Our laboratory investigates how the cutaneous adaptive immune system modulates epithelial stem cell biology in health and disease. The skin is a dynamic barrier tissue exposed to external stressors that houses regenerative epithelial stem cell populations. Understanding how immune, epithelial, and stromal compartments communicate is central to explaining how tolerance is maintained in healthy skin — and why it collapses during autoimmunity and infection.
To study immune tolerance to HFSCs, we generated antigen-specific models in which bulge hair follicle stem cells (HFSCs) express a model neo-antigen, and can undergo autoimmune attack when Tregs are inducibly depleted during immune priming. Using this approach, we showed that skin Tregs actively maintain immune privilege of bulge hair follicle stem cells (HFSCs) (Cohen et al., 2024). These models, which mimic several aspects of human scarring alopecia, will be used to better understand how T cell-derived factors influence HFSC loss and scar formation during autoimmunity, dissect the cellular and molecular mechanisms of immune tolerance to HFSC-derived antigens, and determine the mechanisms that govern T cell persistence and memory during autoimmunity.
A core pillar of our research program investigates the spatial and temporal kinetics, and mechanisms of activation and dysfunction of skin Tregs during chronic inflammation/repair. These studies will be undertaken using an innovative fate-mapping technique in which genetic recombination is restricted to skin Tregs (
Cohen et al., 2024). Using this approach, we will be able to rigorously dissect the spatial, transcriptional, and epigenetic changes Tregs undergo during acute and chronic phases of inflammation. Moreover, we will be able to sophisticatedly track skin Treg movement during skin-specific inflammation and in the setting of inflammation in distant organs. These studies may have broad implications for Treg-modulating and Treg cell-based therapies.
To bridge fundamental discovery with clinical relevance, we integrate findings from mouse models with comprehensive analysis of human skin disease. Using patient-derived and archival samples, we apply cutting-edge multiomics approaches — including single-nucleus sequencing of FFPE tissues (snFFPE-seq) and spatial transcriptomics — to map immune and epithelial states across diverse dermatoses and alopecias. These datasets allow us to identify conserved pathways, human-relevant biomarkers, and molecular signatures that define regulatory dysfunction across disease spectra.
