My research made paradigm-shifting discoveries on the immunologic basis of atopic dermatitis/eczema (AD) in humans, enriching the understanding of the pathophysiology of this very common disorder and opening the door to new therapeutic discoveries. I have developed the only comprehensive molecular maps of AD, defining skin differentiation and immune-circuits characterizing this disease. Although linked to both immune and barrier abnormalities, AD’s primary pathogenesis has not been elucidated. This incomplete mechanistic understanding has resulted in lack of effective targeted therapeutics. My studies led to the first identification in humans of a distinct population of T-cells that independently produce IL-22, without co-producing IL-17 (as in mice), framing the concept that in humans Th22 T-cells are distinct from Th17 T-cells. We found that this novel Th22/IL-22 pathway is highly activated in AD lesions, correlating with disease severity, suggesting a pathogenic role for this axis in this disease. My findings conceptualized AD as a Th2/Th22-polarized disease, expanding the prevailing view of AD as a Th2-skewed disease. I also associated IL-22 as a potential link between the barrier and immune abnormalities characterizing AD, showing that it inhibits differentiation proteins and induces epidermal hyperplasia, both major characteristics of AD, thus paving the path for potential new therapeutics. I have also designed a clinical trial, which has been funded by the NIH (UM1AR063917-01, RFA/PA: PAR11-168) utilizing an anti-IL-22 antibody, the first to explore the biological effects of blocking IL-22 on AD disease activity and associated skin pathology. I have also established the reversibility of the AD phenotype and defined a series of disease- and therapeutic response-biomarkers that will allow testing of targeted therapeutics. My research identified that different phenotypes of atopic dermatitis might differ in terms of immune polarization, with important therapeutic relevance that we are now testing in clinical trials, coupled with blood and skin analyses. I am also testing the effect of specific therapeutics against the defining cytokines of Th2 (IL-4/IL-13), and Th17/IL-23 (IL-23, IL-17) axes, to understand the relative contribution of individual cytokine pathways to the atopic dermatitis disease phenotype.