Projects
Lab Projects (6)
Elucidation of epithelial genes and pathways critical to allergic disease and asthma
Impaired skin barrier integrity is a pathogenic link between atopic dermatitis and allergic comorbidity progression, as allergens can penetrate the epidermal barrier. Local inflammation, such as eczema flare-ups in AD patients, further primes immune responses that drive both local and systemic allergic reactions. Understanding the mechanisms underlying epithelial barrier function and dysfunction is essential for developing new treatments for AD and preventing associated allergic comorbidities. Our lab uses skin tape samples from participants in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort to evaluate skin barrier alterations and investigate genetic links through genome wide association studies (GWAS). From these studies we have identified modulators of skin homeostasis that are involved in cell adhesion, proliferation, differentiation, and function. We continue to explore these modulators and their interactions with the aim of developing targeted therapeutics.
Understanding the pathogenesis of atopic dermatitis and the mechanisms that drive the atopic march
An impaired skin barrier, as seen in atopic dermatitis, allows allergens to breach our body’s natural defenses, initiating immune responses that drive sensitization. Despite this, the specific mechanisms underlying immune sensitization and their contribution to the development of other allergic conditions, such as asthma, remain unclear. To study these immune responses, we characterize immune signatures from MPAACH participants and utilize mouse models of AD to dissect immune cell subtypes and their functions. Our recent findings show the accumulation of hyperinflammatory NK cells in allergen-sensitized AD patients, and we aim to determine how these dysregulated NK cells contribute to the atopic march. We also seek to uncover how immune sensitization in the skin may trigger bystander responses to other allergens at distal sites, which could drive the progression of allergic diseases.
Characterization of the skin biome in children over time and delineation of the mechanisms that promote disease development and atopic march
In patients with AD, dysregulated skin barrier is often associated with the loss of commensal skin microbes and increased colonization of the opportunistic bacterium Staphylococcus aureus (S. aureus). Using the MPAACH cohort, we assess changes in the skin microbiome and skin barrier integrity at several time points during early childhood, aiming to understand how these longitudinal changes may impact allergic sensitization and the progression of the atopic march. Recently, we identified that persistent S. aureus colonization was mediated by reduced RNA expression of filaggrin, a key protein in skin barrier function, at non-lesional skin sites which corresponded to increased severity of AD. These findings suggest that maintaining filaggrin expression may be clinically beneficial in limiting S. aureus colonization, and therefore preventing severe AD outcomes.
Identification of environmental factors and definition of molecular mechanisms that contribute to childhood asthma and allergy phenotypes
Environmental factors play a significant role in the progression of atopic conditions, but the precise mechanisms underlying these interactions remain poorly understood. To address this, our lab leverages extensive clinical cohorts to identify how specific environmental exposures are associated with allergic disease progression. Currently, we are examining the associations of pollution and secondhand smoke exposure to asthma and allergen sensitization. These studies aim to uncover critical environmental factors that drive disease and inform strategies for targeted prevention and treatment.
Delineation of mechanisms underlying health disparities in the diagnosis and management of allergic diseases in vulnerable populations
Health disparities significantly impact the diagnosis and management of allergic diseases in vulnerable populations. Environmental exposures, such as air pollution and secondhand smoke, contribute to a disproportionate burden of allergic conditions in these groups, influencing disease progression and severity. Understanding how systemic factors, including access to healthcare, shape these disparities is crucial for developing targeted interventions. Our research aims to identify key drivers of these disparities and inform strategies to reduce them, ultimately improving the diagnosis, treatment, and management of allergic diseases and asthma in underserved populations.
Identification of molecular endotypes of childhood asthma and allergy
Asthma is a heterogeneous disease with varied presentations, making it challenging to identify the most effective treatments for individual patients. Environmental exposures and genetic factors influence each patient’s phenotypic presentation, which is referred to as the endotype. Understanding asthma and allergy endotypes is critical for advancing personalized treatment options. Our research focuses on studying these endotypes and investigating the underlying immune pathways that distinguish each endotype. Recently, we identified specific characteristics of frequent exacerbators and differentiated their presentation from other asthmatic endotypes. These findings will be pivotal for classifying patients and developing tailored treatment strategies.
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