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The Satish Madala Research laboratory works to identify the cellular and molecular mechanisms involved the initiation, maintenance, and progression of pulmonary fibrosis. Pulmonary inflammation and fibrosis disrupts gas exchange in the tiny air sacs of the lungs and is the leading cause of morbidity and mortality for many respiratory diseases. Nevertheless, despite its enormous impact on human health, there currently are no approved treatments that directly target the mechanism(s) of fibrosis.
We study hematopoietic and non-hematopoietic stromal cell interactions using molecular, biochemical and immunology tools to identify novel therapeutic targets in chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), and cystic fibrosis (CF). We use both in vitro and in vivo models to test the mechanisms involved in pulmonary inflammation and fibrosis.
Our recent studies have helped to define unique functions of fibrocytes and their heterogeneous interactions with other lung stromal cells in causing the expansion of adventitial and pleural fibrotic lesions in the lung. Research trainees of my lab will have opportunity to use several advanced methods in biochemistry and immunology to investigate the mechanisms of pulmonary inflammation and fibrosis.
Madala SK*, Edukulla R, Davis KR, Schmidt SM, Davidson CR, Ikegami M and Hardie WD (2013) Bone marrow-derived stromal cells are invasive and hyperproliferative and alter TGFα-induced fibrosis. Am. J. Respir. Cell Mol. Bio. (in press) *Corresponding author.
Madala SK*, Edukulla R, Davis KR, Schmidt SM, Davidson CR, Kitzmiller JA, Hardie WD and Korfhagen TA. Resistin-like molecule alpha1 (Fizz1) recruits lung dendritic cells without causing pulmonary fibrosis. Res. Res. (2012) 46(3): 380-8 *Corresponding author.
Madala SK, Schmidt SM, Davidson CR, Ikegami M, Susan W, and Hardie WD. MEK-ERK pathway modulation ameliorates pulmonary fibrosis associated with epidermal growth factor receptor activation. Am. J. Respir. Cell Mol. Bio. (2012) 46(3): 380-8.
Wynn TA, Barron L, Thompson RW, Madala SK, Wilson MS, Cheever AW, and Ramalingam TR. Quantitative Assessment of Macrophage Functions in Repair and Fibrosis. Current Protocols in Immunology (2011) 92:14.22.1-14.22.12.
Madala SK, Dolan M, Sharma D, Ramalingam TR, Wilson MS, Mentink-Kane MM and Thomas A. Wynn. Mapping mouse IL-13 binding regions using structure modeling, molecular docking and high-density peptide microarray analysis. Proteins (2011) 79(1):282-93.
Wilson MS, Ramalingam TR, Rivollier A, Shenderov K, Mentink-Kane MM, Madala SK, Cheever AW, Artis D, Kelsall BL, Wynn TA.Colitis and intestinal inflammation in IL10-/- mice results from IL-13Rα2-mediated attenuation of IL-13 activity. (2011) Gastroenterology 140(1):254-64.
Wilson MS, Madala SK, Ramalingam TR, Thompson RW, Mentink-Kane MM, Cheever AW, and Thomas A. Wynn (2009) Bleomycin and IL-1β mediated pulmonary fibrosis is regulated by IL-10 and dependent on IL-17A. J. Exp. Med. (2010) 207(3):535-52.
Madala SK, Pesce J, Ramalingam TR, Wilson MS, Thompson RW, Minnicozzi S, Mentink-Kane MM, Cheever AW and Thomas A. Wynn. Opposing roles for matrix metalloproteinases 12 and 13 in interleukin 13-dependent tissue remodeling during S. mansoni egg induced fibrosis. J. Immunology (2010) 184(7):3955-63.
Ramalingam TR, Pesce JT, Mentink-Kane MM, Madala SK, Cheever AW, Comeau MR, Ziegler SF and Thomas A. Wynn (2009) Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin. J. Immunology 182 (10) 6452-9.
Click image for caption.
TGFα overexpressing mice show invasion and accumulation of fibrocytes (Green) along with resident stromal cells of dense fibrotic lesions in the lung.
Cellular and Molecular Mechanisms of Pulmonary Fibrosis
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