The goal of my lab is to understand the molecular mechanisms underlying the patterning of the mammalian respiratory tract during normal development and congenital disease. We focus on the interactions between two major components of the developing lung: the pulmonary epithelium - that gives rise to the conducting airways and the respiratory surface of the lung - and the mesenchyme - that gives rise to cartilage, muscle, connective tissue. Cross talk between epithelium and mesenchyme is required for differentiation of pulmonary cell lineages. Epithelial-Mesenchymal interactions are mediated by signaling pathways and transcription factors including the Wnt signaling pathway and Sox transcription factors, which are object of our studies. Our experimental approaches include genetic studies using transgenic mice and in vitro cell and organ culture.
Snowball J, Ambalavanan M, Whitsett J and Sinner D. “Endodermal Wnt signaling is required for tracheal cartilage formation”. Developmental Biology. 2015 Sep 1;405(1):56-70.
Snowball J, Ambalavanan M, Cornett B, Lang R, Whitsett J and Sinner D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Developmental Biology. 2015 May 15;401(2):264-75.
Cornett B, Snowball J, Varisco B, Lang R, Whitsett J and Sinner D. Wntless is required for peripheral lung differentiation and pulmonary vascular development. Developmental Biology. 2013 Jul 1;379(1):38-52.
Sinner D, Kim, GJ, Henderson GC and Igal RA. StearoylCoA desaturase-5: a novel regulator of neuronal cell proliferation and differentiation. PLoS ONE. 7. 2012;7(6):e39787.
Tamara Winkler, Eric Mahoney, Debora Sinner, Chris Wylie and Chitra Dahia. Wnt signaling activates Shh signaling in early postnatal discs, and re-activates Shh signaling in old discs in the mouse. PLoS ONE. 2014 Jun 3;9(6):e98444.
Li Y, Rankin S, Sinner D, Kenny A, Krieg P and Zorn AM. Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and non-canonical Wnt11 signaling. Genes and Development. 2008 Nov 1;22(21):3050-63.
Sinner D, Kordich J, Spence J, Opoka R, Rankin S, Suh-Chin J Lin, Jonatan D, Zorn AM and Wells J. Sox17 and Sox4 differentially regulate β-catenin/TCF activity and proliferation of colon carcinoma cells. Molecular and Cellular Biology. 2007 Nov;27(22):7802-15.
Sinner D, Rankin S, Lee M, Zorn AM. Sox 17 and beta-catenin interact to regulate the transcription of endodermal target genes. Development. 2004 Jul;131(13):3069-80.
Molecular mechanisms underlying tracheomalacia
Molecular basis of dorsal-ventral patterning of conducting airways
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