Boggaram, Vijay, Ph.D.
M.S., Biochemistry, 1975, University of Mysore, India
Ph.D., Biochemistry, 1982, University of Stockholm, Sweden
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.
The human lung contains approximately 300 million alveoli that facilitate gas exchange between inhaled air and blood to maintain respiration. Because of the critical roles that the alveoli perform, it is essential to maintain the integrity of the alveoli during respiration. Any perturbations that weaken the stability of the alveoli can lead to lung collapse resulting in respiratory distress and possible death. The stability of the alveoli during the respiratory cycle is maintained by surfactant, a lipid-protein complex produced and secreted by the alveolar type II and Clara (bronchiolar) epithelial cells. Surfactant stabilizes the alveoli by counteracting contractile forces on the alveolar surface to reduce surface tension during respiration. Additionally surfactant plays important roles in the control of host defense and inflammation in the lung. Reduced levels and abnormalities of surfactant contribute to the development of lung injury in newborn and acute respiratory distress syndromes and in pulmonary infections caused by bacteria and virus. Thyroid transcription factor-1 (TTF-1), a transcription factor required 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 pathogenesis 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 factors including tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), bioactive lipids and others have been implicated as causative agents for the aberrant expression of surfactant protein, TTF-1 and IL-8 genes in lung diseases. A better understanding of cellular pathways and mechanisms mediating aberrant expression of surfactant protein, TTF-1 and IL-8 genes may be useful in 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. Our research is aimed at understanding transcriptional and posttranscriptional mechanisms controlling surfactant protein, TTF-1 and IL-8 gene expression in normal and injured lung. Primary lung cells, lung cell lines and animal models of lung injury are being used to understand surfactant protein, TTF-1 and IL-8 gene regulation.
Selected Papers and Abstracts:
- Boggaram V. Thyroid transcription factor-1 (TTF-1/Nkx2.1/TITF1) gene regulation in the lung. Clinical Science 116: 27-35, 2009.
- Boggaram V, Das A. Src protein kinase inhibitor PP2 synergizes dexamethasone induction of surfactant protein B (SP-B) gene expression in H441 lung epithelial cells. A888, ATS International Conference, 2007.
- Griffith D, Girard W M, Kurdowska A, Boggaram V, Stankowska D, McKnight JB, Peterson B. Recovery of surfactant protein B (SP-B) by single-cycle bronchoalveolar lavage (BAL). A605, ATS International Conference, 2007.
- Chandru H Boggaram V. The role of sphingosine-1-phosphate in the TNF-a induction of interleukin 8 (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, 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.
- Alam MN, Berhane K, Boggaram V. Lung surfactant protein B (SP-B) promoter function is dependent on the helical phasing, orientation, and combinatorial actions of cis-DNA elements. Gene 282: 103-111, 2002.
- Berhane K, Boggaram V. Identification of a novel DNA regulatory element in the rabbit SP-B promoter that is a target for ATF/CREB and AP-1 transcription factors. Gene 268:141-151, 2001.
- Adams C, Alam MN , Starcher B, Boggaram V. Cell-specific and developmental regulation of rabbit surfactant protein B promoter in transgenic mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 280:L724-L731, 2001.
- Berhane K, Margana RK, Boggaram V . Characterization of rabbit SP-B promoter region responsive to down regulation by tumor necrosis factor-alpha. Am J. Physiol. Lung Cell. Mol. Physiol. 279:L806-L814, 2000.
- Margana RK, Berhane K, Alam MN , Boggaram V. Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbit SP-B gene. Am. J. Physiol. Lung Cell. Mol. Physiol. 278:L477-L484, 2000.
- Margana RK, Boggaram V . Functional analysis of surfactant protein B (SP-B) promoter: Sp1, Sp3, TTF-1 and HNF-3-alpha transcription factors are necessary for lung cell-specific activation of SP-B gene transcription. J. Biol. Chem 272:3083-3090, 1997.