Association of Phenotypes and Genotype with Treatment Response in Psoriatic Arthritis

项目总结 候选人：Paras Karmacharya，医学硕士，范德比尔特大学风湿科临床讲师 &免疫学。他在风湿病方面有深厚的临床背景，在 他的临床和转化学硕士学位和博士后研究的流行病学研究 临床培训后的研究。他的长期职业计划是成为一名独立的临床研究员 在现实世界的牛皮癣关节炎(PSA)患者中追求以患者为中心的务实研究的领导者 在PSA中推进个性化用药。为了实现这一目标，他将利用他提出的研究项目 高级统计方法、生物信息学和遗传学方面的实践培训。 研究项目：这项建议将研究PSA的临床和遗传异质性与 治疗反应。使用两个独特的现实世界PSA队列，Karmacharya博士将(1)识别PSA PSA的表型及其与治疗反应的关系，以及(2)识别PSA患者的高 在EHR中，对治疗有反应的概率和对治疗有反应的概率较低的人。 这些目标是设计未来的实用试验的基础，利用电子健康记录来更有效和 大力发展个性化治疗方法。 职业发展：Karmacharya博士的职业发展计划将正式课程与 来自导师的个人培训(1)提高先进统计方法的技能，(2)扩大 熟练运用生物医学信息学技术于大型数据库的指导实践 培训范德比尔特的EHR，(3)建立遗传学基础知识，并通过体验式学习 将分析技术应用于遗传生物库，以及(4)发展建立和管理 未来的PSA队列。 环境：VUMC是培养Karmacharya博士成为临床领导者的理想环境 以及PSA中的翻译研究。他的指导团队包括PSA(Ogdie/Ritchlin)、高级 统计学方法(Byrne/Chen/Ogdie)、生物医学信息学(Byrne/Barnado)和遗传学(Cox)。 其他机构资源包括合成衍生品(SD)，这是一种不确定的EHR，超过3.5 百万受试者，BioVU，一个链接到SD的遗传生物库，以及部门对他的多中心的支持 PSA队列。他的导师克罗福德博士和奥格迪博士在风湿病和PSA方面是国际公认的 成功的辅导记录。范德比尔特对年轻调查人员的机构承诺和 在生物医学信息学和遗传学方面的专业知识，Karmacharya博士将成功地利用他的创新 建议独立提供R01资金。

PROJECT SUMMARY Candidate: Paras Karmacharya, MD MS is a Clinical Instructor at Vanderbilt in the Divisions of Rheumatology & Immunology. He has a strong clinical background in rheumatology and an excellent scientific foundation in epidemiological studies from his Master’s in Clinical and Translational Science and post-doctoral research studies following clinical training. His long-term career plan is to become an independent clinical investigator and a leader in pursuing patient-centered, pragmatic research in real-world psoriatic arthritis (PsA) patients and advancing personalized medicine in PsA. To achieve this goal, he will utilize his proposed research project for hands-on training in advanced statistical methods, bioinformatics, and genetics. Research Project: This proposal will study the association of clinical and genetic heterogeneity in PsA with treatment response. Using two unique real-world PsA cohorts, Dr. Karmacharya will (1) Identify PsA phenotypes and their association with treatment response in PsA, and (2) Identify PsA patients with a high probability of responding to therapy and those with a low probability of responding to therapy in the EHR. These aims are foundational to designing future pragmatic trials leveraging the EHR to more efficiently and robustly develop personalized approaches to treatment. Career Development: Dr. Karmacharya’s career development plan integrates formal coursework with individual training from his mentors to (1) Enhance skills in advanced statistical methods, (2) Expand proficiency in applying biomedical informatics techniques to large databases through mentored hands-on training in Vanderbilt’s EHR, (3) Build foundational knowledge in genetics and through experiential learning to apply analytic techniques to a genetic biobank, and (4) Develop expertise in building and managing a prospective PsA cohort. Environment: VUMC is the ideal environment to foster Dr. Karmacharya’s development as a leader in clinical and translational research in PsA. His mentoring team includes experts in PsA (Ogdie/Ritchlin), advanced statistical methods (Byrne/Chen/Ogdie), biomedical informatics (Byrne/Barnado), and genetics (Cox). Additional institutional resources include the Synthetic Derivative (SD), a de-identified EHR with over 3.5 million subjects, and BioVU, a genetic biobank linked to the SD, and departmental support for his multicenter PsA cohort. His mentors, Drs. Crofford and Ogdie, are internationally recognized in rheumatology and PsA with successful track records of mentoring. With Vanderbilt’s institutional commitment to young investigators and expertise in biomedical informatics and genetics, Dr. Karmacharya will successfully leverage his innovative proposal for independent R01 funding.