Association of Phenotypes and Genotype with Treatment Response in Psoriatic Arthritis

项目摘要 候选人：Paras Karmacharya，医学博士，MS是范德比尔特大学流变学系的临床讲师 &免疫学。他在风湿病学方面有很强的临床背景， 他的临床和转化科学硕士和博士后研究的流行病学研究 临床培训后的研究。他的长期职业规划是成为一名独立的临床研究者 在现实世界的银屑病关节炎（PsA）患者中进行以患者为中心的务实研究方面处于领先地位 并推进PsA的个性化治疗。为了实现这一目标，他将利用他提出的研究项目， 在先进的统计方法，生物信息学和遗传学的实践培训。 研究项目：该提案将研究PsA的临床和遗传异质性与 治疗反应。使用两个独特的真实世界PsA队列，Karmacharya博士将（1）识别PsA 表型及其与PsA治疗反应的相关性，以及（2）确定PsA患者的高表型 在EHR中，治疗响应概率低的患者和治疗响应概率低的患者。 这些目标是设计未来实用试验的基础，利用EHR更有效地 大力发展个性化的治疗方法。 职业发展：Karmacharya博士的职业发展计划将正式课程与 从他的导师的个人培训，以（1）提高先进的统计方法的技能，（2）扩大 熟练应用生物医学信息学技术，通过指导实践大型数据库 范德比尔特的EHR培训，（3）建立遗传学的基础知识，并通过体验式学习， 将分析技术应用于遗传生物库，以及（4）发展建立和管理遗传生物库的专业知识。 前瞻性PsA队列。 环境：VUMC是培养Karmacharya博士成为临床领导者的理想环境。 PsA的翻译研究。他的指导团队包括PsA（Ogdie/Ritchlin）的专家， 统计学方法（Byrne/Chen/Ogdie）、生物医学信息学（Byrne/Barnado）和遗传学（考克斯）。 其他机构资源包括合成衍生品（SD），这是一种去识别的EHR， 百万受试者，和BioVU，一个与SD相关的遗传生物库，以及对他的多中心的部门支持。 PsA队列。他的导师Crofford博士和Ogdie博士在风湿病学和PsA领域享有国际声誉， 成功的辅导记录。由于范德比尔特对年轻调查人员的制度承诺， 在生物医学信息学和遗传学的专业知识，Karmacharya博士将成功地利用他的创新 R 01独立融资。

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.