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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.
Sontake V, Betsy DA, Kumar SA, Mario M, Hardie WD, White ES, Madala SK. Fibrocytes Regulate Wilms Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease. The Journal of Immunology. 2015. (In Press)
Huang Y, Powers C, Madala SK, Greis KD, Haffey WD, Towbin JA, Purevjav E, Javadov S, Strauss AW, Khuchua Z. Cardiac metabolic pathways affected in the mouse model of barth syndrome. PLoS One. 2015 Jun 1;10(6):e0128561.
Edukulla R, Singh B, Jegga A, Sontake V, Dillon SR, Madala SK. Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression. J Biol Chem. 2015 May 22;290(21):13510-20.
Madala SK. Reply: tissue fibrocytes are a subpopulation of macrophages. Am J Respir Cell Mol Biol. 2015 Jan;52(1):138.
Madala SK, Edukulla R, Davis KR, Schmidt SM, Davidson CR, Aciani T, LeCras T, Hardie WD. Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2014 Apr 15;306(8):L726-35.
Madala SK, Edukulla R, Davis KR, Schmidt SM, Davidson CR, Aciani T, LeCras T, 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, Davis KR, Schmidt SM, Davidson CR, 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 SM, Davidson CR, Ikegami M and Hardie WD. Bone marrow-derived stromal cells are invasive and hyperproliferative and alter TGFα-induced fibrosis. Am J Respir Cell Mol Biol. 2014 Apr;50(4):777-86. *Corresponding author.
Madala SK*, Edukulla R, Davis KR, Schmidt SM, Davidson CR, 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. *Corresponding author.
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.
Wynn TA, Barron L, Thompson RW, Madala SK, Wilson MS, Cheever AW, Ramalingam TR. Quantitative Assessment of Macrophage Functions in Repair and Fibrosis. Curr Protoc Immunol. 2011 Apr;Chapter 14:Unit14.22.
Madala SK, Dolan M, Sharma D, Ramalingam TR, Wilson MS, Mentink-Kane MM, Wynn TA. Mapping mouse IL-13 binding regions using structure modeling, molecular docking and high-density peptide microarray analysis. Proteins. 2011 Jan;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. Gastroenterology. 2011 Jan;140(1):254-64.
Wilson MS, Madala SK, Ramalingam TR, Thompson RW, Mentink-Kane MM, Cheever AW, Wynn TA. Bleomycin and IL-1β mediated pulmonary fibrosis is regulated by IL-10 and dependent on IL-17A. J Exp Med. 2010 Mar 15;207(3):535-52.
Madala SK, Pesce J, Ramalingam TR, Wilson MS, Thompson RW, Minnicozzi S, Mentink-Kane MM, Cheever AW, Thomas A. Wynn. Matrix metalloproteinase 12-deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13-dependent fibrosis. J Immunol. 2010 Apr 1;184(7):3955-63.
Ramalingam TR, Pesce JT, Mentink-Kane MM, Madala S, Cheever AW, Comeau MR, Ziegler SF, Wynn TA. Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin. J Immunol. 2009 May 15;182(10):6452-9.
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