Genetic Influence in Pediatric Psoriasis

遗传对儿童银屑病的影响

• 批准号: 8299063
• 负责人: Wynnis L Tom
• 金额: $ 13.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-08 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8299063
• 关键词: Acute; Adult; Advisory Committees; Affect; Age; Area; Biological; Biometry; Biopsy; Burn injury; Calcineurin; Calcineurin inhibitor; California; Candidate Disease Gene; Caring; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Collaborations; Comparative Study; Complex; Country; Crohn' s disease; Cyclosporine; DNA; DNA Library; Dermatology; Disease; Disease Outcome; Disease susceptibility; Effectiveness; Ethics; Face; Flexural psoriasis; Gene Expression; Genes; Genetic; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype; HLA-B57; HLA-Cw6; Haplotypes; Human Genetics; Individual; Infant; Infection; Inflammatory; Inositol; Institutes; Interleukin-13; Interleukin-4; Interleukins; K-Series Research Career Programs; Laboratories; Lesion; Letters; Membrane; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Michigan; Molecular; Molecular Profiling; Mucocutaneous Lymph Node Syndrome; NF-kappa B; Onset of illness; PTPN22 gene; Parents; Pathogenesis; Pathway interactions; Patients; Pattern; Pharmacotherapy; Phenotype; Phosphotransferases; Polymerase Chain Reaction; Predisposition; Prevalence; Prognostic Marker; Protein Tyrosine Phosphatase; Proteins; Psoriasis; Research; Research Personnel; Research Proposals; Research Training; Reverse Transcription; Sampling; Scientist; Severity of illness; Signal Pathway; Signal Transduction; Singapore; Single Nucleotide Polymorphism; Skin; Stress; Susceptibility Gene; Systemic Therapy; T-Cell Activation; T-Lymphocyte; Tacrolimus; Testing; Training Programs; Transcript; Translational Research; Trauma; Universities; Utah; Variant; Vasculitis; age group; career development; cohort; drug development; genetic analysis; genome-wide; human IL12B protein; human disease; infancy; insight; interest; meetings; novel; nuclear factors of activated T-cells; patient oriented research; programs; prospective; response; skills; skin disorder; transcription factor

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.

描述（由申请人提供）：在以患者为导向的研究这个指导职业发展奖的主要目标是为候选人，博士Wynnis汤姆，获得的技能和专业知识，成为一个独立的研究者领导的临床和遗传研究儿科炎症性皮肤病，特别是牛皮癣。在Jane Burns和Kelly弗雷泽博士的指导下，候选人构建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方面的正式课程，沿着每周研讨会、定期面对面的导师会议和参加每周实验室会议。此外，这个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，该委员会具有复杂人类疾病遗传分析，大型儿科和父母队列招募和研究以及临床和转化研究的专业知识。这项研究包括儿童和成人银屑病患者基因表达谱的比较研究和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性（SNP）作为儿童银屑病患者的预后标志物。三个具体目标是：1）比较从健康儿童、患有银屑病的儿童、患有儿童期发作的银屑病的成人和患有成人期发作的银屑病的成人获得的病变和未受影响或正常皮肤中的表达; 2）分析先前与成人银屑病相关的14个基因中的SNP和儿科银屑病受试者及其生物学父母中的钙调神经磷酸酶/NFAT途径中的14个基因中的SNP;和3）通过受试者对治疗的反应和疾病严重程度对遗传分析进行分层。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相似或不同。结果可能会确定药物开发的其他目标和疾病过程的预测因子，并在年轻患者患有银屑病药物治疗的反应。