Genetic Analysis of the TNF Pathway in Psoriasis

描述（由申请人提供）：本提案描述了一个为期5年的培训计划，在银屑病遗传学领域的学术生涯的发展。这位候选人在哈佛完成了医学研究，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科住院医师毕业。在过去的一年里，作为加州大学旧金山分校的一名初级教员，这位候选人通过建立一个大型银屑病患者数据库，为发现几个银屑病基因做出了贡献。通过拟议的培训计划，候选人将扩大他的科学技能，成为人类遗传学的独立调查员。他将通过课程，参加研讨会和会议，国家演讲，并在指导研究项目的参与来实现这一目标。 郭培恩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的亨利巴赫杰出教授，也是国际人类基因组单体型图联盟的创始成员。他指导博士后研究员和研究生的记录是一流的。为了加强候选人的培训，一个由德高望重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组成（Anne Bowcock博士，华盛顿大学人类遗传学联合主任和加州大学旧金山分校医学和流变学教授Lindsey Criswell）和免疫学家（加州大学旧金山分校医学和胃肠病学教授Averil Ma）。值得注意的是，Criswell博士和Ma博士自己的研究兴趣与候选人提出的研究计划紧密相关;因此，候选人将通过独特的“团队科学”方法获得比平常更接近的反馈。 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。最近一项大型银屑病全基因组关联研究的结果表明，TNF途径中的两个基因TNFAIP 3和TNIP 1是银屑病发展的主要危险因素。该研究项目将对这两个基因进行精细定位，以识别因果变异，并检查该途径中的其他基因的遗传关联。将采用高通量基因分型、DNA测序和拷贝数测定。汇总数据将提供银屑病中TNF途径基因的第一个详细信息。 拟议的培训计划借鉴了UCSF人类遗传学研究所，UCSF皮肤科和UCSF皮肤病中心的综合资源。这将为候选人成长为独立调查员提供理想的环境。

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.