Our research focuses on pathologic mechanisms of asthma. We use in vivo mouse models involving allergen sensitization of wildtype, transgenic and gene knockout mice. We also use classical genetic studies to identify asthma susceptibility genes in mice and we study new-born mice to identify mechanisms of maternal transfer of allergic susceptibility. We augment these in vivo studies by studying the responses of cultured normal human primary airway epithelial cells to the effects of allergic mediators.
Experimental measurements include in vivo airway physiology (the development of airway hyperresponsiveness to bronchoconstrictors), lung inflammation, airway goblet cell hyperplasia (excessive mucus production), sub-epithelial fibrosis (excessive collagen), and airway smooth muscle increases in mass or contractility. We use quantitative RT-PCR (Taqman) to measure expression of genes. We use computer-assisted stereology to quantify pathologic changes observed in sections of mouse lungs. We use ELISA to measure protein levels of specific mediators in mouse lung lavage samples and serum. We perform gene expression studies in cultured normal human primary airway epithelial cells.
Publications:
Douglas Kuperman, Xiaozhu Huang, Laura Koth, Grace Chang, Gregory Dolganov, Zhou Zhu, Jack Elias, Dean Sheppard, and David Erle. Direct Effects of Interleukin-13 on Epithelial Cells Cause Airway Hyperreactivity and Mucus Overproduction in Asthma. Nature Medicine, 8(8):885-889. August 2002.
Douglas Kuperman, Christina Lewis, Prescott Woodruff, Madeleine Rodriguez, Yee Hwa Yang, Gregory Dolganov, John Fahy, and David Erle. Dissecting Asthma Using Focused Transgenic Modeling and Functional Genomics. Journal of Allergy and Clinical Immunology, 116:305-311. August 2005.
Douglas Kuperman, Xiaozhu Huang, Louis Nguyenvu, Christoph Holscher, Frank Brombacher, and David Erle. IL-4 Receptor Signaling in Clara Cells Is Required for Allergen-Induced Mucus Production. Journal of Immunology, (In Press).
