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        <ExplanationTxt>Cooperation Agreements and Collaborations The Stowers Institute conducts medical research in conjunction with the University of Kansas (KU) and its affiliates the University of Kansas Hospital Authority and the University of Kansas Medical Center (KUMC), pursuant to a written memorandum of understanding. KUMC is the academic health science center for the largest public research university in the state of Kansas. KUMC offers programs and services that focus on education, research, patient care, and community engagement. As of June 30, 2023, five KUMC students have received M.S. degrees and 49 KUMC students have received Ph.D. degrees for thesis work performed in Stowers Institute labs. KUMC is affiliated with the University of Kansas Health System, a nonprofit independent hospital system co-located with the main KUMC campus in Kansas City, Kansas. During January-June 2023, 14 Stowers research program leaders served as adjunct faculty in three KUMC departments. These appointments included 10 full professors, three associate professors, and one assistant professor. During January-June 2023, 19 of the Stowers Institute's 28 original research publications included both Stowers Institute and KUMC affiliations. Ten KUMC students performed predoctoral research in Stowers labs during January-June 2023. The Stowers Institute is also a consortium member of the University of Kansas Cancer Center at KUMC, a cancer research and care partnership spanning two states and involving collaboration among researchers, physicians, and cancer support professionals in foundational, translational, and clinical research areas. In June 2012, the NIH's National Cancer Institute (NCI) named the University of Kansas Cancer Center an NCI-Designated Cancer Center, part of a pillar of federal cancer research efforts and integral to the NCI's programs for studying, treating, and preventing cancer. In 2022, the NCI named the University of Kansas Cancer Center an NCI-Designated Comprehensive Cancer Center - the highest honor bestowed by the NCI, the only such center in the region, and one of only 53 centers in the United States. During January-June 2023, 10 Stowers research program leaders were members of the University of Kansas Cancer Center's Cancer Biology Research Program, including Linheng Li, Ph.D., who serves as co-leader of the program. During January-June 2023, Stowers Investigator Linheng Li, Ph.D., continued a collaboration with the University of Kansas Cancer Center and Children's Mercy Kansas City to investigate approaches to treat leukemia. This research focuses on targeting cancer stem cells to help reduce the recurrence of cancer after a patient goes into remission. The collaboration builds on foundational research from the Li Lab that has characterized cancer stem cells at molecular and cellular levels, has produced peer-reviewed scientific publications, and is related to a Children's Mercy clinical research study. During January-June 2023, the Stowers Institute conducted research in conjunction with the private, nonprofit Marine Biological Laboratory (MBL), an affiliate of the University of Chicago located in Woods Hole, Massachusetts. Since 1888, the MBL has hosted thousands of researchers, students, and faculty from all over the world to fulfill its mission of scientific discovery by exploring fundamental biology, understanding biodiversity and the environment, and informing the human condition through research and education. Since 2022, a Lease Agreement with the MBL provides the Stowers Institute a dedicated, year-round laboratory on the MBL campus and access to services and resources such as shared research and equipment rooms, a shared microscopy facility, and the Marine Resources Center, a highly advanced facility for maintaining, culturing, and providing aquatic organisms. During January-June 2023, Stowers Institute scientists collaborated with researchers at 63 national and 61 international institutions including dozens of hospitals, medical centers, and medical schools. Many of these collaborations resulted in discoveries that merited publication in leading peer-reviewed scientific journals and/or successfully funded grant awards. The Stowers Institute participated in research collaborations in conjunction with the following US hospitals, pursuant to an understanding to maintain continuing close cooperation in the active conduct of medical research during January-June 2023: Atrium Health's Levine Children's Hospital, Baylor College of Medicine, Boston Children's Hospital, Brigham and Women's Hospital, Children's Mercy Kansas City, Cincinnati Children's Hospital Medical Center, Harvard Medical School, Mayo Clinic, Nationwide Children's Hospital, New York University Grossman School of Medicine, Northwestern University Feinberg School of Medicine, Ohio State University School of Medicine, Oregon Health and Science University School of Medicine, Penn State Health Children's Hospital, Seattle Children's Hospital, Sibley Heart Center, Stanford University School of Medicine, University of California Los Angeles David Geffen School of Medicine, University of California San Francisco School of Medicine, University of Cincinnati College of Medicine, University of Colorado School of Medicine, University of Kansas Medical Center, University of Louisville School of Medicine, University of Pittsburgh Cancer Institute, University of Southern California Keck School of Medicine, University of Tennessee Health Science Center, University of Texas Austin Dell Medical Center, and Washington University School of Medicine. 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        <ExplanationTxt>pursuant to which they agreed to establish, develop, administer, and maintain continuing close cooperation in the active conduct of medical research, including through specific cooperative efforts in the areas of research, sharing of information, pursuant of joint grants, interaction of staff, adjunct/joint appointments, and sharing of facilities. To assure the success of their cooperative relationship, each agreed to engage in effective, coordinated, and ongoing planning, oversight, and communication, and to commit the necessary resources, both human and monetary, to support, facilitate, and promote the cooperation. Joint medical research on the characterization of intestinal stem cells: The Li Lab performed joint medical research on the characterization of intestinal stem cells with collaborators at Cincinnati Children's Hospital Medical Center; David Geffen School of Medicine at the University of California, Los Angeles; Oregon Health and Science University School of Medicine; Stanford University School of Medicine; and University of Pittsburgh Cancer Institute. Intestinal diseases ranging from Crohn's disease to colitis to cancer may benefit from intestinal stem cell therapies. This research advances the understanding of the biology of stem cells that reside in the intestine and explores how they can be used to treat and cure intestinal diseases. This research collaboration is supported in part by an NIH grant awarded by the National Institute of Diabetes and Digestive and Kidney Diseases. Joint medical research on sensory hair cell regeneration: The Piotrowski Lab performed joint medical research on zebrafish hair cell regeneration with collaborators at the Stanford University School of Medicine, Keck School of Medicine of the University of Southern California, Baylor College of Medicine, and Sunnybrook Research Institute in Toronto, Canada. In humans, hearing loss caused by inner ear hair cell degeneration is one of the most widespread sensory disabilities in the world with 30% of people between ages 65-75 being affected. In humans and mammals, hair cells are unable to regenerate, so any damage or loss of hair cells is permanent. In zebrafish, however, hair cells regenerate throughout life. The goal of this work is to determine gene regulatory networks underlying zebrafish hair cell regeneration. The results will help identify strategies to restore lost hair cells in mammals. This research is supported in part by a grant from the Hearing Health Foundation. Joint medical research on the molecular origins of female reproductive aging: In collaboration with researchers from Northwestern University Feinberg School of Medicine, the Gerton Lab performed medical research on the molecular origins of female reproductive aging, which impacts fertility, endocrine function, and overall health. The goal of this work is to examine genomic instability in the egg as a driver of the aging ovarian innate immune response. This project provides a novel paradigm for female reproductive aging, a major reproductive transition. This research is supported in part by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Joint medical research on genetic variants underlying rare diseases in children: In collaboration with researchers from Children's Mercy Kansas City, the Trainor Lab performed medical research on the utilization of a pediatric genetic data repository to guide the development of scalable cell-based systems capable of identifying genetic variants and profiling the molecular consequences of disease-associated variants in pediatric rare diseases. A primary goal of this research is to build a first-of-its-kind platform to accelerate the process of translating the clinical detection of birth defect-associated genetic variants into meaningful and potentially actionable diagnoses. This research is supported in part by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and a grant from BioNexus KC. Other US collaborators included Arizona State University, Boston University, Columbia River Inter-Tribal Fish Commission, Columbia University, DePaul University, Harvard University, Howard Hughes Medical Institute, Lehigh University, Marine Biological Laboratory, Michigan State University, National Institutes of Health, New York University, North Carolina State University, Rockefeller University, Stanford University, Texas A&amp;M University, University of California Berkeley, University of California San Diego, University of Chicago, University of Cincinnati, University of Connecticut, University of Illinois at Chicago, University of Kansas, University of Kentucky, University of Michigan, University of Minnesota, University of Missouri-Kansas City, University of Montana, University of Notre Dame, University of Pittsburgh, University of Rochester, University of Southern California, University of Utah, University of Washington, and Yakima Nation Fisheries Resource Management Program. The Stowers Institute collaborated with the following international hospitals, medical centers, and medical schools during January-June 2023: Caen University Hospital Center, France; Cancer Institute of JFCR, Tokyo, Japan; Ealing Hospital, London, United Kingdom; First Faculty of Medicine and General University Hospital, Prague, Czech Republic; John Radcliffe Hospital, Oxford, United Kingdom; McGill University Health Center, Montreal, Canada; Murdoch Children's Research Institute, Melbourne, Australia; Royal Hospital for Children, Glasgow, United Kingdom; University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland; and University Hospital of L. Pasteur, Kosice, Slovak Republic. Other international collaborators included Aarhus University, Denmark; Erasmus MC, Rotterdam, Netherlands; ETH Zurich, Switzerland; European Molecular Biology Laboratory - European Bioinformatics Institute, Cambridge, United Kingdom; European Molecular Biology Laboratory, Heidelberg, Germany; Francis Crick Institute, London, United Kingdom; Guangzhou Laboratory, China; Helmholtz Zentrum Munchen, Germany; Human Technopole, Milan, Italy; Imperial College London, United Kingdom; Indian Institute of Science Education and Research Mohali, Punjab, India; Institute of Molecular and Cell Biology, Singapore; Kaunas University of Technology, Lithuania; KU Leuven, Belgium; McGill University, Montreal, Canada; Monash University, Melbourne, Australia; National Institute of Biological Sciences, Beijing, China; National Institute of Genetics, Mishima, Shizuoka, Japan; National Institute of Water and Atmospheric Research Limited, Hamilton, New Zealand; National Research Council, Naples, Italy; Open University, Milton Keynes, United Kingdom; Safarik University, Kosice, Slovak Republic; Sokendai Graduate University for Advanced Studies, Mishima, Shizuoka, Japan; Sorbonne Universite, Paris, France; Sunnybrook Research Institute, Toronto, Canada; Technical University of Berlin, Germany; Technical University of Munich, Germany; Technion Israel Institute of Technology, Haifa, Israel; Tsinghua University, Beijing, China; Universidad Nacional Autonoma de Mexico, Mexico City; University College London, United Kingdom; University of Basel, Switzerland; University of Bristol, United Kingdom; University of Cambridge, United Kingdom; University of Edinburgh, United Kingdom; University of Groningen, Netherlands; University of Manchester, United Kingdom; University of Melbourne, Australia; University of New South Wales, Sydney, Australia; University of Otago, Dunedin, New Zealand; University of Oxford, United Kingdom; University of So Paulo, Brazil; University of Southampton, United Kingdom; University of Vienna, Austria; University of Zurich, Switzerland; Victor Chang Cardiac Research Institute, Sydney, Australia; Vilnius University, Lithuania; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Wellcome Sanger Institute, Cambridge, United Kingdom; Westlake University, Hangzhou, Zhejiang, China; and Yonsei University, Seoul, South Korea.</ExplanationTxt>
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        <FormAndLineReferenceDesc>Form 990, Part III, Line 4a PROGRAM SERVICE DESCRIPTION</FormAndLineReferenceDesc>
        <ExplanationTxt>2023 PROGRAM SERVICE ACCOMPLISHMENTS THE STOWERS INSTITUTE FOR MEDICAL RESEARCH ("STOWERS INSTITUTE "INSTITUTE") IS a private, nonprofit medical research organization. The Institute was founded in 1994 by Jim and Virginia Stowers, who each survived a bout with cancer and subsequently dedicated their fortune to supporting fundamental research in molecular and cell biology, development, regeneration, genetics, and neuroscience that will provide long-term solutions to human diseases. The Stowers Institute conducts basic biomedical research in the public interest that will ultimately provide a greater understanding of the genes, proteins, and biological processes that control how cells in our bodies multiply, form tissues, and die. Studying the fundamental biology of cells and organisms enables scientists to discover how genes and molecular processes cause many diseases, including cancer, birth defects, and dementia. History has shown that foundational medical research is often a key first step in the development of new treatments, cures, and preventions for many human diseases. January-June 2023 Notable Research Results During January-June 2023, Stowers research teams made discoveries meriting publication in leading peer-reviewed scientific journals - 28 original research papers in all. Stowers research teams also produced 16 other publications including reviews, commentaries, book chapters, and books. Some of the highlights among these papers and other advances involving Stowers research include the following: The Rohner Lab investigated how Mexican tetra cavefish independently and uniquely adapted unusual metabolic mechanisms to exploit their "feast or famine" environments to survive. Cavefish display "couch potato" body types with high levels of fat and blood sugar. Under stress, however, cavefish can swim just as fast as their river fish cousins, and for prolonged time periods. Their unexpected endurance is due to a switch in the way glycogen is stored and utilized, potentially leading to insights on conditions like diabetes, heart disease, and stroke in humans. This work was published in the Proceedings of the National Academy of Sciences USA on January 24, 2023. The Hawley Lab studied how the recent emergence of an extra chromosome in fruit flies could shed light on similar chromosomes arising in humans associated with certain therapy-resistant cancers and infertility. The researchers uncovered the function and dynamics of the extra fruit fly chromosome, barely 20 years old, providing an ideal system for investigating not only how the chromosomes arise but also their structure and potential vulnerabilities that may illuminate more effective cancer and infertility treatments. This study was published in Current Biology on May 4, 2023. The Krumlauf Lab explored the dynamics of DNA elements that control the activity of Hox genes, which are master regulators of the animal body plan. Animal body parts are built in a specific order determined by the linear location of Hox genes along a chromosome. However, regulatory sequences of DNA that precisely control turning these genes on and off are frequently far away. The researchers studied the dynamics and cooperativity of regulatory elements that place them near the target genes they regulate. Unraveling this process is vital for understanding animal development, disease, and evolution. This report was published in Development on May 24, 2023. The Gerton Lab discovered that many cell types comprising the placenta in mice are polyploid, meaning they have multiple copies of genomes. Due to their large size, these cells help form a physical barrier between the mother and baby. Because the placenta can sometimes lead to disease in a baby, understanding its function is paramount. Insights from this study may help inform scientists and clinicians how the placenta supports healthy human pregnancies. This study was published in Development on June 6, 2023. The Halfmann Lab identified the very first step of the formation of protein clumps called amyloids which are associated with neurodegenerative diseases like Huntington's and Alzheimer's. Through a systematic analysis of protein sequence variants, the researchers deduced the initial Huntington's amyloid structure called the nucleus. Discovering the initial spontaneous change that leads to clumping reveals not just how Huntington's starts but also may indicate a novel treatment - prevent the nucleus from ever forming. This work, published online in eLife on June 13, 2023, provides critical insight into how amyloids cause disease. The Gibson Lab uncovered a common genetic toolkit driving development of humans and sea anemones despite obvious differences in body plans. Without a left and right side like humans, mature sea anemones are considered radially symmetric. However, the researchers found that during development sea anemones not only have internal left-right symmetry, but they also use genes conserved throughout evolution that create the blueprints for developing body segments. Comparing the logic of sea anemone and vertebrate development increases our understanding of how the very first animals likely developed. This study was published online in Current Biology on June 13, 2023. COMPREHENSIVE LISTS OF JANUARY-JUNE 2023 ORIGINAL RESEARCH PAPERS, REVIEWS, COMMENTARIES, CHAPTERS, AND BOOKS ORIGINAL RESEARCH PAPERS 1.PARASPECKLES INTERACT WITH SWI/SNF SUBUNIT ARID1B TO REGULATE TRANSCRIPTION AND SPLICING. REDDY D, BHATTACHARYA S, LEVY M, ZHANG Y, GOGOL M, LI H, FLORENS L, WORKMAN JL. EMBO REP 2023;24:E55345. 2.HYU: HYBRID UNMIXING FOR LONGITUDINAL IN VIVO IMAGING OF LOW SIGNAL TO NOISE FLUORESCENCE. CHIANG HJ, KOO DES, KITANO M, BURKITT S, UNRUH JR, ZAVALETA C, TRINH LA, FRASER SE, CUTRALE F. NAT METHODS. 2023;20:248-258. 3.MEIOTIC NUCLEAR PORE COMPLEX REMODELING PROVIDES KEY INSIGHTS INTO NUCLEAR BASKET ORGANIZATION. KING GA, WETTSTEIN R, VARBERG JM, CHETLAPALLI K, WALSH ME, GILLET LCJ, HERNANDEZ-ARMENTA C, BELTRAO P, AEBERSOLD R, JASPERSEN SL, MATOS J, UNAL E. J CELL BIOL. 2023;222:E202204039. 4.OFF-TARGET PIRNA GENE SILENCING IN DROSOPHILA MELANOGASTER RESCUED BY A TRANSPOSABLE ELEMENT INSERTION. MILLER DE, DORADOR AP, VAN VAERENBERGHE K, LI A, GRANTHAM EK, CERBIN S, CUMMINGS C, BARRAGAN M, EGIDY RR, SCOTT AR, HALL KE, PERERA A, GILLILAND WD, HAWLEY RS, BLUMENSTIEL JP. PLOS GENET. 2023;19:E1010598. 5.IDENTIFYING DYNAMICAL PERSISTENT BIOMARKER STRUCTURES FOR RARE EVENTS USING MODERN INTEGRATIVE MACHINE LEARNING APPROACH. DUTTA S, BOX AC, LI Y, SARDIU ME. PROTEOMICS. 2023:E2200290. 6.A MOLECULAR CELL BIOLOGY TOOLKIT FOR THE STUDY OF MEIOSIS IN THE SILKWORM BOMBYX MORI. XIANG Y, TSUCHIYA D, GUO F, GARDNER J, MCCROSKEY S, PRICE A, TROMER EC, WALTERS JR, LAKE CM, HAWLEY RS. G3 (BETHESDA). 2023:JKAD058. 7.DIET-INDUCED LOSS OF ADIPOSE HEXOKINASE 2 CORRELATES WITH HYPERGLYCEMIA. SHIMOBASHI M, THOMAS A, SHETTY S, FREI IC, WOLNERHANSSEN BK, WEISSENBERGER D, VANDEKEERE A, PLANQUE M, DIETZ N, RITZ D, MEYER-GERSPACH AC, MAIER T, HAY N, PETERLI R, FENDT SM, ROHNER N, HALL MN. ELIFE. 2023;12:E85103. 8.AN IMPROVED GERMLINE GENOME ASSEMBLY FOR THE SEA LAMPREY PETROMYZON MARINUS ILLUMINATES THE EVOLUTION OF GERMLINE-SPECIFIC CHROMOSOMES. TIMOSHEVSKAYA N, ESKUT KI, TIMOSHEVSKIY VA, ROBB SMC, HOLT C, HESS JE, PARKER HJ, BAKER CF, MILLER AK, SARACENO C, YANDELL M, KRUMLAUF R, NARUM SR, LAMPMAN RT, GEMMELL NJ, MOUNTCASTLE J, HAASE B, BALACCO JR, FORMENTI G, PELAN S, SIMS Y, HOWE K, FEDRIGO O, JARVIS ED, SMITH JJ. CELL REP. 2023;42:112263. 9.PLURIPOTENCY RETENTION AND EXOGENOUS MRNA INTRODUCTION IN PLANARIAN STEM CELLS IN CULTURE. LEI K, ZHANG W, CHEN J, MCKINNEY SA, ROSS EJ, LEE HC, SANCHEZ ALVARADO A. ISCIENCE. 2023;26:106001. 10.NEXT GENERATION PLASMIDS FOR TRANSGENESIS IN ZEBRAFISH AND BEYOND. KEMMLER CL, MORAN HR, MURRAY BF, SCORESBY A, KLEM JR, ECKERT RL, LEPOVSKY E, BERTHO S, NIEUWENHUIZE S, BURGER S, D'AGATI G, BETZ C, PULLER AC, FELKER A, DITRYCHOVA K, BOTSCHI S, AFFOLTER M, ROHNER N, LOVELY CB, KWAN KM, BURGER A, MOSIMANN C. DEVELOPMENT. 2023 APR 15;150(8):DEV201531. 11.CIRCADIAN RHYTHM DISRUPTION LINKED TO SKELETAL MUSCLE DYSFUNCTION IN THE MEXICAN CAVEFISH. OLSEN L, KRISHNAN J, BANKS C, HASSAN H, ROHNER N. CURR BIOL. 2023;33:R255-R256. 12.DYNAMIC FIBRONECTIN ASSEMBLY AND REMODELING BY LEADER NEURAL CREST CELLS PREVENTS JAMMING IN COLLECTIVE CELL MIGRATION. MARTINSON WD, MCLENNAN R, TEDDY JM, MCKINNEY MC, DAVIDSON LA, BAKER RE, BYRNE HM, KULESA PM, MAINI PK. 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        <ExplanationTxt>14.COLEC12 AND TRAIL SIGNALING CONFINE CRANIAL NEURAL CREST CELL TRAJECTORIES AND PROMOTE COLLECTIVE CELL MIGRATION. MCLENNAN R, GINIUNAITE R, HILDEBRAND K, TEDDY JM, KASEMEIER-KULESA JC, BOLANOS L, BAKER RE, MAINI PK, KULESA PM. DEV DYN. 2023:252:629-646. 15. POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies. Smallwood K, Watt KEN, Ide S, Baltrunaite K, Brunswick C, Inskeep K, Capannari C, Adam MP, Begtrup A, Bertola DR, Demmer L, Demo E, Devinsky O, Gallagher ER, Guillen Sacoto MJ, Jech R, Keren B, Kussmann J, Ladda R, Lansdon LA, Lunke S, Mardy A, McWalters K, Person R, Raiti L, Saitoh N, Saunders CJ, Schnur R, Skorvanek M, Sell SL, Slavotinek A, Sullivan BR, Stark Z, Symonds JD, Wenger T, Weber S, Whalen S, White SM, Winkelmann J, Zech M, Zeidler S, Maeshima K, Stottmann RW, Trainor PA, Weaver KN. Am J Hum Genet. 2023;110:809-825. 16. Selection-driven trait loss in independently evolved cavefish populations. Moran RL, Richards EJ, Ornelas-Garcia CP, Gross JB, Donny A, Wiese J, Keene AC, Kowalko JE, Rohner N, McGaugh SE. Nat Commun. 2023;14:2557. 17. B chromosomes reveal a female meiotic drive suppression system in Drosophila melanogaster. Hanlon SL, Hawley RS. Curr Biol. 2023;33:2300-2306 e2305.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Form 990, Part III, Line 4a PROGRAM SERVICE DESCRIPTION - Cont'd</FormAndLineReferenceDesc>
        <ExplanationTxt>18. Recombination between heterologous human acrocentric chromosomes. Guarracino A, Buonaiuto S, de Lima LG, Potapova T, Rhie A, Koren S, Rubinstein B, Fischer C, Human Pangenome Reference C, Gerton JL, Phillippy AM, Colonna V, Garrison E. Nature. 2023;617:335-343. 19. A Borrelia burgdorferi LptD homolog is required for flipping of surface lipoproteins through the spirochetal outer membrane. He H, Pramanik AS, Swanson SK, Johnson DK, Florens L, Zuckert WR. Mol Microbiol. 2023;119:752-767. 20. DAmFRET measures saturating concentrations and toxicities of protein phase transitions in vivo. Miller T, Wu J, Venkatesan S, Gama AR, Halfmann R. Mol Biol Cell. 2023:mbcE22110503. 21. Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube. Afzal Z, Lange JJ, Nolte C, McKinney S, Wood C, Paulson A, De Kumar B, Unruh J, Slaughter BD, Krumlauf R. Development. 2023;150. 22. Excess shear force exerted on an oscillating plate due to a nearby particle. Fouxon I, Rubinstein BY, Leshansky AM. Phys Rev Fluids. 2023;8:054104. 23. Myc promotes polyploidy in murine trophoblast cells and suppresses senescence. Singh VP, Hassan H, Deng F, Tsuchiya D, McKinney S, Ferro K, Gerton JL. Development; 2023;150:dev201581. 24. Environmental and molecular regulation of asexual reproduction in the sea anemone Nematostella vectensis. Al-Shaer L, Leach W, Baban N, Yagodich M, Gibson MC, Layden MJ. R Soc Open Sci. 2023 Jun 14;10(6):230152. 25. Ac/Ds transposition for CRISPR/dCas9-SID4x epigenome modulation in zebrafish. Chong-Morrison V, Mayes S, Simes FC, Senanayake U, Carroll DS, Riley PR, Wilson SW, Sauka-Spengler T. Biol Open. 2023 Jun 15;12(6):bio059995. 26. Metabolic reprogramming underlies cavefish muscular endurance despite loss of muscle mass and contractility. Olsen L, Levy M, Medley JK, Hassan H, Miller B, Alexander R, Wilcock E, Yi K, Florens L, Weaver K, McKinney SA, Peu R, Persons J, Kenzior A, Maldonado E, Delventhal K, Gluesenkamp A, Mager E, Coughlin D, Rohner N. Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2204427120. 27. Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal. Kandola T, Venkatesan S, Zhang J, Lerbakken BT, Von Schulze A, Blanck JF, Wu J, Unruh JR, Berry P, Lange JJ, Box AC, Cook M, Sagui C, Halfmann R. eLife. 2023 Nov 3;12:RP86939. 28. Spatial transcriptomics reveals a cnidarian segment polarity program in Nematostella vectensis. He S, Shao W, Chen SC, Wang T, Gibson MC. Curr Biol. 2023 Jul 10;33(13):2678-2689. Reviews, Commentaries, Chapters, Books 1. Chromosome-specific behaviors during early meiosis. Billmyre KK. Curr Top Dev Biol. 2023;151:127-154. 2. Off the deep end: What can deep learning do for the gene expression field? Raicu AM, Fay JC, Rohner N, Zeitlinger J, Aronstein DN. J Biol Chem. 2023;299:102760. 3. Cell culture: in vitro model system and a promising path to in vivo applications. Zhao C. J Histotechnol. 2023;46:1-4. 4. Generation of mini-brains from hiPSCs. Wang Y, Tsuchiya D, Zhao C. In: W Wang, Y Wang, and N Rohner, eds. Emerging model organism. New York, New York: Humana, New Yor, NY; 2023;194:291-306. 5. A Generalist's Guide to Quantifying Swimming Behavior Within Traditional and Nontraditional Teleost Models. Olsen L, Alexander R, Krishnan J, Rohner N. In: W Wang, Y Wang, and N Rohner, eds. Emerging Model Organisms; 2023;194: 263-272. 6. Multiplexed Quantitative Proteomics Analysis of Developing Human Brain Organoids. Florens L, Saraf A, Hao Y, Zhang Y, Wang Y, Parmely TJ, Zhao C, Washburn MP. In: W Wang, Y Wang, and N Rohner, eds. Emerging Model Organisms; 2023;194:325-355. 7. Emerging Model Organisms. Wang W, Rohner N, Wang Y, eds. Neuromethods, Springer Protocols: Humana Press. 2023. 8. ISSCR Education Committee Syllabus and Learning Guide for Enhancing Stem Cell Literacy. Perlin JR, Anderson WJ, Bartfeld S, Couturier A, de Soysa Y, Hawley RS, Hu P, Loh YH, Mandal L, Master Z, Muotri AR, Piddini E, Polo JM, Mazzoni EO. Stem Cell Rep. 2023;18:417-419 9. Gene-environment interactions in the pathogenesis of common craniofacial anomalies. Fitriasari S, Trainor PA. Curr Top Dev Biol. 2023;152:139-168. 10. RNA Polymerases I and III in development and disease. Watt KE, Macintosh J, Bernard G, Trainor PA. Semin Cell Dev Biol. 2023;136:49-63. 11. Epithelial to mesenchymal transition during mammalian neural crest cell delamination. Zhao R, Trainor PA. Semin Cell Dev Biol. 2023;138:54-67. 12. Translation and mRNA Stability Control. Wu Q, Bazzini AA. Annu Rev Biochem 2023 Jun 20;92:227-245. 13. Establishment, long-term maintenance, and Characterization of Primary Liver Cells from Astyanax mexicanus. Rajendran N, Deng F, Wang Y, Kenzior O, Krishnan J, Biswas T, Parmely T, Rohner N, Zhao C. Curr Protoc. 2023;3:e736. 14. Emerging questions in transcriptional regulation: What are the sequence rules driving gene regulation? Nora EP, Aerts S, Wittkopp PJ, Bussemaker HJ, Bulyk M, Sinha S, Zeitlinger J, Crocker J, Fuxman Bass JI. Cell Syst. 2023;14:247-251. 15. (mis)Targeting of SWI/SNF complex(es) in cancer. Reddy D, Bhattacharya S, Workman JL. Cancer Metastasis Rev. 2023 Jun;42(2):455-470. 16. Second Special Issue on Methods for Omics Research: Proteome Research and Beyond. Florens L, Dong MQ, LaBaer J. J Proteome Res. 2023;22:1381-1384.</ExplanationTxt>
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      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Form 990, Part III, Line 4a PROGRAM SERVICE DESCRIPTION - Cont'd</FormAndLineReferenceDesc>
        <ExplanationTxt>Competitive Research Grant Funding &amp; Research Awards ions The ability of Stowers scientists to receive competitively awarded research funding attests to the high level of research productivity present at the Institute. During January-June 2023, Stowers scientists worked with the support of 41 grants and fellowships from the National Institutes of Health, two grants from the National Science Foundation, three fellowships from the National Science Foundation, one award from the Pew Charitable Trusts, one grant from the American Cancer Society, one grant from BioNexus KC, one grant from the Hearing Health Foundation, one grant from the American Society for Cell Biology, one fellowship from the Burroughs Wellcome Fund, and one investigator award from the Howard Hughes Medical Institute. Support from new and continuing awards to the Stowers Institute totaled more than $4.1 million during January-June 2023 to supplement income from its endowments. Testifying to the high level of achievement taking place at the Stowers Institute are the awards and honors Stowers members received in January-June 2023: - Ivan Candido-Ferreira, Ph.D., received a Grass Foundation Short-Term Fellowship. - Randal Halfmann, Ph.D., received a National Institute on Aging of the National Institutes of Health R21 Award. - Anna Klompen, Ph.D., received a National Science Foundation Postdoctoral Research Fellowship. - A.J. Treichel received a National Institutes of Health NRSA F31 Predoctoral Fellowship. - Lorena Maili, Ph.D., received an American Association for Anatomy Postdoctoral Fellowship. - Emma Rangel-Huerta, Ph.D., received a Society for Developmental Biology Emerging Research - Organisms Grant. - Paul Trainor, Ph.D., received a BioNexus KC Subaward and a National Institutes of Health Subaward. - Alex Von Schulze, Ph.D., received a National Institutes of Health NRSA F32 Postdoctoral Fellowship. Independent Research Program Leaders Laboratories Individual scientists at the Stowers Institute perform fundamental biomedical research by studying research organisms, tissues, and cells to understand the molecular mechanisms underlying human health and disease. A comprehensive list of research leaders follows: - Alejandro Sanchez Alvarado, Ph.D., President and Chief Scientific Officer, joined the Stowers Institute in 2011 from the University of Utah's School of Medicine, where he held the H.A. &amp; Edna Benning Professorship of Neurobiology and Anatomy. He received a B.S. in molecular biology and chemistry from Vanderbilt University in Nashville, Tennessee, and a Ph.D. in pharmacology and cell biophysics from the University of Cincinnati College of Medicine in Cincinnati, Ohio. Research focus: the molecular and cellular mechanisms underpinning animal regeneration using the planarian Schmidtea mediterranea and other research organisms. - Ariel Bazzini, Ph.D., Associate Investigator, joined the Stowers Institute in 2016 from the lab of Antonio J. Giraldez, Ph.D., in the Department of Genetics at Yale University, where he completed a postdoctoral fellowship. Bazzini received his Ph.D. in molecular biology at the University of Buenos Aires, Argentina. For his doctoral dissertation, he studied plant genetics at the Institute of Biotechnology in Argentina's National Institute of Agricultural Technology (INTA). Research focus: the regulation of gene expression in vertebrates. - Jennifer Gerton, Ph.D., Investigator, joined the Stowers Institute in 2002 from a postdoctoral fellowship in the laboratory of Joseph DeRisi, Ph.D., in the Department of Biochemistry and Biophysics at the University of California-San Francisco. Gerton received a Ph.D. in microbiology and immunology from Stanford University. Research focus: genomic and genetic analysis of chromosome segregation and chromosome dynamics. - Matthew Gibson, Ph.D., Investigator and Dean of the Graduate School, joined the Stowers Institute in 2006 from a Jane Coffin Childs Memorial Fund postdoctoral fellowship with Norbert Perrimon, Ph.D., at Harvard Medical School. Gibson received a Ph.D. in zoology from the University of Washington. Research focus: genetic analysis of mechanisms controlling signal transduction, cell proliferation, and epithelial morphogenesis during fruit fly, sea anemone, and coral development. - Randal Halfmann, Ph.D., Associate Investigator, joined the Stowers Institute in 2015 from The University of Texas (UT) Southwestern Medical Center. He received a Ph.D. in biology from the Massachusetts Institute of Technology, where he was a National Science Foundation Predoctoral Fellow. After completing his graduate studies, Halfmann obtained an independent position at UT Southwestern Medical Center where he was a Sara and Frank McKnight Fellow and received a Director's Early Independence Award from the National Institutes of Health. Research focus: Cellular and evolutionary implications of protein self-assembly using genetic, biochemical, and cell-biological approaches. - R. Scott Hawley, Ph.D., Investigator and Dean Emeritus of the Graduate School, joined the Stowers Institute in 2001 from the University of California-Davis where he was a professor of genetics in the Molecular and Cellular Biology section. Hawley earned a Ph.D. in genetics from the University of Washington and completed postdoctoral training as a Helen Hay Whitney Fellow at the Institute for Cancer Research in Philadelphia. Research focus: investigation of mechanisms that influence how chromosomes pair and segregate during meiosis using Drosophila as an experimental system.</ExplanationTxt>
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      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Form 990, Part III, Line 4a PROGRAM SERVICE DESCRIPTION - CONT'D</FormAndLineReferenceDesc>
        <ExplanationTxt>- Robert Krumlauf, Ph.D., Scientific Director Emeritus and Investigator, joined the Stowers Institute in 2000 from England's National Institute for Medical Research, The Ridgeway, Mill Hill, London, where he was head of the Division of Developmental Neurobiology. Krumlauf received a Ph.D. in developmental biology from Ohio State University. Research focus: analysis of molecular pathways that regulate how the mammalian head, brain and nervous system are built, using a variety of vertebrate research organisms. - Linheng Li, Ph.D., Investigator, joined the Stowers Institute in 2000 from the University of Washington Medical Center where he held a faculty appointment after completing postdoctoral training in the laboratory directed by Leroy Hood, M.D., Ph.D. Li earned his Ph.D. in molecular and cellular biology from New York University Medical School under the mentorship of Edward Ziff, Ph.D. Research focus: Investigation of molecular and genetic pathways controlling adult stem cell development in the hematopoietic and intestinal systems using transgenic and gene targeting animal model approaches. - Tatjana Piotrowski, Ph.D., Investigator, joined the Stowers Institute in 2011 from the University of Utah's School of Medicine, where she was an associate professor in the Department of Neurobiology and Anatomy. She received her master's degree from the University of Tubingen, Germany, and her doctorate degree from the Max Planck Institute for Developmental Biology in Tubingen. Research focus: collective cell migration, cell type specification, and stem cell biology in zebrafish as a research system. - Nicolas Rohner, Ph.D., Associate Investigator, joined the Stowers Institute in 2015 from Harvard Medical School, where he was a postdoctoral fellow in the laboratory of Cliff Tabin, Ph.D. Rohner earned a Ph.D. in biology from the Max Planck Institute for Developmental Biology in Tubingen, Germany. Research focus: genetic mechanisms and mutations that underlie the animal kingdom's tremendous diversity in morphology, physiology, and behavior. - Siva Sankari, Ph.D., Assistant Investigator, joined the Stowers Institute in 2023 from the Massachusetts Institute of Technology where she was a Postdoctoral Research Scientist in the lab of Graham Walker Ph.D. Sankari received a Ph.D. in biochemistry from the State University of New York at Buffalo. Research focus: the mechanisms of action of host-secreted peptides and how they act on symbiotic bacteria which may provide important clues to decipher the fundamental biology of host-microbe interactions. - Tatjana Sauka-Spengler, Ph.D., Investigator, joined the Stowers Institute in 2022 from the Weatherall Institute of Molecular Medicine at the University of Oxford, United Kingdom, where she continues to hold a professor position. Sauka-Spengler earned a Ph.D. in physics and a Ph.D. in biology from the University of Paris and completed postdoctoral training in the lab of Marianne Bronner, Ph.D., at the California Institute of Technology. Research focus: decoding the gene regulatory networks involved in cell function of the neural crest, heart, and nervous system to uncover the mechanisms underpinning inflammation and regeneration and how they have evolved. - Kausik Si, Ph.D., Scientific Director and Investigator, joined the Stowers Institute in 2005 from the laboratory of Eric Kandel, M.D., at Columbia University Center for Neurobiology and Behavior where he was a Jane Coffin Childs Fellow and a Francis Goelet Fellow in Neuroscience. Si earned a Ph.D. in molecular biology from the Albert Einstein College of Medicine. Research focus: role of synaptic protein synthesis in information acquisition and memory storage. - Paul Trainor, Ph.D., Investigator, joined the Stowers Institute in 2001 from a research position at the National Institute for Medical Research at Mill Hill, London, where he completed postdoctoral training. Trainor has a Ph.D. in developmental biology from Children's Medical Research Institute at the University of Sydney, Australia. Research focus: investigation of the interactions between distinct tissues in the body and their regulation during normal development to reveal pathways that regulate normal cranial and facial development. - Jerry Workman, Ph.D., Investigator, joined the Stowers Institute in 2003 from the Pennsylvania State University where he held the Paul Berg Professorship of Biochemistry and was an Associate Investigator of the Howard Hughes Medical Institute. Workman earned a Ph.D. in cell and molecular biology from the University of Michigan and completed postdoctoral training at the Rockefeller University with Bob Roeder, Ph.D. Research focus: study of the protein complexes that modify chromatin. - C. Ron Yu, Ph.D., Investigator, joined the Stowers Institute in 2005 from the laboratory of Richard Axel, M.D., at Columbia University Center for Neurobiology and Behavior where he held a National Institutes of Health Mentored Research Scientist Award from the National Institute of Mental Health. Yu earned his Ph.D. in molecular, cellular, and biophysical studies at Columbia University. Research focus: how olfactory sensory information is detected, integrated, and processed in the brain to influence specific innate behaviors. - SaraH Zanders, Ph.D., Associate Investigator and Vice Dean of the Graduate School, joined the Stowers Institute in 2016 after completion of her postdoctoral training in basic sciences at the Fred Hutchinson Cancer Research Center (Fred Hutch) with support from a Pathway to Independence Award from the National Institutes of Health. Fred Hutch faculty members Harmit S. Malik, Ph.D., and Gerry Smith, Ph.D., advised her research on fertility, genome evolution, and the origin of new species. Zanders received her Ph.D. in genetics and development from Cornell University. Research focus: the effects of genetic conflicts caused by selfish genes that are embedded in eukaryotic genomes. - Julia Zeitlinger, Ph.D., Investigator, joined the Stowers Institute in 2007 from the lab of Richard Young, Ph.D., at the Whitehead Institute for Biomedical Research at Massachusetts Institute of Technology where she was the recipient of a long-term postdoctoral fellowship from the Human Frontier Science Program. Zeitlinger earned a Ph.D. in molecular biology from the European Molecular Biology Laboratory in Heidelberg, Germany. Research focus: analysis of the gene regulatory networks underlying cellular differentiation.</ExplanationTxt>
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        <FormAndLineReferenceDesc>Form 990, Part VI, Line 2 FAMILY/BUSINESS RELATIONSHIPS AMONGST INTERESTED PERSONS</FormAndLineReferenceDesc>
        <ExplanationTxt>JONATHAN THOMAS, RICHARD W. BROWN, DAVID A. WELTE, BRENT KREIDER, CHARLES GERMAN, ALBERZINE FREEMAN, AND ALEJANDRO SANCHEZ ALVARADO, ALL DIRECTORS OF SIMR, HAVE A BUSINESS RELATIONSHIP. JONATHAN THOMAS, RICHARD W. BROWN, CHARLES GERMAN, BRENT KREIDER, AND ALBERZINE FREEMAN, DIRECTORS OF SIMR, AND PENNY M. SPENCE, OFFICER OF SIMR, HAVE A BUSINESS RELATIONSHIP. RICHARD W. BROWN, CHARLES GERMAN, GEORGE L. SATTERLEE AND BRENT KREIDER, DIRECTORS OF SIMR, AND PENNY M. SPENCE, OFFICER OF SIMR, HAVE A BUSINESS RELATIONSHIP.</ExplanationTxt>
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        <FormAndLineReferenceDesc>Form 990, Part VI, Line 12c CONFLICT OF INTEREST POLICY</FormAndLineReferenceDesc>
        <ExplanationTxt>SIMR HAS ADOPTED A "CONFLICTS OF INTEREST AND DIRECTOR INDEPENDENCE POLICY". EACH DIRECTOR, OFFICER, AND ALL OTHER PERSONS IN A POSITION TO EXERCISE SUBSTANTIAL INFLUENCE OVER DECISIONS OF SIMR ARE REQUIRED TO ANNUALLY COMPLETE AND SIGN A DISCLOSURE STATEMENT THAT IS PART OF THE POLICY. A COVERED PERSON MUST ALSO DISCLOSE THE EXISTENCE OF A POTENTIAL CONFLICT AND ALL MATERIAL FACTS TO THE GOVERNING BOARD AS SOON AS THE PERSON HAS KNOWLEDGE THAT A POTENTIAL CONFLICT MIGHT EXIST. PER THE POLICY, THE BOARD THEN REVIEWS THE DISCLOSURE TO DETERMINE WHETHER A CONFLICT EXISTS. AFTER THE COVERED PERSON MAKES THE RELEVANT DISCLOSURE, THEY ARE RECUSED AND MAY NOT PARTICIPATE IN THE DELIBERATIONS AND DECISIONS REGARDING THE TRANSACTION. SIMR CONDUCTS PERIODIC AND ADHOC REVIEWS OF TRANSACTIONS AND AGREEMENTS TO ENSURE THAT IT ENGAGES ONLY IN ACTIVITIES THAT ARE CONSISTENT WITH ITS TAX-EXEMPT PURPOSE.</ExplanationTxt>
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      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Form 990, Part VI, Line 15a PROCESS TO ESTABLISH COMPENSATION OF TOP MANAGEMENT OFFICIAL</FormAndLineReferenceDesc>
        <ExplanationTxt>THE COMPENSATION FOR ALEJANDRO SANCHEZ ALVARADO, PRESIDENT AND CHIEF SCIENTIFIC OFFICER, WAS ESTABLISHED PURSUANT TO THE PROCEDURES OF TREAS. REG. SECTION 53.4958-6, INCLUDING (1) REVIEW AND APPROVAL BY SIMR'S COMPENSATION COMMITTEE COMPRISED OF INDEPENDENT PERSONS, (2) RELYING ON COMPARABILITY DATA, INCLUDING DATA PREPARED BY A NATIONALLY KNOWN COMPENSATION CONSULTANT REGARDING COMPARABLE SALARY AND BENEFITS FOR SIMILARLY QUALIFIED PERSONS IN FUNCTIONALLY COMPARABLE POSITIONS AT SIMILARLY SITUATED ORGANIZATIONS, AND (3) CONTEMPORANEOUS DOCUMENTATION AND RECORD KEEPING OF THE DELIBERATION AND DECISIONS REGARDING THE COMPENSATION ARRANGEMENT. THIS PROCESS WAS LAST UNDERTAKEN IN 2021.</ExplanationTxt>
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        <FormAndLineReferenceDesc>Form 990, Part VI, Line 15b PROCESS TO ESTABLISH COMPENSATION OF OTHER OFFICERS</FormAndLineReferenceDesc>
        <ExplanationTxt>CHARLES GERMAN, RICHARD W. BROWN, BRENT KREIDER , GEORGE L. SATTERLEE AND PENNY M. SPENCE ARE COMPENSATED BY ONE OF THE RELATED ORGANIZATIONS LISTED IN SCHEDULE R FOR THE SERVICES PERFORMED IN THEIR OFFICIAL CAPACITY FOR THE RELATED ORGANIZATION.</ExplanationTxt>
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      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Form 990, Part VI, Line 11b Review of form 990 by governing body</FormAndLineReferenceDesc>
        <ExplanationTxt>THE DATA AND INFORMATION NECESSARY TO PREPARE SIMR'S FORM 990 WAS COMPILED BY SIMR'S ACCOUNTING DEPARTMENT AND THEN REVIEWED BY THE INSTITUTE'S TAX ATTORNEY AT BRYAN CAVE LEIGHTON PAISNER, LLP. FORVIS, LLP, THE INSTITUTE'S EXTERNAL TAX PREPARERS, USED THIS INFORMATION TO PREPARE THE FORM 990. THE COMPLETED FORM 990, INCLUDING REQUIRED SCHEDULES, IS REVIEWED BY THE OFFICERS OF SIMR BEFORE IT IS FILED WITH THE IRS. AFTER THE PREPARATION AND REVIEW PROCESS DESCRIBED ABOVE, THE FORM 990, INCLUDING REQUIRED SCHEDULES, IS PROVIDED TO EACH VOTING MEMBER OF THE ORGANIZATION'S BOARD BEFORE IT IS FILED WITH THE IRS.</ExplanationTxt>
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        <FormAndLineReferenceDesc>Form 990, Part VI, Line 19 Required documents available to the public</FormAndLineReferenceDesc>
        <ExplanationTxt>SIMR'S GOVERNING DOCUMENTS, CONFLICT OF INTEREST POLICY, AND FINANCIAL STATEMENTS ARE AVAILABLE UPON REQUEST.</ExplanationTxt>
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      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Form 990, Part VII, Section A AND SECTION B</FormAndLineReferenceDesc>
        <ExplanationTxt>THE ORGANIZATION CHANGED ITS YEAR END TO JUNE 30 AND IS THEREFORE FILING A SHORT PERIOD TAX RETURN FOR THE PERIOD OF 1/1/2023 TO 6/30/2023. PER THE FORM 990 INSTRUCTIONS, COLUMNS D AND E WILL BE BLANK AND THE ORGANIZATION WILL NOT REPORT ANY KEY EMPLOYEES, HIGHEST COMPENSATED EMPLOYEES NOR HIGHEST COMPENSATED INDEPENDENT CONTRACTORS. THESE ITEMS ARE ALL REPORTED BASED ON THE CALENDAR YEAR ENDING WITHIN THE FISCAL YEAR, WHICH DOES NOT EXIST FOR THE SHORT PERIOD.</ExplanationTxt>
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        <PrimaryActivitiesTxt>SEE PART VII</PrimaryActivitiesTxt>
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        <ExemptCodeSectionTxt>501(c)(4)</ExemptCodeSectionTxt>
        <DirectControllingEntityName>
          <BusinessNameLine1Txt>SIMR</BusinessNameLine1Txt>
        </DirectControllingEntityName>
        <ControlledOrganizationInd>true</ControlledOrganizationInd>
      </IdRelatedTaxExemptOrgGrp>
      <IdRelatedTaxExemptOrgGrp>
        <DisregardedEntityName>
          <BusinessNameLine1Txt>THE GRADUATE SCHOOL OF SIMR</BusinessNameLine1Txt>
        </DisregardedEntityName>
        <USAddress>
          <AddressLine1Txt>1000 EAST 50TH STREET</AddressLine1Txt>
          <CityNm>KANSAS CITY</CityNm>
          <StateAbbreviationCd>MO</StateAbbreviationCd>
          <ZIPCd>64110</ZIPCd>
        </USAddress>
        <EIN>464588696</EIN>
        <PrimaryActivitiesTxt>EDUCATION</PrimaryActivitiesTxt>
        <LegalDomicileStateCd>MO</LegalDomicileStateCd>
        <ExemptCodeSectionTxt>501(c)(3)</ExemptCodeSectionTxt>
        <PublicCharityStatusTxt>2</PublicCharityStatusTxt>
        <DirectControllingEntityName>
          <BusinessNameLine1Txt>SIMR</BusinessNameLine1Txt>
        </DirectControllingEntityName>
        <ControlledOrganizationInd>true</ControlledOrganizationInd>
      </IdRelatedTaxExemptOrgGrp>
      <IdRelatedTaxExemptOrgGrp>
        <DisregardedEntityName>
          <BusinessNameLine1Txt>STOWERS INVESTMENT HOLDING CORPORATION</BusinessNameLine1Txt>
        </DisregardedEntityName>
        <USAddress>
          <AddressLine1Txt>1000 EAST 50TH STREET</AddressLine1Txt>
          <CityNm>KANSAS CITY</CityNm>
          <StateAbbreviationCd>MO</StateAbbreviationCd>
          <ZIPCd>64110</ZIPCd>
        </USAddress>
        <EIN>920365628</EIN>
        <PrimaryActivitiesTxt>TITLE HOLDING</PrimaryActivitiesTxt>
        <LegalDomicileStateCd>DE</LegalDomicileStateCd>
        <ExemptCodeSectionTxt>501(c)(2)</ExemptCodeSectionTxt>
        <DirectControllingEntityName>
          <BusinessNameLine1Txt>SRMSPI</BusinessNameLine1Txt>
        </DirectControllingEntityName>
        <ControlledOrganizationInd>true</ControlledOrganizationInd>
      </IdRelatedTaxExemptOrgGrp>
      <IdRelatedOrgTxblCorpTrGrp>
        <RelatedOrganizationName>
          <BusinessNameLine1Txt>BIOMED VALLEY DISCOVERIESINC</BusinessNameLine1Txt>
        </RelatedOrganizationName>
        <USAddress>
          <AddressLine1Txt>4435 MAIN ST STE 550</AddressLine1Txt>
          <CityNm>KANSAS CITY</CityNm>
          <StateAbbreviationCd>MO</StateAbbreviationCd>
          <ZIPCd>64111</ZIPCd>
        </USAddress>
        <EIN>061646533</EIN>
        <PrimaryActivitiesTxt>SEE PART VII</PrimaryActivitiesTxt>
        <LegalDomicileStateCd>DE</LegalDomicileStateCd>
        <DirectControllingEntityName>
          <BusinessNameLine1Txt>BVC</BusinessNameLine1Txt>
        </DirectControllingEntityName>
        <EntityTypeTxt>C Corporation</EntityTypeTxt>
        <ControlledOrganizationInd>true</ControlledOrganizationInd>
      </IdRelatedOrgTxblCorpTrGrp>
      <ReceiptOfIntAnntsRntsRyltsInd>true</ReceiptOfIntAnntsRntsRyltsInd>
      <GiftGrntOrCapContriToOthOrgInd>false</GiftGrntOrCapContriToOthOrgInd>
      <GiftGrntCapContriFromOthOrgInd>true</GiftGrntCapContriFromOthOrgInd>
      <LoansOrGuaranteesToOtherOrgInd>false</LoansOrGuaranteesToOtherOrgInd>
      <LoansOrGuaranteesFromOthOrgInd>false</LoansOrGuaranteesFromOthOrgInd>
      <DivRelatedOrganizationInd>false</DivRelatedOrganizationInd>
      <AssetSaleToOtherOrgInd>false</AssetSaleToOtherOrgInd>
      <AssetPurchaseFromOtherOrgInd>false</AssetPurchaseFromOtherOrgInd>
      <AssetExchangeInd>false</AssetExchangeInd>
      <RentalOfFacilitiesToOthOrgInd>true</RentalOfFacilitiesToOthOrgInd>
      <RentalOfFcltsFromOthOrgInd>true</RentalOfFcltsFromOthOrgInd>
      <PerformOfServicesForOthOrgInd>false</PerformOfServicesForOthOrgInd>
      <PerformOfServicesByOtherOrgInd>false</PerformOfServicesByOtherOrgInd>
      <SharingOfFacilitiesInd>true</SharingOfFacilitiesInd>
      <PaidEmployeesSharingInd>true</PaidEmployeesSharingInd>
      <ReimbursementPaidToOtherOrgInd>true</ReimbursementPaidToOtherOrgInd>
      <ReimbursementPaidByOtherOrgInd>true</ReimbursementPaidByOtherOrgInd>
      <TransferToOtherOrgInd>true</TransferToOtherOrgInd>
      <TransferFromOtherOrgInd>false</TransferFromOtherOrgInd>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>BIOMED VALLEY DISCOVERIES INC</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>A</TransactionTypeTxt>
        <InvolvedAmt>994749</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>MARKET VALUE</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>BIOMED VALLEY DISCOVERIES INC</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>A</TransactionTypeTxt>
        <InvolvedAmt>7791</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>MARKET VALUE</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>STOWERS RESOURCE MANAGEMENT INC</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>C</TransactionTypeTxt>
        <InvolvedAmt>35067843</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>MARKET VALUE</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>STOWERS REAL ESTATE HOLDING CORP</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>K</TransactionTypeTxt>
        <InvolvedAmt>1115275</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>MARKET VALUE</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>STOWERS RESOURCE MANAGEMENT INC</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>P</TransactionTypeTxt>
        <InvolvedAmt>16171529</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>COST REIMB</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>THE GRADUATE SCHOOL OF SIMR</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>P</TransactionTypeTxt>
        <InvolvedAmt>331445</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>COST REIMB</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>BIOMED VALLEY DISCOVERIES INC</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>Q</TransactionTypeTxt>
        <InvolvedAmt>87002</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>COST REIMB</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <TransactionsRelatedOrgGrp>
        <OtherOrganizationName>
          <BusinessNameLine1Txt>THE GRADUATE SCHOOL OF SIMR</BusinessNameLine1Txt>
        </OtherOrganizationName>
        <TransactionTypeTxt>R</TransactionTypeTxt>
        <InvolvedAmt>974160</InvolvedAmt>
        <MethodOfAmountDeterminationTxt>MARKET VALUE</MethodOfAmountDeterminationTxt>
      </TransactionsRelatedOrgGrp>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part II, Column (b)</FormAndLineReferenceDesc>
        <ExplanationTxt>STOWERS POLICY INSTITUTE INC'S. ("SPI") PRIMARY ACTIVITY IS TO PROMOTE INNOVATIVE AND ETHICAL BIOMEDICAL RESEARCH, THERAPIES AND CURES, AND TO ADVOCATE FOR A POLITICAL, ECONOMIC AND SOCIAL ENVIRONMENT THAT ADVANCES, FACILITATES, AND PROTECTS THAT RESEARCH AND THOSE THERAPIES AND CURES.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part IV, Column (b)</FormAndLineReferenceDesc>
        <ExplanationTxt>BIOMED VALLEY DISCOVERIES, INC.'S ("BVD") PRIMARY ACTIVITY IS THE DEVELOPMENT AND MARKETING OF SCIENTIFIC DISCOVERIES. BIOMED VALLEY CORPORATION ("BVC") IS THE 100% OWNER OF BVD STOCK.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE A, SIMR RECEIVES ROYALTY PAYMENTS FROM BVD PURSUANT TO AN AMENDED AND RESTATED DISCOVERY DEVELOPMENT AGREEMENT DATED JULY 30, 2013. THESE ROYALTY PAYMENTS DO NOT CONSTITUTE GROSS INCOME DERIVED FROM AN UNRELATED TRADE OR BUSINESS UNDER SECTION 512(B)(13). THE ACTIVITY OF BVD WOULD NOT HAVE BEEN UNRELATED BUSINESS INCOME IF BVD WERE EXEMPT UNDER SECTION 501(C)(3) AND HAD THE SAME EXEMPT PURPOSE AS SIMR.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE A, SIMR RECEIVES SUBLEASE PAYMENTS FROM BVD BASED ON COST FOR LESS THAN 300 SQ FT OF SPACE FOR A LIMITED USE PURPOSE. THE ACTIVITY OF BVD WOULD NOT HAVE BEEN UBTI IF BVD WERE EXEMPT UNDER 501(C)(3) AND HAD THE SAME EXEMPT PURPOSE AS SIMR. THEREFORE, NO PORTION OF THE RENT PAYMENTS FROM BVD CONSTITUTES UNRELATED BUSINESS INCOME TO SIMR UNDER SECTION 512(B)(13).</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE C, SRM PROVIDED FINANCIAL SUPPORT TO SIMR TO BE USED BY SIMR IN FURTHERANCE OF SIMR'S EXEMPT PURPOSE OF CONDUCTING MEDICAL RESEARCH.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE K, SIMR ENTERED INTO A LEASE EFFECTIVE JANUARY 1, 2009 WITH SREHC, A 501(C)(2) TAX EXEMPT ORGANIZATION THAT IS A RELATED PARTY TO SIMR. THE LEASE HAS AN ORIGINAL TERM OF 10 YEARS WITH A PROVISION FOR ADDITIONAL OPTION YEARS FOR A 280,000 SQUARE FEET BUILDING. SIMR'S LEASE PAYMENTS TO SREHC TOTAL $1,115,275.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE P, SIMR REIMBURSED SRM FOR COSTS ASSOCIATED WITH SRM'S ADMINISTRATIVE AND SUPPORT SERVICES PROVIDED TO SIMR. SRM IS A SUPPORTING ORGANIZATION TO SIMR.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE P, SIMR REIMBURSED GSSIMR FOR CERTAIN STUDENT EXPENSES INCURRED DURING TIME SPENT IN SIMR LABS.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE Q, BVD REIMBURSED SIMR FOR SERVICES ON THE SERVICE COST METHOD.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>TYPE R, EACH ACADEMIC YEAR, SIMR PROVIDES GSSIMR WITH AN APPROPRIATION PURSUANT TO AN AMOUNT AGREED UPON BY SIMR AND GSSIMR. SIMR PROVIDES GSSIMR THE PER CAPITA APPROPRIATION OF $658,160 AND SUPPLEMENTAL APPROPRIATION OF $316,000 FOR THE TOTAL $974,160.</ExplanationTxt>
      </SupplementalInformationDetail>
      <SupplementalInformationDetail>
        <FormAndLineReferenceDesc>Schedule R, Part V, Line 2</FormAndLineReferenceDesc>
        <ExplanationTxt>ALL OTHER TRANSACTIONS FOR LINE 1 WERE BETWEEN 501(C)(3) PUBLIC CHARITIES AND BELOW REPORTING THRESHOLDS.</ExplanationTxt>
      </SupplementalInformationDetail>
    </IRS990ScheduleR>
  </ReturnData>
</Return>
