M. Sc., 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
- Organic dust induced lung inflammation
- 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 lungs’ primary function is to help oxygen from the air we breathe enrich the blood. Oxygen-rich blood then delivers oxygen to the entire body to be used as fuel to produce energy. Lungs also serve important functions in protection against disease causing bacteria and viruses and irritant particles such as dust. The functional part of the lung also known as lung parenchyma resembles a sponge and makes up 90% of the lung volume. It consists of air-sacs (alveoli), respiratory bronchioles (tiny airways) and blood capillaries.
Inflammation, the body’s response to fight infectious and other foreign agents, when chronic can lead to lung tissue destruction causing lung dysfunction and disease. Because the lungs are in constant contact with the outside environment, lung diseases caused by bacteria, viruses, fungi and other environmental agents are some of the most common medical conditions in the world.
A number of proteins including cytokines, surfactant proteins and others maintain lung homeostasis (balance), and alterations of their levels and/or activity disrupt homeostasis leading to disease. Our laboratory is interested in studying mechanisms responsible for the aberrant production of cytokines, surfactant, and other related molecules and their links to development of lung diseases. Such information could be important for the development of new 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 cytokine, surfactant protein, and thyroid transcription factor-1 (TTF-1) levels in normal and injured lung. We use primary lung cells, lung cell lines and animal models of lung injury induced by influenza A virus infection or organic dust exposure to understand mechanisms mediating altered productions of cytokines, surfactant protein, TTF-1, and other proteins and development of lung disease.
National Institute of Occupational Safety and Health (NIOSH)
Margana, R. K., and Boggaram, V. Functional analysis of surfactant protein B (SP-B) promoter: Sp1, Sp3, TTF-1 and HNF-3α transcription factors are necessary for lung cell-specific activation of SP-B gene transcription. J. Biol. Chem. 272:3083-3090, 1997. PMID: 9006959
Adams, C., Alam, M. N., 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. PMID: 11238013
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. PMID: 15169673
Chandru, H., and 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. PMID: 17306937
Boggaram, V. Thyroid transcription factor-1 (TTF-1/Nkx2.1/TITF1) gene regulation in the lung. Clinical Science 116: 27-35, 2009. PMID: 19037882
Boggaram, V., Chandru, H., Gottipati, K., Thakur, V., Das, A., and Berhane, K. Transcriptional regulation of SP-B gene expression by nitric oxide in H441 lung epithelial cells., Am. J. Physiol. Lung Cell. Mol. Physiol. 299:L252-L262, 2010. PMID: 20418387
Das, A., Acharya, S., Gottipati, K., McKnight, J. B., Chandru, H., Alcorn, J. L., and 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. PMID: 21784970
Boggaram, V., Gottipati, K. R., Wang, X., and Samten, B. The Mycobacterium tuberculosis early-secreted antigenic target of 6-kDa (ESAT-6) induces IL-8 expression in lung epithelial cells via protein kinase signaling and reactive oxygen species. J. Biol. Chem. 288: 25500 – 25511, 2013. PMID: 23867456
Subramaniam, R., Barnes, P. F., Fletcher, K., Boggaram, V., Hillberry, Z., Neuenschwander, P. F., Shams, H. Protecting against post-influenza bacterial pneumonia by increasing phagocyte recruitment and production of reactive oxygen species. J. Infect. Dis. 209 (11) 1827-1836. 2013, PMID: 24367039
Gottipati, K., Bandari, S., Nonnenmann, M. W., Levin, J. L., Dooley, G. P., Reynolds, S. J., and Boggaram, V. Trancriptional and protein kinase signaling mechanisms mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 308: L11-L21, 2015. PMID: 25398986
Courtney Mitchell, B. S., Briana Echols, B. S., Kartiga Natarajan, Ph. D.