Dr. Mallampalli's primary research interests are in the area of acute respiratory distress syndrome, with a focus on the regulation of surfactant phospholipid production. Surfactant is a lipoproteinaceous material that is essential for stabilizing the lung and serves as a critical component of innate immunity in the lung. Dr. Mallampalli's work centers on regulation of the CTP: phosphocholine cytidylyltransferase (CCT), the rate-limiting enzyme that catalyzes the pivotal step in the biosynthesis of phosphatidylcholine, the major phospholipid of eukaryotic membranes and of lung surfactant. He and his team study how lung sphingolipids generated in response to TNF-alpha modify the biophysical activity of surfactant. In addition, during the process of cloning and characterizing the murine CCT gene, Dr. Mallampalli's laboratory discovered that the 5' flanking region of the CCT gene harbors a small, yet robust, core promoter (~200 bp). This observation led to the current hypothesis that the CCT promoter might be useful for driving high-level CTR expression in vectors such as recombinant adeno-associated virus. Current studies in the laboratory include random and site-directed mutagenesis of the CCT gene to define an optimal CCT core promoter, with the aim of subsequently using such a promoter to drive CFTR expression in airway epithelia. The long-term goal is to package CCT-CFTR constructs into viral constructs for long-term expression in vivo.
Selected Publications:
Wu, Y., Xu, Z., Henderson, F.C., Ryan, A.J., Yahr, T.L., and Mallampalli, R.K. 2007. Chronic Pseudomonas aeruginosa infection reduces surfactant levels by inhibiting its biosynthesis. Cell Microbiol 9:1062-1072.
Zhou J., Wu, Y., Henderson, F., McCoy, D.M., Salome, R.G., McGowan, S.E., and Mallampalli, R.K. Adenoviral gene transfer of a mutant surfactant enzyme ameliorates pseudomonas-induced lung injury. Gene Ther. 13:974-985, 2006.
McCoy, D.M, Fisher K., Robichaud J., Ryan, A.J., and Mallampalli, R.K. Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice. Am. J. Respir. Cell Mol. Biol 35: 394-402, 2006.
Zhou, J., You, Y., Zabner, J., Ryan, A.J., and Mallampalli, R.K. 2004. The CCT promoter directs high-level transgene expression in distal lung epithelial cell lines. Am J Respir Cell Mol Biol 30:61-68.