Identification of genetic polymorphisms in Stevens Johnson syndrome and toxic epidermal necrolysis

候选人：赛义德博士是马萨诸塞州眼耳医院(MEEI)的眼科讲师， 哈佛医学院。她于2016年7月在MEEI完成了她的角膜研究员资格，然后参加了 哈佛大学公共卫生学院(HSPH)为期7周的临床有效性强化计划，旨在 向对研究感兴趣的医学专业人员介绍定量和分析研究技能 临床医生-科学家的职业生涯。赛义德博士提出的职业发展计划包括攻读公共卫生硕士学位 在HSPH集中学习遗传流行病学和统计遗传学。她的职业发展计划 包括在三个方面扩展她的技能，以便研究史蒂文斯-约翰逊综合征/中毒的新方面 表皮坏死松解(SJS/TEN)：1)从事遗传流行病学研究的定量方法，2) 罕见病的结果研究，包括数据库开发，3)多中心研究设计。 环境：赛义德博士的职业发展将得到哈佛丰富的学术环境的支持 致力于她作为临床医生和科学家成长的机构。哈佛大学系统拥有世界上最高的 全国每年有10名SJS患者。MEEI和哈佛系统的广泛资源， 包括眼科基因组研究所在内，代表着一个非凡的环境来训练和进行 拟开展的研究。她的导师和合作者包括遗传流行病学的国家专家(珍妮博士 Wiggs和Daniel Chasman博士)、SJS/Ten(James Chodosh博士和Elizabeth Phillips博士)和结果 研究和数据库开发(理查德·格里利希博士)。她得到了系主任的全力支持， 琼·W·米勒博士。研究：SJS/TEN是一种罕见的黏膜皮肤病，大多数 通常表现为对药物的不良反应。眼表受累可导致 角膜失明和85%的幸存者被认为患有慢性眼病。数据表明，在那里 种族和药物依赖的遗传易感性导致SJS/TEN的发生。大多数研究都有 是在基因同质的群体中进行的，样本量相对较小。没有研究表明 利用外显子全基因组测序检测影响SJS/TEN发病机制的罕见变异。赛义德博士寻求 通过多中心协作研究SJS/TEN发生的遗传易感性。没有 SJS/TEN患者的国家登记或生物信息库。这些在前瞻性研究中将是必不可少的。 罕见和毁灭性的疾病，通过拟议的项目和未来在遗传学和 SJS/TEN的免疫致病机制。她与健康统一服务大学的新合作 科学将允许对各种种族和毒品队列进行大规模测序，并将允许她检测 可能导致SJS/TEN风险的基因多态。甲氧苄氨嘧啶(TS)被认为是 一种在美国常见的SJS/TEN煽动剂，将被重点研究。文献中只有一项研究 已经检查了TS诱导的SJS的遗传风险因素，这是一项纯粹的HLA基因分型研究。

Candidate: Dr. Saeed is an Instructor in Ophthalmology at Massachusetts Eye and Ear Infirmary (MEEI), Harvard Medical School. She completed her cornea fellowship at MEEI in July 2016 and then took the intensive 7-week Program in Clinical Effectiveness at the Harvard School of Public Health (HSPH), meant to introduce quantitative and analytic research skills to medical professionals with an interest in pursuing a clinician-scientist career. Dr. Saeed's proposed career development plan includes pursuing an MPH degree with a concentration in Genetic Epidemiology and Statistical Genetics at HSPH. Her career development plan includes expanding her skills in three areas in order to study new aspects in Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN): 1) quantitative methods for engaging in genetic epidemiology research, 2) outcomes research in rare diseases, including database development, 3) multi-center study design. Environment: Dr. Saeed's career development will be supported by a rich academic environment at Harvard institutions dedicated to her growth as a clinician-scientist. The Harvard system has one of the highest volumes of SJS/TEN patients per year in the nation. The extensive resources at MEEI and the Harvard system, including the Ocular Genomics Institute, represent an extraordinary environment to train and conduct the proposed research. Her mentors and collaborators include national experts in genetic epidemiology (Dr. Janey Wiggs and Dr. Daniel Chasman), SJS/TEN (Dr. James Chodosh and Dr. Elizabeth Phillips), and outcomes research and database development (Dr. Richard Gliklich). She has the full support of her department chair, Dr. Joan W. Miller. Research: SJS/TEN are on a spectrum of a rare mucocutaneous disease that most commonly manifest as an adverse reaction to a medication. Involvement of the ocular surface can lead to corneal blindness and 85% of survivors are thought to have chronic ocular disease. Data suggest that there are ethnicity and medication dependent genetic predispositions to developing SJS/TEN. Most studies have been done in genetically homogenous populations and with relatively small sample sizes. No studies have used whole exome sequencing to detect rare variants influencing pathogenesis of SJS/TEN. Dr. Saeed seeks to study the genetic predispositions to developing SJS/TEN through a multi-center collaboration. There is no national registry or biorepository of SJS/TEN patients. These will be essential in prospectively studying this rare and devastating disease, both through the proposed project and in future work on the genetics and immunopathogenesis of SJS/TEN. Her new collaborations with the Uniformed Services University of the Health Sciences will allow for large scale sequencing on various racial and drug cohorts and will allow her to detect genetic polymorphisms that may confer risk of SJS/TEN. Trimethoprim sulfamethoxazole (TS) is thought to be a common inciting agent of SJS/TEN in the US and will be studied in particular. Only one study in the literature has examined genetic risk factors in TS-induced SJS and it was purely an HLA genotyping study.