Overview-This application requests support for a mid-career investigator award for Glenn T. Furuta, MD to further develop two of the pillars of academic medicine, mentorship and patient oriented research (POR). Support from a K24 award is needed to provide protected time from clinical and administrative duties that will allow him to utilize outstanding clinical research and training resources on the Anschutz Medical Campus and the University of Colorado School of Medicine (CUSOM) for high impact POR and to nurture a pipeline of new investigators in Eosinophilic Gastrointestinal Diseases (EGIDs). He has developed a clinical and research program focusing on these diseases, the Gastrointestinal Eosinophilic Diseases Program (GEDP) to accomplish goals. At least four major impacts should result from this application including protection of the PI to;(1) Perform ongoing high quality POR that will lead to publications in high impact journals, (2) Provide pro- active mentorship to sustain a pipeline of new investigators in POR leading to publications and independent grant funding, (3) Develop novel research that will use biosamples to monitor EoE disease activity and determine novel biomarkers relevant to disease pathogenesis and (4) Define diagnostic criteria and the impact of treatments on newly defined clinical phenotypes of EGIDs. The Disease- EGIDs are an increasingly recognized group of diseases affecting children and adults characterized by nausea, vomiting, abdominal pain, dysphagia, food impaction and diarrhea that occur in conjunction with intestinal eosinophilia. Despite an increasing incidence estimated at 4 in 10,000, diagnostic criteria for one type of EGID, eosinophilic esophagitis (EoE), has only recently been defined. A heavy burden exists in defining novel EoE phenotypes, measuring disease activity and identifying therapeutic interventions especially since no FDA approved treatments exist. The Candidate- Dr. Furuta's training and mentorship experiences at three academically rich campuses, Baylor College of Medicine, Harvard Medical School and now CUSOM have allowed him to develop into a physician-scientist who is poised to further develop his skills and productivity in mentorship and POR as they relate to EGIDs. He continues to pursue a longstanding research goal of understanding eosinophil's role in GI diseases and then translating these findings into clinical care. During the course of his career, he has developed a successful track record of clinical and translational studies and spearheaded efforts to identify diagnostic criteria for one type of EGID, EoE. He has a strong track record of successful mentorship of junior investigators. As the Director of the GEDP, and Chair of the Scholarship Oversight Committee for the T32 funded Pediatric Gastroenterology Fellowship at the CUSOM and Digestive Health Institute (DHI) at Children's Hospital Colorado (CHCO), he is in the perfect position to now foster mentorship in POR to physician-scientists of outstanding promise. The Environment- Research resources at CUSOM, DHI and CHCO represent an outstanding opportunity to promote discovery and mentorship. The local Clinical Translational Science Award, termed the Colorado Clinical &Translational Sciences Institute, possesses a wide array of rich resources for mentoring and POR. T32 training programs and research units on campus provides a rich reservoir of trainees for his POR and mentorship. The GEDP's robust clinical program is an ideal source of well-defined POR subjects. The Research-Proposed research described in this K24 expands Dr. Furuta's ongoing, and develops new POR, to: determine pathogenetic mechanisms and therapeutic efficacies using biosamples and a novel device, the Esophageal String Test;define the natural history of EoE;identify diagnostic features that will provide guidance for trials;and measure the impact of treatments on novel phenotypes with feeding dysfunction. Immediate and long-term career goals 1. Short term goals- 1. Develop into an outstanding mentor, Metric-new trainees engaged in POR;2. Develop new and complete ongoing innovative, relevant POR. Metric - grants and publications;3. Engage junior colleagues from the CUSOM campus to publish and obtain grants. Metric-new trainees engaged in POR. 2. Long term goals-1. Provide a legacy of individuals from diverse backgrounds who will perform POR that I will help develop through pro-active mentorship;Metric - independently funded POR investigators;2. Transform current POR within the above academic communities into a self-sustaining EGID research and clinical program. Metric - self-sustaining POR program. 3. Mentoring goals- 1. Encourage the development of trainees in POR by helping them perform hypothesis- driven research within their areas of expertise;2. Promote careers of junior faculty by helping them to develop independently funded POR that will facilitate their recognition as leaders in their field. Key elements of the research career development plan- Described within this proposal are details of trainee selection, integration of the CTSA into POR and mentoring, active support for POR, and specific mentoring plans that include mastering the EGID literature, training in research methodology, engaging and performing POR, applying for POR funding, attending fireside chat and speaking skills series and translational research seminars. Monitoring methodology, metrics for success and impact of each element are listed.

Public Health Relevance

Eosinophilic gastrointestinal diseases, including eosinophilic esophagitis, are an increasingly common, burdensome group of diseases affecting 4 in 10,000 children and adults worldwide. No FDA approved treatments exist for these diseases. This K24 mid-career award will support an investigator in the mentorship of new trainees who will publish novel patient oriented research and develop into independently funded researchers. The public will benefit from this research that1.) utilizes novel techniques to make diagnoses faster and 2.) seeks to develop and provide optimal treatments for affected patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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University of Colorado Denver
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United States
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Mark, Jacob; Fernando, Shahan D; Masterson, Joanne C et al. (2018) Clinical Implications of Pediatric Colonic Eosinophilia. J Pediatr Gastroenterol Nutr 66:760-766
Spergel, Jonathan M; Dellon, Evan S; Liacouras, Chris A et al. (2018) Summary of the updated international consensus diagnostic criteria for eosinophilic esophagitis: AGREE conference. Ann Allergy Asthma Immunol 121:281-284
O'Shea, Kelly M; Aceves, Seema S; Dellon, Evan S et al. (2018) Pathophysiology of Eosinophilic Esophagitis. Gastroenterology 154:333-345
Dellon, Evan S; Liacouras, Chris A; Molina-Infante, Javier et al. (2018) Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology 155:1022-1033.e10
Grozdanovic, Milica; Laffey, Kimberly G; Abdelkarim, Hazem et al. (2018) Novel peptide nanoparticle-biased antagonist of CCR3 blocks eosinophil recruitment and airway hyperresponsiveness. J Allergy Clin Immunol :
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Khoury, Paneez; Akuthota, Praveen; Ackerman, Steven J et al. (2018) Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD). J Leukoc Biol 104:69-83
Sherrill, Joseph D; Kc, Kiran; Wang, Xinjian et al. (2018) Whole-exome sequencing uncovers oxidoreductases DHTKD1 and OGDHL as linkers between mitochondrial dysfunction and eosinophilic esophagitis. JCI Insight 3:
Nguyen, N; Fernando, S D; Biette, K A et al. (2018) TGF-?1 alters esophageal epithelial barrier function by attenuation of claudin-7 in eosinophilic esophagitis. Mucosal Immunol 11:415-426
Whelan, Kelly A; Merves, Jamie F; Giroux, Veronique et al. (2017) Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Gut 66:1197-1207

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