This application entitled ?Circadian Rhythms of Skin Barrier, Pruritus and Inflammation in Atopic Dermatitis,? is being submitted by Dr. Anna Fishbein at Northwestern University Feinberg School of Medicine/ Ann & Robert H. Lurie Children's Hospital of Chicago for a Mentored Patient-Oriented Research Career Development Award. Dr. Fishbein is a pediatrician, allergist and immunologist with a background in translational research. Eczema (atopic dermatitis) is the most common chronic skin disease of childhood, affecting 10% of US children. Nocturnal eczema is the itchy nighttime exacerbation of atopic dermatitis (AD) that afflicts more than 50% of children with AD, resulting in devastating scratch and sleep disturbance. Circadian rhythms are 24 hour biological cycles that appear to underlie the nocturnal worsening of atopic dermatitis. The objective of this project is to elucidate how circadian rhythm dysregulation is related to underlying AD pathophysiology. Dr. Fishbein's novel approach will apply state of the art tools to test her overarching hypothesis that the circadian system drives skin barrier disruption, pruritus and inflammation in nocturnal atopic dermatitis flare. She will test the specific hypotheses that 1) blunting of the normal skin barrier function rhythm in AD is associated with increased scratch and sleep disturbance and 2) melatonin increases release of TH2/TH22 cytokines that are known to disrupt skin barrier function and increase itch. Modified constant routine protocol (28 hours in a controlled-laboratory setting with dim light) will isolate the contribution of the circadian system to atopic dermatitis.
The specific aims to test the hypotheses are: 1) To determine how changes in the skin barrier function rhythm exacerbate nocturnal atopic dermatitis flare; and 2) To determine the role of melatonin in atopic inflammation in AD. Through the proposed research, Dr. Fishbein will work towards her long-term goal of becoming an independent translational physician investigator by developing chronotherapy (timed based treatment) for atopic dermatitis. Her short-term goal is to apply circadian biology to study skin barrier, pruritus and inflammation to determine the mechanism of nocturnal AD flare. Her training goals for this award are to: 1) build a foundation in circadian research techniques and molecular assessment of rhythms to study inflammatory skin disease, 2) enhance her knowledge base in immunology with a focus on circadian rhythms in T-cell biology, 3) advance personalized medicine for children with AD and 4) become an independently funded investigator. Dr. Fishbein's clinical training and prior experience in patient-oriented research make her an ideal candidate to accomplish this multidisciplinary project. Ann & Robert H. Lurie Children's Hospital of Chicago/Northwestern University provides an optimal training environment with top-notch expertise. Primary mentor Dr. Phyllis Zee is an expert in circadian biology and has successfully trained many academicians. Co-mentors Dr. Amy Paller and Dr. Robert Schleimer are world-renowned researchers in atopic dermatitis and immunology. .
Eczema (atopic dermatitis) affects 1 in 10 US children, causing itchy nighttime flares and devastating sleep disturbance. However an understanding of why eczema worsens at night is not known. This project seeks to understand the contribution of circadian rhythms (24-hour cycles) to skin barrier, to itch and to inflammation in eczema, because circadian timing is a potentially modifiable factor that could improve treatment of eczema.