Epigenetic regulation of skeletal patterning and morphogenesis during development

发育过程中骨骼模式和形态发生的表观遗传调控

• 批准号: 9015100
• 负责人: Satya K. Kota
• 金额: $ 11.27万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-14 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9015100
• 关键词: Adult; Affect; Anterior; Area; Basic Science; Bilateral; Binding; Binding Sites; Bioinformatics; Biology; Cells; Cephalic; ChIP-seq; Chromatin; Congenital Abnormality; Congenital Limb Deformities; Cytosine; DNA; DNA Methylation; DNA Modification Process; Data; Defect; Deformity; Development; Developmental Gene; Digit structure; Disease; Distal; Down-Regulation; Educational workshop; Embryo; Embryonic Development; Enzymes; Epigenetic Process; Etiology; Event; Family; Family member; Forelimb; Foundations; Gene Deletion; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genes; Genetic; Genomics; Goals; Growth; Health; Histone Deacetylation; Histones; Homeostasis; Human; Immune System Diseases; In Vitro; Individual; Knowledge; Lead; Limb Bud; Limb Development; Limb structure; Maintenance; Maps; Mediating; Mediator of activation protein; Mentored Research Scientist Development Award; Mentors; Mesenchymal; Mesenchyme; Modification; Molecular; Molecular Analysis; Morphogenesis; Morphology; Motor Skills; Mus; Mutation; Neurodevelopmental Disorder; Newborn Infant; Operative Surgical Procedures; Osteoblasts; Osteogenesis; Pattern; Phase; Phenotype; Positioning Attribute; Protein Binding Domain; Reader; Regulation; Research; Research Methodology; Research Personnel; Research Training; Rett Syndrome; Role; SHFM1 gene; Signal Transduction; Skeletal Development; Stem cells; Stromal Cells; Targeted Research; Therapeutic; Tissues; Training; Universities; Update; abstracting; base; cell type; chromatin remodeling; craniofacial; craniofacial development; developmental disease; epigenetic regulation; epigenomics; experience; gain of function; gene repression; genome-wide; genome-wide analysis; histone methylation; implantation; insight; interest; malformation; member; methyl group; mouse model; multidisciplinary; osteoprogenitor cell; pluripotency; progenitor; response; skeletal; skeletal disorder; skeletal tissue; small hairpin RNA; stem cell biology; transcriptome; transcriptome sequencing

NOTE: Updated Abstract March 2016 Defective skeletal patterning is a major contributor of congenital limb malformations, which are among the most frequent birth defects in humans. Loss of epigenetic regulation has been associated with several debilitating human disorders including immune and neurodevelopmental disorders among others. Aberrant DNA modifications either due to mutations in enzymes that catalyze the establishment, maintenance or the readers of these marks are intricately associated with human developmental disorders. Building on Dr. Kota’s previous training and experience in the fields of epigenetic regulation of monoallelic gene expression and stem cell biology, this K01 application will support advanced research training in the interdisciplinary areas of developmental skeletal biology and epigenomics which will enable him to become an independent investigator in the emerging multidisciplinary area of epigenetic regulation of developmental skeletal biology. Specifically, during the K01 award period, Dr. Kota will receive advanced training in 1) theoretical and practical aspects of skeletal development and homeostasis, 2) analysis of mouse models of skeletal disorders and 3) genomic analysis of early limb progenitor cells, from a team of mentors at Harvard University. Training will be completed via formal coursework, hands-on lab training, mentored research and regular attendance at seminars and workshops. Based on the PI's preliminary findings in the mice, the research will focus on elucidating the role of the epigenetic gene regulation during skeletal patterning and aims to evaluate the transcriptome, epigenetic modifications in skeletal progenitors. In summary, the overall goal of the proposal is to understand the epigenetic regulation and its key targets during embryonic skeletal development to get better insights into human congenital limb abnormalities that eventually will lead to better therapeutic avenues.

NOTE：更新摘要2016年3月