Our laboratory focuses broadly on understanding the transcriptional regulation of T helper cell differentiation and the regulation of inflammation by effector T helper subsets. Our work can currently be divided into three areas.
Transcriptional Regulation of Th1 development:
The Signal Transducer and Activator of Transcription (STAT) protein STAT4 is critical for the development of Th1 cells and inflammatory immunity. Current projects are focused towards defining how STAT4 activates transcription and programs genes for expression in Th1 cells. As part of this goal, we are continuing to identify STAT4 target genes and determine how transcriptional networks are involved in defining Th1 function. We are further examining how STAT4 contributes to the IL-17-secreting Th17 phenotype, and the stability of Th17 cells, using both in vitro and in vivo models of differentiation. Finally, we are examining how splice forms of STAT4 may be used as a biomarker in human inflammatory disease, by defining the function of STAT4 isoforms in patients.
PU.1 in Th9 development:
Th9 cells are a recently described subset of Th cells that secrete IL-9. We have recently defined the transcription factor PU.1 as important for the development of Th9 cells and that Th9 cells are important for the development of allergic inflammation, a function that was thought to be restricted to Th2 cells. We are currently examining how PU.1 contributes to the Th9 phenotype, as well as defining other factors that contribute to Th9 differentiation and IL-9 production. We will also be defining how Th9 cells contribute to allergic inflammation. This Th subset has recently been shown to have potent anti-tumor activity.
Atopic Disease:
Allergic diseases occur in several organs including the lung (asthma) and skin (atopic dermatitis). Using both spontaneous and inducible models of allergic inflammation in mice, and samples from patients with allergic diseases, we are examining transcription factors and cell types that contribute to allergic inflammation. Cytokines that promote allergic inflammation also modulate anti-tumor immunity. One area of interest is how cytokines present in lesions regulate barrier function in the skin. The overall goal of this work is to understand the pathogenesis of allergic inflammation and identify targets for potential treatment of allergic diseases.
