Bogunovic, Dusan PHD

Individuals with Down syndrome (DS) often present with inflammatory skin diseases such as atopic dermatitis (AD) and alopecia areata (AA). They represent a vulnerable population that is seldom included in clinical trials. We propose a clinical trial to evaluate the long-term safety, efficacy, and mechanisms of two novel JAK1 (abrocitinib) and JAK3/TEC (ritlecitinib) inhibitors, recently FDA-approved for AD and AA respectively, in patients with DS, so that individuals with DS can be appropriately treated.

Type I Interferons (IFNs) are important in infection and inflammation. The purpose of this study is to delineate the role of key regulators of IFN response, ISG15 and USP18, via the study of rare ISG15 deficient and USP18 deficient humans. Improved understanding of how ISG15 and USP18 regulate IFN-mediated immune responses will inform the design of both anti-inflammatory and anti-infective therapeutics.

Down syndrome is caused principally by chromosome 21 trisomy, resulting in extra copies of the genes encoding the interferon (IFN-I) receptors, IFNAR1 and IFNAR2. Signaling through these IFN-I receptors initiates the highly potent antiviral and inflammatory functions of the IFN-I response. This study aims to investigate the effects of the presence of additional copies of IFNAR1 and IFNAR2 in Down syndrome, on the IFN-I response, and the contribution of these extra gene copies to the pathogenesis of Down syndrome.

Down syndrome is principally caused by trisomy of chromosome 21, resulting in extra copies of the interferon receptors, IFNAR1 and IFNAR2. Signaling through these IFN receptors to initiates the highly potent antiviral and inflammatory functions of the type I Interferons (IFNs) response. The purpose of this study is to understand how altered IFN receptor availability, as is the case in Downs syndrome individuals, impact the SARS-CoV-2 pathogenesis.