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ARIZONA
RESEARCH
LABORATORIES
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Director:
Dr. Michael Cusanovich
PO Box 210077
Tucson, AZ 85721-0077
cusanovi@u.arizona.edu
Media:
skhelsel@skhelsel.com
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ABCD Director:
Dr. Donata Vercelli
1657 E Helen St.
Tucson, AZ 85719
dvercelli@u.arizona.edu
(520) 626-6387
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Dr. Donata Vercelli
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Degree
M.D., University of Florence, Italy 1978
Department Affiliations
Cell Biology & Anatomy, BIO5 Institute
Program Affiliations
Cell Biology & Anatomy, Genetics GIDP
Research Areas
Immunology, Molecular Genetics, Epigenetics
Center Affiliations
Director, Arizona Initiative for the Biology of Complex Diseases (ABCD)
Arizona Research Laboratories
Assistant Director, Arizona Respiratory Center
Research Interests
The central theme of the Functional Genomics Laboratory is the characterization of the mechanisms through which natural variation in immune genes contributes to the pathogenesis of complex diseases, with special emphasis on respiratory disorders such as 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). The genes currently under study are IL13, TLR2 and CD14. The laboratory evaluates how coding region polymorphisms result in the expression of proteins with altered biological properties (Vladich et al. 2005). Complementary studies test the effect of genetic variation on transcriptional regulation and mRNA stability (LeVan et al. 2001; Cameron et al. 2006, Kiesler et al. 2009). A combination of biochemical purification and functional analysis is used to identify transcription factors that bind differentially to polymorphic alleles (Kiesler et al. 2009). The lab is also investigating the basic epigenetic mechanisms that regulate gene expression (Webster et al. 2007) and the elements involved in gene regulation using a combination of phylogenetic and functional analyses (Strempel et al. 2007, Strempel et al. 2009).
More recently, the lab started conducting genome-wide analyses of DNA methylation and gene expression patterns in relation to specific environmental exposures and genotypes. This work relies on comprehensive genetic databases generated at the Arizona Respiratory Center by resequencing innate and adaptive immunity genes in a large panel of reference DNA samples of known ethnicity as well as in populations of defined allergic disease phenotypes. The next stage of the work, currently in advanced state of development, involves the generation of BAC transgenic mice to model alternative haplotypes of the genes of interest and study their expression, epigenetic regulation and phenotypic correlates in vivo. The ultimate goal of the Functional Genomics Lab is to establish a new paradigm merging analysis of genetic and environmental determinants of disease, functional studies and patient phenotypes in order to understand the causes of disease and predict responsiveness to specific treatments.
Selected Publications
Vercelli D. Aug 2008. Advances in asthma and allergy genetics in 2007.
J Allergy Clin Immunol, 122:267-71
Vercelli D. Mar 2008. Discovering susceptibility genes for asthma and allergy.
Nat Rev Immunol, 8:169-82
Webster RB Rodriguez Y Klimecki WT Vercelli D. Jan 2007. The human IL-13 locus in neonatal CD4+ T cells is refractory to the acquisition of a repressive chromatin architecture.
J Biol Chem, 282:700-709
Stern DA Riedler J Nowak D Braun-Fahrlander C Swoboda I Balic N Chen KW Vrtala S Gronlund H van Hage M Valenta R Spitzauer S Von Mutius E Vercelli D. Feb 2007. Exposure to a farming environment has allergen-specific protective effects on T(H)2-dependent isotype switching in response to common inhalants.
J Allergy Clin Immunol, 119:351-358
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