT THE BOARD OR SENIOR EXECUTIVE LEVEL, THE ICOIC MEETS TO REVIEW AND DECIDE HOW TO MANAGE SUCH POTENTIAL CONFLICTS OF INTEREST IN ACCORDANCE WITH THE COI POLICIES AND PROCEDURES. FORM 990, PART VI, SECTION B, LINE 15 COMPARABILITY DATA FROM EXPERT THIRD PARTY IS OBTAINED AND REVIEWED BY THE INDEPENDENT, JOINT COMPENSATION COMMITTEE OF VAN ANDEL RESEARCH INSTITUTE AND RELATED ORGANIZATIONS TO DETERMINE APPROPRIATE COMPENSATION FOR THE CEO, EXECUTIVE MANAGEMENT OFFICIALS, 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 XI, LINE 9: LOSS ON INTEREST RATE SWAP -19,108,611. CHANGE IN BALANCE SHEET PRESENTATION OF TMS 286,858. FORM 990, PART III, LINE 2 VAN ANDEL RESEARCH INSTITUTE (VARI) IS DEDICATED TO DETERMINING THE EPIGENETIC, GENETIC, MOLECULAR, AND CELLULAR ORIGINS OF CANCER, PARKINSON'S DISEASE, AND OTHER ILLNESSES AND TRANSLATING THOSE FINDINGS INTO EFFECTIVE THERAPIES. THE INSTITUTE'S SCIENTISTS WORK IN ON-SITE LABORATORIES AND PARTICIPATE IN COLLABORATIONS THAT SPAN THE GLOBE. THE INSTITUTE IS ORGANIZED INTO THE CENTER FOR CANCER AND CELL BIOLOGY, THE CENTER FOR EPIGENETICS, AND THE CENTER FOR NEURODEGENERATIVE SCIENCE. THE CORE TECHNOLOGIES AND SERVICES GROUP PROVIDES VALUABLE ON-SITE CAPABILITIES IN IMAGING, PATHOLOGY, BIOINFORMATICS, FLOW CYTOMETRY, A VIVARIUM, AND A BIOREPOSITORY. RESEARCH BY VARI SCIENTISTS IS PUBLISHED IN MAJOR PEER-REVIEWED JOURNALS, INCLUDING, IN 2014, AMERICAN JOURNAL OF CANCER RESEARCH, AMERICAN JOURNAL OF PATHOLOGY, ARTHRITIS RESEARCH AND THERAPY, CANCER CELL, CANCER RESEARCH, GENOME RESEARCH, JOURNAL OF BONE AND MINERAL RESEARCH, JOURNAL OF PARKINSON'S DISEASE, MOLECULAR AND CELLULAR BIOLOGY, MOLECULAR ONCOLOGY, NATURE MEDICINE, NEOPLASIA, NEURO-ONCOLOGY, NEUROSCIENCE, ONCOGENE, PLOS ONE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES U.S.A., PSYCHONEUROENDOCRINOLOGY, AND TRANSLATIONAL RESEARCH, AMONG OTHERS. IN 2014, PETER A. JONES, PH.D., D. SC., BECAME THE RESEARCH DIRECTOR AND CHIEF SCIENTIFIC OFFICER OF VAN ANDEL RESEARCH INSTITUTE. DR. JONES WAS BORN IN SOUTH AFRICA, RAISED AND ATTENDED COLLEGE IN RHODESIA (NOW ZIMBABWE), AND RECEIVED HIS PH.D. FROM THE UNIVERSITY OF LONDON. HE JOINED THE UNIVERSITY OF SOUTHERN CALIFORNIA IN 1977, ATTAINING THE RANK OF PROFESSOR IN 1985 AND DISTINGUISHED PROFESSOR IN 1999. HE ALSO SERVED AS DIRECTOR OF THE USC NORRIS COMPREHENSIVE CANCER CENTER BETWEEN 1993 AND 2011. HIS LABORATORY DISCOVERED THE EFFECTS OF 5-AZACYTIDINE ON DNA METHYLATION AND LINKED THIS PROCESS TO THE ACTIVATION OF SILENCED GENES. HE IS KNOWN FOR HIS STUDIES ON THE MOLECULAR BIOLOGY OF CANCER AND OF BASIC MECHANISMS OF DNA METHYLATION AND ITS ROLE IN CANCER AND DIFFERENTIATION. DR. JONES IS A PAST PRESIDENT OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH AND WAS ELECTED AS A FELLOW OF THE ACADEMY OF THE AACR IN 2013. HE HAS PUBLISHED MORE THAN 300 SCIENTIFIC PAPERS AND RECEIVED SEVERAL HONORS, INCLUDING THE OUTSTANDING INVESTIGATOR GRANT FROM THE NATIONAL CANCER INSTITUTE. HE AND HIS COLLEAGUE DR. STEPHEN BAYLIN SHARED BOTH THE KIRK A. LANDON AWARD FOR BASIC CANCER RESEARCH FROM THE AACR IN 2009 AND THE MEDAL OF HONOR FROM THE AMERICAN CANCER SOCIETY IN 2011. FORM 990, PART III, LINE 4A LINE 4A - PROGRAM SERVICE ACTIVITY #1 CENTER FOR CANCER AND CELL BIOLOGY THE CENTER FOR CANCER AND CELL BIOLOGY, DIRECTED BY BART WILLIAMS, PH.D., COMPRISES 14 LABORATORIES ENGAGED IN BASIC RESEARCH IN MOLECULAR AND STRUCTURAL BIOLOGY AND IN TRANSLATIONAL RESEARCH ON CANCERS, THE TUMOR MICROENVIRONMENT, AND SKELETAL DISEASES. INVESTIGATORS WITHIN THE CENTER IN 2014 RECEIVED AN R01 RENEWAL FROM THE NATIONAL INSTITUTES OF HEALTH, A NEW AWARD FROM THE DEPARTMENT OF DEFENSE, A RENEWAL AWARD FROM THE MICHAEL J. FOX FOUNDATION, A NEW AWARD FROM THE COFFMAN CHARITABLE TRUST, AND TWO AWARDS FROM THE MICHIGAN ECONOMIC DEVELOPMENT CORPORATION (MEDC). THE VAN ANDEL RESEARCH INSTITUTE PATHWAY OF HOPE INITIATIVE PROGRESSED IN 2014 UNDER THE DIRECTION OF JEFFREY MACKEIGAN, ASSOCIATE PROFESSOR AND HEAD OF THE LABORATORY OF SYSTEMS BIOLOGY. TUBEROUS SCLEROSIS COMPLEX (TSC) CAUSES NON-CANCEROUS TUMORS IN MAJOR ORGANS, AND PATIENTS AFFLICTED WITH DISEASE OFTEN SUFFER FROM EPILEPSY, LEARNING DISABILITIES AND OTHER COMPLICATIONS. VARI'S PATHWAY OF HOPE PROJECT INVOLVES TSC INVESTIGATORS FROM ACROSS THE UNITED STATES, WITH FUNDING FROM THE MICHIGAN STRATEGIC FUND, BLUE CROSS BLUE SHIELD OF MICHIGAN, GREAT LAKES SCRIP, ROCKFORD CONSTRUCTION, COLLIERS INTERNATIONAL, TEAM HANNAH TSC, AND INDIVIDUAL DONORS. THE INITIATIVE INVOLVES A COMBINATION OF BASIC BIOLOGY, TRANSLATIONAL AND CLINICAL APPROACHES, WITH THE GOAL OF DEVELOPING NEW, EFFECTIVE TREATMENTS FOR INDIVIDUALS WITH TSC. THE TSC RESEARCH TEAM HAS SCREENED FOR GENES NEVER BEFORE LINKED TO TSC AND IS INVESTIGATING SEVERAL THAT ARE INTRIGUING. THE PATHWAY OF HOPE TEAM HAS ALSO BEGUN A PERSONALIZED MEDICINE FEASIBILITY STUDY, EVALUATING THE TEAM'S ABILITY TO DEVELOP INDIVIDUALIZED TREATMENT PLANS FROM A PATIENT'S GENOMIC DATA. TSC RESEARCH IS BEING FUNDED IN PART THROUGH THE BILL VAN REGENMORTER COLLABORATIVE FOR TRANSLATIONAL BIOMEDICAL RESEARCH, WHICH IS ADMINISTERED BY THE MEDC. RESEARCH CONTINUES INTO THE MIG6 GENE AND ITS RELATIONSHIP TO OSTEOARTHRITIS. INJURED JOINTS ARE PRONE TO DEVELOPING OSTEOARTHRITIS (OA), AND A LACK OF THE MIG-6 PROTEIN INCREASES THE DAMAGE FOUND IN JOINTS FOLLOWING TRAUMA. BONE MINERAL DENSITY AND TRABECULAR THICKNESS AND NUMBER WERE FOUND TO BE LOWER IN SURGICALLY TREATED KNEES FROM MICE LACKING THE MIG6 GENE (JOINER ET AL., ARTHRITIS RESEARCH AND THERAPY 16(2): R81). ANOTHER STUDY EXPLORED THE JOINT TISSUES IN WHICH MIG-6 IS EXPRESSED AND THE ROLE CHONDROCYTES PLAY IN THE OA-LIKE DISORDER CAUSED BY MIG-6 DEFICIENCY IN MICE. MIG-6 WAS FOUND TO BE CRUCIAL IN MAINTAINING JOINT HOMEOSTASIS AND IN REGULATING CHONDROCYTE ACTIVITY IN SYNOVIAL JOINTS, WHICH ARE FOUND IN THE KNEE, SHOULDER, HIP, AND ELBOW, AMONG OTHERS (STAAL ET AL., PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES U.S.A. 111(7): 2590-2595). MITOCHONDRIA ARE THE ENERGY-PRODUCING ORGANELLES OF A CELL. THE SIZE OF MITOCHONDRIA, LARGE VS. COMPACT, WAS FOUND TO CORRELATE WITH MITOCHONDRIAL FISSION OR FUSION EVENTS, RESPECTIVELY (WESTRATE ET AL., PLOS ONE 9(4): E95265). IN RAPIDLY DIVIDING CANCER CELLS, THE MITOCHONDRIA MUST FRAGMENT (FISSION) PRIOR TO CELL DIVISION. FORCED FUSION OF MITOCHONDRIA INHIBITED THE DIVIDING OF CELLS, AND EXTENDED PERIODS OF SUCH FUSION CAUSED THE CELLS TO DIE. THUS, INHIBITING THE REGULATION OF MITOCHONDRIAL FISSION MAY BE A STRATEGY FOR TARGETING CANCER CELLS (WESTRATE ET AL., PLOS ONE 9(3): E91911). ANOTHER STUDY IDENTIFIED A MITOCHONDRIAL ADENYLATE KINASE ENZYME THAT REGULATES CELLULAR ATP LEVELS; THE EXPRESSION OF THAT ENZYME CORRELATED WITH THE SURVIVAL OF GLIOMA PATIENTS. THIS STUDY MAPPED THE BIOENERGETIC LANDSCAPE OF MORE THAN 1000 MITOCHONDRIAL PROTEINS SUBSTRATES, AND IT IS THE BEGINNING OF LINKING KEY METABOLIC GENES WITH CLINICAL DISEASE OUTCOME (LANNING ET AL., CELL REPORTS 7(3): 907-917). STUDIES OF MOLECULAR STRUCTURES AND THEIR PHYSICAL INTERACTIONS HAVE BEEN PROCEEDING ON SEVERAL FRONTS IN 2014. GLUCOCORTICOIDS ARE VALUABLE FOR TREATING DISEASES SUCH AS ASTHMA, LEUKEMIA, AND AUTOIMMUNE DISEASES, BUT THE DRUGS HAVE BOTH BENEFICIAL AND ADVERSE EFFECTS. STUDIES OF THE GLUCOCORTICOID RECEPTOR SHOWED THAT THE Q642 AMINO ACID IN THE LIGAND-BINDING POCKET IS KEY TO THE HIGH POTENCY OF THE GLUCOCORTICOID MOMETASONE FUROATE. THIS STRUCTURE-BASED DESIGN LED TO SYNTHESIS OF SEVERAL NOVEL GLUCOCORTICOIDS WITH MUCH IMPROVED POTENCY AND EFFICACY. THIS RESEARCH PROVIDES A RATIONAL BASIS FOR DEVELOPING DRUGS THAT HAVE AN IMPROVED RATIO OF BENEFICIAL TO ADVERSE EFFECTS (HE ET AL., CELL RESEARCH 24(6): 713-726). A STUDY OF THE SHP RECEPTOR, WHICH ACTS AS A REPRESSOR TO REGULATE BILE ACIDS AND CHOLESTEROL METABOLISM, HAS DEMONSTRATED INTERACTIONS THAT CONTROL SHP ACTIVITY. THE EID1 PROTEIN WAS FOUND TO HAVE A BINDING SITE ON SHP, UNEXPECTEDLY LOCATED AT THE N TERMINUS OF THE RECEPTOR, WHICH MAY HAVE IMPLICATIONS FOR TRANSCRIPTIONAL REPRESSION BY SIMILAR NUCLEAR RECEPTORS. UNDERSTANDING THE FUNCTION AND MECHANISM OF ACTION OF SHP WILL HELP IN DEVELOPING DRUGS TO TREAT METABOLIC DISEASES ARISING FROM BILE ACID AND CHOLESTEROL IMBALANCES (ZHI ET AL., PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES U.S.A. 111(2): 839-844). AN ONGOING STUDY CONTINUES INTO ABSCISIC ACID, A PLANT HORMONE CRUCIAL TO THE ADAPTATION OF PLANTS TO DROUGHT CONDITIONS. VARI RESEARCHERS HAVE FOUND THAT THE HORMONE CAUSES THE GENERATION OF HYDROGEN PEROXIDE, WHICH INHIBITS THE PHOSPHATASE ENZYME HAB1, RESULTING IN THE CLOSING OF PLANT PORES (STOMATA) AND THUS PREVENTING LOSS OF WATER THROUGH TRANSPIRATION (SRIDHARAMURTHY ET AL., PLOS ONE 9(12): E113643). PROGRESS CONTINUES ON THE STUDY OF A VARIETY OF CANCERS. THE AGGRESSIVENESS OF MESENCHYMAL PANCREATIC CANCER CELLS HAS BEEN LINKED TO GENETIC CHANGES IN THE CDKN2A AND RELATED GENES. WHOLE-GENOME COMPARATIVE GENOMIC HYBRIDIZATION MEASUREMENTS ON EPITHELIAL-LIKE AND MESENCHYMAL-LIKE PANCREATIC CANCER CELL LINES FOUND 20 ALTERED GENES THAT SHOWED A MAJOR DIFFERENCE BETWEEN THE GROUPS. ALL 20 ALTERATIONS (18 DELETIONS AND 2 AMPLIFICATIONS) WERE MORE PREVALENT IN THE MESENCHYMAL GROUP (SINHA ET AL., MOLECULAR ONCOLOGY 8(7): 1253-1265). ANOTHER PROJECT STUDIED TWO ACRIDINE DERIVATIVES THAT ACT AS INHIBITORS OF AUTOPHAGY, A DYNAMIC CELL SURVIVAL MECHANISM. IN MELANOMA CELLS DRIVEN BY THE BRAF GENE (WHICH HELPS CONTROL CELL GROWTH AND IS MUTATED IN SOME CANCERS), BOTH DERIVATIVES ACTED TO SENSITIZE THE CELLS TO THE CANCER-THERAPY DRUG VEMURAFENIB (GOODALL ET AL., AUTOPHAGY 10(6): 1120-1136). THE CHROMATIN REMODELING PROTEIN ING4 IS REQUIRED FOR NORMAL DIFFERENTIATION OF PROSTATE CELLS, AND EXPRESSION OF THIS PROTEIN IS LOST IN THE MAJORITY OF PROSTATE CANCERS. THAT LOSS MAY BE A FACTOR IN THE DEVELOPMENT OF SUCH CANCER, AND THERE MAY BE SUBTYPES OF PROSTATE CANCER BASED ON LOSS OF ING4 ALONE OR OF BOTH THE ING4 AND PTEN PROTEINS (BERGER ET AL., CANCER RESEARCH 74(12): 3357-3368.) SOLID TUMORS SUCH AS OSTEOSARCOMA OFTEN HAVE OXYGEN-POOR (HYPOXIC) ENVIRONMENTS. UNDER SUCH CONDITIONS, A VARI STUDY FOUND THAT OSTEOSARCOMA CELLS HAVE LOWER WNT SIGNALING AND THE CANCER CELLS ARE RESISTANT TO DOXORUBICIN. HOWEVER, BY A FURTHER LOWERING OF WNT SIGNALING, THE CANCER CELLS CAN BE MADE SENSITIVE TO DOXORUBICIN TREATMENT (SCHOLTEN ET AL., PLOS ONE, 9(10): E111431). IN A STUDY OF A BENIGN TUMOR CALLED ANEURYSMAL BONE CYST (ABC), THE RANKL SIGNALING PATHWAY WAS SHOWN TO BE ESSENTIAL FOR PROGRESSION OF THIS TUMOR, SUGGESTING FURTHER STUDY OF RANKL-TARGETED THERAPY AS AN ALTERNATIVE TO SURGERY. THE SAME ARTICLE REVIEWED A CASE STUDY OF SUCCESSFUL TARGETING OF AN AGGRESSIVE SACRAL ABC IN A 5-YEAR-OLD BOY THROUGH USE OF RANKL INHIBITION PLUS DENOSUMAB (PELLE ET AL., TRANSLATIONAL RESEARCH 164(2): 139-148). VARI RESEARCHERS HAVE SHOWN THAT HIGH LEVELS OF THE MICRORNA MIR-21, A SMALL NON-CODING RNA, IN THE TUMOR MICROENVIRONMENT-BUT NOT IN THE CANCER CELLS THEMSELVES-ARE ASSOCIATED WITH WORSE CLINICAL OUTCOMES FOR PATIENTS WITH "TRIPLE-NEGATIVE" BREAST CANCER. THIS FINDING SUGGESTS THAT ALTERED MIR-21 EXPRESSION PROVIDES CLINICALLY RELEVANT INFORMATION, THUS IDENTIFYING A POSSIBLE PROGNOSTIC BIOMARKER FOR THIS DISEASE (MACKENZIE ET AL., AMERICAN JOURNAL OF PATHOLOGY 184(12): 3217-3225). FORM 990, PART III, LINE 4B LINE 4B - PROGRAM SERVICE ACTIVITY #2 CENTER FOR EPIGENETICS THE CENTER, ESTABLISHED IN 2014 AND DIRECTED BY PETER JONES, PH.D., D.SC., COMPRISES EIGHT LABORATORIES STUDYING EPIGENETICS AND EPIGENOMICS AND THE ROLE OF EPIGENETIC DYSFUNCTION IN DISEASES SUCH AS CANCER AND NEURODEGENERATIVE DISEASE, CARDIOVASCULAR DISEASE, AND VIRAL TRANSCRIPTION. FOUR NEW FACULTY, THREE WITH FEDERAL FUNDING, WERE RECRUITED TO THE CENTER IN 2014. IN 2014, CENTER RESEARCHERS RECEIVED A NEW GRANT AWARD THROUGH THE BILL VAN REGENMORTER COLLABORATIVE TO ESTABLISH A CENTER OF EXCELLENCE IN EPIGENETICS, AS WELL AS A DEPARTMENT OF DEFENSE SUBAWARD ON THE USE OF EPIGENETIC THERAPY FOR OVARIAN CANCER. IN FEBRUARY 2014, PETER JONES BECAME THE RESEARCH DIRECTOR AND CHIEF SCIENTIFIC OFFICER OF VAN ANDEL RESEARCH INSTITUTE (VARI). WITH HIM CAME HIS ROLE AS CO-LEADER WITH STEPHEN BAYLIN, M.D., OF JOHNS HOPKINS UNIVERSITY- OF THE STAND UP TO CANCER (SU2C) EPIGENETICS DREAM TEAM, WHICH WAS LAUNCHED IN 2009 TO FOCUS ON EPIGENETIC THERAPY IN CANCER TREATMENT. THEIR LEADERSHIP HAS EVOLVED THAT TEAM INTO THE VARI-SU2C EPIGENETICS DREAM TEAM, WHICH INCLUDES CHARLES RUDIN, M.D., PH.D., MEMORIAL SLOAN KETTERING CANCER CENTER IN NEW YORK; JEAN-PIERRE ISSA, M.D., AND PATRICIA KROPF, M.D., TEMPLE UNIVERSITY AND FOX CHASE CANCER CENTER IN PHILADELPHIA; KIRSTEN GRONBAEK, M.D., D.MSC., RIGSHOSPITALET, UNIVERSITY OF COPENHAGEN; AND ANTHONY EL-KHOUEIRY, M.D., UNIVERSITY OF SOUTHERN CALIFORNIA NORRIS COMPREHENSIVE CANCER CENTER. IN OCTOBER 2014, VARI COMMITTED TO PROVIDING $7.5 MILLION IN FUNDING TO CONTINUE THE WORK OF THE TEAM. AS BEFORE, THE TEAM WILL FOCUS ON EPIGENETIC MECHANISMS IN CELLS, WHICH HELP CONTROL WHETHER GENES ARE TURNED ON OR OFF WITHOUT CHANGING THE DNA SEQUENCE ITSELF. VARI'S SUPPORT OVER THREE YEARS WILL ALLOW THE TEAM TO MOVE FORWARD WITH MORE EXTENSIVE CLINICAL TRIALS IN OTHER CANCER TYPES AND ALLOW THEM TO TEST ADDITIONAL EPIGENETIC THERAPY STRATEGIES TO IMPROVE UPON THE PROGRESS ALREADY MADE. THE TEAM WILL CONTINUE TO BE PEER-REVIEWED BY THE AMERICAN ASSOCIATION FOR CANCER RESEARCH. IN EARLY 2014, VAN ANDEL RESEARCH INSTITUTE AND SPECTRUM HEALTH BROUGHT WORLD-RENOWNED CARDIOVASCULAR RESEARCHER AND CARDIOLOGIST STEFAN JOVINGE, M.D., PH.D., TO GRAND RAPIDS. JOVINGE LEADS TEAMS OF RESEARCHERS AND CLINICIANS AT THE SPECTRUM HEALTH FREDERIK MEIJER HEART & VASCULAR INSTITUTE AND VAN ANDEL RESEARCH INSTITUTE IN AN EFFORT TO STIMULATE REGENERATIVE MEDICINE FOR HEART DISEASE. THE RESEARCH WILL HAVE FOUR AREAS OF FOCUS: CELL ENGINEERING; MULTI-CENTER PATIENT TREATMENT AND CLINICAL TRIALS; CELL SOURCE IDENTIFICATION AND SCIENTIFIC TRAINING; AND DEVELOPMENT FOR FUTURE RESEARCHERS INCLUDING INTERNS, FELLOWS, AND GRADUATE STUDENTS. DR. JOVINGE EARNED HIS MEDICAL DEGREE AND PH.D. FROM KAROLINSKA INSTITUTE IN STOCKHOLM, SWEDEN. HE ALSO COMPLETED A RESEARCH FELLOWSHIP IN THE DEPARTMENT OF CARDIOLOGY AT THE CEDARS-SINAI RESEARCH INSTITUTE AT THE UNIVERSITY OF CALIFORNIA LOS ANGELES. IN A STUDY OF ALTERATIONS AT SPECIFIC EPIGENETIC REGULATORY ELEMENTS IN PROSTATE AND BREAST CANCER CELLS, A GLOBAL RECONFIGURATION OF NUCLEOSOME-DEPLETED REGIONS (NDRS) WAS FOUND AT DISTAL ELEMENTS, COUPLED WITH A SUBSTANTIAL REORGANIZATION OF THE CANCER METHYL-GROUP ADDITIONS ONTO DNA. KEY TRANSCRIPTION FACTOR BINDING SITES ALSO SHOWED EXTENSIVE PERIPHERAL NUCLEOSOME PHASING, SUGGESTING THE POTENTIAL FOR SUCH SITES TO ORGANIZE NDRS GENOME-WIDE AND CONTRIBUTE TO DEREGULATION OF CANCER EPIGENOMES. GIVEN THAT NUCLEOSOMES "PACKAGE" DNA IN AN INACTIVE STATE, THESE EVENTS MAY CONTRIBUTE TO AN ALTERED GENOME-WIDE ARCHITECTURE AND EPIGENETIC DEREGULATION IN MALIGNANCY (TABERLAY ET AL., GENOME RESEARCH 24(9): 1421-1432). DBF4-DEPENDENT KINASE (DDK) IS OVEREXPRESSED IN MANY TUMOR CELLS, AND ITS INHIBITION CAUSES APOPTOSIS OF DIVERSE CANCER CELL TYPES. THE BENZOFUROPYRIMIDINONE-BASED DDK INHIBITOR XL413 WAS STUDIED FOR ITS EFFECTS WHEN USED ON TUMOR CELL LINES. WHILE XL413 WAS AN EFFECTIVE BIOCHEMICAL INHIBITOR OF DDK IN THE CELL LINES, IT HAD SIGNIFICANT ANTI-PROLIFERATIVE ACTIVITY AGAINST ONLY ONE OF THE 10 LINES TESTED. IN ADDITION, SOME 400 OTHER KINASE INHIBITORS WERE SCREENED, IDENTIFYING SEVERAL POTENTIAL DDK INHIBITORS THAT HAVE CHEMICAL STRUCTURES DIFFERENT FROM THOSE OF KNOWN DDK INHIBITORS (SASI ET AL., PLOS ONE 9(11): E113300). FORM 990, PART III, LINE 4C LINE 4C - PROGRAM SERVICE ACTIVITY #3 CENTER FOR NEURODEGENERATIVE SCIENCE THE CENTER FOR NEURODEGENERATIVE SCIENCE WAS ESTABLISHED IN 2011 UNDER THE LEADERSHIP OF PATRIK BRUNDIN, M.D., PH.D., WHO IS ALSO ASSOCIATE RESEARCH DIRECTOR OF VARI. THE CENTER CURRENTLY HAS FIVE LABORATORIES STUDYING PARKINSON'S DISEASE, AGING, PRIONS, AND THE RELATIONSHIP BETWEEN DEPRESSION, SUICIDE, AND BRAIN INFLAMMATION. ONE NEW FACULTY MEMBER WAS RECRUITED IN 2014. CENTER RESEARCHERS RECEIVED NEW GRANT AWARDS FROM THE BILL VAN REGENMORTER COLLABORATIVE, THE CURE PARKINSON'S TRUST, AND FROM THE MICHAEL J. FOX FOUNDATION DURING 2014. IN 2014, VARI BEGAN AN INITIATIVE WITH THE UK-BASED RESEARCH CHARITY THE CURE PARKINSON'S TRUST TO IDENTIFY NEW TREATMENTS FOR PARKINSON'S DISEASE. THE COLLABORATION, CALLED THE LINKED CLINICAL TRIALS (LCT) INITIATIVE, IS AIMED AT REPOSITIONING MEDICATIONS APPROVED TO TREAT OTHER DISEASES THAT HAVE ALSO SHOWN PROMISE IN PRECLINICAL LABORATORY EXPERIMENTS FOR TREATING PARKINSON'S DISEASE. THE LCT INITIATIVE COULD SIGNIFICANTLY REDUCE THE TIME AND COST OF MOVING NEW PARKINSON'S TREATMENTS FROM THE LAB TO CLINICAL USE. THE UNDERLYING PREMISE IS THAT CONDUCTING SMALLER, MORE COST-EFFECTIVE TRIALS WITH SIMILAR PROTOCOLS, PATIENTS, AND OUTCOMES WILL ALLOW SCIENTISTS TO SEE WHICH DRUGS ARE MOST EFFECTIVE, WHILE MAXIMIZING THE NUMBER OF TRIALS CONDUCTED. LARGE-SCALE PARKINSON'S DISEASE CLINICAL TRIALS ARE RARE BECAUSE OF PROHIBITIVELY HIGH COSTS, AND THE LACK OF RELIABLE BIOMARKERS AND MODELS FOR THE DISEASE. THE FOCUS ON DRUGS ALREADY APPROVED FOR TREATING OTHER DISEASES WILL SIGNIFICANTLY REDUCE THE TIME AND FUNDING REQUIRED TO BRING AN EFFECTIVE NEW TREATMENT TO MARKET. VARI STUDIES ON PARKINSON'S DISEASE INCLUDE A PROJECT STUDYING ADENO-ASSOCIATED VIRUS (AAV) VECTORS, WHICH ARE USED TO DELIVER GENES IN CLINICAL TRIALS. IN RATS PRE-IMMUNIZED WITH WILD-TYPE AAV-2, INTRACEREBRAL GENE DELIVERY BASED ON AAV-2 WAS COMPROMISED (71% LOWER). BY CONTRAST, LOCAL NEUROINFLAMMATORY RESPONSE TO INTRASTRIATAL A 6-OHDA INJECTION, WHICH MIMICS PARKINSON'S DISEASE NEURONAL DAMAGE, DID NOT AFFECT VIRAL VECTOR-MEDIATED TRANSGENE EXPRESSION. THE RESULTS EMPHASIZE THE IMPORTANCE OF MONITORING CIRCULATING AAV-SPECIFIC NEUTRALIZING ANTIBODIES IN PATIENTS RECEIVING THERAPY USING AAV VECTORS (JANELIDZE ET AL., JOURNAL OF GENE MEDICINE 16(910): 300308). MUTATIONS IN THE LEUCINE-RICH REPEAT KINASE 2 (LRRK2) GENE CAUSE LATE-ONSET, AUTOSOMAL DOMINANT PARKINSON'S DISEASE (PD), AND SUCH MUTATIONS ARE THE MOST COMON CAUSE OF FAMILIAL PD. TO DIRECTLY EXPLORE THE EFFECT OF MUTANT LRRK2 ON THE NIGROSTRIATAL DOPAMINERGIC PATHWAY, WHICH IS DEGRADED IN PD, CONDITIONAL TRANSGENIC MICE WERE BRED THAT SELECTIVELY EXPRESS THE HUMAN R1441C MUTATION OF LRRK2 IN THEIR DOPAMINERGIC NEURONS. THE MUTANT LRRK2 DID NOT PRODUCE DEGENERATION OF SUBSTANTIA NIGRA DOPAMINERGIC NEURONS OR STRIATAL DOPAMINE DEFICITS IN MICE UP TO 2 YEARS OF AGE, AND NO ABNORMAL PROTEIN INCLUSIONS CONTAINING A-SYNUCLEIN, TAU, UBIQUITIN OR AUTOPHAGY MARKERS WERE FOUND. EARLY RESULTS FROM THESE NOVEL R1441C LRRK2 CONDITIONAL TRANSGENIC MICE REVEALED CHANGES IN DOPAMINERGIC NEURONAL MORPHOLOGY WITH ADVANCING AGE. THIS NEW MODEL WILL BE A USEFUL TOOL FOR EXPLORING THE PATHOGENIC MECHANISMS UNDERLYING THE R1441C LRRK2 MUTATION IN PD (TSIKA ET AL., NEUROBIOLOGY OF DISEASE 71: 345-358). THE DEVELOPMENT OF ALZHEIMER'S DISEASE PATHOLOGY FOLLOWS A SPATIOTEMPORAL PATTERN. IN A TRANSGENIC MOUSE MODEL, AMYLOID-BETA (A BETA) PATHOLOGY, WHICH IS IMPLICATED IN HUMAN ALZHEIMER'S, SPREADS ALONG ANATOMICALLY CONNECTED STRUCTURES. IN THIS STUDY, NEURONS TO AND FROM A BRAIN STRUCTURE CALLED THE SUBICULUM WERE DESTROYED USING A NEUROTOXIN, TO DISCONNECT THE NEURAL CIRCUITRY IN THIS MOUSE MODEL. THE RESULT WAS DECREASED A BETA PATHOLOGY IN BRAIN REGIONS ON THE SIDE WHERE THE CIRCUITRY WAS DESTROYED, BUT A BETA PATHOLOGY WAS UNCHANGED ON THE SIDE WHERE THE CIRCUITRY WAS LEFT INTACT. THESE RESULTS SUPPORT THE IDEA THAT A BETA PATHOLOGY IS TRANSMITTED BETWEEN INTERCONNECTED NEURONS IN ALZHEIMER'S DISEASE (GEORGE ET AL., ACTA NEUROPATHOLOGICA COMMUNICATIONS 2: 17). A STUDY OF PERSONS WHO HAD ATTEMPTED SUICIDE SHOWED THAT NEARLY 60% OF THOSE PERSONS WERE DEFICIENT IN VITAMIN D. THERE WAS ALSO A SIGNIFICANT ASSOCIATION BETWEEN LOW VITAMIN D LEVELS AND HIGH LEVELS OF PRO-INFLAMMATORY CYTOKINES (IL-6 AND IL-1 BETA) IN THEIR BLOOD. ROUTINE CLINICAL TESTING OF VITAMIN D LEVELS AND SUPPLEMENTATION AS NEEDED COULD BE BENEFICIAL IN PATIENTS WITH SUICIDAL SYMPTOMS (GRUDET ET AL., PSYCHONEUROENDOCRINOLOGY 50: 210-219). NEURON GLIAL 2 (NG2) CELLS FORM THE MYELIN SHEATH SURROUNDING NERVES AND SUPPORT NEURONS IN A VARIETY OF WAYS. IN INJURED AREAS OF THE BRAIN, THESE CELLS PROLIFERATE AND INCREASE THE SHEDDING OF THE PROTEOGLYCAN NG2 FROM THEIR CELL SURFACE. THIS ANALYSIS, DONE IN RATS THAT HAD SYSTEMICALLY INDUCED NEUROINFLAMMATION, SHOWED LOWER RATES OF CELL PROLIFERATION AND MORE NG2 IN THE CEREBROSPINAL FLUID. HUMAN NG2 CELLS IN CULTURE EXPOSED TO THE PROINFLAMMATORY CYTOKINES IL-6 AND IL-1 BETA FOR 24 HOURS SHOWED THE SAME EFFECTS. SYSTEMIC INFLAMMATION MAY HAVE PROFOUND EFFECTS ON SPECIFIC CELL POPULATIONS IN THE NERVOUS SYSTEM, AND THESE RESULTS MAY BE IMPORTANT IN STUDIES OF DEPRESSION AND SICKNESS BEHAVIOR (WENNSTROM ET AL., PLOS ONE 9(10): E109387). FORM 990, PART X, LINE 33 VARI NET ASSETS ARE CONSIDERED ON A CONSOLIDATED BASIS WITH VAN ANDEL INSTITUTE (VAI), VAN ANDEL EDUCATION INSTITUTE (VAEI), AND RELATED PARTIES. ON A CONSOLIDATED BASIS, NET ASSETS ARE $1,207,293,000 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 DONOR SOLICITATION, GRANT SOLICITATION AND EXTRAMURAL PROPOSAL PREPARATION. 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