Pulmonary Biology
Sinner Lab

Sinner Research Lab

The Sinner lab aims to understand the molecular mechanisms underlying the patterning of the mammalian respiratory tract during normal development and its relevance to congenital disease. We focus on the interactions between the developing respiratory tract's two primary components: the epithelium and the mesenchyme. -The epithelium gives rise to the epithelial lining of the large airways and the respiratory surface of the lung. Cartilage, muscle, and connective tissue arise from the mesenchyme. Epithelial-Mesenchymal interactions are required for cell differentiation and are mediated by signaling pathways, including the Wnt signaling pathway that promotes the cells' differentiation and behavior during development, homeostasis, and disease.

We utilize transgenic mouse models, ex vivo culture systems, and live imaging of embryonic tracheal tissue to study the processes mediating large airways and peripheral lung formation.

Current projects:

Publications

Bottasso-Arias, N; Leesman, L; Burra, K; Snowball, J; Shah, R; Mohanakrishnan, M; Xu, Y; Sinner, D. BMP4 and Wnt signaling interact to promote mouse tracheal mesenchyme morphogenesis. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2022; 322:L224-L242.

Sinner, DI; Carey, B; Zgherea, D; Kaufman, KM; Leesman, L; Wood, RE; Rutter, MJ; de Alarcon, A; Elluru, RG; Harley, JB; et al. Complete Tracheal Ring Deformity. A Translational Genomics Approach to Pathogenesis. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1267-1281.

Gerhardt, B; Leesman, L; Burra, K; Snowball, J; Rosenzweig, R; Guzman, N; Ambalavanan, M; Sinner, D. Notum attenuates Wnt/β-catenin signaling to promote tracheal cartilage patterning. Developmental Biology. 2018; 436:14-27.

Snowball, J; Ambalavanan, M; Whitsett, J; Sinner, D. Endodermal Wnt signaling is required for tracheal cartilage formation. Developmental Biology. 2015; 405:56-70.

Snowball, J; Ambalavanan, M; Cornett, B; Lang, R; Whitsett, J; Sinner, D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Developmental Biology. 2015; 401:264-275.

Cornett, B; Snowball, J; Varisco, BM; Lang, R; Whitsett, J; Sinner, D. Wntless is required for peripheral lung differentiation and pulmonary vascular development. Developmental Biology. 2013; 379:38-52.

Sinner, DI; Kim, GJ; Henderson, GC; Igal, RA. StearoylCoA desaturase-5: a novel regulator of neuronal cell proliferation and differentiation. PLoS ONE. 2012; 7.

Sinner, D; Kordich, JJ; Spence, JR; Opoka, R; Rankin, S; Lin, SJ; Jonatan, D; Zorn, AM; Wells, JM. Sox17 and Sox4 differentially regulate beta-catenin/T-cell factor activity and proliferation of colon carcinoma cells. Molecular and Cellular Biology. 2007; 27:7802-7815.

Sinner, D; Rankin, S; Lee, M; Zorn, AM. Sox17 and beta-catenin cooperate to regulate the transcription of endodermal genes. Development (Cambridge). 2004; 131:3069-3080.

Katz Kadosh, O; Nebor, I; Smith, MM; Hart, CK; Tabangin, ME; Burra, K; Kasten, JL; Sinner, DI; de Alarcon, A. In Reference to Establishing an Endoscopic Chronic Subglottic Stenosis Rabbit Model. Laryngoscope. 2023.

Russell, NX; Burra, K; Shah, R; Bottasso-Arias, N; Mohanakrishnan, M; Snowball, J; Ediga, HH; Madala, SK; Sinner, D. Wnt signaling regulates ion channel expression to promote smooth muscle and cartilage formation in developing mouse trachea. 2023.

Kadosh, OK; Nebor, I; Smith, MM; Hart, CK; Tabangin, ME; Burra, K; Kasten, JL; Sinner, DI; de Alarcon, A. Establishing an Endoscopic Chronic Subglottic Stenosis Rabbit Model. Laryngoscope. 2022; 132:1909-1915.

Zhou, Y; Yang, Y; Guo, L; Qian, J; Ge, J; Sinner, D; Ding, H; Califano, A; Cardoso, WV. Airway basal cells show regionally distinct potential to undergo metaplastic differentiation. eLife. 2022; 11.

Khattar, D; Fernandes, S; Snowball, J; Guo, M; Gillen, MC; Jain, SS; Sinner, D; Zacharias, W; Swarr, DT. PI3K signaling specifies proximal-distal fate by driving a developmental gene regulatory network in SOX9+ mouse lung progenitors. eLife. 2022; 11.

Bottasso-Arias, N; Leesman, L; Burra, K; Snowball, J; Shah, R; Mohanakrishnan, M; Xu, Y; Sinner, D. BMP4 and Wnt signaling interact to promote mouse tracheal mesenchyme morphogenesis. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2022; 322:L224-L242.

Gajjala, PR; Kasam, RK; Soundararajan, D; Sinner, D; Huang, SK; Jegga, AG; Madala, SK. Dysregulated overexpression of Sox9 induces fibroblast activation in pulmonary fibrosis. JCI insight. 2021; 6.

Khattar, D; Fernandes, S; Snowball, J; Guo, M; Gillen, M; Sinner, D; Zacharias, W; Swarr, D. PI3K Signaling Specifies Proximal-Distal Fate by Driving a Developmental Gene Regulatory Network in Sox9+ Lung Progenitors. 2021.

Nasr, T; Holderbaum, AM; Chaturvedi, P; Agarwal, K; Kinney, JL; Daniels, K; Trisno, SL; Ustiyan, V; Shannon, JM; Wells, JM; et al. Disruption of a hedgehog-foxf1-rspo2 signaling axis leads to tracheomalacia and a loss of sox9+ tracheal chondrocytes. DMM Disease Models and Mechanisms. 2021; 14.

Falla-Zuñiga, LF; Sinner, D; Moreno-Martínez, D; Castellanos-Garzón, JA; Salazar-Monsalve, L; Pustovrh, MC. Mus musculus: biomodelo de expresión de Desyodinasa (DIO3) y Transtiretina (TTR) en el desarrollo placentario. Entramado. 2021; 17:218-230.

Igal, RA; Sinner, DI. Stearoyl-CoA desaturase 5 (SCD5), a Δ-9 fatty acyl desaturase in search of a function. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2021; 1866.

Sinner, DI; Carey, B; Zgherea, D; Kaufman, KM; Leesman, L; Wood, RE; Rutter, MJ; de Alarcon, A; Elluru, RG; Harley, JB; et al. Complete Tracheal Ring Deformity. A Translational Genomics Approach to Pathogenesis. American Journal of Respiratory and Critical Care Medicine. 2019; 200:1267-1281.

Yin, W; Kim, H; Wang, S; Gunawan, F; Li, R; Buettner, C; Grohmann, B; Sengle, G; Sinner, D; Offermanns, S; et al. Fibrillin-2 is a key mediator of smooth muscle extracellular matrix homeostasis during mouse tracheal tubulogenesis. European Respiratory Journal. 2019; 53.

Sontake, V; Kasam, RK; Sinner, D; Korfhagen, TR; Reddy, GB; White, ES; Jegga, AG; Madala, SK. Wilms' tumor 1 drives fibroproliferation and myofibroblast transformation in severe fibrotic lung disease. JCI insight. 2018; 3.

Gerhardt, B; Leesman, L; Burra, K; Snowball, J; Rosenzweig, R; Guzman, N; Ambalavanan, M; Sinner, D. Notum attenuates Wnt/β-catenin signaling to promote tracheal cartilage patterning. Developmental Biology. 2018; 436:14-27.

Grants

Molecular mechanisms underlying trachea formation and the pathology of tracheomalacia and complete tracheal rings

R01 HL144774

04/04/2019-03/31/24

NIH NHLBI

Molecular basis of dorsal-ventral patterning of conducting airways

R03

09/01/2016-08/31/2018

NIH NHLBI

Molecular mechanisms underlying tracheomalacia

1K01HL115447-01

08/01/2012-07/31/2017

NIH NHLBI

Epithelium and mesenchyme.
The image depicts a whole mount staining of trachea-lung tissue. The tissue was isolated from the developing mouse embryo. The top inset shows a cross-section of the trachea wherein epithelium is labelled with Nkx2.1 (blue), and the tracheal mesenchyme was stained with aSMA and SOX9 antibodies. Distal lung epithelium was stained with Sox9 antibody (green), and smooth muscle was stained with aSMA antibody (red). Green staining in the trachea and Larynx indicates tissues where cartilage forms.
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