Effects of Temperature Fluctuation on the Skin Barrier - PROJECT SUMMARY/ABSTRACT Project Summary: This proposal describes a 5-year mentored research career development program that will develop Dr. Jessica Hui into an independent clinical and translational physician-scientist. Her long-term career goal is to advance the field of allergy and immunology through determining the role of environmental factors in atopy development and to advance new approaches for the prevention/treatment of allergic diseases influenced by environmental factors and climate change. During this K08 Award, Dr. Hui will gain specific career development training and mentorship closely aligned with her innovative research project. She proposes to study the impact of temperature fluctuation on the skin barrier and how these events contribute to allergic sensitization/atopy. Given the importance of studying origins of allergy, this work is relevant to the NIAID. Candidate: Jessica Hui, MD is a triple board-certified Allergy and Immunology physician-scientist at National Jewish Health (NJH) in Denver, CO. Her record of basic science research, clinical research, funding awards, and scientific publications demonstrates a solid commitment to a career as an academic clinician-scientist. Training: The proposed career development plan strengthens Dr. Hui’s prior mentored research during her undergraduate, medical residency, and fellowship training. She proposes to meet her short-term goals through an integrated combination of intensive mentoring by internationally renowned high-impact experts in the study of the skin barrier and allergy with didactic and hands-on work in mastering studies using 3D organotypic skin and mouse models of atopic dermatitis and food allergy, understanding the technologies and approaches to transcriptomics and epigenetics, data analysis, scientific writing and presentation, and laboratory leadership. Mentor/Environment: Dr. Hui has close working relationships with experienced mentors and collaborators in the field of skin barrier research and atopy (Drs. Leung and Goleva), mouse models (Drs. Gorska and Geha), transcriptomics (Dr. Seibold), epigenetics (Drs. Fingerlin and Farmer), climate health (Drs. Maier and Crooks), and biostatistics (Dr. Crooks). The research activities will be based at NJH, a top-ranked research institution. Research Project: The primary objective of this proposal is to identify the mechanisms by which temperature fluctuation leads to skin barrier dysfunction. Specifically, our studies will test the hypothesis that transient receptor potential vanilloid 1 (TRPV1) expressed in the skin is activated by temperature fluctuation, leading to the release of skin-derived pro-inflammatory cytokines, which induce type 2 immune activation and cause inhibition of key epidermal barrier proteins. This will be rigorously tested in neonatal skin in 2D cell cultures, 3D skin equivalents, and mouse litters. We will perform RT-PCR, Western blot, immunostaining, and time-course experiments utilizing transcriptomics and epigenetic studies to identify how epidermal differentiation is impacted by temperature fluctuations and if it leads to persistent abnormalities. The role of temperature fluctuation driven skin barrier changes in allergic sensitization and allergy development will be explored in proposed mouse models.
