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The focus of the Hardie and Madala Laboratory is to further understand the biology of lung remodeling, specifically pulmonary fibrosis. Pulmonary fibrosis is a complication found in a number of adult and pediatric diseases and is a significant contributor to morbidity and mortality worldwide. Currently there are no approved medical therapies to inhibit progression or reverse established pulmonary fibrosis emphasizing the important need to develop effective therapeutic approaches.
The long-term goal of the laboratory is to identify molecular and biologic mechanisms mediating pulmonary fibrotic processes that can be pharmacologically or genetically targeted to inhibit progression and reverse ongoing lung fibrosis in human diseases. To accomplish these goals the laboratory utilizes advanced methods in cellular biology including cell culture and preclinical models of progressive lung fibrosis.
Madala SK, Korfhagen TR, Schmidt S, Davidson C, Edukulla R, Ikegami M, Violette SM, Weinreb PH, Sheppard D, Hardie WD. Inhibition of the αvβ6 integrin leads to limited alteration of TGFα-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2014 Apr 15;306(8):L726-35
Madala SK, Edukala R, Phatak M, Schmidt SM, Davidson CR, Acciani TH, Korfhagen TR, Medvedovic M, LeCras TD, Wagner K, and Hardie WD. Dual Targeting of MEK and PI3K Pathways Attenuates Established and Progressive Pulmonary Fibrosis. PLoS One. 2014 Jan 27;9(1):e86536.
Madala SK, Edukulla R, Schmidt S, Davidson C, Ikegami M, Hardie WD. Bone marrow-derived stromal cells are invasive and hyperproliferative and alter transforming growth factor-α-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2014 Apr;50(4):777-86.
Madala SK, Edukulla R, Davis KR, Schmidt S, Davidson C, Kitzmiller JA, Hardie WD, Korfhagen TA. Resistin-like molecule alpha1 (Fizz1) recruits lung dendritic cells without causing pulmonary fibrosis. Respir Res. 2012 Jun 22;13:51.
Madala SK, Schmidt SM, Davidson CR, Ikegami M, Susan W, Hardie WD. MEK-ERK pathway modulation ameliorates pulmonary fibrosis associated with epidermal growth factor receptor activation. Am J Respir Cell Mol Biol. 2012 Mar;46(3):380-8.
Hardie WD, Hagood JS, Dave V, Perl AK, Whitsett JA, Korfhagen TR, Glasser S. Signaling pathways in the epithelial origins of pulmonary fibrosis. Cell Cycle. 2010 Jul 15;9(14):2769-76.
LeCras TD, Korfhagen TR, Davidson CR, Schmidt SM, Ikegami M, Whitsett JA, Hardie WD. Inhibition of PI3K by PX-866 prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Pathol. 2010 Feb;176(2):679-86.
Hardie WD, Glasser SW, Hagood JS. Emerging Concepts in the Pathogenesis of Lung Fibrosis. Am J Pathol. 2009 Jul;175(1):3-16.
William Hardie, MDDivision of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center
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