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，旨在发展牛皮癣遗传学领域的学术生涯。这位候选人在哈佛完成了他的医学研究，在美国国立卫生研究院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UCSF的初级教员，候选人通过建立一个大型牛皮癣患者数据库，为发现几个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，成为一名独立的人类遗传学研究者。他将通过课程学习、参加研讨会和会议、全国演讲和参与指导的研究项目来实现这一目标。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杰出教授，也是国际HapMap联盟的创始成员。他指导博士后和研究生的记录非常出色。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。咨询委员会将由两位遗传学家（安妮·鲍考克博士）组成。华盛顿大学人类遗传学联合主任，Lindsey Criswell医学博士，公共卫生硕士，UCSF医学和风湿病学教授，免疫学家（Averil Ma医学博士，UCSF医学和胃肠病学教授）。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是紧密相关的；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TNF通路基因变异在牛皮癣中的作用。最近一项银屑病大基因组关联研究的结果表明，TNF通路中的两个基因TNFAIP3和TNIP1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，以确定因果变异，并进一步研究这一途径中的其他基因的遗传关联。高通量基因分型，DNA测序和拷贝数分析将被采用。综合数据将提供银屑病中TNF通路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综合资源。这将为候选人成长为一名独立调查员提供一个理想的环境。

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.