b'ABSTR ACT / BIOGR APHY19 In-Hyun Park, Ph.D.Associate Professor, Department of Genetics and in the Child Study Center,Yale UniversityGeneration of Integrated Brain Organoids to InvestigateBrain Development and DiseasesHumanbrainorganoidtechniqueshaverapidlyadvancedtofacilitate investigatinghumanbraindevelopmentanddiseases.Sincethefirst report, a number of protocols were reported to produce brain organoids, raising a question whether the brain organoids from different protocols aresimilarordifferent.WeaccruedthescRNA-seqdatafromthe published works, and performed a comparative analysis. We found that regardless of methods, brain organoids produce similar types of cells that are produced in primary brain. We also applied the brain organoids tools to investigate human brain developmental disorders, called Rett syndrome (RTT) that are caused by mutations in MeCP2. We derived hESC lines with mutations in MeCP2 by CRISPR-editing, and applied the genomics tools to neurons and brain organoids derived from the MeCP2 mutant cells. We found that MeCP2 mutations caused the neural dysfunction by the abnormal transcription regulation, and that BET inhibitor JQ1 rescued the phenotypes of MeCP2 null neurons and animal. Overall, our studies demonstrated that brain organoids are important tools that can be readily used to study human brain development and diseases.Dr. Park is an Associate Professor of Genetics,Yale Stem Cell Center, and Child Study Center.Dr. Park received his B.S and M.S. from SeoulNational University at Korea, and Ph.D. from University of Illinois at Urbana-Champaign in the field of Cell and Structural Biology. During his Ph.D. training with Dr. Jie Chen, he studied mTORpathways regulating cell growth, and myogenicdifferentiation. In 2005, he continued his research as a Post-doc fellow inDr. George Daleys lab in Childrens Hospital Boston, where he isolated oneof the first human induced pluripotent stem cells (iPSCs). He started his own lab at Yale University from 2009. As an independent investigator, he pioneered in the generation of region-specific brain organoids, and studythe human neurodevelopment and related disorders.'