Genetic Influence in Pediatric Psoriasis

描述（由申请人提供）：这个以患者为导向的研究指导职业发展奖的主要目标是让候选人Wynnis Tom博士获得技能和专业知识，成为一名独立的研究者，领导儿科炎症性皮肤病，特别是牛皮癣的临床和遗传研究。在博士的指导下。简·伯恩斯（Jane Burns）和凯利·弗雷泽（Kelly Frazer），候选人建立了一个重点培训计划，包括强化课程和研究培训。教学部分将包括关于人类遗传学和基因组学、临床和转化研究、生物统计学和伦理学的正式课程，以及每周研讨会、定期面对面导师会议和参加每周实验室会议。此外，该职业发展计划将受益于一个精心挑选的高级研究科学家咨询委员会的监督，这些科学家在复杂人类疾病的遗传分析，大型儿科和父母队列的招募和研究以及临床和转化研究方面具有专业知识。本研究包括对儿童和成人牛皮癣患者基因表达谱的比较研究，以及一项前瞻性队列研究，该研究将研究候选易感基因的单核苷酸多态性（snp）作为儿科牛皮癣患者预后标志物。三个具体目的是：1)比较健康儿童、牛皮癣儿童、儿童期牛皮癣成人和成年期牛皮癣成人皮肤的病变和未受影响或正常皮肤中的表达；2)分析儿童牛皮癣患者及其亲生父母中14个成人牛皮癣相关基因的snp和钙调磷酸酶/NFAT通路14个基因的snp；3)根据受试者对治疗的反应和疾病严重程度对基因分析进行分层。拟议的研究将揭示与成人相比，儿童牛皮癣患者的分子途径和遗传影响可能相似或不同。研究结果可能为年轻牛皮癣患者的药物开发确定额外的靶点，并预测病程和药物治疗反应。

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.