Genetic Analysis of the TNF Pathway in Psoriasis

银屑病 TNF 通路的遗传分析

• 批准号: 8304853
• 负责人: Wilson Liao
• 金额: $ 11.96万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304853
• 关键词: Advisory Committees; Affect; Age of Onset; American; Animal Model; Area; Autoimmune Diseases; Autoimmune Process; Bioinformatics; Biological Assay; Cellular Assay; Clinical Research; Complement; Copy Number Polymorphism; Custom; DNA Sequence; Data; Data Aggregation; Databases; Dermatology; Development; Disease; Doctor of Philosophy; Economic Burden; Exons; Faculty; Feedback; Functional RNA; Gastroenterology; Gene Dosage; Gene Expression; Genes; Genetic; Genetic Epistasis; Genetic Variation; Genomics; Genotype; Human Genetics; Immunologist; Institutes; International; Joints; Linkage Disequilibrium; Maps; Medical; Medicine; Mentors; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Postdoctoral Fellow; Program Development; Psoriasis; Research; Research Personnel; Research Project Grants; Research Proposals; Research Training; Residencies; Resources; Rheumatology; Risk; Risk Factors; Role; Scanning; Science; Senior Scientist; Severities; Signal Transduction; Skin; TNF gene; Testing; Time; Training; Training Programs; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Universities; Untranslated Regions; Variant; Washington; burden of illness; career; case control; clinically relevant; clinically significant; cohort; design; genetic analysis; genetic association; genome wide association study; graduate student; interest; member; professor; psychologic; response; skills; symposium

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in the field of psoriasis genetics. The candidate completed his medical studies at Harvard, performed a year of clinical research training at the NIH, and recently graduated from a dermatology residency at UCSF. Over the past year, as a UCSF junior faculty member, the candidate has contributed to the discovery of several psoriasis genes through his establishment of a large psoriasis patient database. Through the proposed training program, the candidate will expand upon his scientific skills to become an independent investigator in human genetics. He will accomplish this through coursework, participation in seminars and conferences, national presentations, and engagement in a mentored research project. Dr. Pui-Yan Kwok will mentor the candidate's scientific development. Dr. Kwok is a recognized leader in the field of genetics and genomics. Dr. Kwok serves as the Henry Bachrach Distinguished Professor at UCSF and is a founding member of the International HapMap Consortium. His record of mentoring postdoctoral fellows and graduate students is superb. To enhance the candidate's training, an advisory committee of highly-regarded senior scientists will provide scientific and career advice. The advisory committee will consist of two geneticists (Anne Bowcock, PhD., Joint Director for Human Genetics at Washington University, and Lindsey Criswell, MD, MPH, Professor of Medicine and Rheumatology at UCSF) and an immunologist (Averil Ma, MD, Professor of Medicine and Gastroenterology at UCSF). Of note, Dr. Criswell and Dr. Ma's own research interests are integrally tied to the candidate's proposed research plan; thus, the candidate will receive closer-than-usual feedback through a unique "team science" approach. Research will focus on the role of TNF pathway gene variants in psoriasis. Recent results from a large genome wide association study in psoriasis demonstrate that two genes in the TNF pathway, TNFAIP3 and TNIP1, are major risk factors for the development of psoriasis. The research project will perform fine mapping of these two genes to identify causal variants, and additionally examine other genes in this pathway for genetic association. High throughput genotyping, DNA sequencing, and copy number assays will be employed. The aggregate data will provide the first detailed picture of TNF pathway genes in psoriasis. The proposed training program draws on the combined resources of the UCSF Institute for Human Genetics, UCSF Department of Dermatology, and UCSF Psoriasis Center. This will provide an ideal setting for the candidate's maturation into an independent investigator.

描述(由申请者提供)：本建议书描述了一项为期5年的牛皮癣遗传学领域学术生涯发展培训计划。这位候选人在哈佛大学完成了他的医学研究，在NIH进行了一年的临床研究培训，最近从加州大学旧金山分校的皮肤病住院医生毕业。在过去的一年里，作为加州大学旧金山分校的初级教员，这位候选人通过建立一个大型牛皮癣患者数据库，为发现几种牛皮癣基因做出了贡献。通过拟议的培训计划，候选人将扩展他的科学技能，成为一名人类遗传学的独立研究员。他将通过课程作业、参加研讨会和会议、国家报告和参与有指导的研究项目来实现这一点。郭培仁博士将指导候选人的科学发展。郭博士是遗传学和基因组学领域公认的领导者。郭博士是加州大学旧金山分校Henry Bachrach特聘教授，也是国际HapMap联盟的创始成员之一。他在指导博士后研究员和研究生方面的记录非常出色。为了加强候选人的培训，一个由备受尊敬的资深科学家组成的咨询委员会将提供科学和职业建议。咨询委员会将由两名遗传学家(华盛顿大学人类遗传学联席主任Anne Bowcock博士和加州大学旧金山分校医学和风湿学教授Lindsey Criswell，公共卫生硕士)和一名免疫学家(UCSF医学和胃肠病学教授Averil Ma)组成。值得注意的是，克里斯韦尔博士和马博士自己的研究兴趣与候选人提出的研究计划密不可分；因此，候选人将通过独特的“团队科学”方法收到比往常更接近的反馈。研究将集中在肿瘤坏死因子途径基因变异在银屑病中的作用。最近一项银屑病全基因组关联研究的结果表明，肿瘤坏死因子途径中的两个基因，TNFAIP3和TNIP1，是银屑病发生的主要危险因素。该研究项目将对这两个基因进行精细定位，以确定因果变异，并另外检查这一途径中的其他基因的遗传关联。将采用高通量基因分型、DNA测序和拷贝数分析。综合数据将提供牛皮癣中肿瘤坏死因子途径基因的第一张详细图片。拟议的培训计划利用了加州大学旧金山分校人类遗传学研究所、加州大学旧金山分校皮肤科和加州大学旧金山分校牛皮癣中心的联合资源。这将为候选人成为一名独立的调查员提供理想的环境。