Precision Medicine Approaches for Eosinophilic Esophagitis Using Raman Spectroscopy and Machine Learning

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PROJECT SUMMARY The overarching goal of this K23 Mentored Patient-Oriented Research Career Development Award is to provide essential skills and mentored research experience to prepare Dr. Girish Hiremath as an independent investigator leading a multi-disciplinary team of researchers focused on eosinophilic esophagitis (EoE). EoE is a chronic, allergen-mediated, inflammatory condition of the esophagus. As one of the most common cause of upper gastrointestinal morbidity, it affects 1 out of 2000 individuals in the United States. Our understanding of the pathogenesis of EoE is incomplete and this has contributed towards burdensome approaches to treat EoE patients. There is a critical unmet need to understand all factors related with development of EoE, including determining the biochemical changes in the esophagus that leads to transformation of an unaffected esophagus to an inflamed esophagus in EoE. As a Pediatric Gastroenterologist with clinical and research focus on EoE for more than a decade, the candidate proposes to fill this important knowledge gap by building on his published work through: 1) Validating the esophageal biochemical changes in EoE using Raman spectroscopy (a uniquely suited, highly sensitive, laser-based technique) and machine learning, 2) Determining the correlation between the Raman peaks and the disease activity, and the operating characteristics of the key Raman peaks in distinguishing EoE activity states, and 3) Determining if a combination of the baseline Raman, histologic, endoscopic, and clinical features can predict response to EoE therapy. By defining the key esophageal biochemical alterations this study will offer novel insights into pathogenesis of EoE, and by identifying the baseline predictors of the treatment response it will lay a framework for personalized care of EoE patients. This cutting-edge and clinically relevant research will be conducted in an intellectually stimulating and supportive environment at the Vanderbilt University. Throughout the award period, the candidate will be mentored by Dr. Anita Mahadevan-Jansen (primary mentor, expert in Raman Spectroscopy), Dr. Evan Dellon (co-mentor, expert in EoE), and a team of exceptional mentors in pathology, allergic inflammation, biostatistics and bioinformatics, and data science who mirror the blend of researchers that the candidate will lead in the future Their distinguished career paths will serve as a template for the candidate's success. To achieve his long-term career goal, in conjunction with his mentoring team, the candidate has methodically carved out a 4- year career development program. This program will provide him essential skills in Raman spectroscopy, integration of multidimensional biomedical data, clinical translational research, EoE, grant writing, and leadership. The preeminent mentorship, rigorous career development plan, and clinical time under the auspices of this K23 award will lead to publications, data, and experience that will uniquely situate the candidate as an independent investigator at the intersection of EoE, biophotonics, and data science.