? Function of microRNA in lung development and neonatal disease.
? Role of heme oxygenase in mouse development.
Key words: microRNA, lung development, gene regulation, hyperoxia, mouse development, heme oxygenase.
Description of Research
I am a developmental biologist with a research interest in the molecular mechanism of normal lung development and lung disease.
The focus of our research is to identify and characterize microRNAs that are important for lung development. MicroRNAs are endogenous small RNA molecules modulating numerous cellular functions by regulating the expressions of their target genes. We aim to elucidate the specific functions of microRNAs in alveolar epithelial cell differentiation and lung morphogenesis. With low-density-array techniques and bioinformatics analysis, we have identified microRNAs that are differentially expressed during lung epithelial cell differentiation. We have also established a microRNA expression profile in normal mouse lung development as well as in animal models of neonatal lung disease. Using viral-based and other gene delivery methods, we will examine the functions of these microRNAs in both cell culture system and in vivo mouse models.
We are also investigating the critical role of pulmonary vasculature to the terminal maturation of lung from the embryonic to postnatal stage. Specifically, we focus on one anti-oxidant enzyme, heme oxygenase (HO)-1. HO-1 mediates lung vascular development in both endothelial and smooth muscle cells, promotes vascular endothelial cell proliferation, up-regulates vascular growth factors, and protects vascular tissues from oxidative injury. We have shown that HO-1 deficiency in mice resulted in disrupted postnatal lung development, which is more exaggerating under stressed conditions. The HO-1 knockout mice also display severe defects in the embryonic vasculature, which may cause the loss of some mutants during embryonic development. We are using a combination of cell biology and mouse genetic techniques to determine the precise function of HO-1 in vascular and lung development, and to address whether HO-1 modulates postnatal alveolar development through involvement in angiogenesis.
Haiyan Xiao, M.S. - Research Assistant
Ruth Seabrook, M.D.- Neonatology Fellow
Research Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine (2006 ? present)
PhD, University of Texas Southwestern Medical Center (1997)
BS, Peking University, Beijing (1990)
1. Lin Q, Schwarz J, Bucana C, Olson EN. Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 276:1404-1407, 1997.
2. Lin Q, Srivastava D, Olson EN. A transcriptional pathway for cardiac development. Cold Spring Harbor Symposia on Quantitative Biology 62:405-411, 1997.
3. Molkentin JD, Lin Q, Duncan SA, Olson EN. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes and Development 11:1061-1072, 1997
4. Srivastava D, Thomas T, Lin Q, Kirby M, Brown D, Olson EN. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet 16:154-161, 1997.
5. Lin Q, Lu J, Yanagisawa H, Webb R, Lyons GE, Richardson JA, Olson EN. Requirement of the MADS-box transcription factor MEF2C for vascular development. Development 125(22):4565-4574, 1998.
6. Furulli, BT, McFadden, DG, Lin, Q, Srivastava, D, Olson EN. Heart and extraembryonic mesoderm defects in mouse embryos lacking the bHLH factor eHAND. Nat Genet 18(3):266-270, 1998.
7. Charng, MJ, Frenkel, PA, Lin, Q, Yumada, M, Schwartz, RJ, Olson, EN, Overbeek, P, and Schneider, MD. Constitutive signaling by the serine/threonine kinase receptor, ALK5, arrests cardiac looping morphogenesis. Dev Biol 199(1):72-9, 1998.
8. Pipes GC, Lin Q, Riley SE, Goodman CS. The beat generation: a multigene family encoding IgSF proteins related to the beat axon guidance molecule in Drosophila. Development 128(22):4545-4552, 2001.
9. Lin Q, Wu D, Zhou J. The promoter targeting sequence facilitates and restricts a distant enhancer to a single promoter in the Drosophila embryo. Development 130(3):519-26, 2003.
10. Lin Q, Chen Q, Lin L, Zhou J. The promoter targeting sequence mediates epigenetically heritable transcription memory. Genes & Develop 18:2639-2651, 2004.
11. Chen Q, Lin L, Smith S, Lin Q, Zhou J. Multiple promoter targeting sequences exist in Abdominal-B to regulate long-range gene activation. Dev Biol 286(2):629-636, 2005.
12. Lin Q, Chen Q, Lin L, Smith S, and Zhou J. Promoter targeting sequence mediates enhancer interference in the Drosophila embryo. Proc Natl Acad Sci U S A. 104(9):3237-3242, 2007.
13. Lin Q, Weis S, Yang G, Weng YH, Helston R, Rish K, Smith A, Bordner J, Polte T, Gaunitz F, Dennery PA. Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J Biol Chem 282(28):20621-20633, 2007.
14. Lin QS, Weis S, Yang G, Zhuang T, Abate A, Dennery PA. Catalytic inactive heme oxygenase-1 protein regulates its own expression in oxidative stress. Free Radic Biol Med. 44(5):847-855, 2008.
15. La P, Fernando AP, Wang Z, Salahudeen A, Yang G, Lin Q, Wright CJ, Dennery PA. Zinc Protoporphyrin Regulates Cyclin D1 Expression Independent of Heme Oxygenase Inhibition. (J Biol Chem. 2009 Dec 25;284(52):36302-11.) 2009.
16. Lin Q, Lin L, Zhou J. Chromatin Insulator and the Promoter Targeting Sequence modulate the timing of long-range enhancer-promoter interactions in the Drosophila embryo. Dev Biol 2010. In Press
- Research Assistant Professor of Pediatrics at University of Pennsylvania School of Medicine (2006 – 2010)
- PhD, University of Texas Southwestern Medical Center (1997)
- BS, Peking University, Beijing (1990)