Soichi Tanda, D.Sc.

     My long-term interest is to understand how gene expression is controlled in a coordinated manner. In my laboratory, I pursue this goal using the fruit fly Drosophila melanogaster. Although they are tiny creatures, they have enormous potential in biomedical science. Its genome contains about 14,000 genes, and about 61% of human disease genes have their homologues in Drosophila. Thus, Drosophila genetics will contribute to finding cures for human diseases.

     To this extent, I focus on two model systems in Drosophila. The first one is the hedgehog signal transduction pathway. This pathway is one of the most important signaling pathways in Drosophila as well as humans. In humans, loss of one wild type copy will result in holoprosencephaly (Cyclops). Some teratogens (environmental agents disrupting normal development) are known to inhibit the activity of the hedgehog signal transduction pathway. Since the Hedgehog protein is a secreted molecule, the signal outside the cell must be transmitted to the nucleus via several proteins in the cytoplasm. Participants in the pathway may differ depending on tissue types and developmental stages. In my laboratory, I study two genes called shanti and oroshigane in the embryo. They are likely to be a part of hedgehog signaling. After cloning these genes, I am now exploring how they function in hedgehog signaling using molecular as well as genetic approaches.

     The second system is Drosophila hematopoiesis, blood cell development, which is a less understood area in Drosophila research. An interesting fact is that the known components in hematopoiesis are also found in humans. Transcription factors NF-kBs are among them and known as a key factor for immune and inflammatory responses as well. My pursuit is to understand the role of the semushi gene, whose function is directly connected to NF-kB activity. Interestingly, semushi mutations cause a leukemia-like symptom, which indicates that the regulation of NF-kB activity is also very important for hematopoiesis in Drosophila like humans. With the power of genetics, this system provides us with a unique opportunity for understanding the genetic and molecular mechanisms of hematopoiesis. I hope that my research will contribute to cure leukemia patients in the future.

Selected References:

• Chen, Y., D. B. Carlini, J. F. Baines, J. Parsch, J. M. Braverman, S. Tanda, and W. Stephan, 1999 RNA Secondary Structure and Compensatory Evolution. Genes Genet. Syst. 74: 271-286.

• Parsch, J., W. Stephan, and S. Tanda, 1999 A highly conserved sequence in the 3' untranslated region of the Drosophila Adh gene plays a functional role in Adh expression. Genetics 151: 667-674.

• Chen, F.H., M. Ukhanova, D. Thomas, G. Afshar, S. Tanda, B.-A. Battelle, and R. Payne, 1999 Molecular cloning of a putative cyclic nucleotide-gated ion channel from Limulus polyphemus. J. Neurochem. 72: 461-471.

• Epps, J.L. and S. Tanda, 1998 The Drosophila semushi mutation blocks nuclear import of Bicoid during embryogenesis. Curr. Biol. 8: 1277-1280.

• Parsch J., W. Stephan, and S. Tanda, 1998 Long-range base pairing in Drosophila and human mRNA sequences. Mol. Biol. Evol. 15: 820-826.

• Parsch, J., S. Tanda, and W. Stephan, 1997 Site-directed mutations reveal long-range compensatory interactions in the Adh gene of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 94: 928-933.