Epigenetic control of target gene activity by hairless in skin homeostasis

无毛在皮肤稳态中对靶基因活性的表观遗传控制

• 批准号: 8827678
• 负责人: Liang Liu
• 金额: $ 11.64万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8827678
• 关键词: Ablation; Alopecia; Apoptosis; Applications Grants; Award; Basic Science; Biological; Biological Assay; Biological Process; Biology; Biomedical Research; Candidate Disease Gene; Categories; Cell Cycle; Cell Nucleus; Cell Proliferation; Cell physiology; Cells; ChIP-seq; Chromatin; Clinical; Clinical Research; Core Facility; Cutaneous; DNA; Dermal; Dermatology; Development; Differentiation and Growth; Disease susceptibility; Environment; Environmental Health; Environmental Risk Factor; Epidermis; Epigenetic Process; Exhibits; Functional disorder; Funding; Future; Gene Expression Profiling; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Genome; Genomics; Goals; Growth; Hair; Hair follicle structure; Health; Histone H3; Histones; Homeostasis; Human; Hyperplasia; Institution; Laboratories; Lead; Lesion; Literature; Maps; Mentored Research Scientist Development Award; Mentors; Methods; Microarray Analysis; Molecular; Mutant Strains Mice; Mutation; National Institute of Environmental Health Sciences; PVT1 gene; Pathway interactions; Patients; Play; Population; Postdoctoral Fellow; Process; Protein Family; Proteins; Publications; Reporting; Research; Research Activity; Research Infrastructure; Research Personnel; Resistance; Resources; Role; S Phase; Scientist; Site; Skin; Skin Abnormalities; Stem cells; Stratum Basale; Structure; Subfamily lentivirinae; Testing; Transcriptional Regulation; UV induced; Universities; Wild Type Mouse; Work; Wound Healing; Writing; adult stem cell; base; career; demethylation; design; differential expression; epigenetic profiling; epigenetic regulation; fibroblast growth factor 13; follow-up; histone demethylase; histone methylation; improved; innovation; interest; keratinocyte; member; methylation pattern; mutant; novel; programs; relating to nervous system; research study; self-renewal; skills; skin disorder; skin hyperplasia; small hairpin RNA; stem cell differentiation; stemness; tongue papilla; ultraviolet; ultraviolet irradiation

DESCRIPTION (provided by applicant): The Candidate for this K01 award, Dr. Liang Liu, joined the Department of Dermatology at Columbia University in July, 2010 as an Associate Research Scientist, where he studies epigenetic regulation of epidermal development and homeostasis under the direction of Dr. Angela Christiano, the Mentor of this K01 award. Dr. Liu's research interest centers on elucidating how genes and environment interact to influence development and disease susceptibility. The major goal of this project is to define the genetic and epigenetic pathways by which HR regulates epidermal growth and proliferation in skin homeostasis. Dr. Liu is committed to a biomedical research career. During the first two years of the award, he will focus on building up his research publication record and improving his skills in scientific writing including research articles and grant applications. From the third year of this K01 award, Dr. Liu will actively seek long-term funding support that will allow him to become a fully independent investigator after completion of this K01 award. Dr. Liu's long term career goal is to establish an innovative and independent research program in cutaneous biology. Institutional Environment Columbia University is one of the top research institutions in the US and has outstanding resources for trainees. There are state of the art laboratories for work in basic and clinical research and outstanding core facilities for supporting molecular and clinical research activities. The candidate's more immediate research environment is the Department of Dermatology and the Columbia University Skin Disease Research Center. He is also a member of the NIEHS Center for Environmental Health in Northern Manhattan, which provides additional resources and infrastructure that will facilitate the completion of this project. Research Summary Hairless (HR) belongs to the Jumonji C family of proteins, many of which function as histone demethylases (HDM) that participate in gene regulation via epigenetic mechanisms. We previously reported that mutations in HR are deleterious for skin homeostasis and hair follicle cycling, as exemplified by the clinical manifestations of patients with alopecia with papular lesions. We now have compelling evidence showing that HR is a HDM, regulating a subset of target genes through histone demethylation. We hypothesize that hairless acts as an epigenetic regulator of skin homeostasis via its downstream target genes to control cell proliferation and apoptosis. To test this hypothesis, we will focus on studying the role of hairless and its downstream target genes and pathways in epidermal growth and differentiation. We will employ molecular biological methods such as gene expression profiling, ChIP-Seq analysis, and comprehensive functional assays to rigorously test our hypothesis. Findings from this project will significantly enhance our understandings of the mechanisms underlying the pathophysiology of skin disorders such as hyperplasia and photoaging. The Candidate anticipates being able to complete the studies within a five-year award period through collaborative efforts with his Mentors and collaborators.

描述（由申请人提供）：本次K01奖候选人刘亮博士于2010年7月加入哥伦比亚大学皮肤学系，担任副研究员，在本次K01奖导师Angela Christiano博士的指导下，研究表皮发育和体内平衡的表观遗传调控。刘博士的研究兴趣集中在阐明基因和环境如何相互作用影响发育和疾病易感性。本项目的主要目标是确定HR在皮肤稳态中调节表皮生长和增殖的遗传和表观遗传途径。刘博士致力于生物医学研究事业。在该奖项的前两年，他将专注于建立他的研究发表记录和提高他的技能