Abstract: STAT1 gain-of-function (STAT1-GOF) mutations are associated with immune dysregulation and increased susceptibility to the skin infections, particularly Chronic Mucocutaneous Candidiasis (CMC). These infections are reported to be linked to abnormalities in skin structure and development. To better understand the pathophysiology of CMC in STAT1-GOF patient and evaluate potential therapeutic interventions, we aim to develop a skin infection model using skin organoids derived from expanded potential stem cells (EPSCs) of STAT1-GOF patients. The patient-derived skin organoids recapitulate key structural in human skin, providing a physiologically relevant platform for studying infection dynamics. By infecting the organoids with pathogens, we intend to investigate the pathophysiology of CMC and identify underlying mechanisms driving susceptibility. Furthermore, the model will allow for testing and evaluation of candidate therapeutic compounds and drugs, enabling the identification of effective treatments to mitigate infection and restore skin integrity. The development of this model has the potential to facilitate critical insights into disease mechanisms and accelerate the discovery of targeted therapies for patients with STAT1-GOF mutations.
