Boggaram, Vijay, Ph.D.
M. S., Biochemistry, University of Mysore, India.
Ph. D., Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
Postdoctoral Fellowship, University of Texas Southwestern Medical Center, Dallas, Texas.
- Regulation of gene expression in the lung.
- Mechanisms of acute and chronic lung injury.
- Surfactant protein, interleukin-8 (IL-8) and thyroid transcription factor-1 (TTF-1/Nkx2.1) gene regulation.
- Lung gene regulation in acute influenza A viral infection.
- Organic dust induced lung inflammation.
The human lung has about 300 million alveoli that facilitate gas exchange between inhaled air and blood to maintain respiration. Because of the critical functions the alveoli perform, it is essential to maintain the integrity of the alveoli. Perturbations that injure and weaken alveoli can lead to lung collapse resulting in respiratory distress and possible death. The stability of the alveoli is maintained by surfactant, a lipid-protein complex produced and secreted by the alveolar type II and Clara (bronchiolar) epithelial cells. Surfactant stabilizes alveoli by reducing surface tension in the lung. Additionally surfactant plays important roles in the control of host defense and inflammation to protect lung from damage. Reduced levels and activity of surfactant contribute to the development of lung injury in newborn and acute respiratory distress syndromes (RDS), bacterial and viral lung infections, and occupational lung diseases. Thyroid transcription factor-1 (TTF-1), a transcription factor essential for lung development, controls surfactant protein expression. Because of the important roles that TTF-1 plays in the lung, abnormal levels of TTF-1 probably contribute to the development of lung diseases. Interleukin-8 (IL-8) is a chemokine that is a potent chemoattractant for neutrophils, T cells and other immune cells. IL-8 levels are directly correlated with neutrophil content and severity of lung injury in inflammatory lung diseases. A number of agents such as tumor necrosis factor-alpha (TNF-alpha), bioactive lipids, and reactive nitric and oxygen species serve as causative agents for altered production of surfactant protein, TTF-1 and IL-8 in lung diseases. A better understanding of cellular pathways and mechanisms mediating aberrant production of surfactant protein, TTF-1 and IL-8 is important for the development of novel drugs and treatments for lung diseases.
Transcriptional and posttranscriptional (mRNA stability) mechanisms serve as key regulatory steps in the control of gene expression. Cell signaling pathways control gene expression to maintain tissue homeostasis. Our research is aimed at understanding cellular pathways and gene regulatory mechanisms controlling surfactant protein, TTF-1 and IL-8 levels in normal and injured lung. We use primary lung cells, lung cell lines and animal models of lung injury to understand mechanisms mediating altered productions of surfactant protein, TTF-1 and IL-8 and development of lung disease.
Current Research Funding:
National Institute of Occupational Safety and Health (NIOSH)
Selected Papers and Abstracts:
- Boggaram V Gottipati KR Wang X and Samten B. The Mycobacterium tuberculosis early-secreted antigenic target of 6-kDa (ESAT-6) protein induces IL-8 expression in lung epithelial cells via protein kinase signaling and reactive oxygen species. In press, J Biol Chem, 2013.B
- Bhandary Y, Shetty SK, Marudamuthu AS, Ji HL, Neuenschwander PF, Boggaram V, Morris GF, Fu J, Idell S, Shetty S. Regulation of alveolar epithelial injury and lung fibrosis by p53-mediated changes in urokinase and plasminogen activator inhibitor-1. Am J Pathol 183: 131-43, 2013.
- Das ,A Acharya S, Gottipati K, McKnight JB, Chandru H, Alcorn JL, Boggaram V. Thyroid transcription factor-1 (TTF-1) gene: identification of ZBP-89, Sp1 and TTF-1 sites in the proximal promoter and regulation by TNF-α in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 301: L427-L440, 2011.
- Yasuda S, Yasuda T, Liu MY, Shetty S, Idell S, Boggaram V, Suiko M, Sakakibara Y, Fu J, Liu MC. Sulfation of chlorotyrosine and nitrotyrosine by human lung endothelial and epithelial cells: Role of the human SULT1A3. Toxicol Appl Pharmacol 251: 104-109, 2010.
- Boggaram V, Chandru H, Gottipati K, Thakur V, Das A, and Berhane K. Transcriptional regulation of SP-B gene expression by nitric oxide in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 299: L252-L262, 2010.
- Boggaram V. Thyroid transcription factor-1 (TTF-1/Nkx2.1/TITF1) gene regulation in the lung. Clinical Science 116: 27-35, 2009.
- Chandru H, Boggaram V. The role of sphingosine 1-phosphate in the TNF-alpha induction of IL-8 gene expression in lung epithelial cells. Gene 391: 150-160, 2007.
- Das A, Boggaram V. Proteasome dysfunction inhibits surfactant protein gene expression in lung epithelial cells: Mechanism of inhibition of SP-B gene expression. Am J Physiol Lung Cell Mol Physiol 292: L74-L84, 2007 (selected for journal cover).
- Sparkman L, Chandru H, Boggaram V. Ceramide decreases surfactant protein B gene expression via down regulation of TTF-1 DNA binding activity. Am J Physiol Lung Cell Mol Physiol 290: L351-L358, 2006.
- Sparkman L and Boggaram V. Nitric oxide increases interleukin 8 (IL-8) gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 287: L764-L773, 2004.
- Boggaram V. Regulation of surfactant protein gene expression by hyperoxia in the lung. Antioxid Redox Signal. 6: 185-190, 2004.
- Salinas D, Sparkman L, Berhane K, Boggaram V. Nitric oxide inhibits surfactant protein B (SP-B) gene expression in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 285: L1153-L1165, 2003.
- Boggaram V. Regulation of lung surfactant protein gene expression. Front Biosci 8: d751-764, 2003.