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Dr. Vercelli Lab
The Functional Genomics Laboratory focuses on the mechanisms underlying human complex diseases, particularly asthma and allergy. Human complex diseases are major biomedical challenges, because they are common but difficult to decipher. The complexity of these diseases is reflected by their phenotypic heterogeneity and likely results from intricate interactions among genetic, environmental and developmental factors that modify disease susceptibility and severity. The Functional Genomics Laboratory investigates complex diseases with a three-pronged strategy that involves:
The ultimate goal of the Functional Genomics Laboratory is to establish a new paradigm merging analysis of genetic, environmental and developmental determinants of complex disease, functional studies and patient phenotypes in order to understand the causes of disease and predict responsiveness to specific treatments.
The Laboratory is funded by the NHLBI, NIAID, NIEHS, the Food Allergy and Anaphylaxis Network and the Arizona Biomedical Research Commission.
The characterization of the mechanisms through which natural variation in immune genes contributes to the pathogenesis of allergic inflammation and asthma. The approach taken is to assess the impact of genetic polymorphisms on the function and regulation of specific genes, focusing on those shown to be strongly associated with allergic inflammation and asthma phenotypes (Vercelli 2008, Vercelli & Ober 2011). The genes currently under study are IL13 and IL33. After initial in vitro and ex vivo studies (Vladich et al. 2005, LeVan et al. 2001; Cameron et al. 2006, Kiesler et al. 2009, Kiesler et al. 2010, Strempel et al. 2010), the laboratory is pioneering the development of novel, powerful in vivo models based on the generation of humanized BAC transgenic mice that recapitulate alternative haplotypes of the genes of interest and model their expression, epigenetic regulation and phenotypic correlates in vivo.
The analysis of epigenetic signatures of asthma/allergy and asthma-protective environmental exposures (e.g., farm living, pets: Maier et al., 2010, Von Mutius & Vercelli, 2010) that are detectable in human populations at birth and throughout early life. These signatures, which can provide illuminating insights into the mechanisms underlying risk for and protection from asthma, rely primarily on genome-wide analyses of DNA methylation and gene expression.
The generation of human induced pluripotent stem cells that are differentiated into asthma/allergy-relevant tissue types in order to model subject- and genotype-specific biological phenotypes and gene-environment interactions important for asthma pathogenesis and susceptibility.