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

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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.