Pulmonary Biology

Yan Lab

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My laboratory focuses on elucidating molecular mechanisms of extracellular and intracellular signaling molecules and transcription factors in lung biology.

  1. Surfactant protein B (SP-B) gene regulation. SP-B is a 79 amino acid peptide that facilitates phospholipid spreading at the air-liquid interface in the alveoli. SP-B deficiency causes pulmonary surfactant malfunction and alveolar collapse during respiration. We have identified multiple transcription factors (e.g. TTF-1, RAR, p160 co-activators, STAT3 and PPARĪ³) that positively and negatively regulate SP-B gene regulation in respiratory epithelial cells.
  2. Functional roles of transcription factors in pulmonary alveolarization. A unique doxycycline-inducible transgenic line system has been established to systematically assess functional importance of various transcription factors in lung morphogenesis. Using this system, we have identified that both RAR and STAT3 transcription factors are essential for normal formation of alveoli.
  3. Protection of hyperoxic acute lung injury. Hyperoxic lung injury is a common problem encountered in patients who require treatment with high concentration of inspired oxygen. My laboratory uses the doxycycline controlled transgenic mouse system to identify signaling molecules and transcription factors that play important roles in protection of oxygen injury.
  4. Functional roles of cholesterols and free fatty acids in pulmonary inflammation, remodeling and injury repair. In lysosomal acid lipase (hydrolyzes cholesteryl ester and triglycerides to generate cholesterols and free fatty acids) knock-out mice (lal-/-), a high level of neutrophil influx, foamy broncho-alveolar macrophage proliferation, unwanted alveolar remodeling, emphysema and Clara cell hyperplasia are observed with age progression. Affymetrix GeneChip array analyses show increased mRNA levels of pro-inflammatory cytokines and matrix metalloproteinases in lal-/- mice. Metabolites from free cholesterols and free fatty acids serve as hormonal ligands for many nuclear receptors. The studies will greatly facilitate discovery of drugs for clinical treatment of patients with lung inflammatory diseases.

Publications

Angela Naltner, Manely Ghaffari, Jeffery A. Whitsett and Cong Yan (corresponding author): Retinoic Acid Stimulation of the hSP-B Promoter Is TTF-1 Site Dependent (2000). J. Biol. Chem. 275(1):56-62.

Angela Naltner, Susan Wert, Jeffery A. Whitsett and Cong Yan (corresponding author): Temporal/Spatioal Expression of Nuclear Receptor Coactivators in the Mouse Lung (2000). Am. J. of physiol. 279: L1066.

Cong Yan (corresponding author), Angela Naltner, Conkright, J. and Ghaffari, M.: Protein-protein interaction of RARa and TTF-1 in Respiratory Epithelial Cells (2001). J. Biol. Chem. 276(24): 21686-21691.

Cong Yan (corresponding author), Angela Naltner, Michelle Martin, Michael Naltner, Jessica M. Fangman and Oky Gurel: Transcriptional Stimulation of the Surfactant Protein B Gene by STAT3 in Respiratory Epithelial Cells (2002). J. Biol. Chem. 277(13): 10967-10972.

Li Yang, Angela Naltner, Allison Kreiner, Dong Yan, Angelynn Cowen, Hong Du and Cong Yan (corresponding author): An Enhancer Region Determines hSP-B Gene Expression in Bronchiolar and Alveolar Type II Epithelial Cells in Transgenic mice (2003). Am. J. of physiol. 284: L481-488.

Li Yang, Angela Naltner and Cong Yan (corresponding author): Overexpression of dnRARa Causes Alveolar Abnormality in Transgenic Neonatal Lungs (2003). Endocrinology, 144(7) 3004-3011.

Li Yang, Dong Yan, Cong Yan (corresponding author) and Hong Du: PPARg and ligands inhibit SP-B Gene Expression in the Lung (2003). J. Biol. Chem. 278(38): 36841-36847.

Xuemei Lian, Cong Yan (corresponding author), Li Yang, Yan Xu and Hong Du: Lysosomal Acid Lipase Deficiency Causes Respiratory Inflammation and Destruction in the Lung (2004). Am. J. of Physiol. 268:L801-807.

Li Yang, Xuemei Lian, Angelynn Cowen, Huan Xu, Hong Du and Cong Yan: Synergy between STAT3 and RARa in Regulation of the Surfactant Protein B Gene in the Lung (2004). Mol Endocrinol, 18(6):1520-32.

Cong Yan and Hong Du: Highlighted Topic in Lung Growth and Repair: Alveolus formation - what have we learned from genetic studies (Review) (2004). Journal of Applied Physiology, In Press.

Li Yang, Dong Yan, Molly Bruggeman, Hong Du and Cong Yan (corresponding author): Mutation at A Lysine Acetylation Site in Homeodomain Generates Dominant Negative TTF-1 (2004). Biochemistry, In Press.

Contact Dr. Yan

Cong Yan
Associate Professor of Pediatrics
Division of Pulmonary Biology
Cincinnati Children's Hospital Medical Center
3333 Burnet Ave., Cincinnati, Ohio 45229-3039
Office Phone 513-636-2996
Lab Phone 513-636-7990
E-mail Cong.Yan@cchmc.org