Genetic Influence in Pediatric Psoriasis

描述(由申请者提供)：这项以患者为中心的研究指导职业发展奖的主要目标是让候选人温尼斯·汤姆博士获得技能和专业知识，成为一名领导儿科炎症性皮肤病，特别是牛皮癣的临床和基因研究的独立研究员。在简·伯恩斯博士和凯利·弗雷泽博士的指导下，这位候选人构建了一个重点培训计划，其中包括密集的课程和研究培训。授课部分将包括关于人类遗传学和基因组学、临床和转译研究、生物统计学和伦理学的正式课程作业，以及每周研讨会、定期面对面的导师会议和参加每周的实验室会议。此外，这一职业发展计划将受益于一个精心挑选的咨询委员会的监督，该委员会由资深研究科学家组成，他们在复杂人类疾病的基因分析、大型儿科和父母队列的招募和研究以及临床和翻译研究方面具有专长。这项建议的研究包括对儿童和成人银屑病患者基因表达谱的比较研究，以及一项前瞻性队列研究，该研究将调查候选易感基因中的单核苷酸多态(SNPs)作为儿童银屑病患者预后标志的情况。这三个具体目标是：1)比较健康儿童、银屑病儿童、儿童银屑病成人和成人银屑病患者皮损和正常皮肤中的表达；2)分析以前与成人银屑病相关的14个基因中的SNPs，以及儿童银屑病患者及其亲生父母Cacineurin/NFAT通路中14个基因中的SNPs；以及3)根据受试者对治疗的反应和疾病的严重程度进行基因分层分析。拟议的研究将揭示与成人相比，儿童银屑病患者的分子途径和遗传影响可能是相似的还是不同的。结果可能为年轻牛皮癣患者的药物开发和病程和药物治疗反应的预测因素确定更多的靶点。

DESCRIPTION (provided by applicant): The primary objective of this mentored career development award in patient-oriented research is for the candidate, Dr. Wynnis Tom, to acquire the skills and expertise to become an independent investigator leading clinical and genetic studies on pediatric inflammatory skin diseases, particularly psoriasis. Under the direction of Drs. Jane Burns and Kelly Frazer, the candidate has constructed a focused training program that includes intensive coursework and research training. The didactic component will include formal coursework on human genetics and genomics, clinical and translational research, biostatistics, and ethics, along with weekly seminars, regular face-to-face mentor meetings and participation in weekly laboratory meetings. In addition, this career development program will benefit from the oversight of a carefully selected Advisory Committee of senior research scientists with expertise in genetic analysis of complex human diseases, recruitment and study of large pediatric and parent cohorts, and clinical and translational research. The research for this proposal consists of a comparative study of gene expression profiles in children and adults with psoriasis and a prospective cohort study that will investigate single nucleotide polymorphisms (SNPs) in candidate susceptibility genes as prognostic markers for pediatric psoriasis patients. The three specific aims are: 1) To compare expression in lesional and unaffected or normal skin obtained from healthy children, children with psoriasis, adults with childhood-onset psoriasis, and adults with adult-onset psoriasis; 2) To analyze SNPs in 14 genes previously associated with adult psoriasis and SNPs in 14 genes in the calcineurin/NFAT pathway in pediatric psoriasis subjects and their biological parents; and 3) To stratify genetic analysis by subject response to therapy and disease severity. The proposed studies will reveal how molecular pathways and genetic influences may be similar or different in pediatric psoriasis patients as compared to adults. Results may identify additional targets for drug development and predictors of disease course and response to pharmacotherapy in young patients suffering from psoriasis.