Our research
The Hobbs Lab studies how the Autoimmune Regulator (AIRE) functions as a key coordinator of epithelial stress responses, bridging the worlds of cancer biology and autoimmunity. Using tools that range from advanced imaging to genetically engineered models, we ask how AIRE shapes DNA damage repair, cytokine signaling, and immune tolerance in skin and other barrier tissues. By mapping these fundamental processes, our broader vision is to translate AIRE biology into strategies that prevent cancer, restore immune balance, and ultimately improve patient outcomes.
Uncovering Roles for Aire in skin biology
Autoimmune regulator (AIRE) is a unique transcriptional regulator. Classically, AIRE is known as a master regulator of autoimmunity and is expressed in a subset of medullary thymic epithelial cells. Specifically, AIRE regulates the transcriptional expression of self antigens so that these antigens can be processed and presented to naive T-lymphocytes. Loss of function mutations in AIRE are causative for the disease autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). These patients often present with many skin abnormalities including hair loss, nail dystrophy, vitiligo, and oral mucocutaneous candidiasis.
Our published data indicate AIRE becomes abundantly expressed in skin keratinocytes in response to acute and chronic stressors (Hobbs et al., Nature Genetics, 2015). A central focus of the Hobbs Lab is to elucidate when, where, how, and why AIRE is expressed and functional in skin.
Guiding hypotheses for the Hobbs Lab
1) Aire has an intrinsic role in skin biology, under both physiological and pathological conditions.
2) Understanding Aire function and regulation will reveal novel mechanisms for potential therapeutic targeting.
Current MAJOR Projects
AIRE deficiency as a strategy for stress-induced apoptosis and regression of pre-cancerous skin lesions
Our lab is supported by the American Cancer Society to investigate how the Autoimmune Regulator (AIRE) protein helps skin cancers adapt to DNA damage and evade regression. By uncovering how AIRE sustains tumor growth after UV-induced stress, we aim to design strategies that push precancerous and cancerous lesions toward clearance rather than progression. This work seeks to reduce the need for repeated surgeries and lower the burden of skin cancer in patients.
Uncovering autoimmune regulator function in alopecia areata
Through funding from the National Alopecia Areata Foundation, we are exploring the skin-specific contributions of AIRE to T cell–mediated inflammation and hair follicle immune privilege. This project is helping us define how loss of AIRE disrupts local tolerance in the skin and contributes to autoimmune hair loss, with the long-term goal of identifying new therapeutic entry points.
Subcellular localization and regulation of Aire
Our lab investigates how the Autoimmune Regulator (AIRE) protein is organized inside epithelial cells. Using live-cell imaging, correlative light and electron microscopy, and cryo-electron tomography, we study the subcellular patterns, dynamics, and ultrastructure of AIRE. These approaches allow us to visualize how AIRE rapidly forms nuclear condensates in response to stress, how it associates with chromatin, and how its structure changes under different cellular conditions. By mapping AIRE’s behavior at this ultrastructural level, we are uncovering the mechanisms by which it coordinates gene regulation, DNA damage repair, and immune tolerance in the skin.