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Innate and innate-like lymphocytes are newly appreciated tissue-resident immune cells with vital roles in the initiation of tissue inflammation. As early responders during tissue perturbation, these cells are integral in shaping both protective and pathologic immune responses, as well as contributing during normal tissue development and remodeling. We are particularly focused on innate lymphocytes that are associated with type 2/allergic immune responses. Through understanding the local signals and micro-environments that regulate these innate type 2 immune responses, we hope to manipulate these pathways to limit allergic pathology (asthma, allergy, atopic dermatitis) or promote allergic responses in settings of chronic, low-grade inflammatory diseases (cardiovascular disease, obesity/diabetes,) where we and others have found type 2 immunity to be beneficial.
One area of laboratory focus is on the epidemic of obesity and type 2 diabetes. Obesity promotes local inflammation in visceral adipose tissue that leads to systemic inflammation, insulin resistance, and the development of type 2 diabetes. However, the function and regulation of normal immune cells in healthy adipose tissue is poorly understood. Allergic, type 2 immune cells are surprisingly abundant in healthy, lean adipose tissue and are co-regulated to maintain metabolic health and limit obesity induced inflammation and insulin resistance. These findings suggest allergic immunity, traditionally associated with pathology (asthma, atopy, allergy) as well as protection from multicellular helminthic worms, also plays a central role in the normal physiologic regulation of metabolism, and may participate more broadly in tissue homeostasis and repair.
Our laboratory is studying the allergic immune module in adipose tissue during conditions of metabolic health, obesity, and post infection with helminths, bacteria, or viruses. We are focused on the regulation, interactions, cytokine production, and metabolic impact of the cells in this allergic module, including group 2 innate lymphoid cells (ILC2), eosinophils, alternatively activated macrophages, and tissue regulatory T (Treg) cells. We anticipate this knowledge will accelerate the development of human therapeutics that can restore balanced anti-inflammatory, allergic-type immune responses that decline in adipose tissue with obesity and old age, limiting the progression of insulin resistance and type 2 diabetes. Our group’s long-terms goals are to understand the impact of the allergic immune module in a range of metabolic tissues, infectious and autoimmune models, and human disease.
Active Research Projects:
1) What are the sources, regulation and impact of the signals that regulate ILC2 and the allergic module?
2) How do infections with helminths, viruses, or bacteria alter adipose tissue and systemic immune responses to impact metabolism?
3) How do tissue ILC2 and Treg interact to mediate tissue health and metabolism?